# Examining Sex-Specific Effects on White Matter Integrity and Brain Function in Familial Alzheimer's Disease and Vascular Dementia

> **NIH NIH F31** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $48,974

## Abstract

PROJECT SUMMARY/ABSTRACT
Cerebral small vessel disease (CSVD) is a neurological condition characterized by damage to the small blood
vessels in the brain. It is estimated that 20% to 30% of adults aged 65 and older may have some form of
CSVD, and this prevalence increases with advancing age. In CSVD, vascular impairment can contribute to the
accumulation of amyloid-beta protein, a hallmark feature of Alzheimer's disease (AD), by hindering its
clearance from the brain and promoting the formation of amyloid plaques. Moreover, CSVD can exacerbate
cognitive decline in individuals with Vascular Contributions to Cognitive Impairment and Dementia (VCID). The
combination of vascular and degenerative processes in VCID can lead to more severe cognitive impairment
than expected with either condition alone. Early detection of CSVD is crucial for preventing VCID and AD in
older adults. The examination of underlying mechanisms of CSVD using early onset “pure” hereditary models
for vascular dementia (e.g., due to Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and
Leukoencephalopathy [CADASIL]) and AD (e.g., due to autosomal dominant mutations, ADAD) is a promising
strategy for identifying diagnostic and therapeutic approaches for the more common sporadic forms of these
diseases. In VCID and AD, pathology is already present in the brain for many years before the emergence of
cognitive symptoms, suggesting that treatments may have the best chance of success in the preclinical stage.
An important consideration is that sex differences occur in VCID and AD. Females are disproportionately
affected by AD, comprising two-thirds of diagnosed individuals, whereas the prevalence of vascular dementia
is about 44% higher in males than females. The mechanisms underlying these sex-specific differences remain
unclear. Identifying sex-specific patterns of neurodegeneration in the early stages of cognitive impairment and
dementia will enable tailored interventions, sex-specific preventative strategies, and improved diagnostic
accuracy for both males and females. The overall aim of this project is to examine sex differences in VCID and
AD by measuring white matter integrity, functional brain connectivity, and cognitive function in individuals
genetically determined to develop early-onset VCID (CADASIL) or AD (ADAD, Presenilin-1 E280A). My
overarching hypothesis is that white matter integrity and patterns of functional connectivity can be used as
predictors of cognitive impairment and dementia in CADASIL and ADAD. Further, I expect that white matter
integrity and functional connectivity can serve as biomarkers that predict distinct outcomes for males and
females, not only in VCID but also in ADAD, the latter of which has more traditionally been characterized by
measures of tau and amyloid pathology. Through this project, I will (1) gain expertise in neuroimaging analysis
related to white matter disease in VCID and ADAD, (2) receive training on sex differences ...

## Key facts

- **NIH application ID:** 10899137
- **Project number:** 1F31NS134277-01A1
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Averi Jordin Giudicessi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899137

## Citation

> US National Institutes of Health, RePORTER application 10899137, Examining Sex-Specific Effects on White Matter Integrity and Brain Function in Familial Alzheimer's Disease and Vascular Dementia (1F31NS134277-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10899137. Licensed CC0.

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