# Cognitive and brain imaging correlates of apathy- components in asymptomatic middle aged individuals at high ADRD- risk

> **NIH NIH R21** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $154,642

## Abstract

Apathy is the most prevalent behavioral symptom in Alzheimer’s disease and related disorders
(ADRD). In older adults, presence of apathy is associated with faster cognitive decline, lower brain
volumes and with a higher burden of Amyloid β, tau pathology and white matter hyperintensities. Thus,
in old age, apathy is an important behavioral marker of incipient dementia and its underlying pathology.
Midlife is a critical period for intervening against risk factors for ADRD and when the neurobiological
substrates underlying ADRD begin to aggregate. However, the cognitive and ADRD-related brain
correlates of apathy in midlife are essentially unknown.
 Apathy is a multidimensional construct encompassing three main components: narrowed emotional
reactivity, limited cognitive effort and curiosity and reduced goal- directed behavior. The identification
of its cognitive and brain correlates requires a granular approach, which considers these distinct
components. We will study the relationship of apathy and its components with cognitive function and
ADRD-related brain markers in 500 cognitively asymptomatic middle aged offspring of ADRD patients,
participants of the Israel Registry for Alzheimer’s Prevention (IRAP) study. IRAP participants are deeply
phenotyped for cognitive, behavioral, health, lifestyle, brain imaging and genetic factors. Quantification
of apathy will be based on: (1) Participants' and informants' report on apathy via validated
questionnaires; and (2) Objective measurement of apathy- based on autonomic nervous system (ANS)
and gaze reactivity to emotional and cognitive stimuli. The emotional component of apathy will be
measured via ANS and gaze reactivity to emotional visual stimuli; The cognitive component will be
measured via gaze reactivity to cognitive stimuli and by participants' willingness to invest cognitive effort
in a reward-dependent cognitive task. Participants' report on the type and duration of cognitive, social
and physical activities they performed without being prompted will assess the behavioral component.
If our hypotheses are corroborated, these innovative, simple to use, objective measures of different
components of apathy may facilitate diagnostic accuracy and disentangling their unique value in the
prediction of cognitive decline. The study will provide new knowledge on the cognitive and brain
correlates of apathy in middle aged individuals at high ADRD risk and will set the basis for examining
the longitudinal consequences of midlife apathy on cognitive decline.

## Key facts

- **NIH application ID:** 10792946
- **Project number:** 5R21AG080827-03
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Ramit Ravona
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $154,642
- **Award type:** 5
- **Project period:** 2023-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792946

## Citation

> US National Institutes of Health, RePORTER application 10792946, Cognitive and brain imaging correlates of apathy- components in asymptomatic middle aged individuals at high ADRD- risk (5R21AG080827-03). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10792946. Licensed CC0.

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