# ADRD Supplement for Trajectories of Aging in Psychotic Disorders Over 27 Years

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $397,155

## Abstract

Background: Psychotic disorders, such as schizophrenia, cause severe impairment and account for 10% of
disease burden attributable to mental health causes in the United States. As individuals with psychotic disorders
age, they are at high risk for premature cognitive decline, physical impairment, and worsening psychosis,
especially in APOE4 allele carriers. This pattern is consistent with Alzheimer's disease or a related dementia
(ADRD). Elevated levels of neuroinflammation and tau accumulation have been reported in psychotic disorders,
but prior research has been limited by small sample sizes. The proposed project will be the first adequately
powered study to evaluate the connection between psychotic disorders and ADRD using plasma markers.
Methods: This proposal builds on the parent study (MH094398) that investigates potential accelerated aging in
psychotic disorders by characterizing changes in health and functioning over time. Participants with psychotic
disorders and healthy controls come from the Suffolk County Mental Health Project (SCMHP; R01 MH110434),
the longest running first-episode psychosis study in the world. We have had incredibly consistent participation
from this population. We will use generalized linear modeling (GLM) to examine plasma markers as a function
of APOE genotype and group (case vs control). We also will investigate symptoms, physical and cognitive
impairments as a function of plasma markers.
Impact: If funded, this would be the largest study of plasma markers of ADRD in aging individuals with psychotic
disorders. Likewise it will be the largest study of neuroinflammation in this population. The proposed study
addresses the NIH/NIA's strategic goal to better understand the dynamics of aging with a focus on outlining the
geoscientific underpinnings of a lifelong process linking psychosis to early aging and dementia (Goal A). It will
produce key evidence regarding hypothesized involvement of tau accumulation in these declining outcomes.
Furthermore, we plan to continue following the SCMHP cohort, which will allow us to investigate the role of
neurodegeneration biomarkers in psychotic disorders longitudinally. This work may identify opportunities for
secondary prevention of poor outcomes in psychotic disorders and may help to define a new category of ADRD.
Conclusion: The ultimate goal of this study is to understand why psychotic disorders manifest more rapid onset
of aging-related conditions (parent R01). Neuroinflammation may help explain why participants with psychotic
disorders are experiencing increased risk of cognitive decay, physical functional limitations, and mortality at such
early ages. Crucially, microglial activation is thought to occur early in this population and may cause a
neuropathological cascade that parallels ADRD but converts quickly to tauopathy.

## Key facts

- **NIH application ID:** 10123076
- **Project number:** 3R01MH110434-04S2
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Roman I Kotov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,155
- **Award type:** 3
- **Project period:** 2016-08-19 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123076

## Citation

> US National Institutes of Health, RePORTER application 10123076, ADRD Supplement for Trajectories of Aging in Psychotic Disorders Over 27 Years (3R01MH110434-04S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10123076. Licensed CC0.

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