Age-volume associations in cerebellar lobules by sex and reproductive stage

Abstract

The cerebellum has established associations with motor function and a well-recognized role in cognition. In advanced age, cognitive and motor impairments contribute to reduced quality of life and are more common. Regional cerebellar volume is associated with performance across these domains and sex hormones may influence this volume. Examining sex differences in regional cerebellar volume in conjunction with age, and in the context of reproductive stage stands to improve our understanding of cerebellar aging and pathology. Data from 508 healthy adults (ages 18-88; 47% female) from the Cambridge Centre for Ageing and Neuroscience database were used here. CERES was used to assess lobular volume in T1-weighted images. We examined sex differences in adjusted regional cerebellar volume while controlling for age. A subgroup of participants (n = 370, 50% female) was used to assess group differences in female reproductive stages as compared to age-matched males. Sex differences in adjusted volume were seen across most anterior and posterior cerebellar lobules. Most of these lobules had significant linear relationships with age in males and females. While there were no interactions between sex and reproductive stage groups, exploratory analyses in females alone revealed multiple regional differences by reproductive stage. We found sex differences in volume across much of the cerebellum, linear associations with age, and did not find an interaction for sex and reproductive stage on regional cerebellar volume. Longitudinal investigation into hormonal influences on cerebellar structure and function is warranted as hormonal changes with menopause may impact cerebellar volume over time.

Keywords: Aging; Cerebellum; Menopause; Sex differences; Structural brain imaging.

Fig.1

Example of automated lobule segmentation output from CERES (Romero et al., 2017).

Fig.2

Violin plots demonstrating corrected volume for each lobule in females and males across all participants. The curved edges depict the distribution of volume in the sample and the box plots indicate the mean and interquartile ranges. The asterisk depicts areas that are significantly different by sex when controlling for age after Bonferroni correction (p<.002).

Fig.3

Linear age-volume relationships by sex in each cerebellar region examined. The gray superimposed on each colored line depicts the 95% confidence interval for adjusted volume in each sex.

Fig.4

Mean and interquartile range indicated by black lines on each violin plot. These show adjusted volume distribution for age-matched males and females in categorized female reproductive stages. Visualization was split over three figures due to the number of regions investigated. There were no significant interactions.

Fig.5

Mean and interquartile range indicated by black lines on each violin plot. These show adjusted volume distribution for age-matched males and females in categorized female reproductive stages. Visualization was split over three figures due to the number of regions investigated. There were no significant interactions.

Fig.6

Mean and interquartile range indicated by black lines on each violin plot. These show adjusted volume distribution for age-matched males and females in categorized female reproductive stages. Visualization was split over three figures due to the number of regions investigated. There were no significant interactions.