# Pathways linking neuropsychiatric symptoms with Alzheimer's disease neuroimaging biomarkers and the outcome of incident Mild Cognitive Impairment/ Dementia

> **NIH NIH R01** · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · 2021 · $395,960

## Abstract

PROJECT SUMMARY
Pathophysiological changes in Alzheimer's disease (AD) precede clinical manifestations
by several decades. Accordingly, one of the priorities of the National Alzheimer's Plan
Act is to accelerate efforts to identify the presymptomatic stages of AD by using in-vivo
biomarkers. Neuropsychiatric symptoms (NPS) such as depression and anxiety are
common in the elderly. The key research question of the field of neuropsychiatry of
presymptomatic Alzheimer's disease (AD) is to determine as to which came first, i.e.,
neuropsychiatric symptoms (NPS) or pathophysiological brain changes related to AD.
Such a question can only be answered by using two critically important resources: 1) a
large scale, preferably population-based, neuroimaging cohort, and 2) a research
infrastructure that can clearly document the lifelong pattern of NPS among participants
in the neuroimaging cohort. Building both resources from scratch can be prohibitively
expensive and may take decades. In our proposed 4-years R01 grant, we will conduct
an in-depth investigation of the pathways linking neuroimaging biomarkers, NPS and
cognitive outcomes by using the extensive neuroimaging biomarker resource of the
Mayo Clinic Study of Aging (MCSA) and we will link this with longitudinal psychiatric
data by using the unique resource of the Rochester Epidemiology Project (REP). We
hypothesize that the association between β-amyloid deposition,
neurodegeneration and the outcome of incident MCI/ AD dementia or trajectories
of cognitive changes, is modified by NPS. We will test this hypothesis by
examining the pathways linking NPS and AD biomarkers in a cohort of over 2000
cognitively normal persons aged ≥ 60 years that have undergone all three
modalities of imaging, i.e. amyloid PET, FDG-PET and brain MRI, and psychiatric
assessment at baseline with at least one follow-up event. We will measure NPS by
using two approaches: 1) Our access to REP medical record linkage system will enable
us to rigorously screen for life-time NPS of each study participant. We define NPS as
depressive and anxiety symptoms which will be the focus of the primary analysis. The
secondary analysis will include other NPS such as apathy and agitation. REP is
perhaps the only resource in the world that captures medical data from birth to death on
residents of Olmsted County; 2) We will also utilize the assessments used by MCSA
(e.g., Beck Depression Inventory and Beck Anxiety Inventory) to augment the REP
data. The dependent variables will be trajectories of cognitive changes as continuous
outcomes, as well as categorical outcomes of incident MCI/ AD dementia. In conclusion,
here we propose a 4-years R01 study that will eventually address the time-honored
knowledge gap on time sequence between psychiatric symptoms, AD neuroimaging
biomarkers and the outcome of incident MCI/ AD dementia.

## Key facts

- **NIH application ID:** 10200420
- **Project number:** 7R01AG057708-03
- **Recipient organization:** ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
- **Principal Investigator:** Yonas E Geda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,960
- **Award type:** 7
- **Project period:** 2018-05-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200420

## Citation

> US National Institutes of Health, RePORTER application 10200420, Pathways linking neuropsychiatric symptoms with Alzheimer's disease neuroimaging biomarkers and the outcome of incident Mild Cognitive Impairment/ Dementia (7R01AG057708-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200420. Licensed CC0.

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