Sex differences in the development of mild cognitive impairment and probable Alzheimer’s disease as predicted by hippocampal volume or white matter hyperintensities

Abstract

This study examined biological sex differences in the development of mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) development as predicted by changes in the hippocampus or white matter hyperintensities. A secondary data analysis of the National Alzheimer's Coordinating Center Uniform Data Set was conducted. We selected samples of participants with normal cognition at baseline who progressed to MCI (n = 483) and those who progressed to probable AD (n = 211) to determine if hippocampal volume or white matter hyperintensities (WMH) at baseline predicted progression to probable AD or MCI and whether the rate of progression differed between men and women. The survival analyses indicated that changes in hippocampal volumes affected the progression to probable AD (HR = 0.535, 95% CI [0.300-0.953]) only among women. White men had an increased rate of progression to AD (HR = 4.396, CI [1.012-19.08]; HR = 4.665, 95% CI [1.072-20.29]) compared to men in other race and ethnic groups. Among women, increases in hippocampal volume ratio led to decreased rates of progressing to MCI (HR = 0.386, 95% CI [0.166-0.901]). Increased WMH among men led to faster progression to MCI (HR = 1.048. 95% CI [1.011-1.086]). Women and men who were older at baseline were more likely to progress to MCI. In addition, results from longitudinal analyses showed that women with a higher CDR global score, older age at baseline, or more disinhibition symptoms experienced higher odds of MCI development. Changes in hippocampal volumes affect the progression to or odds of probable AD (and MCI) more so among women than men, while changes in WMH affected the progression to MCI only among men.

Early Changes in Memory, Motor Coordination and Strength in the Transgenic Rat Model of Alzheimer’s Disease, TgF344-AD

“…Research has identified gender differences in AD progression (Burke et al, 2018;Nead et al, 2015;Phung et al, 2010), which has been confirmed using rodent models (Carroll e. al., 2010;Munetumo et al, 2015;Woolley, & McEwen, 1992).…”

“…These differences suggest that males exhibit more abrupt cognitive impairment earlier in life than females but it eventually plateaus. Females; however, exhibit a gradual decline and show worse performances on cognitive tests at later time points in life than males (Burke et al, 2018;Carroll et al, 2010). This study, accordingly, will analyze these gender differences in the development of AD.…”

“…and Aβ load, which may be the result of differences in sex hormones (Burke et al, 2018;Carroll et al, 2010;Irvine, Laws, Gale, & Kondel, 2012;Leranth, Pentnehazy, & Maclusky, 2003;Nead et al, 2015). Muscle strength and coordination will be assessed by a grip strength test and rotarod test (Bioseb, Panlab), respectively.…”

“…These reports identify the impact of sex hormones on brain health although how these hormones specifically impact the rate and development of AD is still unclear. Recently Burke et al (2018) identified that women had greater percentage of hippocampus volume relative to total brain volume compared to men. Additionally, the hippocampal volume ratio showed a significant relationship to the risk of developing MCI and progressing to AD among women but not men (Burke et al, 2018).…”

“…Recently Burke et al (2018) identified that women had greater percentage of hippocampus volume relative to total brain volume compared to men. Additionally, the hippocampal volume ratio showed a significant relationship to the risk of developing MCI and progressing to AD among women but not men (Burke et al, 2018). Among men, increases in white matter hyperintensities were associated with increased rate of progression to MCI but not AD.…”