Sex differences implications in hippocampal volumetry during midlife

Abstract

AbstractBackgroundSex differences in adult brain morphology are frequently reported. Hippocampal and medio‐temporal (MTL) cortices in women and men are frequently implicated in Alzheimer’s Disease (AD) pathology, and women are disproportionally more affected by AD than men. Modifications in these regions’ volumetry are described during aging and in pathology, but their specificities during midlife regarding sex are still debated. Also, the multifaceted interactions between sex and dementia risk factors in these brain areas are not fully established. The aim of this study is to precisely identify the differences between women and men in the volumetry of hippocampal and MTL subregions, as well as the moderation effects of risk factors for dementia such as hypertension (diastolic blood pressure), hypercholesterolemia, obesity (body mass index), physical inactivity, and inflammation (C‐Reactive Protein), on sex.MethodData from 210 cognitively healthy participants were analyzed (106 women; 104 men; age 40‐65). Automatic segmentation was performed to determine the volume of the bilateral anterior and posterior hippocampus, and of entorhinal, perirhinal (BA35 and BA36), and parahippocampal cortices (ASHS‐PMC‐T1 atlas). The total intracranial volume was obtained to calculate adjusted‐volumes for every participant. An analysis of covariance (ANCOVA) was performed to compare women and men subregions’ volumes, corrected for age. Linear regressions were performed to analyze the interactions between sex and dementia risk factors on the volumetry of these regions.ResultWomen and men were significantly different in the volume of the left (p < .001) and right (p < .001) hippocampus, on the right BA35 (p = .008), and on the left (p < .001) and right (p < .001) parahippocampal cortices. No significant interaction was highlighted between sex and risk factor variables.ConclusionBeyond basic demography, sex is essential to consider in research, as women and men appear to be inherently different in their brain morphometry, even from midlife. Volumetric differences in AD‐linked brain regions, regardless of potential dementia risk factors, may be an innocuous sex‐specific feature at the preclinical phase. In this regard, women’s vulnerability to AD may not occur until later in aging, potentially linked to hormonal decline.