# Emotion alterations across the Alzheimer's disease spectrum

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $802,920

## Abstract

ABSTRACT
Changes in emotion and social behavior are early yet overlooked features of Alzheimer's disease (AD). In AD,
there is progressive accumulation of beta amyloid (Aβ) and tau proteins, a pathological process that leads to
neurodegeneration and functional connectivity alterations in distributed brain networks. Episodic memory
decline is a hallmark feature of typical amnestic AD presentations, but AD can also cause atypical
dysexecutive/amnestic, language (i.e., logopenic variant primary progressive aphasia [lvPPA]), and
visuospatial (i.e., posterior cortical atrophy [PCA]) syndromes. In typical AD, default mode network dysfunction
is accompanied by elevated functional connectivity in the salience network, a system that supports emotion
generation and interoception. Enhanced salience network connectivity in AD is associated with greater
affective symptoms such as anxiety. Our previous studies have found that specific types of emotional empathy,
a rudimentary form of affect-sharing, are elevated in typical AD and relate to default mode network atrophy.
Whether emotion elevations are present in atypical AD syndromes is unknown but are suggested by clinical
and neuroimaging data. There is emerging evidence that gains in emotional empathy are evident even in
preclinical AD, a prodromal phase in which people have signs of AD pathology on biomarker testing but lack
cognitive symptoms. A central hypothesis of this proposal is that early neuropathology and neurodegeneration
in AD-vulnerable networks disinhibits the salience network and elevates emotion functioning across AD
syndromes. A more detailed understanding of emotion in AD will help to improve diagnosis by broadening
current conceptualizations of each syndrome, to identify emotion measures that suggest the presence of early
AD, and to uncover new biomarkers that change as neuropathology affects emotion-relevant brain networks. In
the proposed studies, we will conduct laboratory-based assessments of emotion (i.e., autonomic nervous
system activity, facial behavior, and subjective experience) in 200 people with AD, as indicated by elevated Aβ
(Aβ+) and tau deposition on molecular PET scans (110 amnestic/dysexecutive AD, 45 lvPPA, and 45 PCA),
and 150 older healthy controls with and without AD pathology (75 Aβ+ and 75 Aβ-) with varying levels of tau
pathology. By relating emotion measures to clinical data, structural and functional connectivity, Aβ and tau
burden, and affective symptoms, we will address three key aims. In Aim 1, we will quantify emotion, empathy,
and social behavior in AD syndromes and Aβ+ healthy controls. In Aim 2, we will delineate the structural and
functional neural networks underlying emotion alterations across the AD spectrum. In Aim 3, we will elucidate
associations among Aβ and tau pathology, emotion system functioning, and affective symptoms. By forging
links among measures of emotion, neural network dysfunction, affective symptoms, and Aβ and tau deposition,
the propo...

## Key facts

- **NIH application ID:** 10469497
- **Project number:** 5R01AG073244-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Virginia Emily Sturm
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $802,920
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469497

## Citation

> US National Institutes of Health, RePORTER application 10469497, Emotion alterations across the Alzheimer's disease spectrum (5R01AG073244-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10469497. Licensed CC0.

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