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Background: Cerebrovascular disease (CVD) is a major cause of mortality in females, while two-thirds of Alzheimer's disease (AD) patients are female. AD and CVD share many genetic risk factors, one of them being apolipoprotein E (APOE) genotype. Sex differences in APOE and AD are well-established; it is unclear if associations between APOE and CVD are sex-specific.

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Background: Cerebrovascular pathology frequently co-occurs with Alzheimer's disease (AD) pathology and the combinations of these forms of pathology may underly AD dementia. Sex hormones influence many aspects of cerebrovascular systems and may contribute to cerebrovascular pathology, but many studies of aging and AD do not measure hormones. Therefore, in this study, we explored whether a polygenic score predicting sex hormone levels relates to cerebrovascular pathology in the AD brain.

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Basic Science and Pathogenesis.

Alzheimers Dement

December 2024

The Framingham Study, Framingham, MA, USA.

Background: Apolipoprotein (Apo) E4, a main susceptibility gene for Alzheimer's disease (AD) is associated with increased vascular dysfunction, amyloid pathology, and neurodegeneration. The effector pathways leading to increased vascular risk in ApoE4 carriers needs to be established. Platelet aggregation is a key marker of vascular dysfunction and studies need to examine whether a relationship of ApoE4 allele status and platelet biology exists METHOD: We examined cross-sectional associations of platelet aggregation with ApoE genotypes (E2 or E4 against E3, the most common) in middle-aged cognitively normal participants at the Framingham Heart Study (FHS) Gen3, New Offspring Spouse (NOS), and Omni2 Cohorts.

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Background: Cognitive Reserve(CR) a concept based on the brain plasticity, is a mechanism that delays or minimizes clinical manifestations of brain changes due to aging. Prospective epidemiologic studies non-demented individuals have shown that education, occupational duration and complexity, and greater lifetime engagement in cognitively stimulating activities are associated with a reduced risk of dementia. We study the cognitive reserve and its neuroimaging correlate.

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Clinical Manifestations.

Alzheimers Dement

December 2024

Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.

Background: Mild Behavioral Impairment (MBI) is a condition characterized by neuropsychiatric symptoms (NPS) in older adults without dementia, serving as a precursor to various forms of dementia. This study explores the association between NPS and functional connectivity (FC) within the default mode network (DMN), executive control network (ECN), and salience network (SN) across three high-risk cohorts: mild cognitive impairment (due to Alzheimer's) (MCI, n = 79), cerebrovascular disease (CVD, n = 144), and Parkinson's disease (PD, n = 132).

Method: A total of 367 participants were recruited from the Ontario Neurodegenerative Disease Research Initiative (ONDRI).

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