Testosterone and Cognitive Impairment or Dementia in Middle-Aged or Aging Males: Causation and Intervention, a Systematic Review and Meta-Analysis

J Geriatr Psychiatry Neurol. 2021 Sep;34(5):405-417. doi: 10.1177/0891988720933351. Epub 2020 Jun 30.

Abstract

Background and purpose: To investigate the association between testosterone levels and the risk of dementia and to assess the effectiveness of testosterone supplement treatment in patients with cognitive impairment or dementia.

Methods: We searched Pubmed, Cochrane Library, and EMBASE on September 30, 2019.

Results: The risk factor portion of the review included 27 studies with 18 599 participants. Studies revealed inconsistent findings on the association between testosterone levels and the risk of all-cause dementia or Alzheimer disease (AD). The result from our meta-analysis showed an increased risk of all-cause dementia with decreasing total testosterone (total-T, 4572 participants, hazard ratio: 1.14, 95% CI: 1.04-1.26). Some studies also found an increased risk of AD with a lower level of total-T, free testosterone, and bioavailable testosterone. Testosterone supplement treatment may improve general cognitive function and motor response in the short term as measured by the Developmental Test of Visual-Motor Integration (mean difference [MD]: 4.4, 95% CI: 1.20-7.59) and the Mini-Mental State Examination (MD: 3.4, 95% CI: 0.83-5.97) and verbal memory as measured by story recall delay at 3 months (MD: 8.4, 95% CI: 0.49-16.3).

Conclusion: Lower levels of testosterone may be associated with an increased risk of all-cause dementia or AD. Testosterone supplement treatment may or may not improve general cognitive function in patients with cognitive impairment/AD.

Keywords: aging; dementia; males; systematic review; testosterone; testosterone deficiency.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Aging
  • Alzheimer Disease*
  • Cognition
  • Cognitive Dysfunction* / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Testosterone

Substances

  • Testosterone