Psychiatric symptoms of AD dementia
Most patients with AD dementia experience neuropsychiatric symptoms at some point during the course of the disease. These symptoms lead to poorer medical and functional outcomes as well as increased caregiver burden. Recent studies suggest that the distribution of neuropsychiatric symptoms may vary by sex. In a study of patients with newly diagnosed AD dementia who were not treated for AD or neuropsychiatric symptoms, women had a higher mean Neuropsychiatric Inventory score for depression, anxiety, and total neuropsychiatric symptoms.19
Findings from another study indicate that women with AD dementia have higher depressive symptoms, whereas men are more likely to have agitation.20 Better characterization of the sex differences in neuropsychiatric symptoms among AD dementia patients will help to elucidate sex differences in the disease pathophysiology and to identify better treatment targets for women and men.
The study of sex and gender differences in the AD field is in its infancy compared with other areas of medicine such as cardiology. Research in the field of cardiology has shown that there are sex and gender differences in risk factors, symptom presentation, mortality, and treatment response for cardiovascular diseases. Better understanding of these sex and gender differences has led to improved care and treatment for both women and men.
The same positive outcome can occur for the prevention and treatment of AD dementia. We must move beyond the notion that women are at greatest risk and that AD dementia is a women’s disease to focus on sex and gender differences.
This overview provided a few scenarios of sex and gender differences in risk factors for, and clinical presentation of, AD dementia. There will not be sex or gender differences in all risk factors or mechanisms. Identifying where there are differences, however, will provide better treatment and care for both women and men.
Acknowledgement—This work was supported by RF1 AG55151 and U54 AG44170.
Dr Mielke is Professor, Department of Health Sciences Research, Division of Epidemiology and Department of Neurology, Mayo Clinic, Rochester, MN. Dr Mielke reports that she serves as a consultant to Eli Lilly and Lysosomal Therapeutics, Inc. She receives research support from the NIH (R01 AG49704, U54 AG44170, U01 AG06786, RFI AG55151), the Department of Defense (W81XWH-15-1), and unrestricted research grants from Biogen and Lundbeck.
1. Alzheimer Association. Alzheimer disease facts and figures. Alzheimer Dement. 2017;13:325-373.
2. Institute of Medicine. Exploring the Biological Contributions to Human Health: Does Sex Matter? Washington, DC: National Academies Press; 2001.
3. Edland SD, Rocca WA, Petersen RC, et al. Dementia and Alzheimer disease incidence rates do not vary by sex in Rochester, MN. Arch Neurol. 2002;59:1589-1593.
4. Fratiglioni L, Viitanen M, von Strauss E, et al. Very old women at highest risk of dementia and Alzheimer disease: incidence data from the Kungsholmen Project, Stockholm. Neurol. 1997;48:132-138.
5. Letenneur L, Gilleron V, Commenges D, et al. Are sex and educational level independent predictors of dementia and Alzheimer’s disease? Incidence data from the PAQUID project. J Neurol Neurosurg Psychiatry. 1999;66:177-183.
6. Matthews FE, Stephan BC, Robinson L, et al. A two-decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II. Nat Commun. 2016;7:11398.
7. Kessler RC, McGonagle KA, Swartz M, et al. Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. J Affect Disord. 1993;29:85-96.
8. Goveas JS, Espeland MA, Woods NF, et al. Depressive symptoms and incidence of mild cognitive impairment and probable dementia in elderly women: the Women’s Health Initiative Memory Study. J Am Geriatr Soc. 2011;59:57-66.
9. Ownby RL, Crocco E, Acevedo A, et al. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry. 2006;63:530-538.
10. Bixler EO, Vgontzas AN, Lin HM, et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med. 2001;163:608-613.
11. Russ TC, Stamatakis E, Hamer M, et al. Socioeconomic status as a risk factor for dementia death: individual participant meta-analysis of 86 508 men and women from the UK. Br J Psychiatry. 2013;203:10-17.
12. Pankratz VS, Roberts RO, Mielke MM, et al. Predicting the risk of mild cognitive impairment in the Mayo Clinic Study of Aging. Neurol. 2015;84:1433-1442.
13. Mielke MM, Milic NM, Weissgerber TL, et al. Impaired cognition and brain atrophy decades after hypertensive pregnancy disorders. Circ Cardiovasc Qual Outcomes. 2016;9:S70-76.
14. Epperson CN, Sammel MD, Freeman EW: Menopause effects on verbal memory: findings from a longitudinal community cohort. J Clin Endocrinol Metab. 2013;98:3829-3838.
15. Rocca WA, Grossardt BR, Shuster LT: Oophorectomy, menopause, estrogen treatment, and cognitive aging: clinical evidence for a window of opportunity. Brain Res. 2011;1379:188-198.
16. Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA. 2004;291:2947-2958.
17. Gleason CE, Dowling NM, Wharton W, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS-Cognitive and Affective Study. PLoS Med. 2015;12:e1001833.
18. Barry MJ, Delorenzo MA, Walker-Corkery ES, et al. The rising prevalence of androgen deprivation among older American men since the advent of prostate-specific antigen testing: a population-based cohort study. BJU Int. 2006;98:973-978.
19. Spalletta G, Musicco M, Padovani A, et al. Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease. Am J Geriatr Psychiatry. 2010;18:1026-1035.
20. Lee J, Lee KJ, Kim H: Gender differences in behavioral and psychological symptoms of patients with Alzheimer disease. Asian J Psychiatry. 2017;26:124-128.