# Biological and environmental factors driving behavioral symptoms in Alzheimer's disease

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $1

## Abstract

Project Summary
This project will investigate how different environmental, personal and disease related factors contribute to the
experience of behavioral symptoms of patients with Alzheimer's disease (AD). Patients with AD will experience
behavioral symptoms of dementia (BSD) at some point during their illness, though most patients will not
experience all types of BSD or experience them in a predictable pattern. This has made development of effective
treatments and symptom management approaches for AD highly challenging. Our pilot data shows a high degree
of intraindividual heterogeneity in daily reports of BSD both in type of symptom and frequency of occurrence.
Others report significant intraindividual heterogeneity in the rate of change in BSD over a 3-month period. It is
currently unclear what mechanisms contribute to these within- and between-person variations in BSD. While
BSD subsyndromes have been proposed it is unclear how the types of BSD within the subsyndromes are
temporally dependent or distinct from each other. As applied to AD, the Revised Symptom Management Model,
points to environmental (i.e., unmet needs, stressors), personal (i.e., genetic, microbiome, ethnicity), and disease
(i.e., HSV1 infection, systemic inflammation) factors as mechanistic pathways for BSD. We hypothesize that
these factors across multiple systems contribute to the mechanistic development of BSD, and thus the variability
in individual BSD expression. Elucidation of these factors across multiple systems will help create personalized
approaches to treatment of BSD spanning from caregiving behavioral training to pharmacological interventions.
Dyads of co-residing caregivers and persons with AD or mixed-type AD (with vascular involvement) (N=162
dyads) will be recruited. Equal numbers of Caucasian and Hispanic dyads will be enrolled so that the contributing
role of ethnicity can be examined. Using a micro-longitudinal design, caregivers will complete daily diaries for 30
days reporting on their observations of environmental exposures, including type, frequency, duration, and
severity of BSD. At enrollment and at the start of each new week of diaries, dyads will visit the research clinic
where blood and stool samples will be collected from the person with AD (for 5 samples total). BSD will be
reported in the daily diary entries, with BSD type measured as presence or absence of 22 symptoms across 17
domains. We will use a multi-level model analytic framework to examine hypotheses outlines in the research
strategy in order to complete the following aims: (1) Determine how environmental (i.e., unmet needs, stressors),
personal (i.e., genetic, microbiome, ethnicity) and disease (i.e. HSV1 infection, systemic inflammation) factors
impact probability of daily BSD, either directly or through interaction effects, and (2) Identify subsyndromes of
BSD, and predictors of group membership. Impact: By competitively testing leading hypotheses for BSD, this
project will eluci...

## Key facts

- **NIH application ID:** 10455646
- **Project number:** 5R01MH121928-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Andrew Michael Pickering
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2019-09-23 → 2023-08-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455646

## Citation

> US National Institutes of Health, RePORTER application 10455646, Biological and environmental factors driving behavioral symptoms in Alzheimer's disease (5R01MH121928-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10455646. Licensed CC0.

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