# Multidimensional Approaches to Understanding Consequences and Mechanisms of Apathy in Frontotemporal Degeneration

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $539,023

## Abstract

Project Abstract
Apathy is the most common and disabling of the behavioral symptoms shared across many Alzheimer's
Disease and Related Disorders (ADRDs), including behavioral variant frontotemporal degeneration (bvFTD).
Apathy manifests as a decrease in goal-directed behavior (GDB), with deficits such as poor planning, poor
motivation and inability to initiate even the simplest self-care activities, contribute to disability and greatly
reduced quality of life. Thus, apathy is a poor prognostic indicator, having a profound impact on clinical decline
in everyday patient functional activities. Recent work shows that apathy is associated with a disruption in
impairments in GDB--initiation, planning and motivation--suggesting that apathy is a heterogenous syndrome
with distinct underlying mechanisms. Furthermore, these functionally dissociable GDB processes map onto
distinct and distributed brain regions. While previous imaging efforts have predominantly focused on the
identification of structural MRI correlates of single brain regions involved in apathy, the overall goal of this
proposal is to investigate large-scale functional networks underlying impaired GDB in bvFTD--where apathy is
highly prevalent. Building on our previous work, the framework proposed here will capture the complex
associations of impaired GDB encompassing the various domains of apathy and will examine the ways the
breakdown of large-scale intrinsic networks can lead to the clinical syndrome of apathy. In Aim 1, we will study
how distinct impairments in GDB contribute to rate of longitudinal clinical decline in everyday functional
activities. In Aim 2, we will use resting-state fMRI to identify relationships between impaired GDB and
breakdown of large-scale neurocognitive networks. In Aim 3, we will examine how change in configuration of
functional network connectivity over time contributes to decline in components of GDB and we will assess how
degrading networks underlying GDB mediate rate of clinical decline in everyday functional activities. This
proposal addresses a critically unmet need to elucidate the role of degenerative disease in compromising the
network mechanisms that support goal-directed behavior in ADRD. Given the limited effectiveness of
pharmacological treatment for apathy in dementia, this translational work is necessary to guide future clinical
trials for this debilitating syndrome.

## Key facts

- **NIH application ID:** 10889229
- **Project number:** 5R01AG076832-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lauren M Massimo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $539,023
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889229

## Citation

> US National Institutes of Health, RePORTER application 10889229, Multidimensional Approaches to Understanding Consequences and Mechanisms of Apathy in Frontotemporal Degeneration (5R01AG076832-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10889229. Licensed CC0.

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