Sex differences in the association of adverse childhood experiences with brain and cognition along a continuum of risk for Alzheimer’s disease

Abstract

Introduction: Women make up two-thirds of people with Alzheimer’s disease (AD). Research has focused on biological explanations for this sex difference, while contributions of psychosocial risk factors are less well understood.

Methods: We examined sex differences in the effects of adverse childhood experiences (ACEs) on late-life cognition in groups along a continuum of AD risk: cognitively unimpaired controls (CU; n = 128), subjective cognitive decline (SCD; n = 113), mild cognitive impairment (MCI; n = 241), and AD (n = 77), from the Canadian Consortium on Neurodegeneration in Aging Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study.

Results: Women reported more ACEs than men. There were negative associations between ACEs and hippocampal and prefrontal cortical volumes in CU men and prefrontal volumes in men with SCD. In MCI, ACEs were linked to poorer executive function and associative memory in women. No ACE-related effects were found in AD.

Discussion: ACEs may have enduring effects on late-life cognition that differ between men and women and vary by cognitive status.

Plain Language Summary

The question we studied: Are there sex differences in the associations of adverse (difficult) childhood experiences with cognitive aging and dementia risk?

How we studied it: We studied this question in four groups along a continuum of Alzheimer’s disease risk: cognitively unimpaired controls, people with subjective cognitive decline, people with mild cognitive impairment (a middle stage between healthy aging and dementia), and people with Alzheimer’s disease.

What we found: We found that women were more likely than men to report having difficult experiences during childhood. These early life experiences affected the brain and thinking abilities later in life, but in different ways for men and women. For men without memory problems, difficult childhood experiences were linked to changes in brain areas important for memory and thinking. For women with mild cognitive impairment, childhood hardships were tied to more trouble with attention and memory. In people with Alzheimer’s disease, difficult early experiences no longer affected brain structure or thinking abilities.

Why it matters: This study was the first to provide a comprehensive examination of sex differences in the association between difficult childhood experiences and cognition in both healthy and those at risk of developing or living with dementia. The findings suggest that effects of early-life adversity differ between older men and women, and that these differences could influence the risk of developing Alzheimer’s.