Tau Networks in Psychotic Alzheimer's Disease
- Conditions
- Alzheimer DiseaseAlzheimer Disease With DelusionsAlzheimer Disease With Psychosis
- Interventions
- Diagnostic Test: [18F]-PI2620 PET scan
- Registration Number
- NCT05847192
- Lead Sponsor
- Northwell Health
- Brief Summary
This research project aims to understand the brain mechanisms behind the manifestation of psychotic symptoms in Alzheimer´s disease (AD), and nature of the unique relationship with tau pathology. Amongst the cognitive manifestations of psychosis are impairments related to frontal circuits (social cognition, working memory and executive function deficits). The investigator's previous work suggests a role of tau pathology (one of the hallmarks of AD neuropathology) in the manifestation of psychosis in AD. However, the cerebral mechanisms that underly this association remain poorly understood. The overarching aim of the study is is to investigate the mechanisms by which tau network pathology may promote the presentation of psychosis in AD.
- Detailed Description
The specific aims of this application are:
1. To measure the regional distribution of tau aggregation in AD patients with psychosis (AD+P) compared to AD without psychosis (AD-P) and Cognitively Unimpaired Healthy (CUH) participants with the PET radiotracer \[18F\]-PI2620;
2. To measure structural and functional brain networks properties in AD+P compared to AD-P patients and CUH participants using MRI;
3. To examine the association of tau pathology with structural/functional network properties; electrophysiologic biomarkers of neurotransmission and neuroplasticity; and psychotic symptoms. The current project will determine whether identification of tau pathology, and associated network connectivity disruptions and sensorimotor gating impairments, may be informing as potential biomarkers for psychosis in AD. As severe adverse events are associated with atypical antipsychotics in AD psychosis, this work will provide insights into whether anti-tau therapies such as monoclonal antibodies to tau, now being investigated in clinical trials, may be effective in the antipsychotic treatment of AD.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 91
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Alzheimer's disease [18F]-PI2620 PET scan * Age 65-85 years old. * Diagnosis of probable AD dementia according to NIA-AA criteria. * Mini-Mental State Examination (MMSE) score ≥ 10 and ≤ 26 at the screening visit. * Clinical Dementia Rating (CDR) score ≥ 0.5. * Logical Memory delay score of ≤8 for 16+ years of education, ≤4 for 8-15 years of education, and ≤2 for 0-7 years of education Participants will undergo neuropsychological examination, blood collection, sensorimotor gating/ERP testing, MRI and \[18F\]-PI2620 PET scan. Cognitively Unimpaired Healthy [18F]-PI2620 PET scan Age 65-85 years old. * No known genetic risk factors for dementia. * No cognitive complaint * Mini-Mental State Examination (MMSE) score ≥ 26 at the screening visit. * Logical Memory delay score of ≥9 for 16+ years of education, ≥5 for 8-15 years of education, and ≥3 for 0-7 years of education Participants will undergo neuropsychological examination, blood collection, sensorimotor gating/ERP testing, MRI and \[18F\]-PI2620 PET scan. Alzheimer's disease with psychosis [18F]-PI2620 PET scan - All the criteria for AD are met. Presence of one (or more) of the following symptoms: * Visual or auditory hallucinations (e.g., seeing silent individuals standing in the room, seeing children in the yard, or seeing animals in the house). * Delusions (fixed false beliefs that the patient believes to be true, e.g., that the spouse is unfaithful, that possessions are being stolen, or that one is not who one claims to be). Participants will undergo neuropsychological examination, blood collection, sensorimotor gating/ERP testing, MRI and \[18F\]-PI2620 PET scan.
- Primary Outcome Measures
Name Time Method Tau PET scan 5 years To measure the distribution of tau aggregation in AD patients with and without psychosis, compared to cognitively unimpaired healthy subjects with the PET radiotracer \[18F\]-PI2620.
- Secondary Outcome Measures
Name Time Method MRI of the brain 5 years To measure brain networks in AD patients with and without psychosis compared to Cognitively Unimpaired Healthy subjects.
Trial Locations
- Locations (1)
The Feinstein Institutes for Medical Research
🇺🇸Manhasset, New York, United States