Tau Networks in Psychotic Alzheimer's Disease

NCT ID: NCT05847192

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

91 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-04-13

Study Completion Date

2029-12-31

Brief Summary

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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

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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.

Conditions

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Alzheimer Disease Alzheimer Disease With Delusions Alzheimer Disease With Psychosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Alzheimer's disease

* 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.

[18F]-PI2620 PET scan

Intervention Type DIAGNOSTIC_TEST

The PET scan will measure the regional distribution of tau aggregation in AD patients with and without psychosis compared to Cognitively Unimpaired Healthy participants with the PET radiotracer \[18F\]-PI2620.

Alzheimer's disease with psychosis

\- 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.

[18F]-PI2620 PET scan

Intervention Type DIAGNOSTIC_TEST

The PET scan will measure the regional distribution of tau aggregation in AD patients with and without psychosis compared to Cognitively Unimpaired Healthy participants with the PET radiotracer \[18F\]-PI2620.

Cognitively Unimpaired Healthy

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.

[18F]-PI2620 PET scan

Intervention Type DIAGNOSTIC_TEST

The PET scan will measure the regional distribution of tau aggregation in AD patients with and without psychosis compared to Cognitively Unimpaired Healthy participants with the PET radiotracer \[18F\]-PI2620.

Interventions

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[18F]-PI2620 PET scan

The PET scan will measure the regional distribution of tau aggregation in AD patients with and without psychosis compared to Cognitively Unimpaired Healthy participants with the PET radiotracer \[18F\]-PI2620.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Age 65-85 years old.
* Diagnosis of probable AD dementia according to National Institute on Aging-Alzheimer's Association (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


* 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).


* 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

Exclusion Criteria

* Rosen-modified Hachinski Ischemia Score \> 4 at the screening visit.
* History of stroke.
* Evidence of a clinically relevant neurological disorder other than probable AD at the screening visit. Participants with insulin dependent type 2 diabetes, a history of CVD, a history of epilepsy, a history of TBI with greater than 15 minutes of loss of consciousness, a movement disorder, autoimmune disease affecting the CNS, or delirium.
* Evidence of a clinically relevant or unstable psychiatric disorder, based on DSM-5 criteria, including schizophrenia or other psychotic disorder, bipolar disorder, delirium, or current/active major depression.
* History of alcoholism or drug dependency/abuse within the last 5 years before screening.
* Presence of metal implants such as pacemakers, ear implants, internal bullet fragments or shrapnel.
* Inability to lie flat for 1 hour approximately.
* hearing impairment as evidenced by the inability to hear 500, 1000 and 6000 Hz bilaterally on an OAE evaluation. Subjects with hearing aides will be allowed to participate if they meet minimum hearing requirements.


\- Same criteria as AD participants above.
Minimum Eligible Age

65 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Northwell Health

OTHER

Sponsor Role lead

Responsible Party

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Jeremy Koppel

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jeremy Koppel, MD

Role: PRINCIPAL_INVESTIGATOR

Northwell Health

Locations

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The Feinstein Institutes for Medical Research

Manhasset, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Erica Christen, MS

Role: CONTACT

516-562-3492

Michelle Gong, AS

Role: CONTACT

516-562-3492

Facility Contacts

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Erica Christen, MS

Role: primary

516-562-3492

Michelle Gong, AS

Role: backup

516-562-3492

Other Identifiers

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22-0394_AFA

Identifier Type: -

Identifier Source: org_study_id

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