Sex and gender differences in the causes of dementia: a narrative review

Abstract

This is a narrative review of new ideas and concepts related to differences between men and women in their risk of developing dementia or Alzheimer's disease (AD). We introduce the concept of dimorphic neurology and the distinction between sex and gender. We then provide three examples of risk factors related to sex and gender from the literature. Apolipoprotein E genotype is equally common in men and women but has a stronger effect in women. Apolipoprotein E genotype is a biological factor that cannot be modified but interacts with sex or gender related factors that can be modified. Low education has a similar harmful effect in men and women but has been historically more common in women. Education is a social factor related to gender that can be modified. Finally, bilateral oophorectomy is a factor restricted to women. Bilateral oophorectomy is a surgical practice related to sex that can be modified. Consideration of risk and protective factors in men and women separately may accelerate etiologic research for neurological diseases in general, and for dementia and AD in particular. Similarly, future preventive interventions for dementia should be tailored to men and women separately.

Keywords: APOE genotype; Dementia; Education; Gender; Oophorectomy; Sex.

Figure 1

Schematic representation of three examples of sex and gender differences related to the risk of dementia or Alzheimer's disease (AD). Men are represented by blue boxes, arrows, and ovals and women by red boxes, arrows and ovals. In all three examples, women experienced a higher risk of dementia or AD attributable to the specific risk factors (bigger red oval). Panel A: APOE E4 allele is equally frequent in men and women (equal boxes) but has a stronger effect in women (thicker red arrow). Panel B: low education has the same effect on the risk of dementia or AD in both men and women (equal strength of the blue and red arrow). However, low education has been historically more common in women than men in many countries (bigger red box in women). Panel C: oophorectomy increases the risk of dementia or AD in women but is not applicable to men. RR = relative risk; APOE = apolipoprotein E: AD = Alzheimer's disease.