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March 8, 2025Neurobiology of AgingOpen Access

Sex and APOE4-specific links between cardiometabolic risk factors and white matter alterations in individuals with a family history of Alzheimer's disease

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Key result

Cardiometabolic risk factors link to worse white matter microstructure, especially higher LDL-C in APOE4 carriers.

Why the study?

White matter alterations are among the earliest changes in Alzheimer disease, but limited work has comprehensively characterized the effects of risk factors on white matter.

Do cardiometabolic risk factors affect white matter microstructure in older adults with a family history of Alzheimer's disease, and does this vary by sex and APOE genotype?

Population

Older adults with a family history of Alzheimer's disease

Comparison

Cardiometabolic risk factors stratified by sex and APOE genotype

Design

Observational study

Authors

STStefanie A TremblayRSR. Nathan SprengAWAlfie Wearn

Discussion

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Member takes

Overview

Supports hypothesis generation on cardiometabolic effects in AD risk; leaves open whether LDL modification alters white matter outcomes in APOE4 carriers.

Study Design

Type

Observational

Structured PICO

Do cardiometabolic risk factors affect white matter microstructure in older adults with a family history of Alzheimer's disease, and does this vary by sex and APOE genotype?

P
Population
Older adults with a family history of Alzheimer's disease
O
Outcome
White matter (WM) microstructure alterations measured by MRI-derived metrics integrated using Mahalanobis distance (D2)surrogate

Combined exposure to multiple cardiometabolic risk factors negatively impacts white matter microstructural health in older adults at risk for Alzheimer's disease, with LDL-cholesterol showing a distinct detrimental effect specifically in APOE4 carriers.

Cite This Study

Tremblay et al. (2025) conducted an observational in Alzheimer's disease risk. Cardiometabolic risk factors and APOE4 genotype was evaluated on White matter microstructure alterations (Mahalanobis distance D2). Cardiometabolic risk factors negatively impact white matter microstructure in older adults with a family history of AD, with LDL-cholesterol having a specifically detrimental effect in APOE4 carriers.

synapsesocial.com/papers/6a11caff35a4eec8fedcd9fdhttps://doi.org/10.1016/j.neurobiolaging.2025.03.003
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Sex differences in brain aging among adults with family history of Alzheimer’s disease and APOE4 genetic risk2021 · 42 citations
  2. 2<i>APOE</i> -ε4 count predicts age when prevalence of AD increases, then declines1999 · 402 citations
  3. 3Voxel-based meta-analysis of grey matter changes in Alzheimer’s disease2015 · 129 citations
  4. 4Regional specificity of MRI contrast parameter changes in normal ageing revealed by voxel-based quantification (VBQ)2011 · 321 citations
  5. 5White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease2014 · 86 citations