Sex differences in cognitive impairment in Alzheimer’s disease

Abstract

Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimer’s disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.

Keywords: Dementia; Gender; Sex differences; Cognition

Core tip: This review assesses evidence that women with Alzheimer’s disease (AD) show greater cognitive impairment than men. The evidence shows that female AD patients are outperformed by males in multiple cognitive domains including visuospatial, verbal processing, semantic and episodic memory. This disadvantage is not attributable to sex differences in age, education level, or dementia severity. Possible explanations include estrogen loss in women or a greater cognitive reserve in men, which may provide protection against the disease process. Such findings have implications for tailoring more specific gender-based treatments.