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How Does Alzheimer’s Affect Women and Men Differently?

How Does Alzheimer’s Affect Women and Men Differently?

More than 5.5 million Americans are living with Alzheimer's disease, of whom two-thirds are women. Women also account for 60 percent of caregivers of those afflicted with Alzheimer's disease. The Society for Women's Health Research Interdisciplinary Network convened an expert panel of scientists and clinicians to review what is currently known in regard to sex differences in Alzheimer's disease and highlighted knowledge gaps as well as priority research areas in the field. These findings were recently published in the journal Alzheimer's & Dementia [1].

Here are a few notable differences between women and men.


Age is the major risk factor for Alzheimer's disease, and women on average live longer than men. However, longevity alone does not fully explain why two-thirds of Alzheimer's patients are women. Even after taking into account the difference in longevity, some studies have suggested that women are still at a higher risk [2]. Results varied though based on when and where the studies were carried out, and gender differences in educational and occupational opportunities may also have contributed to these mixed results [3]. Less education (e.g., none or primary school only) is associated with increased dementia risk, while higher levels of cognitive activity at mid- or late-life are linked to delayed onset of cognitive impairment [4][5]. Interestingly, a recent analysis of numerous studies across the world did not find that the prevalence of Alzheimer's was significantly higher in women than in men after controlling for sex differences in longevity [6]. Greater educational and occupational attainment for women in the past few decades may be closing the gap in dementia incidence between women and men [7]. But unless sex differences in longevity diminish, women will continue to make up a large proportion of Alzheimer's patients.


Depression is linked to higher dementia risk [4][8][9] and women are two-fold more likely to have depression than men [10]. Additionally, depression is associated with a smaller hippocampus, a brain region important for memory formation, in women, but this association was not observed in men [11]. A history of depression is also associated with faster shrinkage of the hippocampus in women but not in men. The reasons for these sex differences, however, are currently unknown.


People who exercise are less likely to develop dementia, particularly Alzheimer's disease [12]. A recent observational study reported that women who were at high fitness level were 88% less likely to develop dementia compared to those who were at medium fitness level [13]. Despite numerous studies reporting benefits with exercise, women exercise less than men, which is only partly accounted for by gender differences in parenting roles [1]. Interestingly, the magnitude of the benefit from exercise appears to vary in women depending on estrogen levels, with greater benefits observed when estrogen levels are high [14].


Women make up about 60% of all family caregivers for Alzheimer's patients. These rates are especially high for Hispanic and African-American caregivers [1][15]. Women caregivers also have a two-fold higher caregiver burden than male caregivers and are more likely to leave their job to care for a family member. Some studies suggest that spousal caregivers may be at a higher risk of cognitive impairment or dementia than non-caregivers [16].


Apolipoprotein E, known as APOE, is a gene associated with varying risk of Alzheimer's. Of the three different APOE types (APOE2, APOE3, and APOE4), the APOE4 type is associated with an increased risk for Alzheimer's disease. Women with APOE4 are more likely to develop mild cognitive impairment or Alzheimer's disease than men with APOE4 [17][18]. They are also more likely than men to have worse memory performance [19], greater brain atrophy, and lower brain metabolism [20]. In APOE4 carriers with mild cognitive impairment, women have higher levels of biological markers associated with Alzheimer's than men.


A diagnosis of Alzheimer's disease involves tests of verbal memory, a function that women on average have an advantage for over men [21]. The downside is women can perform well on these tests even in the presence of pathology, so diagnosis for mild cognitive impairment and Alzheimer's disease may be delayed. By the time women are diagnosed with these conditions, they already have a more severe disease burden and decline more rapidly compared to men. Alternative ways to improve early detection in women are warranted, such as using sex-specific cutoff scores or memory tests that do not show sex differences [1].

More research is needed to better understand how Alzheimer’s disease differs between women and men.

The expert panel identified these priority areas that merit further investigation:

  • The extent to which sex differences in Alzheimer's risk is due to differences in longevity and chronic diseases
  • The impact of factors that affect only one sex, such as pregnancy and menopause
  • The influence of estrogens and hormone therapy on brain function and Alzheimer's risk
  • Differences between women and men in genetic risk factors for Alzheimer's, such as APOE
  • The impact of factors that affect both sexes, such as cardiovascular disease, diabetes, and depression
  • Sex differences in Alzheimer's disease progression, including changes in cognitive functions and biological markers of Alzheimer's disease
  • Sex differences in brain development and brain aging
  • Sex differences in risk factors and disease progression in racial and ethnic subgroups
  • Gender differences in the burden of caregiving and its influence on Alzheimer's risk for the caregiver
  • Sex differences in the response to current Alzheimer’s therapeutics and those in clinical development
  • Sex differences in detection, diagnosis, and treatment of Alzheimer's

More research in these areas will extend our understanding of how biological, societal, and cultural factors affect brain health and Alzheimer's risk, which in turn will lead to improved diagnosis, management, and individualized treatment options for both women and men.


  1. Nebel RA, Aggarwal NT, Barnes LL et al. (2018) Understanding the impact of sex and gender in Alzheimer's disease: A call to action. Alzheimers Dement.
  2. Prince M, Ali GC, Guerchet M et al. (2016) Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther 8, 23.
  3. Mielke MM, Vemuri P, Rocca WA (2014) Clinical epidemiology of Alzheimer's disease: assessing sex and gender differences. Clin Epidemiol 6, 37-48.
  4. Livingston G, Sommerlad A, Orgeta V et al. (2017) Dementia prevention, intervention, and care. Lancet.
  5. Vemuri P, Lesnick TG, Przybelski SA et al. (2014) Association of lifetime intellectual enrichment with cognitive decline in the older population. JAMA Neurol 71, 1017-1024.
  6. Fiest KM, Roberts JI, Maxwell CJ et al. (2016) The Prevalence and Incidence of Dementia Due to Alzheimer's Disease: a Systematic Review and Meta-Analysis. Can J Neurol Sci 43 Suppl 1, S51-82.
  7. Langa KM, Larson EB, Crimmins EM et al. (2017) A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012. JAMA Intern Med 177, 51-58.
  8. Dotson VM, Beydoun MA, Zonderman AB (2010) Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment. Neurology 75, 27-34.
  9. Singh-Manoux A, Dugravot A, Fournier A et al. (2017) Trajectories of Depressive Symptoms Before Diagnosis of Dementia: A 28-Year Follow-up Study. JAMA Psychiatry 74, 712-718.
  10. Kessler RC, McGonagle KA, Swartz M et al. (1993) Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. J Affect Disord 29, 85-96.
  11. Elbejjani M, Fuhrer R, Abrahamowicz M et al. (2015) Depression, depressive symptoms, and rate of hippocampal atrophy in a longitudinal cohort of older men and women. Psychol Med 45, 1931-1944.
  12. Blondell SJ, Hammersley-Mather R, Veerman JL (2014) Does physical activity prevent cognitive decline and dementia?: A systematic review and meta-analysis of longitudinal studies. BMC Public Health 14, 510.
  13. Horder H, Johansson L, Guo X et al. (2018) Midlife cardiovascular fitness and dementia: A 44-year longitudinal population study in women. Neurology 90, e1298-e1305.
  14. Erickson KI, Colcombe SJ, Elavsky S et al. (2007) Interactive effects of fitness and hormone treatment on brain health in postmenopausal women. Neurobiol Aging 28, 179-185.
  15. Pinquart M, Sorensen S (2005) Ethnic differences in stressors, resources, and psychological outcomes of family caregiving: a meta-analysis. Gerontologist 45, 90-106.
  16. Vitaliano PP, Murphy M, Young HM et al. (2011) Does caring for a spouse with dementia promote cognitive decline? A hypothesis and proposed mechanisms. J Am Geriatr Soc 59, 900-908.
  17. Altmann A, Tian L, Henderson VW et al. (2014) Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol 75, 563-573.
  18. Farrer LA, Cupples LA, Haines JL et al. (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278, 1349-1356.
  19. Fleisher AS, Sun S, Taylor C et al. (2008) Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment. Neurology 70, 191-199.
  20. Sampedro F, Vilaplana E, de Leon MJ et al. (2015) APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls. Oncotarget 6, 26663-26674.
  21. Kramer JH, Yaffe K, Lengenfelder J et al. (2003) Age and gender interactions on verbal memory performance. J Int Neuropsychol Soc 9, 97-102.

Yuko Hara, PhD, is Director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation. Dr. Hara was previously an Assistant Professor in Neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain's synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. Dr. Hara has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.

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