Light treatment equipment for inhibiting or preventing Alzheimer's disease

Abstract

The present application provides a light treatment device for suppressing or preventing Alzheimer's disease. A light treatment device includes a carrier structure and an array of near-infrared irradiation units. The bearing mechanism forms an accommodating space for the head of the object and bears the array of the near-infrared irradiation units. The array of near-infrared irradiation units is configured such that near-infrared light is emitted into the accommodation space, when the head of the subject is in place, an irradiation space range covering at least the anterior upper cranial portion, the top cranial portion, the left cranial portion and the right cranial portion is formed, and the time-average total irradiation power of the head cover portion acting on the head of the subject is 27.5 W or more, 31 W or more, 40 W or more, or 60 W or more, and the irradiation power of the head cover portion acting on the head of the subject is 27.5 W or more, 31 W or more, 40 W or more, or 60 W or more. Or more than 70W, and the space-time average optical power density irradiated to each part does not exceed 230mW / cm < 2 >. The light treatment device does not depend on nasal and ocular irradiation, achieves an optimized treatment effect on AD patients from MCI to dementia during the course of treatment, and not only effectively maintains the treatment effect but also continuously increases the treatment effect when the light treatment is interrupted.

Description

[0001] This application is a divisional application of Chinese invention patent application No. 202480003954.X, filed on October 16, 2024, entitled "A phototherapy device for inhibiting or preventing Alzheimer's disease". Technical Field

[0002] This application belongs to the technical field of phototherapy devices for brain and cognitive diseases, and particularly relates to a phototherapy device for inhibiting or preventing Alzheimer's disease. Background Technology

[0003] Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease that primarily affects older adults, especially those over 60. The disease is characterized by memory loss, loss of social and occupational function, executive function decline, speech and motor deficits, personality changes, and behavioral and psychological disturbances.

[0004] According to international guidelines for clinical staging, the course of Alzheimer's disease (AD) can be divided into three stages: preclinical stage, mild cognitive impairment (MCI) stage, and dementia stage. The dementia stage can be further subdivided into mild, moderate, and severe dementia stages.

[0005] In the early clinical stages, biological samples taken from an individual's brain show changes in biomarkers that can be detected by medical means, such as abnormal changes in amyloid and tau proteins that can be identified by PET scans or biochemical tests of cerebrospinal fluid / blood, but do not show any symptoms, such as memory loss.

[0006] It's important to note that many years before a diagnosis of Alzheimer's disease (AD), there may be no AD symptoms, but pathological changes may have already occurred, such as amyloid plaques (Aβ) in the cerebral cortex. It is currently speculated that these pathological changes require the synergy of other pathological changes, such as neurofibrillary tangles (i.e., a positive tau-PET test), to progress to the next pathological stage—the mitochondrial incoordination (MCI) stage. In the MCI stage, along with changes in AD biomarkers, cognitive function alterations occur, such as a slow and slight decline in memory, language, and thinking abilities.

[0007] Patients typically experience a period of cognitive impairment (MCI) before progressing to dementia. 15% of MCI cases progress to dementia within 2 years; approximately one-third of MCI cases progress to dementia within 5 years; and about 26% of MCI cases revert to cognitive normalization.

[0008] Once dementia progresses, patients experience significant abnormalities in memory, language, thinking, and behavior that affect their daily living abilities, and AD-related biomarkers also show marked abnormalities.

[0009] In recent years, photobiological modulation (PBM) has been introduced to treat Alzheimer's disease (AD). PBM involves applying red or near-infrared light with wavelengths ranging from 600 to 1100 nm to the head, which penetrates the scalp and skull to act on brain tissue. Through various mechanisms of action, such as increasing Aβ clearance, reducing abnormal Tau protein aggregation, improving metabolism and mitochondrial function, increasing cerebral blood flow, and improving antioxidant stress and anti-inflammatory capabilities, it can treat AD non-invasively.

[0010] The photobiological modulation devices (hereinafter referred to as phototherapy devices) from different manufacturers vary considerably in their irradiation areas, leading to problems in practical applications. For example, many manufacturers' phototherapy devices rely on irradiation at the subject's eyes (see Liang Chen, etc., A Pilot Study of Near-Infrared Light Treatment for Alzheimer's Disease, Journal of Alzheimer's Disease 91 (2023) 191–201) or via the subject's nasal cavity (see Anita E. Saltmarche, etc., Signi (This section discusses the treatment of Alzheimer's disease (AD) by irradiating the olfactory bulb with near-infrared light. A significant portion of the therapeutic effect of these devices relies on the near-infrared light dose delivered to the olfactory bulb via the eye or nose, and subsequently to the frontal lobe. However, the majority of AD patients are elderly. During research and clinical trials in nursing homes, the inventors found that most elderly patients exhibited significant resistance to eye and nasal irradiation, making it difficult to implement. Furthermore, irradiation of the eye carries uncontrollable risks and damage, including but not limited to infrared cataracts, retinal and choroidal damage, photosensitive cell damage, and corneal damage.)

[0011] In addition, some phototherapy devices typically irradiate near-infrared light onto the default mode network (DMN), or the irradiation modules are concentrated in the corresponding area of ​​the occipital lobe without irradiating the parietal lobe. The irradiation areas vary and there is no definitive conclusion.

[0012] Currently, in the clinical efficacy of phototherapy devices, people usually only focus on whether there is a decrease in ADAS-cog scale scores and an increase in MMSE scale scores during treatment. They pay the most attention to the decrease and increase in scores, but do not pay attention to the details of the change process: such as the stagnation of score optimization during phototherapy, or the rapid deterioration and rebound of the patient's cognitive status after phototherapy is stopped, or the learning effect caused by too short follow-up intervals.

[0013] Correspondingly, current research on the mechanisms of action of phototherapy devices during and after treatment is relatively rudimentary. There is considerable room for improvement in order to achieve optimized treatment outcomes throughout the entire treatment process in a broader population of AD patients (from MCI to severe dementia, including those who do not receive nasal or ocular transluminal therapy). Summary of the Invention

[0014] In view of the above-mentioned problems existing in the prior art, the purpose of this application is to provide a phototherapy device for inhibiting or preventing Alzheimer's disease, which does not rely on nasal and ocular irradiation, achieves optimized treatment effects for AD patients from MCI to dementia during the course of treatment, and effectively maintains and continuously increases the treatment effect when phototherapy is interrupted.

[0015] According to a first aspect of this application, a phototherapy device for inhibiting or preventing Alzheimer's disease is provided. The phototherapy device includes a support structure and an array of near-infrared irradiation units. The support structure is configured to form a receiving space for a subject's head and to support the array of near-infrared irradiation units. The array of near-infrared irradiation units is configured to emit near-infrared light into the receiving space, thereby forming an irradiation space covering at least the upper front part, the top of the skull, the left side of the skull, and the right side of the skull, when the subject's head is positioned in the receiving space. The time-averaged total irradiation power acting on the subject's head reaches 27.5W or more, 31W or more, 40W or more, 60W or more, or 70W or more, and the spatiotemporal average light power density does not exceed 230 mW / cm². 2 .

[0016] Compared with existing technologies, the beneficial effects of the embodiments of this application are as follows. This phototherapy device is not limited by specific structures, nor is it limited to whether the near-infrared irradiation unit is a common LED or a low-energy laser diode. It can irradiate at least the upper anterior part, top of the skull, along with the left and right sides of the skull, with sufficient total power of near-infrared light onto the surface of the subject's head, avoiding transnasal and transcranial irradiation that may cause discomfort or resistance in some patients. This irradiation spatial range ensures that near-infrared light can irradiate the core network nodes and brain regions of the Default Mode Network (DMN), Central Executive Network (ECN, also known as the executive control network), Seminarization Network (SN), Sensorimotor Network (SMN), and Dorsal Attention Network (DAN). By synergistically applying a time-averaged total irradiation power of 27.5W or more to the aforementioned parts of the subject's head, the development of neurodegenerative diseases caused by Aβ plaques and Tau protein abnormalities along the brain's functional networks can be effectively inhibited or interrupted. In clinical trials, this phototherapy device has demonstrated therapeutic effects on various individual AD patients ranging from MCI to dementia. Furthermore, in a clinical trial involving approximately 27 patients (including treatment and control groups) with mild and moderate dementia, the phototherapy device demonstrated a steady increase in efficacy throughout the treatment course. Even during periods of interruption after each treatment course, the therapeutic effect was maintained, and the biochemical reactions induced by previous phototherapy continued to trigger inhibitory effects, leading to further improvement in the patients' conditions. Although the exact mechanism of action is not fully understood, the phototherapy device of this application has indeed demonstrated excellent "photocharging depth" and "endurance" in inhibiting the progression of Alzheimer's disease, avoiding regression during interruptions, continuously increasing benefits, and without any adverse reactions in patients.

[0017] It should be understood that the foregoing general description and the following detailed description are exemplary and illustrative only, and are not intended to limit the invention.

[0018] The overview of various implementations or examples of the technology described in this application is not a full disclosure of the entire scope or all features of the disclosed technology. Attached Figure Description

[0019] In drawings that are not necessarily drawn to scale, the same reference numerals may describe similar parts in different views. The same reference numerals with or without letter suffixes may indicate different instances of similar parts. The drawings generally illustrate various embodiments by way of example rather than limitation and, together with the description and claims, serve to explain embodiments of the invention. Where appropriate, the same reference numerals are used in all drawings to refer to the same or similar parts. Such embodiments are illustrative and not intended to be exhaustive or exclusive embodiments of the apparatus or method.

[0020] Figure 1 This is a longitudinal cross-sectional structural diagram of the headgear of the phototherapy device according to the first embodiment of this application.

[0021] Figure 2 This is a longitudinal cross-sectional structural diagram of the headgear of the phototherapy device according to the second embodiment of this application.

[0022] Figure 3 This is a bottom view of the headgear of the phototherapy device according to the first or second embodiment of this application.

[0023] Figures 4(a)-4(f) illustrate the characteristic parameters of a reference head model of a therapist's head or a group of therapists according to the third embodiment of this application.

[0024] Figure 5(a) shows a front view of a reference head model as an example of a subject head according to the fourth embodiment of this application. The electrode positions of the 10-10 international standard lead system, the overall boundary line of the reference head, and the boundary lines between the upper front part of the skull, the left side of the skull, and the right side of the skull are shown on the subject head.

[0025] Figure 5(b) shows a left-side view of a reference head model as an example of an object head according to the fourth embodiment of this application. The object head shows the electrode positions of the 10-10 international standard lead system, the overall boundary line of the reference head, and the boundary lines between the upper front part of the skull, the left side of the skull, the top of the skull, and the back part of the skull.

[0026] Figure 5(c) shows a right-side view of a reference head model as an example of an object head according to the fourth embodiment of this application. The object head shows the electrode positions of the 10-10 international standard lead system, the overall boundary line of the reference head, and the boundary lines between the upper front part of the skull, the right side of the skull, the top of the skull, and the back part of the skull.

[0027] Figure 5(d) shows a top view of a reference head model as an example of an object head according to the fourth embodiment of this application. The object head shows the electrode positions of the 10-10 international standard lead system, the overall boundary line of the reference head, and the boundary lines between the upper front part of the skull, the top of the skull, the left side of the skull, the right side of the skull, and the back part of the skull.

[0028] Figure 5(e) shows a rear view of a reference head model as an example of an object head according to the fourth embodiment of this application, showing the electrode positions of the 10-10 international standard lead system, the overall boundary line of the reference head, and the boundary lines between the top of the skull, the left side of the skull, the right side of the skull, and the back of the skull.

[0029] Figure 5(f) shows an example diagram of the irradiation area according to the fifth embodiment of this application.

[0030] Figure 6(a) shows a schematic diagram of the electrode positions of the upper anterior part of a reference head model, which serves as an example of the subject head, based on the 10-10 international standard lead system, according to the sixth embodiment of this application.

[0031] Figure 6(b) shows a schematic diagram of the electrode positions of the upper anterior cranial portion of a reference head model, which serves as an example of the subject head, according to the seventh embodiment of this application, based on the 10-10 international standard lead system.

[0032] Figure 6(c) shows a schematic diagram of the electrode positions of the upper anterior cranial portion of a reference head model, which serves as an example of the subject head, according to the eighth embodiment of this application, based on the 10-10 international standard lead system.

[0033] Figures 7(a)-7(c) show the division of the upper front part of the skull, the top of the skull, the left side of the skull, and the right side of the skull according to three embodiments of this application.

[0034] Figure 8 This diagram illustrates the spatial locations of the Default Mode Network (DMN), Central Executive Network (ECN, also known as the Executive Control Network), Spokesperson Network (SN), Sensorimotor Network (SMN), Dorsal Attention Network (DAN), and Visual Network (VN) in the brain.

[0035] Figure 9 A schematic diagram of the arrangement structure of the lamp panel according to the eighth embodiment of this application is shown.

[0036] Figure 10 A schematic diagram of the arrangement structure of the lamp holder according to the ninth embodiment of this application is shown.

[0037] Figure 11 A schematic diagram illustrating the process of conducting a clinical trial on AD patients using a phototherapy device according to an embodiment of this application is shown.

[0038] Figure 12(a) shows the changes in ADAS-Cog scale scores of the control group before, during and after near-infrared phototherapy.

[0039] Figure 12(b) shows the changes in ADAS-Cog scale scores of the experimental group before, during and after near-infrared phototherapy.

[0040] Figure 13(a) shows the changes in MMSE scores of the control group before, during and after near-infrared phototherapy.

[0041] Figure 13(b) shows the changes in MMSE scores of the experimental group before, during and after near-infrared phototherapy.

[0042] Figure label: 1-Outer shell; 2-Middle shell; 3-Inner shell; 4-Lamp panel receiving cavity; 5-Lamp panel; 6-Cold air chamber; 7-Ventilation hole; 701-Upper ventilation hole unit; 702-Middle ventilation hole unit; 703-Lower ventilation hole unit; 8-Cold air inlet; 9-Lamp panel fixing shell; 10-First layer lamp panel; 11-Second layer lamp panel; 12-Third layer lamp panel; 13-Fourth layer lamp panel; 14-Fifth layer lamp panel; 15-Sixth layer lamp panel; 16-Ventilation opening; 17-Lamp panel fixing bracket; 18-Connecting part. Detailed Implementation

[0043] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this application. All other embodiments obtained by those skilled in the art based on the described embodiments of this application without creative effort are within the scope of protection of this application.

[0044] Unless otherwise defined, the technical or scientific terms used in this application shall have the ordinary meaning understood by one of ordinary skill in the art to which this application pertains. The terms "first," "second," and similar terms used in this application do not indicate any order, quantity, or importance, but are merely used to distinguish different components. Terms such as "comprising" or "including" mean that the element or object preceding the word encompasses the elements or objects listed following the word and their equivalents, without excluding other elements or objects. Terms such as "connected" or "linked" are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. Terms such as "upper," "lower," "left," and "right" are used only to indicate relative positional relationships; when the absolute position of the described object changes, the relative positional relationship may also change accordingly.

[0045] The term "inhibition or prevention of Alzheimer's disease" in this application refers to its role in preventing, reducing the probability, alleviating, inhibiting, terminating, or even reversing the progression of Alzheimer's disease. The term "progression of Alzheimer's disease" encompasses both the appearance of clinical symptoms of AD and its subsequent development, as well as the occurrence of pathological or physiological phenomena associated with AD that have a certain probability of developing into AD, even before the appearance of obvious clinical symptoms. In other words, the statement "inhibition or prevention of Alzheimer's disease" in this application includes treating Alzheimer's disease that has already occurred, as well as preventing its occurrence or reducing its probability. Specifically, according to the 2018 diagnostic criteria for Alzheimer's disease from the National Institute on Aging and the Alzheimer's Disease Association (NIA-AA), based on the levels of β-amyloid (Aβ) and tau in the brain or cerebrospinal fluid, and the results of cranial MRI and FDG-PET scans, biomarkers can be classified into four categories, further dividing cognitive function into six levels. Level 1 is characterized by normal objective cognitive neuropsychological tests, no subjective cognitive complaints, no neurobehavioral symptoms, no informed reports of cognitive decline or neurobehavioral symptoms, and no follow-up test evidence of cognitive decline. Level 2 includes subjective cognitive decline (SCD), objective mild cognitive decline (Obj-SCD), and neurobehavioral symptoms. Levels 1 and 2 are collectively referred to as the preclinical stage. Level 3 is characterized by abnormal or impaired objective cognitive tests, but not reaching dementia, i.e., MCI. Levels 4-6 are mild, moderate, and severe dementia, respectively. Each stage within these six levels, if accompanied by positive biomarker test results, can be considered part of the Alzheimer's disease course as defined in this application. Furthermore, for individuals who carry genes associated with the risk of AD but whose current test results are negative for Aβ, such as APOEε4, ABCA7, CLU, CR1, PICALM, PLD3, and TREM2, even if their cognitive function is at level 1, implementing medical intervention to reduce their risk of developing AD and slow down their progression to AD can also be considered as "inhibition or prevention of Alzheimer's disease" in this application.

[0046] Unless otherwise specified, the term "cranioides" in this application is intended to encompass "cranioides" as defined in various ways in the fields of anthropology and medicine. For example, "cranioides" can be defined using the boundary established by Friess et al. (2002) when measuring the area of ​​the cranium. Alternatively, the portion of the head above the plane formed by the glabella and the upper edges of the external auditory meatuses on both sides can be considered the "cranioides." Furthermore, "cranioides" can also refer to the portion of the head surface enclosed by a general boundary line, defined according to the 10-10 international standard lead system, which extends from the glabella of the subject's head, passing through the preauricular points on both sides, posteriorly around the occipital protuberance, and converging between the electrode positions O1, OZ, and O2 of the 10-10 international standard lead system.

[0047] In this application, the term "acting on the scalp of the subject's head" refers to the thin outer irradiation surface immediately adjacent to the hair (or scalp where there is no hair) of the subject's scalp. Near-infrared light irradiating this thin outer irradiation surface means that the irradiation energy of the near-infrared light is transferred to the scalp of the head, which includes the hair, scalp, skull, and brain tissue. Furthermore, after absorption by the hair and attenuation by the scalp and skull, the remaining energy capable of acting on the cortex or even deeper parts of the brain tissue is related to attenuation along the transmission path.

[0048] The term “time-averaged total irradiance” in this application is distinct from peak irradiance and is intended to represent the total irradiance level obtained by averaging the total irradiance energy accumulated over a period of time.

[0049] In this application, the term "time-average optical power density" refers to the optical power density averaged over time. For example, the "time-average optical power density" of a target site refers to the optical power density at that target site averaged over time. As another example, the "time-average optical power density" of a target portion refers to the "time-average optical power density" representing a location on that target portion. Specifically, the "time-average optical power density" of the target portion is 30-60 mW / cm². 2 This means that the time-averaged optical power density at various representative positions on the target surface, such as, but not limited to, the position corresponding to the center of the lamp panel, is 30-60 mW / cm². 2 It fluctuates within a certain range.

[0050] The so-called "spatiotemporal average optical power density" of the target region is intended to represent the time-averaged optical power density relative to the surface area of ​​the target region, that is, the optical power density after performing averaging operations relative to both surface area and time.

[0051] According to a first aspect of this application, a phototherapy device for inhibiting or preventing Alzheimer's disease is provided. The phototherapy device may include a support mechanism, such as, but not limited to, [other types of]... Figures 1-3 The headgear shown has a support mechanism configured to form a receiving space for the object's head and to support an array 5 of near-infrared irradiation units. In some embodiments, the support mechanism may employ, for example... Figures 1-3 The loose-fitting cap shown allows for an appropriate distance, on the order of several centimeters, between the AD patient's head and the inner wall of the cap when positioned within it. This provides sufficient leeway for head movement without causing anxiety or distress due to excessive openness. Note that the phrase "the subject's head is positioned within the receiving space" in this text means that the subject's head is in a standard treatment position within the receiving space, or within an allowable deviation from the standard treatment position. For example, in the standard treatment position, the subject's head's center of gravity can be aligned with the center of the receiving space, and their front-to-back axes can be aligned. Alternatively, in the standard treatment position, the subject's head can be centered within the receiving space, with approximately equidistant front-to-back and equidistant lateral distances from the front and back walls of the receiving space. For example, with... Figures 1-3 Taking the phototherapy headgear shown as an example, when in place, the brow bone of the subject's head can be aligned with the front edge of the headgear, and the subject's head can be positioned in the center inside the headgear, so that the front and back distances from the irradiation surface of the inner shell are basically the same, and the left and right distances from the irradiation surface of the inner shell are also basically the same.

[0052] In some embodiments, the support mechanism can also be implemented as a skeleton structure that fits closely to the head of the AD patient, so that the infrared irradiation unit or its subarray can be mounted as a module on the skeleton structure. In still other embodiments, the support mechanism can also be implemented as a non-headgear-type support frame further away from the head of the AD patient, using various structures such as arc shape, cone shape, spatial grid shape, etc., as long as it supports the array 5 of the near-infrared irradiation unit, which will not be described in detail here.

[0053] The array 5 of the near-infrared irradiation unit is specifically configured to emit near-infrared light into the accommodating space. When the subject's head is positioned in the accommodating space, it forms an irradiation space covering at least the upper front part of the skull, the top of the skull, and the left and right sides of the skull, covering the surface of the subject's head. The time-averaged total irradiation power acting on the subject's head reaches 27.5W or more, and the spatiotemporal average optical power density does not exceed 230mW / cm². 2 To avoid the risk of heat damage.

[0054] In some embodiments, a controller and drive circuit may be provided in a host unit located away from the headgear and wired to the near-infrared irradiation units to control and drive each near-infrared irradiation unit via wiring, so as to provide the required time-averaged total irradiance and spatiotemporal average optical power density. Alternatively, the controller and drive circuit may also be provided in the headgear to control and drive each near-infrared irradiation unit to provide the required time-averaged total irradiance and spatiotemporal average optical power density.

[0055] Specifically, the upper anterior part of the skull surface is mainly associated with the frontal lobe, the top of the skull surface is mainly associated with the parietal lobe, and the left and right sides of the skull surface are mainly associated with the left and right temporal lobes. However, it's important to understand that this association is not merely spatial; it also involves connections in the brain's functional networks. In other words, sufficient near-infrared light irradiation of the upper anterior part of the skull can achieve neural modulation of the frontal lobe, and the same applies to other parts. The inventors have discovered that by directly applying a time-averaged total irradiation power of 27.5W or higher to the scalp of the subject, with the irradiation area covering at least the upper anterior cranial region, the top of the skull, along with the left and right sides of the skull, sufficient energy of near-infrared light can be irradiated onto the core network nodes and brain regions of the Default Mode Network (DMN), Central Executive Network (ECN, also known as the executive control network), Seminarization Network (SN), Sensorimotor Network (SMN), and Dorsal Attention Network (DAN). This effectively inhibits or interrupts the propagation of neurodegenerative diseases caused by Aβ plaques and Tau protein abnormalities along the brain's functional networks. The inventors have also creatively discovered that by focusing solely on the average irradiation power per unit area (i.e., the light power level per unit area, mW / cm²), 2 Or simply focus on the irradiation energy (J / cm²) per unit area that is "filled" 2However, this does not guarantee robust therapeutic efficacy against global Alzheimer's disease (AD). Specifically, AD is a global brain disease where lesions spread from certain regions along functional connectivity areas of the brain's functional networks rather than along less spatially connected sites. Furthermore, AD lesions induce specific responses in specific cell populations (e.g., but not limited to, astrocytes, microglia, oligodendrocytes, neurons, vascular cells, peripheral glial cells, and the extracellular matrix). By applying sufficient time-averaged total irradiation power to these cell populations, they not only induce altered responses that inhibit AD but also disseminate these altered responses along functional connectivity areas to other cell populations. Please note that the positioning and extent of the anterior superior cranial region, cranial top, along with the left and right cranial regions in this application precisely correspond to or target the core network nodes and brain regions of the aforementioned brain networks. By irradiating the core network nodes and brain regions of these networks with sufficient time-averaged total irradiation power, the propagation path along the functional connectivity regions is smoother, and the propagation and transmission of inhibitory responses are more efficient, thereby achieving optimized AD inhibition effects across the entire brain. If the process of irradiating the subject's head with near-infrared light is analogous to the battery charging process, for example, called a "photocharging" process, the phototherapy device according to this application can make the subject's brain have a larger "photocharging capacity," a deeper "photocharging depth," and a faster "photocharging speed," thus resulting in superior subsequent "endurance" (i.e., the time during which the therapeutic effect can be maintained or even continuously increased after being charged with light energy). In addition to the total power used in the large-scale clinical trials described below, the inventors also employed multiple levels of total power, such as above 31W, 40W, 60W, or 70W, specifically ranging from 29W to 135W in 1W increments. Examples include total power levels of 30W, 32W, 34W, 35W, 38W, 45W, 50W, 60W, 65W, 70W, 75W, 80W, 85W, 90W, 95W, 100W, 105W, 110W, 115W, 120W, 125W, 130W, and 135W. Individual tests of light therapy on AD patients confirmed that no adverse reactions occurred within this range of total power levels. AD patients also reported some relief from previous cognitive impairments, such as recent memory loss, muscle stiffness, and weakened spatial abilities.

[0056] The head of the object includes the head of the therapist, or a reference head model of a group of therapists.

[0057] In some embodiments, during the manufacturing of phototherapy devices, a reference head model of the patient population can be used to simulate the attenuation and transmission of near-infrared light. Specifically, a reference head model with a representative size can be selected based on the patient population. For example, since the majority of AD patients are over 60 years old, the parameters of the reference head model for this age group can be: head width of 140-166 mm, head length of 170-196 mm, head circumference of 525-583 mm, morphological surface length of 104-130 mm, sagittal arc of 304-372 mm, intertragus arc of 320-375 mm, and head height of 206-253 mm. These parameters are shown in Figures 4(a)-4(f).

[0058] Specifically, the parameter range of this reference head model falls at the intersection of the parameter values ​​of P1, P5, P10, P50, P90, P95, and P99 for women in this age group and the parameter values ​​of P1, P10, P50, P90, P95, and P99 for men in this age group. Therefore, it is highly representative of both men and women in this age group.

[0059] In some embodiments, the parameters of the reference head model can be refined as follows: head width 152 mm, head length 184 mm, head circumference 536.7 mm, morphological surface length 109.3 mm, sagittal arc 355.6 mm, intertragic arc 324.1 mm, and head height 206 mm. These refined parameters are at least partially determined based on the P50 parameter values ​​for women and men of this age group. For example, the head width and head length here are the average of two corresponding P50 parameter values. The P50 parameter values ​​for women of this age group are as follows: head width 149 mm, head length 180 mm, head circumference 548 mm, morphological surface length 111 mm, sagittal arc 335 mm, intertragic arc 342 mm, and head height 228 mm. The P50 parameters for men in this age group are as follows: head width 155mm, head length 188mm, head circumference 565mm, morphological face length 121mm, sagittal arc 343mm, intertragic arc 351mm, and head height 231mm. It can be seen that the parameters of this baseline head model have a good match with the P50 parameters of women and men in this age group, thus making it more representative. Furthermore, the cephalofacial index of this parameter is 82%, which is also consistent with the range of cephalofacial indices of the dominant head shape in Chinese people (also East Asian populations)—the brachycephaly type. Therefore, the parameters of this baseline head model are particularly representative of Chinese and East Asian populations. In some embodiments, for populations with other cephalofacial indices, such as, but not limited to, major human populations in Europe, South Asia, and Africa, the parameters can be adaptively adjusted to achieve good representativeness.

[0060] The phototherapy device of this application has been tested on multiple reference head models (such as, but not limited to, those representing elderly East Asian men and women, elderly African American men and women, etc.) and it has been confirmed that, when each reference head model is in place in the receiving space, it can cover at least the upper front part of the skull, the top of the skull, together with the left and right sides of the skull, and provide sufficient time-averaged total irradiation power.

[0061] In some embodiments, when manufacturing a phototherapy device, a representative reference head model can be prepared for the target population, and the irradiation space range can be verified on the scalp surface of the reference head model. Subsequently, the irradiation space range on the scalp surface is verified for a predetermined range of target populations to ensure that, when the head of an individual in the target population is positioned in the receiving space, at least the upper front part of the skull, the top of the skull, along with the left and right sides of the skull, are adequately covered and receive sufficient time-averaged total irradiation power.

[0062] In the fourth embodiment of this application, the scalp, upper anterior skull, top of the skull, and together with the left and right sides of the skull, are defined on the subject's head according to the electrode positions of the 10-10 international standard lead system, as shown in Figures 5(a)-5(e). In Figures 5(a)-5(f), protrusions are drawn at each electrode position for clearer illustration; however, in some embodiments, the reference head mold surface may not have protrusions. The 10-10 international standard lead system is a standard for electrode placement in electroencephalography (EEG) recording, providing a precise and consistent way to mark and locate electrodes on the head. That is, the 10-10 system can be applied directly to the subject's head without transcranial transcranial translocation. This system is an extension of the earlier 10-20 system, proposed by the International Society for Electroencephalography (IEA) to standardize electrode positions in EEG recordings.

[0063] In the 10-10 system, electrode placement is based on anatomical landmarks of the head, including the nasal root, the inion, and the pre-auricular points. These landmarks are used to determine the anterior-posterior and lateral midlines of the head, allowing for electrode placement at a 10% ratio.

[0064] The 10-10 system's naming convention is based on the 10-20 system, but provides denser electrode placement, particularly in the base and anterior temporal lobe and the frontal lobe, locating positions often overlooked in the 10-20 system. Furthermore, the 10-10 system introduces new electrodes to allow for more precise subdivision of brain region boundaries, such as FC for the frontocentral region, FT for the frontotemporal region, CP for the central-parietal region, and PO for the parieto-occipital region. The 10-10 system's electrode placement effectively eliminates the influence of individual head shape and size differences, allowing for relatively accurate localization of the same brain region nodes in different individuals using the same electrode. Its denser electrode placement, especially for the temporal and frontal lobes, enables more detailed subdivision of the anterior superior cranium, the top of the skull, and the left and right sides of the skull on the surface of the skull (outside the skull, scalp, and hair), correspondingly achieving more detailed subdivision of various brain regions (frontal, parietal, and temporal lobes) within the skull and subdural space.

[0065] Referring to Figures 5(a)-5(e), the upper anterior cranial portion 500a, the top cranial portion 500b, the left cranial portion 500c, and the right cranial portion 500d, together with the posterior cranial portion 500e, are arranged in blocks and are located within the total area enclosed by the overall boundary line 501. The overall boundary line 501 starts from the glabella of the subject's head (see Figure 5(a)), passes through the two preauricular points (see Figures 5(b) and 5(c)), and then circles backward, passing between the occipital protuberance and the electrode positions O1, OZ, and O2 of the 10-10 international standard lead system, where it converges (see Figure 5(e)). Note that, in order to make the electrode positions clearer, this application identifies the small protrusions and the names of the electrode positions at each electrode location; however, it should be understood that the small protrusions may not be present.

[0066] The total boundary line 501 can be used to define the surface of the skull; that is, the area of ​​the total region enclosed by the total boundary line 501 is the total surface area of ​​the skull. Although in Figures 5(a)-5(e), the anterior upper part of the skull 500a, the top of the skull 500b, the left side of the skull 500c, and the right side of the skull 500d, together with the posterior part of the skull 500e, occupy the entire total region, this is merely an example; these parts may occupy only a portion of the total region. For example, they may occupy more than 60%, or more than 70%, or more than 80% of their surface. Furthermore, the percentage of the total surface area occupied by these parts can range from 60% to 100%, distributed in 1% increments.

[0067] In some embodiments, the upper anterior portion 500a, the top portion 500b, together with the left lateral portion 500c and the right lateral portion 500d, occupy more than 60%, 70%, or 80% of the surface area of ​​the first region defined by the fifth boundary line 502a from the total region, as shown in Figure 5(e). According to the 10-10 standard lead system, the fifth boundary line 502a sequentially passes between the following electrode positions (see Figures 5(b), 5(c), and 5(e)): between P7 and PO7, between P5 and PO5, between P3 and PO3, between P1 and POZ, between PZ and POZ, between P2 and POZ, between P4 and PO4, between P6 and PO6, and between P8 and PO8. The term "passing between electrode positions A and B" in this application is intended to refer to the intermediate point on the line connecting electrode positions A and B. For example, the intermediate point can be the midpoint of the line or other points on the line, such as points at which the distances from electrode positions A and B are in a 1:2 ratio. In some embodiments, for the same boundary line, such as the fifth boundary line 502a, the points that pass between the paired electrode positions can be located at different ratios on the line so that the boundary line formed by the sequential connection is smooth. By delivering sufficient time-averaged irradiation power, such as 27.5W or more, 31W or more, 40W or more, 60W or more, or 70W or more, to more than 60%, 70%, or 80% of the surface area of ​​the first region, it is possible to substantially cover the core network nodes and brain regions of the Default Mode Network (DMN), Central Executive Network (ECN, also known as the executive control network), Seminarization Network (SN), Sensorimotor Network (SMN), and Dorsal Attention Network (DAN), or occasionally deviate. Sufficient irradiation power also ensures that the irradiation power component at the deviated node breaks through the spatial interval and spreads to the adjacent core network nodes and brain regions.

[0068] Furthermore, by having the upper front part 500a, the top of the head 500b, together with the left side of the head 500c and the right side of the head 500d, collectively bear sufficient time-averaged irradiation power, the dependence on eye and nasal irradiation is eliminated, making the treatment experience more comfortable and relaxing for the patient. For example, when using a light-guiding comb such as the inventor's, dark hair is separated on the forehead, top of the head, and sides of the head to leave unobstructed areas on the scalp, optimizing the transmission of near-infrared light. Specifically, the transmittance of dense black hair and scalp can be increased by 20-30%, but the separated hair is combed back of the head and eventually overlaps on the occipital region. Once the occipital region (corresponding to the back of the head 500e) is no longer relied upon, the irradiation range is as shown in Figure 5(f), for example, the dark hair in the upper front part 500a, the top of the head 500b, together with the left side of the head 500c and the right side of the head 500d can be better separated to improve transmittance. Furthermore, given the complex curved shape of the occipital region, which is lower and partially concave, the surrounding near-infrared light is easily and significantly blocked unless the irradiation unit is placed in close proximity. This is addressed by utilizing the technology of this application. Figures 1-3 The phototherapy device shown was also verified during irradiation tests: modifying the near-infrared irradiation scheme to increase the light power density at the upper anterior part of the skull (500a), the top of the skull (500b), together with the left side of the skull (500c) and the right side of the skull (500d) was significantly more effective and less difficult to modify than increasing the light power density at the posterior part of the skull (500e).

[0069] In some embodiments, the anterior superior cranial portion 500a, the top cranial portion 500b, together with the left cranial portion 500c and the right cranial portion 500d, may be divided as follows, such that each portion more precisely corresponds to the core network nodes and brain regions covering the default mode network (DMN), central executive network (ECN), salience network (SN), sensorimotor network (SMN) and dorsal attention network (DAN).

[0070] In some embodiments, the anterior upper part 500a, the top of the skull 500b, together with the left side of the skull 500c and the right side of the skull 500d, can be divided according to their boundary lines. Specifically, in the first sub-region enclosed by the first boundary line 502b and the total boundary line 501, according to the 10-10 standard lead system, the first boundary line 502b sequentially passes through the following electrode positions: between F7 and FT7, between F5 and FC5, between FC3 and C3, between FC1 and C1 (see Figure 5(b)), between FCZ and CZ (see Figure 5(d)), between FC2 and C2, between FC4 and C4, between F6 and FC6, and between F8 and FT8 (see Figure 5(c)). In some embodiments, the anterior upper part 500a occupies more than 60%, or more than 70%, or more than 80% of the surface area of ​​the first sub-region. Taking the upper anterior cranial region 500a as an example, it can be divided into blocks surrounding grouped electrode positions (see Figure 6(a)) or connected regions with multiple openings (see Figure 6(b), where the opening positions may or may not correspond to electrode positions) to achieve the desired percentage of the surface area relative to the first sub-region. In some embodiments, the upper anterior cranial region 500a can also cover the entire first sub-region (see Figure 6(c)) to achieve omnidirectional irradiation of the first sub-region. This can also be applied to other parts, such as the top cranial region 500b, together with the left side cranial region 500c and the right side cranial region 500d, which will not be elaborated here.

[0071] In some embodiments, the cranial vault 500b is located within a second sub-region enclosed by a second boundary line 502c. According to the 10-10 standard lead system, the second boundary line 502c sequentially passes between the following electrode positions: between FC3 and C3, between FC1 and C1, between FCZ and CZ, between FC2 and C2, between FC4 and C4 (see Figure 5(d)), between C6 and C4, between CP6 and CP4, between P6 and P4 (see Figure 5(c)), between PO4 and P4, between PO4 and P2, between POZ and P2, between POZ and PZ, between POZ and P1, between PO3 and P1, between PO3 and P3 (see Figure 5(e)), between P5 and P3, between CP5 and CP3, and between C5 and C3 (see Figure 5(b)), and the cranial vault 500b occupies more than 60%, or more than 70%, or more than 80% of the surface area of ​​the second sub-region.

[0072] In some embodiments, the left cranial portion 500c is located within a third sub-region enclosed by the third boundary line 502d and the total boundary line 501, and the right cranial portion 500d is located within a fourth sub-region enclosed by the fourth boundary line 502e and the total boundary line 501. According to the 10-10 standard lead system, the third boundary line 502d sequentially passes through the following electrode positions (see Figure 5(b)): between FT7 and F7, between FC5 and F5, between FC5 and FC3, between C5 and C3, between CP5 and CP3, between P5 and P3, between P5 and PO5, and between P7 and PO7; the fourth boundary line 502e sequentially passes through the following electrode positions (see Figure 5(c)): between FT8 and F8, between FC6 and F6, between FC6 and FC4, between C6 and C4, between CP6 and CP4, between P6 and P4, between P6 and PO6, and between P8 and PO8. Specifically, the left side portion of the skull 500c occupies more than 60%, or more than 70%, or more than 80% of the surface area of ​​the third sub-region, and the right side portion of the skull 500d occupies more than 60%, or more than 70%, or more than 80% of the surface area of ​​the fourth sub-region.

[0073] In some embodiments, the upper anterior cranial portion 500a, the top cranial portion 500b, together with the left side cranial portion 500c and the right side cranial portion 500d, can be divided according to the set of electrode positions they contain. For example, according to the 10-10 standard lead system, referring to Figure 7(a), each portion can contain the following electrode positions: The upper anterior cranial portion 500a contains electrode positions FP2, FPZ, FP1, AF3, AF4, AF7, AF8, AFZ, FZ, F1, F2, F3, F4, F5, F6, F7, F8, FC1, FC2, FC3, FC4, and FCZ. The top cranial portion 500b contains electrode positions CZ, C1, C2, C3, C4, CPZ, CP1, CP2, CP3, CP4, PZ, P1, P2, P3, and P4. The left side portion of the skull 500c includes electrode positions FT7, FC5, T7, C5, TP7, CP5, P7, and P5, and the right side portion of the skull 500d includes electrode positions FT8, FC6, T8, C6, TP8, CP6, P8, and P6.

[0074] In some embodiments, the various portions may contain sparser electrode positions, i.e., a reduced coverage area. For example, according to a 10-10 standard lead system, the upper anterior cranial portion 500a may contain electrode positions AFZ, FZ, F1, F2, FP1, and FP2. The top cranial portion 500b contains electrode positions CZ, C1, C2, and CPZ. The left lateral cranial portion 500c contains electrode positions FT7, FC5, T7, and C5, or TP7, CP5, P7, or P5, and the right lateral cranial portion 500d contains electrode positions FT8, FC6, T8, and C6, or TP8, CP6, P8, and P6. Although the coverage area of ​​each part is reduced, by providing sufficient time-averaged irradiation power to each part, it is still possible to break through spatial intervals and spread to the core network nodes and brain regions near the default mode network (DMN), central executive network (ECN, also known as executive control network), salience network (SN), sensorimotor network (SMN), and dorsal attention network (DAN). This allows AD inhibition to be performed along the spread path of functional connectivity areas, such as inhibiting or eliminating the deposition of Aβ plaques, inhibiting or eliminating the abnormal aggregation of Tau protein, and inhibiting or improving neurofibrillary tangles. In this way, it can effectively inhibit or cut off the development of neurodegenerative diseases caused by Aβ plaques and Tau protein abnormalities along the brain's functional networks.

[0075] In some embodiments, the anterior superior cranial region 500a, the top cranial region 500b, together with the left cranial region 500c and the right cranial region 500d, can be divided as needed based on the set of electrode locations they contain. Note that this division can be for the convenience of illumination control of the phototherapy device, or for the specific structural requirements of the phototherapy device—especially the spatial arrangement of the units in the array of near-infrared irradiation units. Thus, the set of electrode locations contained in each of the anterior superior cranial region 500a, the top cranial region 500b, together with the left cranial region 500c and the right cranial region 500d can be flexibly divided, as long as it covers or is sufficiently close to the core network nodes and brain regions of the Default Mode Network (DMN), Central Executive Network (ECN, also known as the executive control network), Seminarization Network (SN), Sensorimotor Network (SMN), and Dorsal Attention Network (DAN).

[0076] For example, according to the 10-10 standard lead system, the division of each part can be seen in Figure 7(b). The upper anterior cranial part 500a includes FP2, FPZ, FP1, AF3, AF4, AF7, AF8, AFZ, FZ, F1, F2, F3, F4, F5, F6, F7, FC5, F8, FC1, FC2, FC3, FC4, FCZ, FC6, CZ, C1, C2; the top cranial part 500b includes electrode positions C5, C3, C4, C6, CPZ, CP1, CP2, CP3, CP4, CP5, CP6, PZ, P1, P2, P3, P4. The left lateral cranial part 500c includes electrode positions FT7, T7, TP7, P7, and the right lateral cranial part 500d includes electrode positions FT8, T8, TP8, P8.

[0077] For example, according to the 10-10 standard lead system, the division of each part can be seen in Figure 7(c). The upper anterior cranial part 500a includes electrode positions FP2, FPZ, FP1, AF3, AF4, AF7, AF8, AFZ, FZ, F1, F2, F3, F4, F5, F6, FC1, FC2, FC3, FC4, FC5, FC6, FCZ, CZ, C1, C2. The top cranial part 500b includes electrode positions C3, C4, C5, C6, CPZ, CP1, CP2, CP3, CP4, CP5, CP6, PZ, P1, P2, P3, P4. The left lateral cranial part 500c includes electrode positions F7, FT7, T7, TP7, P5, and the right lateral cranial part 500d includes electrode positions F8, FT8, T8, TP8, P6.

[0078] Figure 8 This diagram illustrates the spatial locations of the Default Mode Network (DMN), Central Executive Network (ECN, also known as the Executive Control Network), Spokesperson Network (SN), Sensorimotor Network (SMN), Dorsal Attention Network (DAN), and Visual Network (VN) in the brain. Figure 8As shown, the sites in the anterior part of the DMN include the medial prefrontal cortex, anterior cingulate cortex, dorsal prefrontal cortex, and lateral temporal lobe, while the sites in the posterior part include the medial temporal lobe, hippocampus, angular gyrus, inferior parietal lobule, posterior cingulate cortex, and ventral prefrontal cortex. More than a decade before the onset of identifiable cognitive states, β-amyloid (Aβ) begins to significantly deposit in the DMN, spreading along functional connectivity regions rather than along spatially related, less connected sites. In patients with dementia and MCI, brain functional networks are frequently damaged in the posterior cingulate cortex, medial temporal lobe (especially the hippocampal nodes), and posterior parietal lobe. In MCI patients, Aβ deposition initially occurs in the posterior cingulate cortex, prefrontal lobe, precuneus, and parietal-temporal lobes, leading to reduced and weakened functional connectivity in other brain regions within these areas. These lesion sites are well covered by the anterior superior cranial region (500a), cranial parietal region (500b), left cranial region (500c), and right cranial region (500d).

[0079] The salience network (SN), also known as the ventral attention network, together with the dorsal attention network (DAN), constitutes the attention network (AN). The salience network is mainly distributed in the anterior cingulate cortex, frontal insula cortex, and ventral prefrontal cortex. Abnormal increases in its internal function are related to damage to its functional network, leading to hyperactivity symptoms, especially in dementia patients, such as, but not limited to, irritability, abnormal motor behavior (restless pacing), anger, and aggressive behavior. In fact, weakened functional connectivity in the DMN can compensate by increasing SN-related functional connectivity; for example, enhanced SN connectivity in the right anterior genicular cingulate cortex. The DAN is mainly distributed in the intraparietal sulcus and oculomotor area of ​​the frontal lobe. Reduced functional connectivity between the DAN and SN is also closely associated with attention deficits in AD patients. Specifically, both the DAN and SN are damaged in AD patients, while in MCI patients, DAN function is impaired while the internal functional connectivity of the SN is somewhat preserved. See also Figure 8 The anterior superior cranial region 500a, cranial top 500b, left cranial region 500c, and right cranial region 500d fully cover the frontal lobe, especially adjacent to the temporal lobe, as well as the parietal lobe, thus fully covering the important sites of lesions in SN and DAN in AD patients.

[0080] The central executive network (ECN, also known as the executive control network) is mainly distributed in the dorsolateral prefrontal cortex, ventral prefrontal cortex, medial prefrontal cortex, and parietal cortex, etc. See [link to relevant documentation]. Figure 8In the early stages of Alzheimer's disease (AD), the functional connectivity patterns of the ECN (external coronary neural network) have already changed. For example, functional connectivity between the left frontal cortex and other brain regions is reduced, as is functional connectivity in the left parietal cortex, which is associated with visuospatial impairment. For instance, in patients during the dementia stage and MCI (Minimal Cognitive Impairment), functional connectivity in the right frontal lobe and superior frontal gyrus of the ECN is significantly reduced, which is associated with cognitive decline. Not only is internal functional connectivity within the ECN reduced, but functional connectivity between the ECN and the DMN (Digital Superior Brain Narrowing) is also reduced, leading to the spread of impaired executive control. The anterior superior cranial region (500a), cranial vertex (500b), left cranial region (500c), and right cranial region (500d) adequately cover these lesion sites.

[0081] The sensorimotor network (SMN) is responsible for body perception and movement, and mainly includes the precentral gyrus and postcentral gyrus. See [link to relevant documentation]. Figure 8 The SMN is mainly distributed in the adjacent areas before and after the central sulcus, extending laterally to the temporal lobe along the central sulcus. Impaired functional connectivity of the SMN leads to motor dysfunction in AD patients. Furthermore, in patients in the dementia and MCI stages, reduced functional connectivity between the SMN and DAN is closely associated with attention deficit; as AD progresses, the internal functional connectivity of the SMN deteriorates further, as does its functional connectivity with the DAN. The anterior superior cranial region 500a and the apical cranial region 500b tightly cover the adjacent areas before and after the central sulcus, and together with the left lateral cranial region 500c and the right lateral cranial region 500d, they extend longitudinally to the temporal lobe, fully covering these lesion sites.

[0082] Unlike phototherapy devices that only focus on the DMN and lack coverage at the top of the skull, the phototherapy device of this application ensures that sufficient time-averaged irradiation power is comprehensively applied to the core sites of lesions in the Default Mode Network (DMN), Central Executive Network (ECN, also known as the executive control network), Seminarization Network (SN), Sensorimotor Network (SMN), and Dorsal Attention Network (DAN). Furthermore, the phototherapy device of this application uses a 10-10 standard lead system to precisely divide the upper anterior cranial region (500a), top cranial region (500b), left cranial region (500c), and right cranial region (500d), ensuring precise localization of sites at brain region junctions within these networks, as well as sites connecting different functional networks, thereby reducing the loss or omission of sites of action within the networks. Therefore, the near-infrared light irradiation applied by the phototherapy device of this application has a smoother propagation path along functional connectivity areas, resulting in more efficient propagation and transmission of inhibitory responses, thus achieving optimized AD inhibition effects across the entire brain. If we compare the process of irradiating a subject's head with near-infrared light to the process of charging a battery, for example, calling it a "photocharging" process, then the phototherapy device of this application, because it fully "photocharges" the core sites of DMN, ECN, SN, SMN, and DAN that occur in AD lesions, can make the subject's brain have a larger "photocharging capacity," a deeper "photocharging depth," and a faster "photocharging speed." The subsequent "endurance" ability, that is, the biochemical reaction is still continuously triggered after the phototherapy is interrupted, can achieve continuous benefits and cumulative benefits, which is also better. This effect has also been verified by clinical trial results, which will be detailed below.

[0083] In some embodiments, the irradiation space also covers the posterior cranial region 500e, which is a fifth sub-region defined by the fifth boundary line 502a from the total region, and the fifth sub-region is located below the first region. Referring to Figure 5(e), the first region is above the fifth boundary line 502a and the fifth sub-region is below it. The posterior cranial region 500e may occupy the entire fifth sub-region as shown in Figure 5(e), or it may occupy only a portion of the fifth sub-region.

[0084] In some embodiments, the posterior cranial portion 500e may also be defined by the electrode locations it contains, for example, the posterior cranial portion 500e may contain electrode locations PO7, PO5, PO3, PO2, PO4, PO6, PO8, O1, O2 and O2.

[0085] In some embodiments, the posterior cranial portion 500e may also be defined using anatomical features, for example, the posterior cranial portion 500e may at least include the occipital region above the external occipital protuberance.

[0086] In some embodiments, the time-averaged total irradiance directly applied to the head cover of the object can be higher as needed, for example, but not limited to 31W or more, or 40W or more, or 60W or more, or 70W or more, or even higher, but the spatiotemporal average optical power density cannot exceed 230mW / cm². 2 To avoid thermal damage to brain tissue.

[0087] Figures 1-3 The phototherapy device is an example of a loose-fitting headgear. Specifically, its support mechanism includes a canopy positioned in the air, shaped to form a cavity. When the subject's head is positioned within this cavity, the cavity's size is suitable for loosely accommodating the head without applying pressure. This provides greater freedom and comfort during phototherapy for individuals who do not tolerate confined spaces. The first group of near-infrared irradiation units has preset emission angles and preset spacing and drop configurations, creating multiple converging regions above the top and upper front of the skull. At each converging region, near-infrared light from several near-infrared irradiation units converges at different incident angles. (Comparison) Figures 1-3 As shown in Figure 5(d), the area on the skull includes both the top of the skull and a portion of the upper front of the skull, and this area is not obstructed by other parts of the head. In some embodiments, for black or dark hair, the hair on the skull can be parted and bundled using a light guide comb to further improve light transmittance.

[0088] In some embodiments, the near-infrared irradiation units corresponding to the top of the skull and the upper front part of the skull are arranged along an arched curved surface, and when the object's head is positioned in the receiving space, the first average distance between the top of the skull and the upper front part of the skull and the corresponding near-infrared irradiation unit 5 is greater than a predetermined average distance. This results in a high spatiotemporal average optical power density, for example, 58 mW / cm², at the convergence region above the top of the skull and the upper front part of the skull via multi-beam focusing. 2 Above, 60mW / cm 2 Above, 62mW / cm 2 Above, 64mW / cm 2 Above, 66mW / cm 2 Above, 68mW / cm 2 Above, 70mW / cm 2 Above, 72mW / cm 2 And so on.

[0089] Figures 1-3The phototherapy device is also an example of an array of near-infrared irradiation units at multiple heights in a surrounding configuration. Specifically, the supporting mechanism includes a dome suspended in the air, the dome being shaped to form a cavity. The dome carries at least three sets of near-infrared irradiation units at different heights, with each set of units spaced circumferentially at their corresponding heights. This circumferential spacing allows for a stable treatment effect when the subject's head rotates in place, and also maintains a balanced and stable treatment effect on different circumferential positions and areas of the head.

[0090] Unlike designs that completely enclose the head and neck area within a cover, such as Figures 1-3 The hood shown is a "hat" type construction, not a "helmet" type construction. Specifically, the cavity formed by the hood increases in cross-sectional area downwards, and when the object's head is in place within the receiving space, the lower part of the hood is located on either side of the tragus or its periphery (e.g., 5cm around the tragus). 2 Within a certain range, on the posterior side, it is located near the external occipital protuberance (e.g., within a predetermined distance above or below the external occipital protuberance, such as 2cm), and on the anterior side, it is located above the brow bone. In this way, the subject's vision is not obstructed, and the external occipital protuberance, which has the largest diameter, maintains a sufficient distance from the inner wall, like wearing a hat rather than being enclosed in a head covering, reducing the subject's psychological pressure; this gradually expanding cavity makes it less likely for the subject to touch the inner wall when sliding down due to fatigue or suddenly raising their head, thus avoiding localized high temperatures caused by blocking the air vents on the inner wall, and also avoiding contact with high-temperature areas on the inner wall.

[0091] Figures 1-3The structure illustrates an example of including a light-transmitting protective portion within a housing. The housing includes this light-transmitting protective portion, for example, an inner shell 3 formed from a light-transmitting material. This light-transmitting protective portion forms a front upper portion, a top portion, a rear portion, a left side portion, and a right side portion, and surrounds the cavity. This light-transmitting protective portion protects the subject's head from direct contact with the near-infrared irradiation unit. In some embodiments, the front upper portion corresponds to the front upper part of the skull, the top portion corresponds to the top of the skull, the rear portion corresponds to the back of the skull, the left side portion corresponds to the left side of the skull, and the right side portion corresponds to the right side of the skull. In some embodiments, the near-infrared light emitted from the top, front upper, rear, left, and right sides of the light-transmitting protective portion forms a flawless irradiated surface on the surface of the subject's head. In this way, the near-infrared beam emitted from the array of near-infrared irradiation units and exited through the light-transmitting protection section has no irradiation dead zones, and can provide comprehensive radiation to all parts of the scalp of the subject's head. This not only applies transcranially to the core sites of lesions in the default mode network (DMN), central executive network (ECN, also known as executive control network), salience network (SN), sensorimotor network (SMN), and dorsal attention network (DAN), but also ensures that sufficient radiation is applied to sites on the functional connectivity pathways between these core sites.

[0092] For example, the light-transmitting protective part can be an integral shell, and the inner walls of the light-transmitting protective part emit near-infrared light.

[0093] Below we combine Figures 1-3 The structural examples of light therapy equipment (especially headgear) are illustrated. However, it should be noted that... Figures 1-3 The headgear structure is merely an example. The phototherapy device of this application can adopt different structures. The various structures of the phototherapy device defined in the claims, as well as the descriptions of various components and parts of the phototherapy device in the specification, can be used independently or freely combined with each other as embodiments of the phototherapy device of this application, and will not be elaborated here.

[0094] like Figure 1 and Figure 2 As shown, this application provides a headgear for a phototherapy device. The headgear includes an outer shell 1, a middle shell 2, and an inner shell 3 arranged sequentially from the outside to the inside. A lamp plate receiving cavity 4 with multiple lamp plates 5 is formed between the outer shell 1 and the middle shell 2. A cooling air cavity 6 is formed between the middle shell 2 and the inner shell 3. The inner shell 3 encloses inward to form a receiving space. In some embodiments, each lamp plate may include 4-9 near-infrared LEDs, the time-averaged light power of each near-infrared LED is 80mw-100mw, and the irradiation area of ​​each near-infrared irradiation unit is 5-9cm². 2 .

[0095] In some embodiments, the phototherapy device may further include a cooling mechanism configured to ensure that, when the average total irradiation power over the time of irradiation to the subject's head reaches 27.5-120W and the duration of a single continuous irradiation session reaches 30 minutes, the air temperature in the space adjacent to but not in contact with the subject's head does not exceed 41°C. The cooling mechanism can employ various different constructions. The cooling mechanism in the phototherapy device of this application introduces cold air from the outside and utilizes heat transfer based on the temperature difference between the cold air and the thermal environment surrounding the subject's head in the accommodating space, simultaneously achieving gas convection, to achieve efficient cooling. Figures 1-3 For example, the cooling mechanism can be designed to introduce cold air from the outside and enter the receiving space through the air vent 7 via the cold air chamber 6, but it should be noted that other cooling mechanisms are also possible.

[0096] The inner shell 3 has multiple ventilation holes 7, allowing cold air from the cooling chamber 6 to enter the receiving space through these holes. Ventilation holes 7 can be provided in the first region near the top of the head and the second region below the first region of the inner shell 3. The second region has multiple ventilation hole units arranged in layers from top to bottom. The upper and lower ventilation hole units are arranged differently to better cool different areas of the patient's head, improve the synchronization of cooling, and ensure a more uniform temperature across the patient's head during phototherapy, thus increasing patient comfort when wearing the headgear for phototherapy.

[0097] The inner shell 3 is the shell closest to the patient's head when worn by the patient. The middle shell 2 and the inner shell 3 form a cold air cavity 6. The outer shell 1 and the middle shell 2 form a lamp panel receiving cavity 4. The inner shell 3 and the middle shell 2 are designed to be light-transmitting. The light emitted by the lamp panel 5 can pass through the light-transmitting middle shell 2 and the inner shell 3 in sequence and enter the receiving space so as to perform phototherapy on the patient.

[0098] In this embodiment, the inner shell 3 includes a first region near the top and a second region located below the first region. Ventilation holes 7 may be provided in both the first and second regions. Figure 3 As shown, the middle shell 2 is provided with a cold air inlet 8 that communicates with the cold air chamber 6. A ring of vents can be provided at least around the outer edge of the first area, reserving space for a protective pad on the top of the head. Thus, after the cold air enters the cold air chamber 6 through the cold air inlet 8, it is then blown onto the patient's head through the vents 7, ensuring a good cooling experience around and on the top of the head during phototherapy. Furthermore, this structure allows the cold air to flow downwards from the patient's head, which helps improve the heat exchange efficiency within the containment space, resulting in a more uniform temperature within the headgear's containment space.

[0099] In some embodiments, the air inlet 8 of the air-cooled chamber 6 is located in the first region, and is closer to the rear of the inner shell 3 than to the front of the inner shell 3, wherein the front of the inner shell 3 is in the direction corresponding to the forehead of the headgear, and the rear of the inner shell 3 is in the direction corresponding to the back of the head of the headgear. Figure 1 and Figure 2 As shown, Figure 2 The air inlet 8 shown is closer to the rear of the inner shell 3. The arrangement of the air inlet 8 closer to the rear of the inner shell 3 than the front of the inner shell 3 makes the distances from the air inlet 8 to the front end of the inner shell 3 (i.e., the front edge of the inner shell 3) and the distance from the air inlet 8 to the rear end of the inner shell 3 (i.e., the rear edge of the inner shell 3) similar. This avoids the problem of uneven cooling in some areas and the overall cooling due to the large difference in distance between the air inlet 8 and the front and rear edges of the inner shell 3 caused by improper positioning.

[0100] In other embodiments of this application, to ensure that the cold air inlet 8 can uniformly deliver cold air into the accommodating space through the vent 7 of the cold air cavity 6, the headgear for the phototherapy device may include multiple cold air inlets 8, which are distributed at different locations within the inner shell to fill the cold air cavity 6 with cold air, thereby improving the overall cooling uniformity of the headgear. The position of the cold air inlets 8 can be adjusted according to the specific headgear structure and the arrangement of the phototherapy lamp panel.

[0101] In this application, both the first region and the second region below the inner shell 3 are provided with ventilation holes 7, which helps to reduce the temperature at the top and around the patient's head. In addition, the position and number of cold air inlets 8 are adjusted so that they are located in the first region, which can ensure effective cooling at the top of the head. Moreover, the position is closer to the rear of the inner shell 3 than the front of the inner shell 3, so that the time it takes for the cold air to reach the front and rear ends of the inner shell 3 is similar. This can coordinate the cooling of various brain regions and make the temperature felt by the entire head more even during phototherapy. The forehead area is not too cold, while the back of the head can feel a better cooling effect, thereby improving the patient's comfort when wearing the headgear for phototherapy.

[0102] like Figure 2 and Figure 3As shown, in some embodiments, the second region is layered with multiple vent units from top to bottom. The upper vent unit 701 and the lower vent unit 703 are arranged differently, while the upper vent unit 701 and the middle vent unit 702 are arranged in the same way. The number of vents in a single lower vent unit 703 is less than the number of vents in a single upper vent unit 701 or middle vent unit 702, and there are vents 7 with a relatively smaller vent density between adjacent upper vent units 701 compared to the vent density of the upper vent units 701. This arrangement allows the upper vent units 701 and the middle vent units 702 to release more cold air compared to the lower vent units 703.

[0103] In some embodiments, the upper vent unit 701 and the middle vent unit 702 may each be composed of vents 7 evenly distributed in the inner ring and vents 7 evenly distributed in the outer ring. For example, there may be 6 vents 7 evenly distributed in the inner ring and 6 vents 7 evenly distributed in the outer ring. The lower vent unit 703 may be composed of only one ring of vents 7 evenly distributed. For example, there may be only 6 vents 7 evenly distributed.

[0104] In some embodiments, adjacent upper vent units 701 are further provided with vent holes 7 having a relatively smaller arrangement density compared to the vent holes 7 of the upper vent units 701, such as... Figure 3 As shown, the vent holes 7 arranged between the upper vent hole units 701 are relatively sparse. However, no other vent holes 7 are arranged between the middle vent hole units 702 and the lower vent hole units 703.

[0105] Because the breathability of the headgear varies from top to bottom during phototherapy, the skin on the top of the head is relatively sealed within the enclosure, while the skin on the back of the head is closer to the outside, facilitating air exchange. Therefore, more ventilation holes are placed in areas with poorer airflow to increase the cooling rate, while fewer ventilation holes are placed in areas with better airflow to allow for heat dissipation from the external environment. Utilizing the principle of cool air sinking and hot air rising, this achieves optimal cooling of the patient's head while releasing an equal amount of cool air into the enclosure. The arrangement of the ventilation holes helps to balance the temperature from top to bottom, increasing comfort during phototherapy. Furthermore, the spacing between adjacent ventilation hole units in each layer can be the same.

[0106] In some embodiments, the vent 7 is provided at least at the corresponding position of the lamp plate 5. During phototherapy, the area of ​​the patient's skin irradiated by the lamp plate 5 is more prone to heat accumulation due to the high intensity of the light. By providing the vent 7 at least at the position corresponding to the lamp plate 5 on the inner shell 3, it is possible to prevent the lamp plate 5 from generating excessive heat accumulation on the patient's skin and to efficiently transfer the accumulated heat.

[0107] In some embodiments, the density of the vent holes 7 at the position corresponding to the lamp plate 5 is greater than the density of the vent holes 7 at the position where the lamp plate 5 is not provided. This helps to achieve a more balanced temperature between the position where the lamp plate 5 is not provided and the position where the lamp plate 5 is provided, which can effectively enhance the breathability of the headgear's containment space, improve the air heat exchange efficiency in the containment space, and further improve the patient's wearing comfort.

[0108] In some embodiments, a plurality of lamp panels 5 are mounted on the middle shell 2 via lamp panel fixing housings 9, the lamp panel fixing housings 9 being located on the side of the middle shell 2 closest to the outer shell 1. For example... Figure 9 As shown, in some embodiments, a lamp plate fixing shell 9 is provided inside the lamp plate receiving cavity 4. The lamp plate fixing shell 9 covers the middle shell 2 on the side near the outer shell 1. Multiple lamp plates 5 are arranged in layers from top to bottom along the lamp plate fixing shell 9, and the distance between two lamp plates 5 on the upper layer is greater than the distance between two adjacent lamp plates 5 on the lower layer, so as to ensure that effective time-averaged radiation dose is delivered to various parts of the scalp surface of the subject's head, namely the upper front part of the skull, the top of the skull, the left side of the skull, and together with the right side of the skull (optionally the posterior part of the skull), thereby providing sufficient and effective time-averaged radiation dose to the core sites and regions of the subject's brain functional network via the cranium.

[0109] Specifically, the spatiotemporal average optical power density irradiated the top and upper anterior parts of the skull was 55 mW / cm². 2 The above-mentioned spatiotemporal average optical power density irradiated the left and right sides of the skull is 35 mW / cm². 2 The above. In some embodiments, it can be understood that when multiple light panels 5 are distributed on a spatial curved surface covering the head of the object with predetermined gaps, the spatiotemporal average optical power density obtained based on the time-averaged optical power density of representative positions irradiated to the top and upper front of the skull is higher than the spatiotemporal average optical power density obtained based on the time-averaged optical power density of representative positions irradiated to the left and right sides of the skull. This is particularly applicable to Figures 1-3The diagram shows an array of near-infrared irradiation units at multiple heights and a loose-fitting headgear design. Specifically, while this design is highly acceptable to AD patients who dislike constriction, it can easily obstruct the left and right sides of the skull, or weaken the superposition effect, resulting in lower light power density. By maximizing the light power density distribution in the top of the skull, where near-infrared light can be fully concentrated, and in the sparsely haired, unobstructed anterior upper skull, these areas, with their largest surface areas, can provide greater overall power to the anterior upper skull, top skull, left skull, and even the right skull. Furthermore, the anterior upper skull and top skull correspond to more core sites and regions of brain functional networks, thus achieving efficient "light filling" of these core sites and regions of brain functional networks prone to AD lesions. The applied near-infrared irradiation energy spreads more smoothly along the functional connectivity areas, resulting in more efficient dissemination and transmission of inhibitory responses, thereby achieving optimized AD suppression throughout the entire brain.

[0110] In some embodiments, the posterior cranial region may also be selectively included within the irradiation space, and the required spatiotemporal average optical power density irradiated onto the posterior cranial region may be reduced, for example, to 1-30 mW / cm². 2 That's it. Through extensive irradiation tests, the inventors discovered a significant deviation in the time-averaged optical power density on the posterior skull. See [link to relevant documentation]. Figures 1-3 The structure, especially for loose-fitting headgear designs, features a low-set, concave shape at the back of the head, corresponding to the occipital region. This three-dimensional structure easily blocks near-infrared light directed towards this area. Furthermore, the varying heights at different locations result in highly variable blocking; for example, the time-averaged optical power density at various points can be as low as a few mW / cm². 2 It could also be as high as 30 or even 40 mW / cm 2 This results in instability in the spatiotemporal average optical power density in the posterior part of the skull. To address this, the headgear structure of the phototherapy device in this application, even when covering the posterior part of the skull, ensures that the spatiotemporal average optical power density irradiated to the top and upper anterior parts of the skull, as well as the spatiotemporal average optical power density irradiated to the left and right sides of the skull, is significantly higher than that irradiated to the posterior part. In other words, by minimizing the impact of varying occlusion on the posterior part of the skull on the spatiotemporal average optical power density and total irradiation power, the therapeutic effect of AD suppression or prevention can still be ensured for the target individual.

[0111] In some embodiments, the representative positions include at least one of the following: electrode positions in a 10-10 standard lead system contained in each part, or a predetermined proportion thereof; electrode positions in a 10-10 standard lead system contained in each part and non-electrode positions between the electrode positions, or a predetermined proportion thereof; a predetermined number of positions in each part selected in a predetermined manner, the predetermined manner including at least one of the following: randomly selecting a predetermined number of positions; uniformly dividing each part into a predetermined number of grids and selecting the predetermined number of positions corresponding to the grids; selecting the predetermined number of positions excluding edge positions; selecting the position of the projection point in each of the central parts of the near-infrared irradiation unit.

[0112] In other embodiments of this application, multiple light panels 5 can be directly disposed on the middle shell 2.

[0113] In the embodiments of this application, such as Figure 9 As shown, six layers of lamp panels 5 are spaced apart on the lamp panel fixing housing 9, and the lamp panels 5 include at least one of the following configuration methods.

[0114] In one embodiment, in the first layer of light panels 10 closest to the top of the headgear, there is a first gap between adjacent light panels. The narrowest point a of the first gap has a length ranging from 23mm to 26mm, and the widest point b has a length ranging from 57mm to 60mm. Further, the narrowest point a of the first gap has a length ranging from 23.5mm to 25.5mm, and the widest point b has a length ranging from 57.5mm to 59.5mm. Preferably, the narrowest point a of the first gap has a length of approximately 24mm, and the widest point b has a length of approximately 59mm.

[0115] In the second method, in the second layer light panel 11 adjacent to the first layer light panel 10, there is a second gap between adjacent light panels. The narrowest part of the second gap has a length ranging from 15mm to 18mm, and the widest part of the second gap has a length ranging from 41mm to 44mm. Further, the narrowest part of the second gap has a length ranging from 16mm to 17.5mm, and the widest part of the second gap has a length ranging from 41mm to 43mm. Preferably, the narrowest part of the second gap is approximately 16.7mm, and the widest part of the first gap is approximately 42.5mm.

[0116] In method three, in the third layer light panel 12 located below the second layer light panel 11, there is a third gap between adjacent light panels. The narrowest part of the third gap has a length ranging from 13mm to 16mm, and the widest part has a length ranging from 24mm to 27mm. Further, the narrowest part of the third gap has a length ranging from 13.5mm to 15.5mm, and the widest part has a length ranging from 24mm to 26mm. Preferably, the narrowest part of the third gap is approximately 14.2mm, and the widest part is approximately 25.3mm.

[0117] In method four, among the fourth, fifth, and sixth light panels 15 arranged sequentially from top to bottom below the third light panel 12, the fourth light panel 13 has a fourth gap between adjacent light panels. The narrowest part of the fourth gap ranges from 12mm to 15mm in length, and the widest part ranges from 19mm to 22mm in length. Further, the narrowest part of the fourth gap ranges from 13.5mm to 14.5mm in length, and the widest part ranges from 19.5mm to 21.5mm in length. Preferably, the narrowest part of the fourth gap is approximately 14mm in length, and the widest part is approximately 20.5mm in length.

[0118] In method five, a fifth gap exists between two adjacent light panels of the fifth layer light panel 14. The narrowest part of the fifth gap has a length ranging from 12mm to 15mm, and the widest part has a length ranging from 16mm to 19mm. Further, the narrowest part of the fifth gap has a length ranging from 13mm to 14.5mm, and the widest part has a length ranging from 16.5mm to 18.5mm. Preferably, the narrowest part of the fifth gap is approximately 13.8mm, and the widest part is approximately 18mm.

[0119] In method six, the sixth layer of light panel 15 is divided into left and right parts, each part having 3 light panels. A sixth gap exists between adjacent light panels. The narrowest point of the sixth gap ranges in length from 11mm to 14mm, and the widest point ranges in length from 15mm to 18mm. Further, the narrowest point of the sixth gap ranges in length from 12mm to 14mm, and the widest point ranges in length from 15mm to 17mm. Preferably, the narrowest point of the sixth gap is approximately 13mm, and the widest point is approximately 16.2mm.

[0120] The spacing of the light panels 5 and the arrangement between adjacent layers of the light panels 5 reduce the problem of excessively high local temperatures inside the headgear caused by concentrated heat dissipation of the light panels 5, and also save energy.

[0121] In further optional embodiments of this application, such as Figure 9 As shown, the gaps between adjacent lamp panels 5 in each layer have their narrowest and widest positions, respectively. Furthermore, the width of the gap between adjacent lamp panels 5 on each layer from top to bottom is greater than the width of the gap between adjacent lamp panels 5 on the next lower layer. This reduces the probability of excessively high local temperatures inside the phototherapy headgear caused by concentrated heat dissipation from the densely packed lamp panels 5, while ensuring adequate illumination for phototherapy. Due to the structural design of the phototherapy headgear, the inner diameter of the accommodating space gradually increases from top to bottom. Therefore, the spacing between the first layer of lamp panels 10 and the second layer of lamp panels 11 is increased. This ensures uniform light power density while preventing heat accumulation within the headgear, facilitating cooling. To achieve uniform light power density throughout the accommodating space, the optimal average light power of the first layer of lamp panels 10 and the second layer of lamp panels 11 can be between 75mW and 125mW, preferably around 100mW.

[0122] like Figure 9 As shown, in some embodiments, the vertical spacing between the first lamp panel 10 and the second lamp panel 11 is 19mm to 25mm, preferably 19.5mm to 24.5mm. The vertical spacing between the second lamp panel 11 and the third lamp panel 12 is 14mm to 21mm, preferably 15mm to 20mm.

[0123] like Figure 9 As shown, in some embodiments, the vertical spacing between the remaining two adjacent light panels is 13mm to 19mm, preferably 14mm to 18mm. The vertical spacing between the two adjacent light panels is set so that the entire brain area can be irradiated, and the heat emitted by the light panel 5 can be prevented from accumulating in the accommodating space.

[0124] Therefore, the arrangement of the light panel 5 can illuminate the entire area of ​​the patient's head, including the upper front part of the skull, the top of the skull, the left side of the skull, and the right side of the skull, without affecting the normal progress of phototherapy, and can also improve the comfort of the treatment process.

[0125] In addition, such as Figure 10 As shown, the lamp panel 5 is connected to the lamp panel fixing frame 17, and the lamp panel 5 is detachably fixed to the lamp panel fixing shell 9 through the lamp panel fixing frame 17. In some embodiments, the spacing between adjacent lamp panel fixing frames 17 in each layer is similar to or the same as the spacing between the corresponding adjacent lamp panels 5.

[0126] Back Figure 3In some embodiments, the headgear has an annular connecting portion 18, with the bottoms of the outer shell 1 and the middle shell 2 respectively connected to the connecting portion 18. The connecting portion 18 has multiple ventilation openings 16 communicating with the lamp panel receiving cavity 4, and the area of ​​each ventilation opening 16 located at the rear end of the headgear is larger than the area of ​​each ventilation opening 16 located at the front end of the headgear. Furthermore, the ventilation openings 16 can be elongated. This can increase the airflow entering from the rear end of the headgear, thereby improving the cooling effect of the lamp panel receiving cavity 4 and balancing the cooling effect at the back of the head and forehead. Furthermore, this can also reduce the heat transfer from the lamp panel receiving cavity 4 to the cold air cavity 6, thereby improving the cooling effect on the receiving space.

[0127] In some embodiments, the top of the headgear is provided with an exhaust vent, which communicates with the lamp panel receiving cavity 4 and is used to extract the hot air inside the lamp panel receiving cavity 4.

[0128] In some embodiments, a total of 80 lamp panels 5 are distributed inside the headgear. The size of the near-infrared light emission port of each lamp panel 5 is 28mm×28mm with a tolerance of ±0.2mm, and the lamp beads are arranged in a 3×3 array.

[0129] This application also provides a phototherapy device, which includes a trolley control device and a headgear according to any embodiment of this application. The trolley control device includes a cooling device and a ventilation device. The cooling device is connected to a cold air inlet 8 and is used to introduce cold air into the cold air chamber 6 through the cold air inlet 8. The ventilation device is connected to the ventilation port of the headgear. Through the cooperation of the trolley control device and the headgear, phototherapy is performed on the patient, and the comfort of the wearer can be improved during the phototherapy.

[0130] We conducted a series of clinical trials using a phototherapy device with this structure. As an example, the near-infrared irradiation unit array emits near-infrared light with a center wavelength of 810 nm, a duty cycle of 50%, and a frequency of 10 Hz; however, this is merely an example. In some embodiments, near-infrared light can be emitted with a duty cycle of 30%-70%, a wavelength of 650-1100 nm, and a frequency falling within the frequency range of alpha waves, the frequency range of gamma waves, or a neighborhood of both; these details are omitted here.

[0131] In some embodiments, the array of near-infrared irradiation units is specifically configured to irradiate the subject's head with at least 8260-42260 joules of energy over a continuous irradiation period of 5 minutes, as a unit dose. 8260 joules of energy irradiation over 5 minutes is equivalent to continuous irradiation of the head cover at a time-averaged power of 27.5 W, with a head cover surface area of ​​612.35 cm². 2 Based on calculations, the spatiotemporal average optical power density is 45 mW / cm². 2A 5-minute irradiation of 42,260 joules of energy is equivalent to continuous irradiation of the skull with a time-averaged power of 140.8 W, given a skull surface area of ​​612.35 cm². 2 Based on calculations, the spatiotemporal average optical power density is 230 mW / cm². 2 The inventors discovered in clinical trials that it is difficult for some patients with moderate to severe Alzheimer's disease (AD) to irradiate continuously for 10 to 30 minutes without interruption. Some AD patients have severe cognitive impairment and are uncooperative, while others frequently experience abnormalities in limb movement, such as muscle stiffness and flexion, muscle atrophy and weakness, and apraxia. Using 5-minute intervals as the unit dose means that every 5 minutes of irradiation has a certain degree of inhibitory effect on AD.

[0132] For example, the required energy dose to the subject's head within a one-hour timeframe, such as three unit doses (at least 24,800-126,800 joules), can be delivered in separate or continuous effective unit doses. The cumulative dose delivered in this way, compared to a continuous 15-minute cumulative dose, can achieve comparable AD suppression effects. In actual treatment, even if interruptions occur due to the AD patient's own reasons or operational malfunctions, the operator only needs to ensure the cumulative irradiation time within the single timeframe meets the requirements. There is no need to restart the phototherapy equipment, reset the current irradiation dose to zero, or rigidly interrupt irradiation for fixed rest periods. Specifically, if the subject is cooperative and treatment is progressing smoothly, continuous irradiation for 15 minutes can be performed. If the subject is uncooperative or treatment is not progressing smoothly, for example, if the subject needs to go to the restroom after 6 minutes, treatment should be temporarily interrupted until the subject returns. The interruption time can be flexibly adjusted according to the subject's needs, as long as the total irradiation time is achieved within one hour. This significantly reduces the difficulty of phototherapy for AD patients with severe cognitive impairment or motor abnormalities who are uncooperative, as well as for groups with varying degrees of AD severity (such as nursing home residents of different age groups), and even for caregivers with insufficient experience in caring for AD patients.

[0133] In some embodiments, the array of near-infrared irradiation units is specifically configured to irradiate the subject's head with at least 24,800 to 1,014,100 joules of energy within a single day, serving as the daily cumulative dose. It can be seen that the daily cumulative dose can have a range of nearly 40 times, with a lower limit of 15 minutes of cumulative irradiation at a time-averaged irradiation power of 27.5 W and an upper limit of 2 hours of irradiation at a time-averaged irradiation power of 140.8 W. The inventors have discovered that, using the phototherapy device of this application, the daily cumulative dose can be adjusted over a wide range according to the subject's adaptability. Specifically, if the subject has high compliance with phototherapy and a good individual response, the array of near-infrared irradiation units is specifically configured to provide an accelerated daily cumulative dose by continuously irradiating for more than 30 minutes within a single hour, and this can be done up to four times a day. This accelerated daily cumulative dose is equivalent to several days' worth of a smaller daily cumulative dose. In cases where treatment needs to be interrupted for a few days due to specific circumstances, an accelerated daily cumulative dose can be administered first, thus increasing the flexibility and convenience of phototherapy. Furthermore, although the mechanism of action is not yet fully understood, the improvement in cognitive performance after administering an accelerated daily cumulative dose to individual volunteers was even better than the effect of administering the same cumulative dose over several days.

[0134] In some embodiments, the array of near-infrared irradiation units is specifically configured to deliver at least 124,000 joules (27.5W - 15 minutes - 5 times) - 7,099,000 joules (230mw / cm²) at separate single-time cumulative doses over a week. 2 - 2 hours per day - 7 days) Joules of energy are irradiated onto the subject's head as a weekly cumulative dose. The cumulative dose for a single period can be administered 1, 2, 3, 4, 5, 6, 7 or 8 times per week.

[0135] Specifically, the array of near-infrared irradiation units is configured such that the cumulative weekly dose is more than 8 times over 8 weeks, preferably more than 16 times over 16 weeks, as the cumulative dose for the treatment course.

[0136] In some embodiments, the interruption time between two treatment sessions shall not exceed half the duration of the treatment session in order to minimize the risk of a relapse in AD lesions caused by treatment interruption.

[0137] The applicant uses, for example Figures 1-3The phototherapy device shown was used in a clinical trial on the experimental group (i.e., the treatment group). The spatiotemporal average optical power density of the phototherapy device at various points on the reference head model of the subject's head is shown in Table 1. In this clinical trial, with the subject's head positioned within the space created by the supporting mechanism, the phototherapy device formed an irradiation space covering the upper anterior part of the skull, the top of the skull, along with the left and right sides of the skull and the posterior part of the skull. The time-averaged total irradiation power acting on the subject's head reached over 31W, approximately 32W-48W, and the spatiotemporal average optical power density did not exceed 230mW / cm². 2 .

[0138] Table 1. Spatiotemporal average optical power density of the phototherapy device at various parts of the reference head model.

[0139] The applicant conducted a clinical trial on the experimental group (i.e., the treatment group) using the operating parameters in Table 2 with the phototherapy equipment.

[0140] Table 2 Operating parameters of phototherapy equipment

[0141] The inclusion criteria for this clinical trial are as follows: (1) meeting the core criteria for probable Alzheimer's disease (AD) as defined by the National Institute on Aging-Alzheimer's Association (NIA-AA); (2) cranial MRI results (within 6 months) supporting a possible diagnosis of AD; (3) age between 50 and 85 years, regardless of gender; (4) MMSE score < 26 points, able to cooperate in completing the scale assessment; (5) patients are not currently taking medication. If they are taking psychotropic or cognitive-improving medications, the dosage must be stable for at least 12 weeks before the trial and remain unchanged during treatment.

[0142] Exclusion criteria: (1) Contraindications to MRI, such as metal implants or claustrophobia; (2) Other types of dementia or other mental or neurological disorders, such as depression or Parkinson's disease; (3) History of stroke or epilepsy; (4) Photosensitivity to sunlight or visible light, or increased skin sensitivity in the treatment area; (5) Severe visual or hearing impairment; (6) History of alcohol or drug addiction; (7) Any other condition that would make a person unsuitable to participate in this study.

[0143] Based on inclusion and exclusion criteria, a total of 27 patients were enrolled, with 13 in the experimental group and 14 in the control group. The treatment group received whole-head near-infrared light stimulation: wavelength 810 nm, frequency 10 Hz, with each participant receiving 30 minutes of treatment once daily, 6 days a week, for 4 months. The sham treatment group followed the same protocol as the near-infrared light therapy group, but used a sham treatment headgear. The light emitted by the sham treatment device was visually identical to that of the near-infrared treatment device, and it produced similar sounds and a warm sensation on the scalp during treatment. However, the light power was extremely weak and was largely absorbed by the tissue, failing to achieve the desired effect of stimulating brain tissue. See [link to relevant documentation]. Figure 11 As shown.

[0144] The scale assessments were conducted at months 2 and 4 during treatment, and at months 6 and 8 after treatment ended. Figure 11 As shown, the clinical trial in this application set the interval between each scale calculation to 2 months instead of 1 month, which weakens the learning effect of the subjects and makes the scale scores more objective and accurate.

[0145] The assessors, participants, and their caregivers were unaware of the treatment allocation throughout the study, until its conclusion. Furthermore, the allocation was not discussed by any personnel involved during the entire study. All participants believed they received genuine near-infrared therapy.

[0146] Ultimately, a total of 18 patients (9 in the treatment group and 9 in the control group) completed 4 months of treatment and 4 months of assessment. One patient only completed the MMSE scale assessment, failing to complete the ADAS-Cog scale. The ADAS-Cog scale consists of 12 items covering memory, orientation, language, use of language, and attention. It can assess the severity of cognitive symptoms in Alzheimer's disease (AD) and changes in treatment, and is commonly used to assess the efficacy of treatment for mild to moderate AD (an improvement of 4 points is usually considered the clinical criterion for significant drug efficacy). The MMSE scale is the most widely used cognitive screening scale both domestically and internationally, covering orientation, memory, attention, calculation, language, and visuospatial abilities. Studies on the MMSE have found that in professional institutions such as memory clinics or in community hospitals, the MMSE has a sensitivity and specificity of over 80% in distinguishing between normal elderly individuals and those with dementia, demonstrating significant value in dementia screening.

[0147] To investigate the sustainability of the therapeutic effect of near-infrared light on AD patients, follow-up visits were conducted after treatment. A total of 14 subjects completed the 8-month follow-up (4 months after the end of treatment, 8 in the treatment group and 6 in the control group).

[0148] Referring to Figures 12(a) and 12(b), it can be seen that after 2 months of phototherapy, the ADAS-cog scale scores of the subjects in the treatment group decreased by an average of 1.11 points from baseline. After 4 months of treatment, the decrease continued at a greater rate, with an average reduction of 6.04 points from baseline. The statistical significance within the group was p=0.034<0.05, both significantly better than the scores in the control group. In the 2 months following the end of treatment, the ADAS-cog scale scores of the treatment group fluctuated less, remaining at an average reduction of 5.59 points from baseline by the end of 2 months. The statistical significance within the group was p=0.009<0.05. At the follow-up visit 2 months after the end of treatment, the ADAS-cog scale scores of the treatment group even began to decline further, reaching an average reduction of 8.25 points from baseline by 4 months after the end of treatment. The statistical difference within the group was p=0.008<0.05. Based on the ADAS-cog scale score, the phototherapy device of this application achieved beneficial effects that have never been seen in other existing phototherapy devices in papers and related literature: within 4 months of phototherapy, the ADAS-cog scale score showed a greater slope of decline after the second month compared to the first two months; after the end of phototherapy, follow-up visits every 2 months revealed that the biochemical reaction caused by the irradiation energy of the near-infrared light delivered to the subject's head continued to trigger the inhibitory effect after the end of phototherapy, not only maintaining the inhibitory effect on AD to a certain extent, but also continuing to promote the inhibitory effect on AD, and no deterioration or regression of the ADAS-cog scale score occurred.

[0149] Referring to Figures 13(a) and 13(b), it can be seen that after 2 months of phototherapy, the subjects in the treatment group showed an average increase of 0.67 points in their MMSE scores from baseline. During the subsequent 2 months of phototherapy, the MMSE scores continued to increase with a greater slope, reaching an average increase of 2.78 points from baseline by 4 months of phototherapy, both significantly better than the control group (p=0.025<0.05). Both the ADAS-cog and MMSE scores showed similar improvement effects during the first and last 2 months of phototherapy: a greater slope of increase during the last 2 months. Furthermore, similar to the continued improvement in ADAS-cog scores after phototherapy, even after phototherapy was discontinued, the MMSE scores continued to rise for 2 months after the end of phototherapy, maintaining a similar upward slope as during phototherapy, reaching an average increase of 3.89 points from baseline by 2 months after the end of phototherapy (p=0.004<0.05). Four months after the phototherapy ended, the MMSE score in the treatment group remained comparable to the MMSE score obtained four months after phototherapy, without any regression. In other words, based on the MMSE score, the biochemical response caused by the near-infrared light irradiation energy delivered to the subject's head continued to trigger an inhibitory effect even after the phototherapy ended. This not only maintained the inhibitory effect on AD to a certain extent but also further enhanced the inhibitory effect on AD, without any regression in the ADAS-cog score.

[0150] The results of follow-up visits during and after phototherapy, combined with ADAS-Cog and MMSE scores, also confirmed the optimized "photocharging" and sustained benefit process of the phototherapy device mentioned above: the subject's brain had a larger "photocharging capacity," a deeper "photocharging depth," and a faster "photocharging speed." The scale scores improved significantly in the first two months and the last two months of phototherapy, and the improvement occurred at a stable slope without stagnation. The subsequent "endurance" and sustained benefits were better. The effect of phototherapy for two months was maintained for at least two months after the end of phototherapy, and even for more than four months after the end of phototherapy. Moreover, the biochemical reaction caused by "photocharging" continued to trigger inhibitory effects after the end of phototherapy and continued to promote the inhibitory effect on AD without deterioration or regression.

[0151] Furthermore, four months after receiving near-infrared light therapy, resting-state functional magnetic resonance imaging (fMRI) of the treatment group showed enhanced ALFF in multiple brain regions of the frontal, occipital, and temporal lobes (P<0.05), indicating increased neuronal excitability and spontaneous activity, providing neuroimaging evidence for the corresponding improvement in cognitive function. Meanwhile, no adverse events related to the experimental device were observed in this trial.

[0152] Although phototherapy lasted for 4 months in this clinical trial, it demonstrated deep regulation and sustained, even cumulative, benefits. With continued use for longer periods, such as 6 months, 8 months, 10 months, ... more than 1 year, or even year-round use, the benefits are expected to continue to increase, showing a more significant disease-modifying effect.

[0153] The above description is intended to be illustrative and not restrictive. Those skilled in the art can make variations, modifications, substitutions, and alterations to the above embodiments within the scope of this disclosure. Moreover, the above examples (or one or more of them) can be used in combination with each other, and these embodiments can be combined with each other in various combinations or arrangements.

Claims

1. A phototherapy device for inhibiting or preventing Alzheimer's disease, characterized in that, The phototherapy device is configured to emit near-infrared light toward the subject's head, and when the subject's head is in place, form a preset irradiation space covering the surface of the subject's head, so that the total irradiation power is applied to the specific cell population of AD lesions with sufficient time-averaged total irradiation power, so that not only do they themselves produce a change response that inhibits AD, but they also transmit this change response along the functional connectivity region to other specific cell populations.

2. The phototherapy device according to claim 1, characterized in that, The sufficient time-averaged total irradiation power is at least 27.5W, while avoiding the risk of thermal damage.

3. The phototherapy device according to claim 1, characterized in that, The emitted near-infrared light acts on at least the following areas of the object's head: The cingulate gyrus, temporal lobe, posterior parietal lobe, ventral prefrontal lobe, dorsolateral prefrontal lobe, medial prefrontal lobe, and adjacent areas anterior and posterior to the central sulcus; and / or Island leaves and / or cuneate leaves.

4. The phototherapy device according to any one of claims 1-3, characterized in that, The specific cell population for AD lesions is selected from at least one of the following: astrocytes, microglia, oligodendrocytes, neurons, and vascular cells.

5. The phototherapy device according to any one of claims 1-3, characterized in that, Sufficient time-averaged total irradiation power is applied to the specific cell population of AD lesions, and the biochemical reactions of the specific cell population are still continuously triggered after phototherapy is interrupted.

6. The phototherapy device according to claim 5, characterized in that, If the interruption time between two treatment courses does not exceed half the duration of the treatment course, the deterioration of AD lesions caused by the interruption of treatment can be avoided or mitigated.

7. The phototherapy device according to any one of claims 1-3, characterized in that, The emitted near-infrared light affects at least the default mode network (DMN), central executive network (ECN), salience network (SN), sensorimotor network (SMN), and dorsal attention network (DAN).

8. The phototherapy device according to claim 7, characterized in that, The phototherapy device is also configured such that the emitted near-infrared light also acts on the visual network (VN).

9. The phototherapy device according to claim 7, characterized in that, The phototherapy device is further configured such that the emitted near-infrared light also acts on the sites of functional connections between functional networks to regulate the functional connections between functional networks.

10. The phototherapy device according to claim 7, characterized in that, The emitted near-infrared light acts on at least some core network nodes or adjacent regions of each functional network in the Default Mode Network (DMN), Central Executive Network (ECN), Seminarization Network (SN), Sensorimotor Network (SMN), and Dorsal Attention Network (DAN).

11. The phototherapy device according to any one of claims 1-3, characterized in that, The preset irradiation space range of the scalp surface of the object's head is defined or located based on the electrode positions of the 10-10 standard lead system.

12. The phototherapy device according to claim 11, characterized in that, According to the 10-10 standard lead system, the preset irradiation space range includes the electrode positions: AFZ, FZ, F1, F2, FP1, FP2, CZ, C1, C2, and CPZ; and, FT7, FC5, T7, C5, or TP7, CP5, P7 or P5, or FT7, T7, TP7, P7, or F7, FT7, T7, TP7, P5; and, FT8, FC6, T8, C6, or TP8, CP6, P8, P6, or FT8, T8, TP8, P8, or F8, FT8, T8, TP8, P6.

13. The phototherapy device according to any one of claims 1-3, characterized in that, The phototherapy device is specifically configured to perform at least one of the following: During a continuous irradiation period of 5 minutes, the subject's head is irradiated with an energy density of at least 8260 joules over the surface area of ​​the skull. The phototherapy device is specifically configured to irradiate the subject's head with an energy density of at least 24,800 joules over the surface area of ​​the scalp at a separate or continuous effective unit dose within a single 1-hour period. The target's head will be irradiated with an energy density equivalent to at least 24,800 joules over the surface area of ​​the skull within a single day.

14. The phototherapy device according to any one of claims 1-3, characterized in that, The phototherapy device is configured to emit near-infrared light with a center wavelength of 650-1100nm, a duty cycle of 30%-70%, and a frequency falling within the frequency range of Alpha waves, Gamma waves, or the vicinity of both, to the head of the subject, thereby forming a preset irradiation space covering the surface of the head cap when the head of the subject is in place.

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