Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer\u2019s disease

Dongwha Sohn,Jeffrey R Petrella,Andrew J Saykin,Nagiza F Samatova,Joseph E Lucas,Katie Shpanskaya,Rudolph E Tanzi,P Murali Doraiswamy

doi:10.1038/s41598-018-25377-w

Abstract

Sex differences in Alzheimer’s disease (AD) biology and progression are not yet fully characterized. The goal of this study is to examine the effect of sex on cognitive progression in subjects with high likelihood of mild cognitive impairment (MCI) due to Alzheimer’s and followed up to 10 years in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cerebrospinal fluid total-tau and amyloid-beta (Aβ42) ratio values were used to sub-classify 559 MCI subjects (216 females, 343 males) as having “high” or “low” likelihood for MCI due to Alzheimer’s. Data were analyzed using mixed-effects models incorporating all follow-ups. The worsening from baseline in Alzheimer’s Disease Assessment Scale-Cognitive score (mean, SD) (9 ± 12) in subjects with high likelihood of MCI due to Alzheimer’s was markedly greater than that in subjects with low likelihood (1 ± 6, p < 0.0001). Among MCI due to AD subjects, the mean worsening in cognitive score was significantly greater in females (11.58 ± 14) than in males (6.87 ± 11, p = 0.006). Our findings highlight the need to further investigate these findings in other populations and develop sex specific timelines for Alzheimer’s disease progression.

Highlights

Our study systematically examined sex differences in longitudinal cognitive outcomes using pooled mild cognitive impairment (MCI) data from two multicenter studies, Alzheimer’s Disease Neuroimaging Initiative (ADNI)-1 and ADNI-2
This is the first report to examine sex differences in outcomes of MCI subjects defined using pathological Cerebrospinal fluid (CSF) biomarkers to have a high likelihood for MCI due to Alzheimer’s
Our study found that APOE ε4 has an effect on both slope and curvature of ADAS-Cog[11] decline and with both heterozygotes and homozygotes declining faster than non-carriers

Summary

Introduction

The higher prevalence of AD in females was largely assumed to be due to their longer life spans compared to men but recent studies are beginning to paint a more complex picture[1,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]. New NIA-AA recommendations for defining “MCI due to AD – high likelihood”[27], which require positive pathological (molecular imaging or spinal fluid tests of beta-amyloid and tau) and/or neuronal loss (structural MR imaging) biomarkers in addition to clinical criteria, were, in part, based on MCI data from ADNI. These data have not yet been fully examined to study potential sex differences in the progression of subjects with MCI due to AD.

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