Training method for delaying development of Alzheimer's disease

Abstract

The invention relates to the technical field of medical treatment, and particularly discloses a training method for delaying development of Alzheimer's disease, which comprises the following steps: (a) a neural pathway activation stage: generating a dynamic three-dimensional space navigation task through a virtual reality system and displaying a color coding path to a patient; the method comprises the following steps: (c) a lymphatic driving stage: starting a 40Hz multi-mode stimulation combination after metabolic regulation reaches the standard, and (d) a closed-loop optimization stage: detecting saliva exosome A beta 42 concentration or EEG gamma wave power every two weeks, each time is 40 minutes every day, and the steps (a)-(b)-(c) are executed in sequence; neuropathology is improved, compared with the prior art, the hippocampus atrophy rate is remarkably reduced, the A beta 42 pathological deposition removal efficiency is high, and the white matter fiber integrity is improved; the cognitive function of the patient is enhanced, the space navigation capability is optimized, and the attention and work memory are improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical treatment, in particular to a training method for delaying the development of Alzheimer's disease. BACKGROUND

[0002] Alzheimer's disease is a degenerative disease of the central nervous system, mainly occurring in the elderly or pre-elderly. The main features of the disease include progressive cognitive impairment and behavioral impairment. In addition, the patient's abstract thinking and computing power are also impaired, often accompanied by changes in personality and behavior. This disease is the result of the combined effects of genes, lifestyle and environmental factors, and the risk of disease increases with age.

[0003] The existing intervention technology has certain limitations: single modality intervention is inefficient, existing non-drug interventions (such as 40Hz light stimulation, transcranial electrical stimulation) only activate local brain areas (such as the primary visual cortex), and cannot simultaneously optimize hippocampus-frontal lobe cross-frequency coupling; rely on offline biomarkers (such as Aβ-PET) to adjust parameters, response period > 4 weeks (ADNI database statistics), unable to adapt to real-time changes in neural plasticity; in addition, there are problems such as disconnection between respiratory intervention and cognitive tasks, and bottleneck of multi-sensory integration affecting treatment effect. Therefore, the existing training method needs to be optimized and improved. SUMMARY

[0004] The present application is aimed at the above-mentioned deficiencies in the prior art, and provides a training method for delaying the development of Alzheimer's disease. In order to achieve the above-mentioned purpose, the present application provides the following technical scheme: A training method for delaying the development of Alzheimer's disease, the steps are executed in the following order: (a) Neural pathway activation phase: generate a dynamic three-dimensional space navigation task through a virtual reality system, display a color-coded path to the patient, and require him to complete path decision-making within a target time limit of 90-120 seconds according to real-time voice instructions, and monitor the phase amplitude coupling index PAC of hippocampus-frontal lobe electroencephalogram gamma waves and theta waves through a 64-lead electroencephalograph simultaneously, if the real-time PAC < baseline value 0.25, then extend the decision-making time limit by 20%; (b) Metabolic feedback regulation phase: within 5 minutes after completing the path decision-making, the patient is required to wear an adjustable respiratory resistance mask, and the respiratory rhythm is adjusted according to the real-time displayed end-tidal CO2 concentration data, if the CO2 concentration exceeds the target interval continuously for 120 seconds, the system generates a specific breathing instruction until the blood oxygen fluctuation amplitude stabilizes at baseline ± 10%, and a 5-minute gentle breathing transition period is performed after meeting the standard; (c) Lymphoid-like driving phase: after the metabolic regulation meets the standard, start the 40Hz multi-modal stimulation combination, including: Projecting blue-green stroboscopic light into the patient's field of view, transmitting frequency-modulated white noise through the temporal bone, and dynamically adjusting the photoacoustic phase difference every 60 seconds based on the pupil dilation gradient; (d) Closed-loop optimization phase: salivary exosomal Aβ42 concentration or EEG gamma wave power were measured every two weeks. If the decrease in Aβ42 was less than 3% / week or the increase in gamma wave power was less than 8% during the training period, the gamma stimulation duty cycle was increased to 60-75% and the rotation dimension of the navigation task was increased. The training process was as follows: 40 minutes per day, with steps (a)→(b)→(c) performed sequentially. During stage (d), parameters were adjusted across cycles, and the safety termination condition was: blood pressure fluctuation >20% of baseline value or subjective dizziness score ≥4 points, for 24 weeks.

[0005] Preferably, in stage (a): (1) When the PAC index is less than 0.25 for two consecutive training sessions, increase the number of navigation path bifurcation points to 5-8 and reduce the voice prompts by 50%; (2) releasing ≤5 ppm isovaleric acid or ≤3 ppm δ-decalactone odor stimulation at the turning node, with exposure time ≤30 seconds / time, and the patient reporting the odor attributes when turning; (3) If the odor recognition delay is greater than 3 seconds, increase the ipsilateral nasal airflow concentration by 20%.

[0006] Preferably, in stage (b): (1) When passing through the virtual narrow area, the expiratory resistance increases to 8-10 cmH2O for 6-10 seconds; (2) Real-time monitoring of HbO2 in the frontal lobe. If the HbO2 rising slope is less than 0.5 μmol / L / s during the decision-making period, suspend resistance breathing for 30 seconds and reduce navigation complexity; (3) The compliance criteria are: end-tidal CO2 is maintained at 38-42 mmHg for three consecutive times and the HRV low-frequency / high-frequency ratio fluctuation is ≤15%.

[0007] Preferably, in stage (c): (1) When the cerebrospinal fluid pulsation increase detected by transcranial Doppler is less than 15%, the light intensity is increased stepwise and the 38-42 Hz sweep frequency mode is activated; (2) The initial phase difference between sound and light is 0°. If the pupil dilation rate is less than 0.3 mm / s, it is increased in steps of 10°. (3) When the Aβ42-week decrease was less than 3%, a pulsed white noise of ≤75dB was added.

[0008] Preferably, during the transition between (a) and (b): (1) Analyze the N400 latency of the EEG. If the latency is >380 ms, reduce the number of bifurcation points to ≤4 and prioritize metabolic regulation. (2) Based on the pupil diameter algorithm, the cognitive load is predicted to exceed the limit, and VR rendering resources are dynamically allocated to the contralateral brain area.

[0009] Preferably, in stage (a), (1) when a turning action is detected that is inconsistent with the voice command, the odor concentration at the node is increased by 20-30% while the background brightness is reduced by 40%; (2) starting from the 17th week of the training cycle, a mixed odor is released at the bifurcation point, and the patient is required to report the dominant odor within 5 seconds; (3) in the fMRI assessment every 4 weeks, if the increase in hippocampal activation volume compared to the previous fMRI scan is less than 5%, the odor combination is changed to rose aldehyde-menthol.

[0010] Preferably, a stressor is added during phase (b): (1) during metabolic feedback regulation phase (b), respiratory resistance is adjusted according to real-time HRV monitoring; (2) a sudden decision-making task is added during the respiratory plateau; and (3) if HRV recovery time is >60 seconds, the subsequent stress intensity is reduced by 30%.

[0011] Preferably, in stage (c): (1) During the silent interval of EEG acquisition, 0.5-1.2 mA 40 Hz tACS was applied to the forehead; (2) The 5 Hz tACS in the posterior parietal lobe was phase-shifted by 90° and phase-locked with the light pulse.

[0012] Preferably, stage (d) comprises: (1) DTI scanning was performed every 12 weeks, and if the hippocampal FA increase was <0.02, a three-dimensional rotation was added; (2) When the monthly increase in the MoCA attention sub-item is less than 10%, the CO2 tolerance threshold is expanded to ±6 mmHg; Preferably, the effect is continuously assessed: (1) salivary P-tau217 or EEG θ / γ ratio is measured within 48 hours before the start of phase (d); (2) basilar artery pulse amplitude is verified at the end of training, and if it is <20%, the phase difference is reset to 0°.

[0013] Compared with the prior art, the present invention has the following beneficial effects: 1. Compared with the existing technology, the present invention improves neuropathology, significantly reduces the hippocampal atrophy rate, has a high efficiency in clearing Aβ42 pathological deposits, and improves the integrity of white matter fibers; enhances the patient's cognitive function, optimizes spatial navigation ability, and improves attention and working memory; and realizes the synergy of "neural oscillation activation-metabolic respiratory optimization-glymphatic drive" through a multi-system collaborative regulation mechanism, breaking through the bottleneck of single-modal intervention, strengthening neural oscillation coupling, optimizing metabolic-respiratory synergy, and doubling the glymphatic clearance efficiency, thereby improving the therapeutic effect.

[0014] 2. The present invention dynamically adjusts navigation difficulty based on the PAC index, sets respiratory load according to HRV stratification, and optimizes phase lock through pupil response to achieve precise individual adaptation, making training more targeted.

[0015] 3. Through dynamic regulation of the PAC index in VR navigation tasks, the present invention improves hippocampal-prefrontal functional connectivity by 35%±6%, multimodal 40Hz stimulation increases cerebrospinal fluid pulsation by ≥15% (measured by transcranial Doppler), and salivary exosomal Aβ decreases by 5.2%±1.8% over 42 weeks; respiratory resistance training expands the CO2 tolerance range to 36-44 mmHg, compresses blood oxygen fluctuations to ±8% of the baseline, and reduces HRV low-frequency / high-frequency ratio fluctuations from 28% of the baseline to 12%±3%, thereby enhancing parasympathetic nervous system regulation; based on multidimensional monitoring of pupil dilation + EDR + N400 latency, the accuracy rate of cognitive load over-limit warning reaches 92%, and the dynamic phase-locking algorithm ensures that the coherence value of light-acoustic-electrical stimulation is ≥0.85, avoiding the risk of epilepsy induction. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a system architecture diagram of the present invention. DETAILED DESCRIPTION

[0017] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0018] like Figure 1 As shown, a training method to delay the progression of Alzheimer's disease is performed in the following order: (a) Neural pathway activation phase: A dynamic three-dimensional spatial navigation task was generated using a virtual reality system. Patients were presented with a color-coded path (dominant wavelength 470-630 nm) and were required to make a path decision within a target time limit of 90-120 seconds based on real-time voice commands. The phase amplitude coupling index (PAC) of the hippocampal-prefrontal EEG gamma waves (38-42 Hz) and theta waves (4-8 Hz) was simultaneously monitored using a 64-lead electroencephalogram (EEG). If the real-time PAC was less than the baseline value of 0.25, the decision time limit was extended by 20%. EEG monitoring module: acquisition frequency 0.1-100Hz, common mode rejection ratio ≥110dB; VR navigation module: FOV ≥ 110°, latency ≤ 20ms; Breathing regulation module: error ±0.5cmH2O; Photoacoustic stimulation module: optical wavelength accuracy ±5nm; (b) Metabolic feedback adjustment phase: Within 5 minutes after the path decision is made, the patient wears an adjustable breathing resistance mask (range 0-12 cmH2O) and adjusts the breathing rhythm according to the real-time displayed end-tidal CO2 concentration data (target value 38-42 mmHg). If the CO2 concentration exceeds the target range for 120 consecutive seconds, the system generates specific breathing instructions until the blood oxygen fluctuation amplitude stabilizes to ±10% of the baseline. After reaching the target, a 5-minute gentle breathing transition period (resistance ≤ 2 cmH2O) is implemented; (c) Lymphatic drive stage: After metabolic regulation reaches the target, a 40 Hz multimodal stimulation combination is initiated, including: Project a blue-green stroboscopic light (wavelength 480±20nm, intensity 600-1200lux) into the patient's field of view; The same frequency modulated white noise (center frequency 40 Hz, sound intensity ≤ 75 dB) was conducted through the temporal bone; Dynamically adjust the photoacoustic phase difference every 60 seconds based on the pupil dilation gradient (step 5°-10°); (d) Closed-loop optimization phase: salivary exosomal Aβ42 concentration or EEG gamma wave power were measured every two weeks. If the decrease in Aβ42 was less than 3% / week or the increase in gamma wave power was less than 8% during the training period, the gamma stimulation duty cycle was increased to 60-75% and the rotation dimension of the navigation task was increased. The training process was as follows: 40 minutes per day, with steps (a)→(b)→(c) performed sequentially. During stage (d), parameters were adjusted across cycles, and the safety termination condition was: blood pressure fluctuation >20% of baseline value or subjective dizziness score ≥4 points, for 24 weeks.

[0019] 0 points: no discomfort, heart rate variability (HRV) fluctuation ≤5%; 1-3 points: slight floating feeling, no impact on the task, pupil diameter dilation ≤10%; ≥4 points: Clear need for active eye closure / pause of training due to vertigo; vestibulo-ocular reflex (VOR) gain ≤ 0.7; galvanic skin response (EDR) increase ≥ 3 μS.

[0020] In phase (a): (1) When the PAC index is less than 0.25 for two consecutive training sessions, increase the number of navigation path bifurcation points to 5-8 and reduce the voice prompts by 50%; (2) releasing ≤5 ppm isovaleric acid (left turn) or ≤3 ppm δ-decalactone (right turn) odor stimulation at the turning node, with exposure time ≤30 seconds / time, and the patient reports the odor attributes when turning; (3) If the odor identification delay is greater than 3 seconds, increase the ipsilateral nasal airflow concentration by 20% (total exposure ≤ OSHA threshold value).

[0021] When it detects that the steering action is inconsistent with the voice command, the odor concentration of the node increases by 20-30% and the background brightness decreases by 40%; (2) Starting from the 17th week of the training cycle, a mixed odor (concentration ratio 2:1) was released at the bifurcation point, and the patient was required to report the dominant odor within 5 seconds; (3) During the fMRI assessment every 4 weeks, if the increase in hippocampal activation volume compared to baseline was less than 5%, the odor combination was changed to rosealdehyde-menthol (1.2 ppm:0.8 ppm).

[0022] In phase (b): (1) When passing through a virtual narrow area (width < 1.2 times the virtual shoulder width), the expiratory resistance increases to 8-10 cmH2O for 6-10 seconds; (2) Real-time monitoring of HbO2 in the frontal lobe. If the HbO2 rising slope is less than 0.5 μmol / L / s during the decision-making period, suspend resistance breathing for 30 seconds and reduce navigation complexity; (3) The compliance criteria are: end-tidal CO2 is maintained at 38-42 mmHg for three consecutive times and the HRV low-frequency / high-frequency ratio fluctuation is ≤15%.

[0023] In stage (c): (1) When the transcranial Doppler ultrasound detected that the cerebrospinal fluid pulsation increased by <15%, the light intensity was increased stepwise (+50 lux every 20 seconds) and the 38-42 Hz sweep frequency mode was started; (2) The initial phase difference between the sound and light is 0°. If the pupil dilation rate is less than 0.3 mm / s, the system gradually adjusts the phase difference between the sound wave and the light pulse in fixed angle increments (10°) (up to an upper limit of 60°); (3) When the Aβ42-week decrease was less than 3%, a pulsed white noise of ≤75 dB was added (lasting 0.5 s / interval 10 s, cumulative duration ≤120 s / time).

[0024] During the transition between (a) and (b): (1) Analyze the N400 latency of the EEG. If the latency is >380 ms, reduce the number of bifurcation points to ≤4 and prioritize metabolic regulation. (2) Based on the pupil diameter algorithm, the cognitive load is predicted to exceed the limit, and VR rendering resources are dynamically allocated to the contralateral brain area.

[0025] Stage (b) Adding stressors: (1) During the metabolic feedback regulation phase (b), based on the real-time monitored HRV (time domain indicator SDNN): when the baseline HRV is > 50 ms (based on a 5-minute rest period) and the navigation task is in a stable phase (path curvature < 0.5 rad / m), the respiratory resistance is increased to 10-12 cmH2O for ≤ 60 seconds; if the real-time HRV decreases by > 20% compared to the baseline, the resistance is immediately reduced to 4 cmH2O and the recovery period is extended to 90 seconds; (Physiological basis: HRV > 50 ms indicates that the parasympathetic nervous system reserve is sufficient and can tolerate the increase in respiratory load).

[0026] HRV detection criteria: time domain analysis method is used to calculate the standard deviation of consecutive RR intervals (SDNN), with a sampling window of ≥120 seconds; Resistance gradient control: Dynamically adjusts the resistance limit based on the actual HRV value: Emergency termination conditions: respiratory resistance is cut off when systolic blood pressure is >180 mmHg or ST segment depression is >0.1 mV.

[0027] (2) Add a sudden decision-making task during the respiratory plateau (resistance ≤ 4 cmH2O) of the metabolic regulation phase (b): the path splits into three branches and requires a choice within 15 seconds; (3) If the HRV recovery time is greater than 60 seconds, the subsequent stress intensity is reduced by 30%.

[0028] In stage (c): (1) Time-sharing control protocol: 40 Hz tACS (0.5-1.2 mA) was applied to the forehead during the silent interval of EEG acquisition (lasting 150 ± 20 ms). 峰峰值 Synchronization mechanism: EEG acquisition is started 50ms after tACS is turned off (to avoid the electrode polarization decay period); (2) Multi-source phase locking: a) 5 Hz tACS in the posterior parietal lobe phase-locked to γ ​​light pulses (90° ± 5° phase shift); b) Dynamic calibration algorithm: Calculate the coherence value of the optical pulse -5Hz tACS in real time. If it is less than 0.85, adjust the phase in steps (±5°); The tACS stimulation duration is fixed at 150ms, the EEG acquisition window is 150ms, and the polarization decay period is separated by 50ms (cycle duration is 350ms), which both avoids artifacts and ensures 85% signal integrity. Based on real-time coherence value feedback (sampling rate is 1kHz), optical-electrical phase locking with an accuracy of ±5° is achieved. 40Hz targets Aβ deposition inhibition in the forehead, and 5Hz phase locking in the posterior parietal lobe enhances glymphatic clearance.

[0029] Phase (d) includes: (1) DTI scanning was performed every 12 weeks, and if the hippocampal FA increase was <0.02, a three-dimensional rotation was added; (2) When the monthly increase in the MoCA attention sub-item is less than 10%, the CO2 tolerance threshold is expanded to ±6 mmHg; (3) When the enhanced gamma regimen was ineffective for 4 weeks, baseline parameters were returned and fMRI network assessment was performed.

[0030] Effect evaluation: (1) Salivary P-tau217 or EEG θ / γ ratio was measured within 48 hours before the start of stage (d); (2) At the end of the training, verify the basilar artery pulsation amplitude. If it is less than 20%, reset the phase difference to 0°; (3) Establish a blood oxygen-MoCA correlation model (R² threshold 0.5) and calibrate the gradient coefficient of the respiratory resistance curve K∈[0.8,1.2].

[0031] Training process implementation Step (a) neural pathway activation; Patients wore a VR headset to perform a virtual supermarket navigation task, where the path contained four initial bifurcations; Voice commands prompt the target shelf (such as "Please go to the dairy area") and require arrival within 90 seconds; Real-time monitoring: When the θ-γ PAC index is <0.25, the system automatically extends the time limit to 108 seconds; If PAC < 0.25 for two consecutive training sessions, increase the number of bifurcation points to 6 and reduce the voice prompts by 50%; Step (b) Metabolic feedback regulation: Immediately after navigation, wear a breathing mask with the initial resistance set to 4 cmH2O; The patient adjusts his respiratory rate according to the real-time displayed end-tidal CO2 concentration (target 40 mmHg): If CO2>42mmHg lasts for 120 seconds, the system will issue the command "inhale for 3 seconds - hold your breath for 2 seconds - exhale for 6 seconds"; Compliance criteria: CO2∈[38,42mmHg] for 3 consecutive respiratory cycles and HRV fluctuation ≤15%; Step (c) Lymphoid drive: Synchronous application of 40Hz blue-green strobe light (wavelength 480nm, 800lux) and bone-conducted 40Hz white noise; Dynamic Phase Calibration: The pupil dilation rate was measured every 60 seconds, and if it was <0.3 mm / s, the acousto-optic phase difference was increased by 10°; The upper limit of phase difference adjustment is 60° and the lower limit is 0°.

[0032] Step (d) Closed-loop optimization: Measure salivary Aβ42 concentration every two weeks: If the weekly decrease is <3%, increase the gamma stimulation duty cycle to 70%; If the increase in the MoCA attention sub-item is less than 10%, expand the CO2 target range to 34-46 mmHg; Effect verification example: Participants: 65-year-old patients with mild AD (MoCA score 18 / 30); Training results (after 24 weeks): The θ-γ PAC index increased from 0.21 to 0.38; Salivary Aβ42 decreased by 32% ± 5%; The hippocampal FA value (DTI) increased by 0.03; The basilar artery pulsation amplitude increased by 22%, maintaining the current phase difference configuration.

[0033] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. A training method for delaying the progression of Alzheimer's disease, characterized by: Perform the steps in the following order: (a) Neural pathway activation phase: A dynamic three-dimensional spatial navigation task was generated using a virtual reality system. Patients were presented with a color-coded path and were required to make a path decision within a target time limit of 90–120 seconds based on real-time voice commands. The phase-amplitude coupling index (PAC) of the hippocampal-prefrontal electroencephalogram (EEG) gamma and theta waves was simultaneously monitored using a 64-lead electroencephalogram (EEG). If the real-time PAC was less than the baseline value of 0.25, the decision time limit was extended by 20%. (b) Metabolic feedback adjustment phase: Within 5 minutes after the path decision is made, the patient wears an adjustable respiratory resistance mask and adjusts the breathing rhythm according to the real-time end-tidal CO2 concentration data. If the CO2 concentration exceeds the target range for 120 consecutive seconds, the system generates breathing commands until the blood oxygen fluctuation amplitude stabilizes to ±10% of the baseline. After reaching the target, a 5-minute gentle breathing transition period is implemented; (c) Lymphatic drive stage: After metabolic regulation reaches the target, a 40 Hz multimodal stimulation combination is initiated, including: Projecting blue-green stroboscopic light into the patient's field of view, transmitting frequency-modulated white noise through the temporal bone, and dynamically adjusting the photoacoustic phase difference every 60 seconds based on the pupil dilation gradient; (d) Closed-loop optimization phase: salivary exosomal Aβ42 concentration or EEG gamma wave power were measured every two weeks. If the decrease in Aβ42 was less than 3% / week or the increase in gamma wave power was less than 8% during the training period, the gamma stimulation duty cycle was increased to 60-75% and the rotation dimension of the navigation task was increased. The training process was as follows: 40 minutes per day, with steps (a)→(b)→(c) performed sequentially. During stage (d), parameters were adjusted across cycles, and the safety termination condition was: blood pressure fluctuation >20% of baseline value or subjective dizziness score ≥4 points, for 24 weeks.

2. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: In phase (a): (1) When the PAC index is less than 0.25 for two consecutive training sessions, increase the number of navigation path bifurcation points to 5-8 and reduce the voice prompts by 50%; (2) releasing ≤5 ppm isovaleric acid or ≤3 ppm δ-decalactone odor stimulation at the turning node, with exposure time ≤30 seconds / time, and the patient reporting the odor attributes when turning; (3) If the odor recognition delay is greater than 3 seconds, increase the ipsilateral nasal airflow concentration by 20%.

3. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: In phase (b): (1) When passing through the virtual narrow area, the expiratory resistance increases to 8-10 cmH2O for 6-10 seconds; (2) Real-time monitoring of HbO2 in the frontal lobe. If the HbO2 rising slope is less than 0.5 μmol / L / s during the decision-making period, suspend resistance breathing for 30 seconds and reduce navigation complexity; (3) The compliance criteria are: end-tidal CO2 is maintained at 38-42 mmHg for three consecutive times and the HRV low-frequency / high-frequency ratio fluctuation is ≤15%.

4. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: In stage (c): (1) When the cerebrospinal fluid pulsation increase detected by transcranial Doppler is less than 15%, the light intensity is increased stepwise and the 38-42 Hz sweep frequency mode is activated; (2) The initial phase difference between sound and light is 0°. If the pupil dilation rate is less than 0.3 mm / s, it is increased in steps of 10°. (3) When the Aβ42-week decrease was less than 3%, a pulsed white noise of ≤75dB was added.

5. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: During the transition between (a) and (b): (1) Analyze the N400 latency of the EEG. If the latency is >380 ms, reduce the number of bifurcation points to ≤4 and prioritize metabolic regulation. (2) Based on the pupil diameter algorithm, the cognitive load is predicted to exceed the limit, and VR rendering resources are dynamically allocated to the contralateral brain area.

6. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: In phase (a), (1) when a turning movement was detected that was inconsistent with the voice command, the odor concentration at the node was increased by 20-30% and the background brightness was reduced by 40%; (2) starting from the 17th week of the training cycle, a mixed odor was released at the bifurcation point, and the patient was required to report the dominant odor within 5 seconds; (3) in the fMRI assessment every 4 weeks, if the increase in hippocampal activation volume compared to the previous fMRI scan was less than 5%, the odor combination was changed to rose aldehyde-menthol.

7. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: Add stressors in phase (b): (1) During metabolic feedback regulation phase (b), respiratory resistance was adjusted according to real-time HRV monitoring; (2) a sudden decision-making task was added during the respiratory plateau; (3) if HRV recovery time was >60 seconds, the subsequent stress intensity was reduced by 30%.

8. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: In stage (c): (1) During the silent interval of EEG acquisition, 0.5-1.2 mA 40 Hz tACS was applied to the forehead; (2) The phase difference of 5 Hz tACS in the posterior parietal lobe was 90°±5° and phase-locked with the light pulse.

9. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: Phase (d) includes: (1) DTI scanning was performed every 12 weeks, and if the hippocampal FA increase was <0.02, a three-dimensional rotation was added; (2) When the monthly increase in the MoCA attention sub-item is less than 10%, the CO2 tolerance threshold is expanded to ±6 mmHg.

10. The training method for delaying the progression of Alzheimer's disease according to claim 1, characterized in that: Continuous evaluation of efficacy: (1) salivary P-tau217 or EEG θ / γ ratio within 48 hours before the start of phase (d); (2) verification of basilar artery pulse amplitude at the end of training; if <20%, reset the phase difference to 0°.

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