Multiparity, Brain Atrophy, and Cognitive Decline

Abstract

Background: Multiparity - grand multiparity (i.e., five or more childbirths) in particular - has been reported to have an association with increased risk of Alzheimer's disease (AD) dementia or related cognitive decline in women. However, the pathological links underlying this relationship are still unknown. This study was conducted to examine the relationships of multiparity with cerebral amyloid-beta (Aβ) deposition, brain atrophy, and white matter hyperintensities (WMHs).

Methods: In this study, total of 237 older women with 148 cognitively normal and 89 mild cognitive impairment from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) were included. Participants underwent clinical and neuropsychological assessments in addition to ¹¹C-labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. The associations of parity with Aβ deposition, hippocampal volume, cortical volume, WMH volume and mini-mental status examination (MMSE) score were examined.

Results: Participants with grand multiparity showed significantly reduced adjusted hippocampal volume, spatial pattern of atrophy for recognition of AD volume and spatial pattern of atrophy for recognition of brain aging volume even after controlling for potential confounders. Furthermore, MMSE score was also significantly lower in this group. In contrast, grand multiparity did not show any association with global Aβ retention, Aβ positivity rate, or WMH volume, regardless of covariates.

Conclusion: Our findings suggest that grand multiparity contributes to cognitive decline or increased dementia risk in older women by aggravating amyloid-independent hippocampal or cortical atrophy.

Keywords: Alzheimer’s disease; beta-amyloid; childbirth; hippocampus; multiparity; neurodegeneration.

FIGURE 1

The relationships (A) between parity and global Aβ retention, (B) between parity and adjusted hippocampal volume, (C) between parity and SPARE-AD volume, and (D) between parity and SPARE-BA volume with standard errors. Adjusted for age, education, APOE4 positivity, cognitive status, VRS, income level at early adulthood, level of lifetime occupation, age at menarche age and age at menopause. Aβ, β-amyloid; SPARE-AD, spatial patterns of abnormality for recognition of early AD; SPARE-BA, spatial pattern of atrophy for recognition of brain aging; APOE4, apolipoprotein E ε4; VRS, vascular risk factors score.