CLearing Alzheimer's Disease Molecular Pathology Without Medications

Study Overview
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Brief Summary
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According to the most popular pathophysiological models of Alzheimer's disease, the amyloid hypothesis, amyloid deposition is the causative event triggering a chain of other downstream events which finally lead to Alzheimer's disease and dementia. In mouse models of Alzheimer's disease, 40 Hz multi-sensory (auditory and visual) stimulation was able to reduce the number and size of amyloid plaques throughout cortex and improve cognitive performance. The primary objective of this study is to assess whether an intervention consisting of 40 Hz multi-sensory (auditory and visual) stimulation is able to reduce the amyloid load in non-demented amyloid-positive individuals. As secondary objectives, the investigators will assess whether such intervention is able to: improve the brain electrical activity, improve or slow down the worsening of Alzheimer's blood-based biomarkers, improve or slow down the worsening of cognition.

Official Title
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CLearing Alzheimer's Disease Molecular Pathology Without Medications

Conditions
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Alzheimer Disease, Amyloid Plaque, Amyloidosis

Intervention / Treatment
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* Other: 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training
* Other: Cognitive training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by signature (Appendix Informed Consent Form), age 40-80, ≥5 years of education, previous evidence of brain amyloidosis (assessed by PET, CSF, or blood-based biomarkers). Exclusion Criteria: history of epilepsy; clinically relevant visual or auditory diseases/deficits; clinical diagnosis of dementia; contraindication to amyloid-PET; inability to undergo the procedures of the study, e.g. severe behavioral disturbances; severe diseases: Malignant neoplasm within 5 years, Life threatening diseases, Severe systemic diseases (e.g. kidney insufficiency, cardiac insufficiency, decompensated diabetes, decompensated metabolic diseases, decompensated hypothyroidism, uncontrolled autoimmune diseases); the participation to a clinical trial involving potential Alzheimer's disease modifying therapies; documented pregnancy or intention to become pregnant during the course of the study or breast feeding.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training<br>40 Hz multi-sensory (auditory + visual) stimulation and cognitive training (1 hour/day, per 5 days/week, for a total of 8 weeks). | Other: 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training<br>* 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training (1 hour/day, per 5 days/week, for a total of 8 weeks)<br>|
| Active Comparator: Cognitive training only<br>Cognitive training only (1 hour per day, per 5 days/week, for a total of 8 weeks). | Other: Cognitive training<br>* Cognitive training (1 hour/day, per 5 days/week, for a total of 8 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in amyloid load | Changes in amyloid load assessed by longitudinal amyloid-PET | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in brain electrical activity | Changes in brain electrical activity (e.g. gamma power spectral density) assessed by longitudinal EEG | 8 weeks | 
| Changes in Alzheimer's blood-based biomarkers | Changes in Alzheimer's blood-based biomarkers (e.g. plasma Aβ42/Aβ40 ratio, Aβ42, Aβ40, p-tau, and neurofilament light) assessed by longitudinal blood sample collection | 8 weeks | 
| Changes in cognition | Changes in cognition (using the Preclinical Alzheimer Cognitive Composite (PACC) score) assessed by longitudinal neuropsychological assessment | 8 weeks |