CLearing Alzheimer's Disease Molecular Pathology Without Medications

Not Applicable

• Conditions: Alzheimer Disease; Amyloid Plaque; Amyloidosis
• Interventions: Other: Cognitive training; Other: 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training

• Registration Number: NCT04913454
• Lead Sponsor: University Hospital, Geneva

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2021-05
• Study First Submitted: 2021-05-25
• Study First Submitted QC: 2021-05-28
• Last Update Submitted: 2021-05-28
• Study First Posted: 2021-06-04
• Last Update Posted: 2021-06-04
• Study Start: 2021-08-01
• Primary Completion: 2022-06-30
• Study Completion: 2022-07-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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:

  1. Malignant neoplasm within 5 years,
  2. Life threatening diseases,
  3. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cognitive training only	Cognitive training	Cognitive training only (1 hour per day, per 5 days/week, for a total of 8 weeks).
40 Hz multi-sensory (auditory + visual) stimulation and cognitive training	40 Hz multi-sensory (auditory + visual) stimulation and cognitive training	40 Hz multi-sensory (auditory + visual) stimulation and cognitive training (1 hour/day, per 5 days/week, for a total of 8 weeks).

Primary Outcome Measures

Name	Time	Method
Changes in amyloid load	8 weeks	Changes in amyloid load assessed by longitudinal amyloid-PET

Secondary Outcome Measures

Name	Time	Method
Changes in brain electrical activity	8 weeks	Changes in brain electrical activity (e.g. gamma power spectral density) assessed by longitudinal EEG
Changes in Alzheimer's blood-based biomarkers	8 weeks	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
Changes in cognition	8 weeks	Changes in cognition (using the Preclinical Alzheimer Cognitive Composite (PACC) score) assessed by longitudinal neuropsychological assessment