title: Sex differences in the association between AD biomarkers and cognitive decline.
abstract: Women are disproportionately affected by Alzheimer's disease (AD) in terms of both disease prevalence and severity. Previous autopsy work has suggested that, in the presence of AD neuropathology, females are more susceptible to the clinical manifestation of AD. This manuscript extends that work by evaluating whether sex alters the established associations between cerebrospinal fluid (CSF) biomarker levels and brain aging outcomes (hippocampal volume, cognition). Participants were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and included individuals with normal cognition (n = 348), mild cognitive impairment (n = 565), and AD (n = 185). We leveraged mixed effects regression models to assess the interaction between sex and baseline cerebrospinal fluid biomarker levels of amyloid-β42 (Aβ-42) and total tau on cross-sectional and longitudinal brain aging outcomes. We found a significant interaction between sex and Aβ-42 on longitudinal hippocampal atrophy (p = 0.002), and longitudinal decline in memory (p = 0.017) and executive function (p = 0.025). Similarly, we observed an interaction between sex and total tau level on longitudinal hippocampal atrophy (p = 0.008), and longitudinal decline in executive function (p = 0.034). Women with Aβ-42 and total tau levels indicative of worse pathological changes showed more rapid hippocampal atrophy and cognitive decline. The sex difference was particularly pronounced among individuals with MCI, with lower education, and varied by APOE ε4 allele. These results suggest females may be more susceptible to the clinical manifestation of AD.
authors: Vanderbilt Memory & Alzheimer's Center, Vanderbilt University School of Medicine, 1207 17th Ave S, Suite 204F, Nashville, TN, 37212, USA.
authors: Mary Ellen I
authors: MEI
authors: Koran
authors: Vanderbilt Memory & Alzheimer's Center, Vanderbilt University School of Medicine, 1207 17th Ave S, Suite 204F, Nashville, TN, 37212, USA.
authors: Madison
authors: M
authors: Wagener
authors: Vanderbilt Memory & Alzheimer's Center, Vanderbilt University School of Medicine, 1207 17th Ave S, Suite 204F, Nashville, TN, 37212, USA. Timothyjhohman@gmail.com.
authors: Timothy J
authors: TJ
authors: Hohman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000473:pathology / Q000502:physiology / Q000523:psychology; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D001284:Atrophy; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012044:Regression Analysis; D012727:Sex Characteristics; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; Biomarkers; Cognition; Hippocampus; Sex differences