Cognition and memory enhancement via multiple odorant stimulation

Abstract

To provide methods, kits and devices for improving the cognitive function and memory through olfactory stimulation.SOLUTION: The olfactory stimulation is performed by releasing one or more scents according to an olfactory stimulation regimen or schedule. The methods, kits and devices can provide a large impact on cognition with minimal effort and cost. They can be used widely and effectively among older adults, children, and other populations in need of improved cognitive performance.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 657,621, filed April 13, 2018, entitled "Enhancing Cognition and Memory with Multiple Odor Stimuli," which is incorporated herein by reference in its entirety. [Background technology]

[0002] Environmental enrichment has been shown to have a positive impact on cognitive function, including improving cognitive decline in various animal models. Environmental enrichment can be achieved in a variety of ways, including but not limited to the introduction of various objects, sounds, smells, colors, animals, and other elements. Thousands of published studies have reached this conclusion, and cognitive benefits have been shown to reduce or overcome animal models of human neurological disorders, including Alzheimer's disease, memory loss, vascular dementia, age-related neuronal death, traumatic brain injury, head injury, Parkinson's disease, seizures, stroke, multiple sclerosis, anxiety, autism, ADHD, Huntington's disease, Down syndrome, stress, depression, cerebral palsy, chemical brain, schizophrenia, prenatal alcoholism, lead exposure, poisoning, and cancer. Significant behavioral changes have been observed in children with autism after just six months of environmental enrichment exercises.

[0003] Of the various stimulants used in environmental enrichment, cognition has been found to be strongly linked to the sense of smell. Smell is the only sense with a large, direct pathway to the cognitive and emotional regions of the brain. Loss of smell precedes memory loss due to aging and all forms of dementia. Loss of smell causes a massive loss of neurons in the brain. After age 50, olfactory ability has been shown to accurately predict all-cause mortality within the next five years.

[0004] Biologically, olfactory stimulation activates the entorhinal cortex, which declines with age and other factors, such as Alzheimer's disease and other dementias. When the entorhinal cortex declines, the dentate gyrus and CA3 (hippocampal subregion) are released from inhibition, thereby impairing memory. Therefore, restoring olfactory function should increase neurogenesis and / or neural complexity in the entorhinal cortex, thereby normalizing dentate / CA3 activity and restoring memory.

[0005] As with exercise, environmental enrichment-based interventions can be expensive or difficult to maintain. Currently, there is a lack of environmental enrichment modalities that are low-cost, easy to use, and maintain, while still effectively improving cognitive function and memory. More specifically, there is a lack of environmental enrichment modalities that utilize the strong connection between olfaction and cognitive and emotional regions of the brain. Summary of the Invention

[0006] Provided herein are methods, kits, and devices for improving cognitive function and memory and preventing the loss of these functions. In some embodiments, the aging brain environment is improved by reversing and / or preventing the decline of sensory systems in elderly people and those suffering from or at risk of neurodegenerative conditions and / or cognitive decline. In some embodiments, cognitive outcomes in children and / or younger adults are improved. In other embodiments, the methods can be used to alleviate colic in infants, normalize brain development in premature babies, lower cognitive age in adults, and alleviate or prevent migraines and headaches. The methods, kits, and devices described herein can have a significant impact on cognition with minimal effort and cost. They can be widely and effectively used among elderly people, children, and other populations in need of cognitive improvement.

[0007] Generally, the present invention relates to a method and apparatus for improving brain cognitive function by stimulating the sense of smell. In most embodiments, stimulation is achieved by exposing the recipient to unique scents on a rotating schedule of intervals. While potentially pleasant, a single specific odor has been found to not provide significant cognitive benefits. However, when the recipient is exposed to a daily rotation of different scents, olfactory stimulation has been shown in mice to induce accelerated generation of new neurons (neurogenesis) and / or increased neural complexity, leading to greater improvements in overall cognition and memory (far-transfer effect) compared to practice effects on the same task (near-transfer effect).

[0008] Far transfer is an improvement in memory that is unrelated to practicing that specific task, thereby improving people's overall memory. Near transfer is the ability to become better at a specific task by practicing that task, without leading to improvements in other cognitive abilities. There are many computer games and other activities that are advertised as brain-improving activities. All of these activities are examples of near transfer.

[0009] One aspect of the present invention maximizes the far-transfer effect by providing an olfactory stimulation schedule that includes a variety of odors, some of which are novel to the recipient.

[0010] Another aspect of the present invention maximizes the far-transfer effect by providing an olfactory stimulation schedule that rotates the odors presented to the recipient.

[0011] Yet another aspect of the present invention provides an olfactory stimulation schedule that provides a recipient with a pleasant odor.

[0012] Yet another aspect of the present invention provides an olfactory stimulation schedule that is delivered consistently over several months.

[0013] Treatment programs, especially those self-administered or administered over an extended period by family members in their own homes, require commitment and discipline. Naturally, the effectiveness of a treatment program is enhanced if the treatment is administered consistently. Thus, one aspect of the present invention seeks to maximize the potential consistency of administration by making the program as enjoyable, easy to administer, and as minimally disruptive to the recipient's lifestyle as possible. This is achieved through the "ease of use factor."

[0014] One aspect of the present invention is to provide a pleasant scent as an ease of use factor.

[0015] Another aspect of the present invention is a device that creates a rotating scent as an ease of use factor.

[0016] Another aspect of the present invention is a device that rotates scents according to a schedule as an ease of use factor.

[0017] Another aspect of the present invention provides an automatic aroma schedule while the treatment recipient is asleep, as an ease of use factor.

[0018] It has been determined that odors do not awaken a recipient while they are asleep. Thus, a recipient will not be awakened by exposure to unpleasant odors. Thus, unpleasant odors may generally be more novel to a recipient than pleasant odors. With this in mind, one aspect of the present invention provides a potentially unpleasant odor while the recipient is asleep.

[0019] Another aspect of the present invention provides a schedule including a potentially pleasant odor and a potentially less pleasant odor, where the less pleasant odor is emitted during an interval that will not awaken the recipient. For example, the pleasant odor is scheduled for times when the recipient is likely falling asleep and in the morning when the recipient is likely waking up. The less habitual, or potentially unpleasant, odor is scheduled for exposure in the middle of the night when the recipient is unlikely to be awake.

[0020] Another aspect of the present invention provides an identification system that allows the recipient to tag scents as unpleasant or give scents a scale rating, so that the scent delivery system schedules the lowest rated scents during times when the recipient is most likely to be asleep.

[0021] Yet another aspect of the present invention tracks the scents received by the recipient throughout the treatment program to ensure novelty is maintained. Through experimentation, it has been determined that a variety of scents provides the greatest benefit. In one embodiment, at least seven scents are used.

[0022] In another embodiment, at least four scents are used, however, these scent-providing devices can "fire" or emit one or more of the scents simultaneously, allowing two or more base scents to be mixed together to create new scents.

[0023] In another embodiment, a device is provided that can run multiple base scents simultaneously (also called scent blending) and with varying intensities of each base scent, thus allowing for the creation of a nearly infinite number of scents using only four base scents.

[0024] As those skilled in the art know, the sleep cycle consists of various stages that repeat every 90 to 110 minutes. One model divides the sleep cycle into five stages. Stage 1 is light sleep, characterized by a decrease in muscle, brain, and eye activity. In stage 2, heart rate and breathing patterns slow, and body temperature drops slightly. Stage 3 marks the onset of deep sleep and is accompanied by very slow delta waves produced by the brain. Stage 4 is very deep sleep, accompanied by rhythmic breathing, restricted muscle activity, and continuous delta wave production. The fifth stage is called the REM (Rapid Eye Movement) stage. This is the dream stage, characterized by increased blood pressure, heart rate, respiratory rate, and rapid eye movement. The therapeutic effects of the olfactory stimulation therapy of the present invention are likely to vary depending on the sleep stage in which the recipient is in. For example, it may be determined that a treatment delivered during stages 3 and 4 is ineffective, while a treatment delivered during REM is the most effective of all stages.

[0025] With this in mind, one aspect of the present invention includes a sleep stage tracking system, such as a heart rate monitor, a respiration monitor, a blood pressure monitor, an EEG sensor, or any combination thereof, used in conjunction with a scent delivery schedule to ensure that rest intervals (periods between scent delivery intervals) occur during less effective sleep stages and scent intervals occur during most effective sleep stages.

[0026] Described herein is a method for improving at least one of cognitive function and memory by treating a subject in need thereof according to an olfactory stimulation regimen.In one embodiment, this method includes: a) releasing one or more scents to the subject at a first stage on a first day; b) releasing one or more scents to the subject at a later stage on a later day.The one or more scents at the later stage are not the same as the one or more scents at the first stage, thereby improving at least one of cognitive function and memory of the subject.In some embodiments, this method is provided in conjunction with other forms of environmental, sensory, or tactile stimulation.In other embodiments, olfactory stimulation is provided in the absence of tactile stimulation or other forms of environmental or sensory stimulation.

[0027] In one embodiment, the subject treated by this method experiences statistically improved cognitive function compared to untreated subjects, as measured by Stroop test, Rey Auditory Verbal Learning Test (RAVLT), Wechsler Adult Intelligence Scale (WAIS) test, or a combination thereof.In one embodiment, this method improves or alleviates the age-related memory loss of the subject.In one embodiment, the memory of the subject is improved.In one embodiment, this method improves cognition, memory, intelligence quotient (IQ), or a combination thereof.

[0028] In one embodiment, the method prevents, reverses, halts, or slows the progression of a neurodegenerative disease or condition, hi one embodiment, the neurodegenerative disease or condition is Alzheimer's disease, Parkinson's disease, motor neuron disease, Huntington's disease, or dementia.

[0029] In one embodiment, the method improves memory, intelligence, sleep, brain health, gait, balance, Alzheimer's disease, Parkinson's disease, motor neuron disease, Huntington's disease, other forms of dementia, agitation, post-traumatic stress disorder (PTSD), panic attacks, stress, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), social anxiety disorder (SAD), phobias, depression, major depressive disorder (MDD), premenstrual syndrome (PMS), high blood pressure, colic, migraines, sleep disorders, or a combination thereof.

[0030] In one embodiment, the method improves the progression or outcome of stroke rehabilitation, seizures, prenatal alcohol syndrome, lead exposure, multiple sclerosis, addiction, schizophrenia, Down syndrome, μ-opioid receptor loss, Fragile X syndrome, Rett syndrome, Potocki-Lupski syndrome, repetitive behaviors, dementia with Lewy bodies, frontotemporal dementia, or Creutzfeldt-Jakob disease.

[0031] In one embodiment, the method reduces dementia or dementia-related disruptive behavior, increases self-esteem, reduces stress, lowers blood pressure, increases relaxation, prevents oxidative damage, improves postural stability, improves gait, enhances deep sleep, improves mood, reduces anxiety, improves energy, improves quality of life, improves cognition, or improves depression or symptoms of depression.

[0032] In one embodiment, the method improves cognitive processing speed, attention, executive function, or a combination thereof. In one embodiment, the method improves sequential processing, mental operations, attention, concentration, memory span, short-term auditory memory, verbal learning and memory, sequential processing, memorization and retention, encoding, auditory processing, working memory, information transformation, visuospatial imaging, or a combination thereof. In one embodiment, the method improves cognition, memory, intelligence quotient (IQ), or a combination thereof.

[0033] In one embodiment, the subject is an elderly person. In one embodiment, the subject is experiencing age-related cognitive deficits, including but not limited to memory deficits. In one embodiment, the subject is at least about 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or about 100 years old. In one embodiment, the subject is an elderly person aged 55 or older. In another embodiment, the subject is a younger adult between the ages of 18 and 55.

[0034] In one embodiment, the subject is a child. In some embodiments, the child is a child who exhibits normal cognitive abilities (regardless of achievement or performance on cognitive assessments), such as a child who does not meet the criteria for a diagnosis of autism. In some embodiments, the child is a typical child who does not exhibit or experience particular challenges to his or her environment or cognitive abilities. In some embodiments, the child has one or more developmental disorders. Representative examples of developmental disorders include, but are not limited to, autism, ADHD, and developmental delay. In one embodiment, the child has autism. In other embodiments, the child has one or more developmental disorders other than autism.

[0035] In some embodiments, the olfactory stimulation regimen is carried out over a period of 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In some embodiments, the olfactory stimulation regimen is carried out over a period of 2 days or more. In some embodiments, the olfactory stimulation regimen is carried out over a period of at least 1, 2, 3, or 4 weeks. In some embodiments, the olfactory stimulation regimen is carried out over a period of at least 1, 2, 3, 4, 5, or 6 months. In some embodiments, the olfactory stimulation regimen is carried out over a period of at least 7, 8, 9, 10, 11, or 12 months. In some embodiments, the olfactory stimulation regimen is carried out over a period of about 3 months. In some embodiments, the olfactory stimulation regimen is carried out over a period of about 6 months.

[0036] In some embodiments, the scents used in the olfactory stimulation regimen are from one or more scent categories selected from the group consisting of floral, woody, and aromatic. In some embodiments, the scents used are from two or three of these categories. Optionally, in some embodiments, additional scent categories such as oriental and / or fresh can be used.

[0037] In some embodiments, the scents used in the olfactory stimulation regimen are from one or more scent categories selected from the group consisting of fruity, floral, woody, resinous, and aromatic, and in some embodiments, the scents used are from two, three, four, or all five of these categories.

[0038] In some embodiments, the scent used in the olfactory stimulation regimen is selected from the group consisting of lavender, citrus, jasmine, lilac, mint, cinnamon, peppermint, clove, lemongrass, coffee, anise, basil, thyme, chamomile, rosemary, cucumber, coconut, fresh cotton, violet, vanilla, forest pine, pomegranate, pear, orange, apple, rosehip, saffron, sage, eucalyptus, frankincense, nutmeg, and sandalwood. In some embodiments, the scent used is derived from any combination of two or more members of these groups.

[0039] In some embodiments, the steps of the olfactory stimulation regimen are performed at night. In some embodiments, the steps of the olfactory stimulation regimen are performed during the day. In some embodiments, the steps of the olfactory stimulation regimen are performed both during the day and at night.

[0040] In some embodiments, the olfactory stimulation regimen is implemented as a series of stimulation cycles, each stimulation cycle comprising at least two olfactory stimulation steps. In some embodiments, the olfactory stimulation regimen comprises at least one stimulation cycle comprising at least 3, 4, 5, 6, 7, 8, 9, or 10 steps. In some embodiments, the olfactory stimulation regimen comprises repeating at least one stimulation cycle for a specified period of time. In some embodiments, the olfactory stimulation regimen comprises a 6-step stimulation cycle. In some embodiments, the olfactory stimulation regimen comprises a 7-step stimulation cycle.

[0041] In some embodiments, at least one step of the olfactory stimulation regimen includes: a) continuously emitting at least one scent for a first duration; and b) ceasing the emission of the at least one scent for a second duration. In one embodiment, the first duration is about 5 minutes. In one embodiment, the second duration is about 1 minute.

[0042] In one embodiment, at least one step further comprises repeating a) and b). In one embodiment, a) and b) are repeated until the subject is exposed to at least one scent for a specific exposure period. In one embodiment, the specific exposure period is about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In one embodiment, the specific exposure period is up to about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes.

[0043] In some embodiments, each step of the olfactory stimulation regimen includes: a) continuously emitting at least one scent for a first duration; and b) ceasing the emission of the at least one scent for a second duration.

[0044] In some embodiments, each step of the olfactory stimulation regimen is administered using a nebulizer or diffuser.In some embodiments, each step of the olfactory stimulation regimen is administered by ventilation, heating, humidification or vaporization, spraying or atomization, or a combination thereof, of one or more scents.In some embodiments, each step of the olfactory stimulation regimen is administered using at least one candle, tealight diffuser, atomizing diffuser, room spray, evaporative diffuser, evaporative fan diffuser, evaporative diffuser, wearable evaporative diffuser, ultrasonic diffuser, thermal evaporative diffuser, evaporative pad diffuser, cream, wick, open odorant container, or any combination thereof.

[0045] In some embodiments, at least one step of the olfactory stimulation regimen exposes the subject to one scent. In some embodiments, each step of the olfactory stimulation regimen exposes the subject to one scent. In some embodiments, at least one of the olfactory stimulation steps exposes the subject to multiple scents. In some embodiments, each of the olfactory stimulation steps exposes the subject to multiple scents.

[0046] In some embodiments, each step of the olfactory stimulation regimen involves exposing the subject to one or more scents for at least about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In some embodiments, each step of the olfactory stimulation regimen involves exposing the subject to one or more scents for up to about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In some embodiments, each step of the olfactory stimulation regimen involves exposing the subject to one or more scents for about 30 minutes.

[0047] In some embodiments, the olfactory stimulation regimen comprises performing at least 2, 3, 4, or 5 steps per day. In some embodiments, the olfactory stimulation regimen comprises performing two steps per day. In one embodiment, the two steps utilize one or more scents that are the same.

[0048] In some embodiments, the olfactory stimulation regimen comprises releasing one or more scents once a day.In some embodiments, the olfactory stimulation regimen comprises successive steps of exposing the subject to different scents.In some embodiments, the olfactory stimulation regimen comprises successive steps of exposing the subject to the same scent.

[0049] In some embodiments, the method comprises cyclically performing the olfactory stimulation step of the olfactory stimulation regimen. In some embodiments, the olfactory stimulation regimen comprises releasing one or more scents at least once a day. In some embodiments, the olfactory stimulation regimen comprises releasing one or more scents at least twice a day. In some embodiments, the olfactory stimulation regimen comprises releasing one or more scents daily.

[0050] Also provided by the present invention is a method for improving cognitive function and / or memory by treating a subject in need thereof with olfactory stimulation. In one embodiment, the method includes: a) an earlier step of exposing the subject to one or more scents; and b) a later step of exposing the subject to one or more scents that are not identical to the one or more scents of the earlier step, thereby improving the cognitive function of the subject. Further provided is a method for improving cognitive ability in a subject in need thereof. In one embodiment, the method includes exposing the subject to multiple scents during a treatment period comprising a series of exposures, at least two of which have a set of one or more scents that are not identical.

[0051] Further provided is a method for improving cognitive ability through olfactory stimulation using a series of odorant exposure steps.In one embodiment, this method comprises an earlier odorant exposure step, comprising exposing a subject to a first set of one or more odorants, and a later odorant exposure step, comprising exposing the subject to a second set of one or more odorants, wherein the first set and the second set do not have the same odorants.Also provided is a method for improving cognitive function and / or memory by performing olfactory stimulation steps.In one embodiment, this method comprises exposing a subject to a first set of one or more scents, and exposing the subject to a second set of one or more scents, wherein the first set and the second set do not have the same scents.

[0052] Also provided is a method for improving cognitive function and / or memory by exposing a subject to multiple scents over a period of time. In one embodiment, the method comprises exposing the subject to a first set of one or more scents and exposing the subject to a second set of one or more scents, wherein the first set and the second set have different scents.

[0053] Also provided is a method for improving cognitive function and / or memory by treating a subject in need thereof with an olfactory stimulation regimen. In one embodiment, the method includes a series of steps, each of which releases one or more scents to the subject, wherein no two consecutive steps release the same scent.

[0054] Also provided is a method for improving cognitive function and / or memory by treating a subject in need thereof with an olfactory stimulation regimen. In one embodiment, the method includes alternating olfactory stimulation steps, each of which releases one or more scents to the subject, wherein no two consecutive steps release the same scent.

[0055] Also provided is a method for improving cognitive function and / or memory by treating a subject in need thereof with an olfactory stimulation regimen.In one embodiment, this method comprises performing one olfactory stimulation step per day, each step comprising releasing one or more scents to the subject at least once, and no two consecutive olfactory stimulation steps release the same scent.In one embodiment, at least one step comprises releasing one or more scents to the subject at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 times.In one embodiment, each step comprises releasing one or more scents to the subject at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 times.

[0056] Also provided is a method for improving cognitive function and / or memory by treating a subject in need thereof with an olfactory stimulation regimen. In one embodiment, the method includes: a) performing an olfactory stimulation cycle including a series of olfactory stimulation steps, where only one olfactory stimulation step is performed per day, and each step includes releasing one or more scents to the subject at least once; and b) repeating the olfactory stimulation cycle of a). In one embodiment, the method further includes repeating the olfactory stimulation cycle of a) for a specific period of time.

[0057] Olfactory stimulation kits are also provided. In one embodiment, the kit comprises: a) a scent-releasing device adapted to release multiple scents; and b) a schedule for releasing the multiple scents. In one embodiment, the schedule comprises: (i) releasing one or more scents from the scent-releasing device in a first step on a first day; and (ii) releasing one or more scents from the scent-releasing device in a later step on a later day, wherein the one or more scents in the later step are not the same as the one or more scents in the first step. In one embodiment, the schedule is described in an instruction sheet.

[0058] In some embodiments, the plurality of scents is from one or more scent categories selected from the group consisting of floral, oriental, woody, aromatic, and fresh. In one embodiment, the plurality of scents is from one or more scent categories selected from the group consisting of floral, woody, and aromatic. In some embodiments, the plurality of scents is from one or more scent categories selected from the group consisting of fruity, floral, woody, resinous, and aromatic. In some embodiments, the plurality of scents is selected from the group consisting of lavender, citrus, jasmine, lilac, mint, cinnamon, peppermint, clove, lemongrass, coffee, anise, basil, thyme, chamomile, rosemary, cucumber, coconut, fresh cotton, violet, vanilla, forest pine, pomegranate, pear, orange, apple, rosemary, saffron, sage, eucalyptus, frankincense, nutmeg, and sandalwood.

[0059] In some embodiments, the schedule includes steps that are performed at night. In some embodiments, the schedule includes steps that are performed during the day. In some embodiments, the schedule includes steps that are performed over a period of 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In some embodiments, the schedule includes steps that are performed over a period of more than two days. In some embodiments, the schedule includes steps that are performed over a period of at least 1, 2, 3, or 4 weeks. In some embodiments, the schedule includes steps that are performed over a period of at least 1, 2, 3, 4, 5, or 6 months. In some embodiments, the schedule includes steps that are performed over a period of about 3 months. In some embodiments, the schedule includes steps that are performed over a period of about 6 months. In some embodiments, the schedule includes steps that are performed as a series of stimulation cycles, each stimulation cycle including at least two olfactory stimulation steps. In some embodiments, the schedule includes at least one stimulation cycle including at least 3, 4, 5, 6, 7, 8, 9, or 10 steps. In some embodiments, the schedule includes repeating at least one stimulation cycle for a specified period of time. In some embodiments, the schedule includes a 6-step stimulation cycle. In some embodiments, the schedule comprises a 7-step stimulation cycle.

[0060] In some embodiments, at least one step of the schedule includes: a) continuously emitting at least one scent for a first duration; and b) ceasing emission of the at least one scent for a second duration. In one embodiment, the first duration is about 5 minutes. In one embodiment, the second duration is about 1 minute. In one embodiment, the at least one step further includes repeating a) and b). In one embodiment, a) and b) are repeated for a specified emission period. In one embodiment, the specified emission period is about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In one embodiment, the specified exposure period is up to about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes.

[0061] In some embodiments, each step of the schedule includes: a) continuously emitting at least one scent for a first duration; and b) ceasing the emission of the at least one scent for a second duration.

[0062] In some embodiments, the scent-releasing device comprises a nebulizer or a diffuser.

[0063] In some embodiments, the scent-emitting device is adapted to emit multiple scents by ventilation, heating, humidification or vaporization, spraying or atomization, or a combination thereof, through the scent-emitting device. In some embodiments, the scent-emitting device comprises at least one candle, tealight diffuser, nebulizing diffuser, room spray, evaporative diffuser, evaporative fan diffuser, evaporative diffuser, wearable evaporative diffuser, ultrasonic diffuser, thermal evaporative diffuser, evaporative pad diffuser, cream, wick, open odorant container, or any combination thereof from the scent-emitting device.

[0064] In some embodiments, at least one step of the schedule releases one scent. In some embodiments, each step of the schedule releases one scent. In some embodiments, at least one step of the schedule releases multiple scents. In some embodiments, each step of the schedule releases multiple scents. In some embodiments, each step of the schedule releases one or more scents for at least about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In some embodiments, each step of the schedule releases one or more scents for up to about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In some embodiments, each step of the schedule releases one or more scents for about 30 minutes. In some embodiments, the schedule includes releasing one or more scents at least 2, 3, 4, or 5 times per day. In some embodiments, the schedule includes releasing one or more scents twice per day.

[0065] In one embodiment, the one or more scents emitted on a given day are the same. In some embodiments, the schedule comprises emitting one or more scents once per day. In some embodiments, the schedule comprises successive steps of emitting different scents. In some embodiments, the schedule comprises successive steps of emitting the same scent. In some embodiments, the schedule comprises cyclical administration of olfactory stimulation steps. In some embodiments, the schedule comprises emitting one or more scents at least once per day. In some embodiments, the schedule comprises emitting one or more scents at least twice per day. In some embodiments, the schedule comprises daily release of one or more scents.

[0066] These and other aspects, features and advantages of which embodiments of the present invention are possible will become apparent and elucidated from the following description of embodiments of the invention, in which reference is made to the accompanying drawings. [Brief explanation of the drawings]

[0067] [Figure 1] 1 is a graph showing cognitive decline over time. [Figure 2] 1 is a timeline illustrating the administration of an embodiment of a method of the present invention. [Figure 3] 1 is a timeline illustrating an embodiment of a daily schedule for a method of the present invention. [Figure 4] 1 is a graph showing a human sleep cycle. [Figure 5] FIG. 1 is a diagram of a fragrance wheel. [Figure 6] 1 is a chart illustrating one embodiment of scent rotation of the present invention. [Figure 7] FIG. 1 shows a Henning prism. [Figure 8] FIG. 1 is a diagram of a fragrance wheel formed from one side of a Hennig prism. [Figure 9] 1 is a perspective view of an embodiment of an apparatus of the present invention; [Figure 10] FIG. 10 is a cutaway view of an embodiment of the device of FIG. 9. [Figure 11] 1 is a perspective view of an embodiment of a cartridge of the present invention. [Figure 12] FIG. 12 is a cutaway view of the cartridge of FIG. [Figure 13] 1 is an elevational view of one embodiment of the scent pad package of the present invention. [Figure 14] FIG. 1 is a perspective view of an embodiment of a gel tab of the present invention. [Figure 15] FIG. 1 is a side view of an embodiment of a CPAP mask of the present invention. [Figure 16] 1 is a graph showing the change in Stroop score using the present invention. [Figure 17] 1 is a graph showing the change in Rey Auditory Verbal Learning Test scores using the present invention. [Figure 18] 1 is a graph showing the change in Wechsler Adult Intelligence Scale-III Letter-Number Sequencing scores using the present invention. [Figure 19] 1 is a graph showing the change in Wechsler Adult Intelligence Scale-III Backwards Digit Span scores using the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0068] Specific embodiments of the present invention will now be described with reference to the accompanying drawings. However, the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. The terminology used in the detailed description of the embodiments illustrated in the accompanying drawings is not intended to be limiting of the invention. In the drawings, like numbers refer to like elements.

[0069] definition All scientific and technical terms used in this application have the meanings commonly used in the art unless otherwise specified. As used in this application, the following words or phrases have the meanings specified:

[0070] As used herein, "releasing" or "exposing" a subject to a scent means providing the scent to the subject's environment in a manner sufficient to stimulate the subject's olfactory system.

[0071] As used herein, "decreasing" or "increasing" means decreasing or increasing by a detectable or noticeable amount, respectively. In some embodiments, such decreasing or increasing is measured using one of the assessment tools described herein. In some embodiments, the decreasing or increasing represents a "significant difference."

[0072] As used herein, "ameliorate" means to bring about an improved condition, e.g., amelioration of the symptoms of a deleterious condition, or an improvement in a desired condition, such as memory.

[0073] As used herein, "significant difference" refers to a difference that can be detected by a method that is considered reliable by those skilled in the art, such as a statistically significant difference, or a difference that is large enough to be detected with a reasonable level of reliability under the circumstances. In one example, a 10% increase or decrease compared to a reference value is a significant difference. In another example, a 20%, 30%, 40%, or 50% increase or decrease compared to a reference value is considered a significant difference. In yet another example, a 2-fold increase compared to a reference value is considered significant. The reference value can be, for example, an untreated subject, or the baseline (pre-treatment) value of the same subject.

[0074] As used herein, ranges and amounts can be expressed as "about" a particular value or range. About includes the exact amount. Thus, "about 5 minutes" means "about 5 minutes" and "5 minutes." Generally, the term "about" includes amounts 10% below to 10% above a particular value or range. For example, "about 10 minutes" means "9 to 11 minutes."

[0075] As used herein, "a" or "an" means at least one, unless otherwise specified.

[0076] environmental enhancement In over a dozen animal models of human neurological conditions, environmental enrichment has been shown to ameliorate their human-like symptoms, including cognitive decline in aging (Patel et al., 2012; Segovia et al., 2006; Valero et al., 2007) and Alzheimer's disease (Arendash et al., 2004; Arranz et al., 2011; Basak et al., 2008; Berardi et al., 2007; Costa et al., 2007; Jankowsky et al., 2015; Lazarov et al., 2005; Polito et al., 2014). In humans, environmental enrichment, including exercise, computer games, social behavior, and nutritional intake, has been shown to reduce the risk of cognitive decline during aging and disease (Herzog et al., 2008; Kirk-Sanchez and McGough, 2014; Klimova, 2016; Williams and Kemper, 2010). However, demonstrating that cognitive decline can be reversed has been difficult, and when such improvements exist, the effect sizes tend to be modest (Herzog et al., 2008; Rodakowski et al., 2015). Furthermore, getting people to adhere to interventions such as daily exercise programs has been shown to be difficult (Williams et al., 2007).

[0077] The olfactory system experiences significant deterioration in the elderly, with 18% of older adults experiencing olfactory impairment and 46% of people over 80 years of age having very limited olfactory abilities (Doty et al., 1984; Hoffman et al., 1998; Liu et al., 2016; Murphy et al., 2002; Pinto et al., 2015; Toussaint et al., 2015). The onset of this decline is consistent with that observed in cognitive abilities in older adults (Park et al., 2003; Salthouse, 2009). The age-related decline in cognitive function is illustrated in Figure 1. Figure 1 shows an initial decline around age 60 that continues as individuals age, with inductive reasoning, spatial orientation, perceptual speed, numerical ability, verbal ability, and verbal memory all affected. The olfactory system, unlike other sensory systems, projects directly to cognitive areas, and loss or compromise of the olfactory system results in massive volume loss in these cognitive areas in humans of all ages (Bitter et al., 2010a; 2010b; 2011; Yao et al., 2014). Normal human aging is accompanied by a deterioration of olfactory abilities (Dong et al., 2017; Hoffman et al., 2016; Seubert et al., 2017), which is accompanied by a deterioration of olfactory projection sites, including cognitive areas of the brain (Kollndorfer et al., 2015; Segura et al., 2013). Furthermore, reduced olfactory ability predicts an increased risk of minimal cognitive impairment (MCI) and who among those with MCI will develop Alzheimer's disease (Adams et al., 2017; Devanand et al., 2000; Lafaille-Magnan et al., 2017; Peter et al., 2003; Roberts et al., 2016; Schubert et al., 2008; 2017; Swan and Carmelli, 2002). Notably, olfactory function also predicts all-cause mortality in older adults (Gopinath et al., 2011; Pinto et al., 2014).

[0078] Loss of olfactory function precedes or parallels the onset of various cognitive disorders, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, Creutzfeldt-Jakob disease, mild cognitive impairment, and schizophrenia (Conti et al., 2013; Devanand et al., 2000; Devanand et al., 2010; Doty et al., 1988; Li et al., 2010; Luzzi et al., 2007; Meusel et al., 2010; Nguyen et al., 2010; Parrao et al., 2012; Ponson et al., 2004; Ross et al., 2006; Tabaton et al., 2004; Wattendorf et al., 2009). Given the widely different etiologies of these cognitive disorders, this raises the possibility that loss of olfactory stimuli may contribute to cognitive decline in each of these disorders.

[0079] In humans experiencing olfactory loss due to various issues, including post-infectious olfactory dysfunction, head trauma, Parkinson's disease, and aging, increased olfactory experience has been shown to improve olfactory discrimination, odor discrimination, and, to a lesser extent, olfactory thresholds (Damm et al., 2014; Geissler et al., 2014; Haehner et al., 2013; Hummel et al., 2009; Konstantinidis et al., 2013; Patel et al., 2017). These results were achieved by exposure to four odorants taken from each of four odor groups: resinous (eucalyptus), floral (rose), fruity (lemon), and aromatic (clove). Further improvements in olfactory ability were observed with increased exposure time, increased odorant concentration, and increased number of odorants (Altundag et al., 2015; Damm et al., 2014; Konstantinidis et al., 2016). In addition to improved sensory abilities, older adults exposed to increased olfactory stimulation experience improvements in cognitive function, as evidenced by increased verbal fluency, improved depressive symptoms, and improved well-being (Wegener et al., 2018). Olfactory stimulation in older adults also reduces falls in this group (Sakamoto et al., 2012).

[0080] Individuals with autism have olfactory dysfunction with abnormal sniffing responses to both differentially valenced odors (Rozenkrantz et al., 2015) and social odors (Endevelt-Shapira et al., 2018). They also have abnormal olfactory responses (Boudjarane et al., 2017; Tonacci et al., 2017). Various rodent models of autism ameliorate human-like symptoms of the disorder when placed in enriched environments (Kerr et al., 2010; Kondo et al., 2008; Lacaria et al., 2012; Lonetti et al., 2010; Nag et al., 2009; Restivo et al., 2005; Reynolds et al., 2013; Schneider & Przewlocki, 2005; Schneider et al., 2006).

[0081] Environmental enrichment, including olfactory stimulation paired with tactile stimulation, has been successfully used to treat children with typical autism (Woo and Leon, 2013; Woo et al., 2015). In two randomized clinical trials, parents provided novel multisensory stimulation, featuring olfactory stimulation, for 15–30 minutes each morning and evening for a period of 6 months. 42% of the enriched children showed significant symptom improvement as measured by the subjective Childhood Autism Rating Scale, compared with 7% of standard-care controls. IQ increased by more than 8 points in the enriched children, compared with an improvement of approximately 1 point in the controls. The Short Sensory Profile revealed an 11-point improvement in the enriched children compared with an improvement of approximately 1 point in the controls. Receptive language, measured by the objective Reynell Developmental Language Scale, improved by more than 200% in the enriched children with autism and less than 20% in the controls. Finally, after 6 months, 21% of the children with autism were considered cured using the objective Autism Diagnostic Observation Schedule, while no control children reached that level of improvement.

[0082] A review of the outcomes of over 1,000 children across the autism spectrum who received this treatment at home (Aronoff et al., 2016) found that these children outperformed children in university clinical trials, with an effect size of 1.85. Not only did core autism symptoms improve, but comorbid symptoms associated with nearly all children with this disorder, including sensory processing, self-awareness, communication, mood, sleep, eating, motor skills, learning, memory, anxiety, and attention span, also improved. The treatment had similar effects on children across the autism spectrum, with both girls and boys improving equally, and the treatment worked across all ages tested (2–18 years). There were also dose / response results for parental compliance and improvement in children's symptoms.

[0083] schedule Referring now to the figures, and initially to Figures 2 and 3, a general diagram of the method 10 of the present invention is shown. Method 10 generally involves having a treatment recipient follow a daily schedule 20 of scent intervals 30 separated by breaks 40. The daily schedule is administered over a period of days, weeks, months, or years, depending on the treatment recipient and the desired results. Because there are no negative side effects or drawbacks to treatment method 10, except perhaps for the cost of the fragrance, benefit may be found in continuing schedule 20 indefinitely.

[0084] 3 provides a non-limiting example of a daily schedule 20 that begins at bedtime B. Bedtime is chosen because it is easy, as the treatment can be delivered to a person who is stationary, and effective, as the scent can be delivered to a person who is in a relatively small, enclosed room, such as a bedroom. Note, however, that the effectiveness of the treatment may not be reduced if the treatment is delivered during the day, such as to a person sitting in front of a computer, driving a vehicle, or otherwise stationary relative to the delivery device, or if the delivery device moves with the recipient throughout the recipient's daily activities, as is the case with a wearable device.

[0085] In the embodiment of Figure 3, the recipient activates a scent delivery device (described in more detail below) that includes a timer set to deliver various odors at predetermined intervals. In this example, the intervals 30 are approximately 30 minutes long and are separated by breaks 40 that are 5 minutes in duration. However, it should be understood that these interval and break times are merely non-limiting examples and may vary based on recipient preference, subjective results, physician recommendations based on empirical evidence, sleep duration, etc. As a starting point, good results have been obtained with 30-minute intervals that include a 5-minute break.

[0086] The daily schedule 20 begins each day with a start event. For recipients with regular routines, the start event may not begin at bedtime but may occur at a set time of day. For example, in this embodiment, the first interval 30 of the daily schedule 20 may begin at 12:00 AM and continue until 12:30 AM. Thus, the first break 40 may range from 12:30 AM to 12:35 AM, and the second interval 30 may begin at 12:35 AM and continue until 1:05 AM. These intervals 30 and breaks repeat this pattern until a predetermined number N of intervals 30 and breaks 40 have occurred. Like the length of the intervals 30, the number N may vary based on the recipient's typical sleep duration and subjective or objective results. Generally, for optimal results, N should be at least 3.

[0087] In another embodiment, the initiating event may be tied to the recipient's sleep cycle. FIG. 4 is a diagram of a human sleep cycle 50. The sleep cycle 50 consists of various stages that repeat every 90 to 110 minutes. One model divides the sleep cycle into five stages. Stage 1 is light sleep, characterized by a decrease in muscle, brain, and eye activity. In stage 2, the heart rate and breathing pattern slow, and body temperature drops slightly. In stage 3, deep sleep begins, and very slow delta waves are produced by the brain. Stage 4 is very deep sleep, accompanied by rhythmic breathing, limited muscle activity, and the continuous production of delta waves. The fifth stage is called the rapid eye movement (REM) stage. This is the dream stage, characterized by increased blood pressure, heart rate, breathing rate, and rapid eye movements.

[0088] Referring again to Figure 4, the sleep cycle begins in stage 1 and progresses rapidly to stage 4 within the first hour of falling asleep. After an hour or so, heart rate, blood pressure, and breathing rate rapidly increase as the person enters REM sleep, which typically lasts only about five minutes. After REM sleep, the cycle repeats to some degree.

[0089] In particular, throughout the night, the extent to which a sleeper enters deep sleep decreases. For example, as shown in the graph of Figure 4, during the second cycle, stage 4 is rarely achieved. The end of the second cycle is also indicated by a REM phase lasting 10 minutes instead of 5 minutes. The third cycle only falls into stage 2 sleep, followed by a 15-minute REM phase. The fourth cycle also only falls into stage 2 sleep, followed by a REM phase lasting 30-60 minutes.

[0090] Much remains to be learned about the human sleep cycle. Scientists have often assumed that experience and knowledge are converted into long-term memory during sleep, and that REM sleep plays an essential role in the acquisition of learned material, both declarative and procedural memory (both forms of near transfer). In recent years, researchers have begun to hypothesize that deep, restorative sleep, also known as "slow-wave sleep" (SWS), plays a key role in declarative memory by processing and consolidating newly acquired information.

[0091] With this in mind, one aspect of the present invention includes a sleep stage tracking system, such as a heart rate monitor, a respiratory monitor, a blood pressure monitor, an EEG sensor, or any combination thereof. The sleep stage tracking system is used in conjunction with a scent delivery schedule to ensure that rest intervals (periods between scent delivery intervals) occur during less effective sleep stages and scent intervals occur during the most effective sleep stages. The therapeutic effect of the olfactory stimulation therapy of the present invention may likely vary depending on the sleep stage in which the recipient is. For example, a treatment delivered during stages 3 and 4 may be ineffective, while a treatment delivered during REM may be determined to be the most effective of all stages.

[0092] Given that there is likely no reduction in efficacy if scent is delivered during a point in the sleep cycle that is not optimal for far transfer, a benefit of tracking the sleep cycle may simply be to avoid breaks 40 occurring during peak far transfer effects. For example, if REM sleep is determined to be the sleep cycle stage best for far transfer effects, it may be beneficial to avoid breaks 40 during REM stages, particularly the first two or three REM stages, which only last 5 to 15 minutes.

[0093] Similarly, if stage 4 is determined to be the most beneficial time for olfactory stimulation to be administered, it is important to ensure that interval 30 is scheduled during the first two sleep cycles, as these are typically the only cycles in which stage 4 occurs.

[0094] One embodiment of the method of the present invention provides intervals 30 that coincide with sleep cycles through the use of monitoring. Because sleep cycles coincide with fluctuations in biological factors such as blood pressure, heart rate, respiratory rate, brain wave activity, and eye movement, those skilled in the art will recognize that many techniques exist for monitoring various sleep stages. As such, the duration of intervals 30 and the duration of rest periods 40 can be selected to synchronize with sleep cycles. In this embodiment, there may be as few as three intervals or as many as six or seven intervals, depending on the length of sleep desired by the recipient.

[0095] One embodiment of this synchronized method involves recording the recipient's sleep patterns over several days to establish a typical pattern. The delivery device is then scheduled to approximate the synchronized schedule. In this way, the recipient would not need to use the monitoring device unless recalibration is required.

[0096] Another embodiment of this synchronized method involves continuous monitoring of one or more of the above biological factors. For example, heart rate monitors are common in many forms, including but not limited to optical wearables, chest straps, airbed pulse detectors, etc. The biological factors are continuously monitored, and the sleep cycle is determined based on the data collected therefrom. The device then activates and deactivates various scents according to a schedule created based on the data. As such, the schedule may vary slightly from evening to evening. This method may be ideal for recipients with varying daily routines.

[0097] rotation One aspect of the present invention is that the scents delivered to the recipient are new. This does not mean that the scents will be completely unfamiliar to the recipient throughout their lifetime, but simply that the scents will change every interval and not be reintroduced for a predetermined number of intervals. In one embodiment, at least seven different scents are used, and no scent is repeated until six other scents have been used. In other embodiments, a large number of scents are used so that it is unlikely that a scent will be used twice during the entire treatment program.

[0098] As a general guideline, it is believed that the more recent the scent, the greater the impact. Furthermore, it is believed that successive scents should be as different as possible during a particular daily schedule 20. To accomplish this, one embodiment provides a rotation that avoids placing two aromas from the same scent family next to each other.

[0099] Scents may be classified into scent groups, commonly referred to as a fragrance wheel or chart. Various fragrance charts exist. One widely used chart, used here merely as an example, was developed by perfume taxonomist Michael Edwards in 1992 and has since been modified several times. The 2010 version of the Michael Edwards Fragrance Wheel is provided as Figure 4 and was published in 2011 in Fragrances of the World by Michael Edwards & Co., which is incorporated herein by reference.

[0100] As can be seen in Figure 5, there are four major fragrance families: floral, oriental, woody, and fresh. These are divided into subgroups, which are arranged to show their relationship to each other. For example, the floral family is divided into floral, sort floral, and floral oriental. The oriental family is divided into soft oriental, oriental, and woody oriental. The floral oriental subgroup of the floral oriental family is placed next to the soft oriental subgroup of the oriental family. This is because these two are the most similar, despite being in different families.

[0101] The fragrance wheel in Figure 5 is useful because further scent differences are easily visualized by their respective proximity on the wheel. For example, scents in the Mossy Woods subgroup are opposite scents in the Floral subgroup. Thus, it is easy to appreciate that the brain processes the smell of amber as very different from the smell of fresh-cut flowers.

[0102] When creating a rotation, guidelines for scent diversity can be established using the fragrance wheel in Figure 5. For example, spacing subgroups by one to five scents between consecutive scents can maximize the effectiveness of the olfactory stimulation schedule 20. Similarly, it can be determined that over the course of a single daily schedule 20, at least one fragrance from each of the four families should be represented.

[0103] FIG. 6 provides an example of a rotation 60 in which all four families are represented across seven intervals 30 of the schedule 20, with at least one subgroup separating consecutive intervals 30.

[0104] Figure 7 provides another example of a fragrance schematic developed by German psychologist Hans Henning in 1916. Henning H (1916) Der Geruch. Leipzig, Germany. The schematic in Figure 7, known as the Henning Prism, is a three-dimensional prism consisting of three rectangular faces, each of which can be used as a fragrance wheel. The corners of the prism contain the following fragrance families: fragrant (flower or floral), ethereal (fruity), stale, resinous, burning, and spicy. Each face shares two families with its neighboring face. Thus, one face of the prism contains the flowery, fruity, spicy, and resinous families. Another face contains the flowery, spicy, burning, and stale families. The third face contains the burning, stale, fruity, and resinous families. Because the stale and burning families are generally less desirable, the face shown in Figure 8 is considered preferable. Figure 8 takes this face and forms a wheel containing subgroups between families.

[0105] strength The strength or intensity of the aroma produced during treatment must be strong enough to affect the recipient, but not so strong that it creates a lingering odor in the furniture or other objects in the room where treatment is being administered. Optimally, the aroma delivered during each interval 30 dissipates during the break 40 between intervals 30. Interestingly, since scents are not affected during sleep, a scent strong enough to interrupt sleep patterns is not a problem. However, as previously mentioned, loss of smell occurs with age and should be enhanced by treatment. Therefore, an embodiment of the present invention is to adjust the intensity level prior to the treatment program to a level that is easily detected by the recipient without being overpowering.

[0106] Another embodiment of the present invention includes a device that allows for the mixing of fragrances by "activating" two or more cartridges simultaneously. The device also allows for the intensity of each fragrance cartridge to be adjusted by increasing or decreasing the airflow through the cartridge. In this way, a "recipe" can be changed not only by adjusting which cartridge is activated, but also by adjusting the intensity of each activated cartridge. For example, if a "recipe" includes a mixture of cherry and vanilla, the cherry cartridge can be activated at 50% intensity and the vanilla cartridge can be activated at 10% intensity. This will produce a different scent than if, for example, vanilla were activated at 50% intensity and cherry was activated at 10% intensity.

[0107] Device Various devices are contemplated that can be used to practice the method 10 of the present invention. These devices can generally be divided into two categories: forced air devices and vaporizers. Forced air devices generally include one or more scent cartridges engaged with a mechanism that pumps air through the cartridges by one or more fans, bellows, turbines, etc., preferably at selectable speeds so that the intensity can be varied. Some embodiments include multiple cartridges on a selectable carousel that activates one cartridge at a time. Other devices include multiple cartridge-engaging assemblies, or "actuation heads," to allow the cartridges to be activated simultaneously.

[0108] The evaporation device may be contained within the dispensing device or may comprise scent cartridges, pads, or gels that may be layered such that, once opened, an exposed layer having a first scent begins to evaporate, thereby releasing the first scent. The scented layers may be separated by unscented layers to provide a break 40 between scent intervals 30. The dispensing device may have a mechanized cover that selectively covers and exposes the scent cartridges, or may have a heater associated with each scent cartridge that raises the temperature of the gel to the point where evaporation occurs.

[0109] Referring now to Figure 9, a first embodiment of a device 100 of the present invention is shown. Device 100 is a forced air device that houses four cartridges 102, 104, 106, and 108. Each cartridge may be a disposable device that allows air to flow through the cartridge to release the fragrance. Alternatively, for ecological and cost reasons, the cartridges may be refillable and reusable. Details of the individual cartridges are provided below.

[0110] 9 and 10, an embodiment of device 100 includes a housing 110 with cavities 112, 114, 116, and 118 sized and shaped to accommodate cartridges 102, 104, 106, and 108, respectively. Each cavity 112, 114, 116, and 118 may include a retractable cover 122, 124, 126, and 128, respectively, to preserve unused cartridges and prevent the development of aroma therefrom.

[0111] It is contemplated that each cartridge and corresponding cartridge will have a unique shape corresponding to a fragrance family. In this manner, the recipient must place a cartridge belonging to each fragrance family into device 100. In the example of device 100, the selected shapes are circle, square, triangle, and oval for cartridges 102, 104, 106, and 108. Alternatively, each cartridge can be coded, and each cavity can be equipped with a code reader so that device 100 knows which fragrance has been inserted into each cavity.

[0112] The housing has a vent 110 formed in one wall through which the fragrance from the cartridge is released. The side wall was chosen because most users will place the device 100 on a bedside table. The vent 110 can then be positioned so that it faces the recipient.

[0113] Inside, the device contains one or more fans 130 positioned below the cavity. Fans 130 are powered by motors 132 and connected to the motors by shafts 134. A control board 140 drives the logic that activates and deactivates each motor, along with logic functions detailed below. In embodiments with one fan, the flow through the individual cartridges is controlled by covers 122, 124, 126, and 128.

[0114] Device 100 is shown drawing air downward through the cartridges into central housing cavity 120. Considering that the covers are closed on unused cavities and a fan is operating in each cavity with the cover open, air is forced to exit through vent 110, as this is the only exit for the cavity. This design allows central housing cavity 120 to be used as a mixing chamber when multiple fragrance cartridges are being used simultaneously. A barrier 121 is provided to protect electronic components such as motor 132 and control board 140, shielding these components from central housing cavity 120.

[0115] Those skilled in the art will appreciate that the device 100 may be designed so that the airflow is reversed without departing from the spirit of the present invention. The reverse airflow may be achieved by simply reversing the direction of the fan 130. This design may be advantageous in that there is less risk of residue buildup within the cavity 120.

[0116] The control panel 140 is electrically connected to the fan motor 132 and includes wireless connection technology such as Bluetooth that allows it to connect to an electronic device such as a smartphone or reader. A downloadable application for the device contains control logic that allows the user to customize the treatment schedule. Alternatively, a physician can create a schedule 20 that the user can download.

[0117] The application provides a variety of controls and options that can be incorporated into the daily schedule, including scent rotation, intensity, timing, reminders, scent shuffling, etc. The application preferably tracks scent rotation to assess which scents may have been repeated over the course of a treatment program. These scents can be marked by the application as no longer novel so they can be removed from rotation or mixed with another scent the next time they are used.

[0118] The application may wirelessly connect to various biometric sensors listed above so that the schedule is dynamically timed. For example, a user may wear a heart rate monitor while sleeping. Activation of the heart rate monitor is sensed by the application, which then begins monitoring the user's sleep stages, as described above, to determine the timing of the daily schedule 20.

[0119] Alternatively, if a biometric sensor is not used, the handheld electronic device itself can be used by the control panel to indicate the start of the daily schedule 20. For example, the device 100 may include a USB charging port 111 connected to the control panel. A user can use this USB port to charge their phone during the evening. Plugging the phone into the device 100 can be used as an indicator that the daily schedule 20 should begin. This maximizes ease of use, as most people are accustomed to charging their smartphones in the evening, minimizing disruption to their daily routine.

[0120] The control panel 140 is also used to track cartridge usage. Depending on the cartridge's construction, an application can be used to indicate to the user that a particular cartridge needs to be replaced.

[0121] 11 shows an embodiment of a cartridge 102 of the present invention. This embodiment is a disposable embodiment and includes a housing 150 with a top surface 152 and a bottom surface 154. The top surface 152 and the bottom surface 154 are vented to allow air to pass through. The cartridge 102 is shipped with a removable film (not shown) that covers the top surface 152 and the bottom surface 154, thus preserving the odorants contained therein, until the cartridge is ready to be used.

[0122] 12 shows a cutaway view of the cartridge 102, revealing the absorbent odorant pad 156. The pad 156 can be formed as a wad, such as a cotton ball or polyester fiber-filled wad, and should be loosely packed to allow air to flow through it. Alternatively, the pad 156 may be slightly smaller than the interior of the cartridge to allow air to flow around the pad 156. In this embodiment, a denser padding material can be used, which may retain odorant better than embodiments that require air to flow through the pad 156.

[0123] In one embodiment of the cartridge 150 of Figure 12, the top surface 152 is removable and replaceable. This embodiment reduces plastic waste and costs. Rather than replacing the entire cartridge, the odorant pads 156 can be provided or sold individually or in packages containing multiple pads. Figure 10 shows a package 160 of pads 156 arranged so that each row 162 represents a different scent family, and thus each column 164 represents a different day of the week.

[0124] As introduced above, one aspect of the present invention provides an evaporation device that includes a scent cartridge, pad, or gel that can be contained within a dispensing device or layered such that, once opened, an exposed layer having a first scent begins to evaporate, thereby releasing the first scent. The scented layers can be separated by an unscented layer to provide a break 40 between scent intervals 30.

[0125] One embodiment of an evaporation device 180 is shown in Figure 14. This device is a gel tab consisting of multiple odorant layers 182 separated by odorless layers 184. In this example, there are six odorant layers 182 separated by five odorless layers. The odorant layers are designed to evaporate at a desired rate, with each odorant layer representing an interval 30. The odorless layers are designed to evaporate at a desired rate, with each odorless layer representing a break 40. The desired timing of each layer can be controlled by the layer thickness during the manufacturing process. In that case, the odorless layers 184 would be thinner than the odorant layers 182. The gel tab 180 is provided on a substrate 186 so that only the top layer evaporates.

[0126] The gel tab 180 provides a base for the various delivery mechanisms included in the present invention. It is further envisioned that the gel tab 180 can be shaped so that it can be removed from the substrate 186 and applied directly to the recipient's upper lip or chin like a tap. In this embodiment, it may be desirable to include an odorless layer 184 as a top layer so that the user has a few minutes to fall asleep before experiencing the odorant.

[0127] 15 shows a CPAP mask 200 slightly modified to accommodate a gel tab 180. The mask 200 has a nozzle 206 that connects to the gas delivery tubing of a typical CPAP machine (not shown). The nozzle 206 includes a compartment 202 with a lid 204 that can be opened to allow the gel tab 180 to be placed therein. The tab 180 is positioned with the base 186 facing up. During use, gas flowing from the CPAP machine through the nozzle 206 passes under the exposed layer at the bottom of the tab 180 and is inhaled by the user. In the morning, the empty base 186 is discarded.

[0128] Other devices that utilize gel tabs 180 are envisioned, including, but not limited to, plug-in style air refreshers, non-CPAP masks, pendants and other wearable devices, nose plugs, heat-activated devices, diffusers, and the like. [Example]

[0129] The following examples are presented to illustrate the present invention and to assist one of ordinary skill in making and using the same. These examples are not intended to limit the scope of the invention.

[0130] Example 1: Enhancing the classroom environment in an inner city This example demonstrates enhanced brain response following multiple olfactory stimuli in schoolchildren. Inner-city school children were exposed to 30 minutes of olfactory stimulation in their classrooms daily using essential oil fragrances, rotating through five different scents (n = 25 children), once per day for three months. Another group of 23 children was left without such stimulation to serve as controls. Stroop test scores were monitored over the period. This test assesses cognitive processing speed, attention, and executive function. Furthermore, the Stroop test has been strongly correlated with IQ, general behavior, and school grades (Imbrosciano and Berlach, 2005).

[0131] As shown in Figure 16, the children whose sense of smell was enhanced had an improvement of more than 10 times that observed in the controls on that test. Because the classes were team-taught by the same teacher, this phenomenon is unlikely to be due to differences in the teachers' teaching abilities. There have been many attempts to improve the cognitive outcomes of elementary school children, but such attempts have generally not been successful in increasing their cognitive abilities.

[0132] Example 2: Environmental enrichment for older adults This example demonstrates the positive impact of olfactory stimulation on cognitive performance in older adults. Elderly adults were tested using a standard validated cognitive assessment and retested after daily olfactory stimulation. Stimulated older adults demonstrated improvements of 181%, 268%, and 1,258% greater than controls.

[0133] Elderly participants were given a pair of pleasant scents and asked to use a provided nebulizer to expose themselves to the scents for 30 minutes in the morning and 30 minutes in the evening daily for six months. Forty elderly participants (aged 60-75 years) were assigned to either self-administer the patterned olfactory stimulation at home or to no-op therapy. Three cognitive tests were administered at the start of the trial and again six months later.

[0134] In a test of verbal learning and memory (the Rey Auditory Verbal Learning Test), older adults with enhanced olfaction performed 181% better than controls (Figure 17). In a test of sequential processing, mental operations, attention, concentration, memory span, and short-term auditory memory (the WAIS III Letter-Number Sequencing), the enhanced group had a 268% advantage over controls (Figure 18). Finally, in a test of rote learning and memory, attention, encoding, and auditory processing, working memory, information transformation, mental operations, and visuospatial imaging (the WAIS III Backward Digit Span), the enhanced group performed 1,258% better than controls (Figure 19).

[0135] These cognitive benefits are approximately one to two orders of magnitude superior to computer games, direct brain stimulation, exercise, or social interaction ( Clememson and Stark, 2015 ; Ezzyat et al., 2018 ; Hertzog et al., 2009 ; Kirk-Sanchez and McGough, 2014 ; Kucewisc et al., 2018 ). References

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[0222] While the present invention has been described with respect to particular embodiments and applications, those skilled in the art, in light of this teaching, can make additional embodiments and modifications without departing from the spirit and beyond the scope of the claimed invention. Accordingly, it should be understood that the drawings and descriptions herein are provided by way of example to facilitate understanding of the invention and should not be construed as limiting its scope.

Claims

1. 1. A system for providing cognitive-enhancing olfactory therapy, the system comprising: a housing defining a cavity; a carousel having a plurality of scent cartridges disposed in a cavity of the housing and configured to activate one cartridge at a time, each cartridge containing a scent belonging to a subgroup of a fragrance family, and adjacent cartridges not containing scents from the same scent group; and one or more fans adjacent to the cavities and capable of moving air through any of the cavities; one or more motors, each motor capable of rotating a respective one of the one or more fans; a control panel capable of individually controlling the one or more motors according to a schedule including a plurality of intervals separated by rest periods, and initiating the schedule with a start event; During the interval, at least one fan is activated to move air through the cavity, thereby emitting odors from the scent cartridges of the plurality of scent cartridges; During a subsequent interval of the schedule, a second scent cartridge is activated and at least one fan is activated to emit a different odor from the second scent cartridge, and no scent is repeated during the schedule. system.

2. 10. The system of claim 1, further comprising a movable cover associated with each of the scent cartridges and mechanized to move between an open position and a closed position, the cover being controlled by the control panel.

3. The system of claim 1 , wherein the starting event comprises a time of day.

4. The system of claim 1 , wherein the initiating event comprises data received from a biometric sensor indicating that a user has begun a sleep cycle.

5. The system of claim 1 , further comprising a personal electronic device wirelessly connected to said control panel, said personal electronic device providing said daily schedule.

6. The system of claim 5 , wherein the initiating event is determined by the personal electronic device.

7. 10. The system of claim 1, wherein in the fragrance wheel, consecutive scent cartridges do not have scents adjacent to each other.

8. The system of claim 1 , wherein successive scent cartridges have scents belonging to subgroups that are 1 to 5 subgroups apart.

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