Sex and APOE4-specific links between cardiometabolic risk factors and white matter alterations in individuals with a family history of Alzheimer's disease DOI Creative Commons
Stefanie A Tremblay, R. Nathan Spreng, Alfie Wearn

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 22, 2024

ABSTRACT INTRODUCTION White matter (WM) alterations are among the earliest changes in Alzheimer’s disease (AD), yet limited work has comprehensively characterized effects of AD risk factors on WM. METHODS In older adults with a family history AD, we investigated sex-specific and APOE genotype-related relationships between WM microstructure factors. Multiple MRI-derived metrics were integrated using multivariate approach based Mahalanobis distance (D2). The links D2 cognition also explored. RESULTS several regions was associated high systolic blood pressure, BMI, glycated hemoglobin, low cholesterol, both males females. APOE4+ displayed distinct pattern, LDL-cholesterol having detrimental effect only carriers, this pattern linked to immediate memory performance. Myelination main mechanism underlying alterations. DISCUSSION Our findings reveal that combined exposure multiple cardiometabolic negatively impacts microstructural health, which may subsequently affect cognition. Notably, APOE4 carriers exhibited different especially role LDL, suggesting mechanisms group.

Язык: Английский

Sex and APOE4-specific links between cardiometabolic risk factors and white matter alterations in individuals with a family history of Alzheimer's disease DOI Creative Commons
Stefanie A Tremblay, R. Nathan Spreng, Alfie Wearn

и другие.

Neurobiology of Aging, Год журнала: 2025, Номер 150, С. 80 - 96

Опубликована: Март 8, 2025

Early detection of pathological changes in Alzheimer's disease (AD) has garnered significant attention the last few decades as interventions aiming to prevent progression will likely be most effective when initiated early. White matter (WM) alterations are among earliest AD, yet limited work comprehensively characterized effects AD risk factors on WM. In older adults with a family history we investigated sex-specific and APOE genotype-related relationships between WM microstructure factors. Multiple MRI-derived metrics were integrated using multivariate approach based Mahalanobis distance (D2). To uncover specific biological underpinnings these alterations, then extracted contribution each MRI feature D2 clusters. Lastly, links cognition explored. several regions was associated high systolic blood pressure, BMI, glycated hemoglobin, low cholesterol, both males females. APOE4 + displayed distinct pattern, LDL-cholesterol having detrimental effect only carriers, this pattern linked immediate memory performance. Myelination main mechanism underlying alterations. Our findings reveal that combined exposure multiple cardiometabolic negatively impacts microstructural health, which may subsequently affect cognition. Notably, carriers exhibited different especially role LDL, suggesting mechanisms group.

Язык: Английский

Процитировано

0
Sex and APOE4-specific links between cardiometabolic risk factors and white matter alterations in individuals with a family history of Alzheimer's disease DOI Creative Commons
Stefanie A Tremblay, R. Nathan Spreng, Alfie Wearn

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 22, 2024

ABSTRACT INTRODUCTION White matter (WM) alterations are among the earliest changes in Alzheimer’s disease (AD), yet limited work has comprehensively characterized effects of AD risk factors on WM. METHODS In older adults with a family history AD, we investigated sex-specific and APOE genotype-related relationships between WM microstructure factors. Multiple MRI-derived metrics were integrated using multivariate approach based Mahalanobis distance (D2). The links D2 cognition also explored. RESULTS several regions was associated high systolic blood pressure, BMI, glycated hemoglobin, low cholesterol, both males females. APOE4+ displayed distinct pattern, LDL-cholesterol having detrimental effect only carriers, this pattern linked to immediate memory performance. Myelination main mechanism underlying alterations. DISCUSSION Our findings reveal that combined exposure multiple cardiometabolic negatively impacts microstructural health, which may subsequently affect cognition. Notably, APOE4 carriers exhibited different especially role LDL, suggesting mechanisms group.

Язык: Английский

Процитировано

0