# Decoding neural systems underlying anosognosia for memory loss in aging and Alzheimer's disease

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $849,603

## Abstract

ABSTRACT
Disordered awareness of cognitive and behavioral deficits, i.e. anosognosia, is a common symptom of
Alzheimer’s disease (AD) that is particularly frustrating to families, and may impact early detection. There is a
growing yet incomplete understanding of the neurobiological mechanisms that underlie the breakdown of
memory self-awareness in AD. Recent neuroimaging findings, including our own work, suggest that
anosognosia in AD not only reflects functional alteration in discrete brain regions but likely results from
functional connectivity disruption between different brain regions, i.e. network breakdown, particularly in the
brain networks subserving self-referential processing. The proposed research aims to test our central
hypothesis that anosognosia occurs as a symptom of functional, structural and pathological changes in self-
referential brain networks. To address these aims, self-awareness of memory measures will be related to multi-
tracer Positron Emission Tomography (PET) to assess amyloid burden and tau burden, and functional
magnetic resonance imaging during rest (rsfc-MRI) as well as diffusion-weighted imaging (dMRI), obtained
from a total of 150 older subjects ranging from clinically normal to mild cognitive impairment and mild AD
individuals. Specifically, in Aim 1 we will assess the functional integrity of brain networks (as assessed with
rsfc-MRI) recruited during self-referential processing and examine the extent memory self-awareness predicts
the resting state intrinsic connectivity strength across the clinical spectrum of early AD. We will also investigate
whether executive skills might influence this relationship as well as the specificity of the functioning of the self-
referential networks as compared to other brain networks to insight of memory abilities. In Aim 2 we will use
dMRI to investigate the structural integrity of white tracts that are critical for self-referential processing and
investigate whether decoupling between local structural and functional connectivity is related to altered
memory self-awareness. Finally, in Aim 3 we will investigate the role of molecular pathology e.g. fibrillary
amyloid (Aβ) deposition (as assessed with PiB-PET) and tau deposition (as assessed with flortaucipir PET,
FTP-PET or T807) in the decoupling process and its relation to altered memory self-awareness across the
clinical spectrum of AD. This project may provide critical information about factors contributing to decline in
functional status, development of disability, and loss of independence. As such, the results from this study may
have important clinical and practical implications for patients and their families, particularly for the development
and use of dementia management interventions.

## Key facts

- **NIH application ID:** 9986605
- **Project number:** 5R01AG061083-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Patrizia Vannini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $849,603
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986605

## Citation

> US National Institutes of Health, RePORTER application 9986605, Decoding neural systems underlying anosognosia for memory loss in aging and Alzheimer's disease (5R01AG061083-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9986605. Licensed CC0.

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