Review
Sex differences in cognitive impairment and Alzheimer’s disease

https://doi.org/10.1016/j.yfrne.2014.01.002Get rights and content

Highlights

  • Neurobiology of sex-type spatial memory from young to old.

  • Sex differences in prevalence of Alzheimer’s disease.

  • Potential protective role of sex hormones in Alzheimer’s disease.

Abstract

Studies have shown differences in specific cognitive ability domains and risk of Alzheimer’s disease between the men and women at later age. However it is important to know that sex differences in cognitive function during adulthood may have their basis in both organizational effects, i.e., occurring as early as during the neuronal development period, as well as in activational effects, where the influence of the sex steroids influence brain function in adulthood. Further, the rate of cognitive decline with aging is also different between the sexes. Understanding the biology of sex differences in cognitive function will not only provide insight into Alzheimer’s disease prevention, but also is integral to the development of personalized, gender-specific medicine. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of sex differences in cognitive function from young to old, and examines the effects of sex hormone treatments on Alzheimer’s disease in men and women.

Introduction

The popular quote, “Men are from Mars and women are from Venus”, has been commonly applied to many different situations including physiology, sociology and pathology; the gender differences in cognitive functioning are no exception. The differences of learning and memory between male and female brains are confirmed by both human and animal studies from early development stages throughout their life spans. In addition, many neurological diseases exhibit gender biases, such that one sex has a greater prevalence or severity of the disease than the other. Neurological diseases in the young and the elderly also demonstrate gender-specific responses to therapies. However, the question is how much, rather than whether or not, the biology of sex contributes to normal cognitive function. Accordingly, such understanding may provide better insight into the factors that contribute to the risk of cognitive impairment. Here, we will be focusing on sex hormones – especially the role of estrogens, progesterone and testosterone – on mechanisms that relate to neuronal function and associated cognitive ability in the adult and aged individual.

Section snippets

Sex differences in cognition

Gender differences in cognitive function in adulthood and ageing have been well demonstrated. For example, men perform better on spatial memory while women excel at verbal and object location (Table 1). The sex differences in cognitive function and brain structures in later life have been demonstrated by magnetic resonance imaging (MRI) in human studies. For instance, studies found that men demonstrated larger amygdala and thalamus volumes compared to women (Neufang et al., 2009, Bramen et al.,

Sex differences in prevalence of Alzheimer’s disease

AD is the most common cause of dementia in the elderly and is characterized by two major pathological lesions: intracellular inclusions of tau protein in the form of neurofibrillary tangles, and extracellular plaque formation by accumulations of amyloid beta peptide (Aβ) derived from the β-amyloid precursor protein (APP). Accumulating Aβ, a proteolytic byproduct of amyloid precursor protein (APP) metabolism, is an important aspect of AD pathology. APP is processed by two competing pathways, the

The potential protective role of estrogens, progestins and androgens in AD – evidence from pre-clinical and clinical studies

While studies that reported impairments (or increased vulnerability) of brain function resulting from surgical removal of the ovaries supported the potential benefit of estrogens in maintaining a healthy brain, it is important to recognize that ovariectomy (like the menopause) leads to a significant reduction in not only circulating estradiol, but also in circulating progesterone. As such, the structural and functional impairments that are reported to occur following ovariectomy may result from

Summary

The differences in learning and memory between male and female brains are confirmed by both human and animal studies from early development stage throughout their life spans. In addition, many neurological diseases exhibit sex differences, exemplified by one sex having a greater prevalence or severity of the disease than the other sex. Women not only have a higher prevalence of AD than age-matched men, but also showed significantly age-related faster decline and greater deterioration of

Acknowledgments

This work was supported by the American Health Assistance Foundation (G2006-118), and the National Institutes of Health (R01AG032441-01, AG022550, AG027956). We also thank Juliet Shen for editing and proofreading.

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