Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study

Ross J Marriott¹, Kevin Murray¹, Leon Flicker^{2

3}, Graeme J Hankey², Alvin M Matsumoto^{4

5}, Girish Dwivedi^{2

6}, Leen Antonio⁷, Osvaldo P Almeida^{2

3}, Shalender Bhasin⁸, Adrian S Dobs⁹, David J Handelsman¹⁰, Robin Haring^{11

12}, Terence W O'Neill¹³, Claes Ohlsson^{14

15}, Eric S Orwoll¹⁶, Dirk Vanderschueren⁷, Gary A Wittert¹⁷, Frederick C W Wu¹⁸, Bu B Yeap^{2

19}

Affiliations

¹ School of Population and Global Health, University of Western Australia, Perth, Australia.
² Medical School, University of Western Australia, Perth, Australia.
³ Western Australian Centre for Healthy Ageing, University of Western Australia, Perth, Australia.
⁴ Department of Medicine, University of Washington School of Medicine, Seattle, USA.
⁵ Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, USA.
⁶ Harry Perkins Institute of Medical Research, Fiona Stanley Hospital, Perth, Australia.
⁷ Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
⁸ Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
⁹ Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, USA.
¹⁰ ANZAC Research Institute, University of Sydney, Sydney, Australia.
¹¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
¹² European University of Applied Sciences, Faculty of Applied Public Health, Rostock, Germany.
¹³ Centre for Epidemiology Versus Arthritis, University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK.
¹⁴ Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁵ Region Vastra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁶ Oregon Health and Science University, Portland, USA.
¹⁷ Freemasons Centre for Men's Health and Wellbeing, School of Medicine, University of Adelaide, Adelaide, Australia.
¹⁸ Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, UK.
¹⁹ Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.

PMID: 34978125
DOI: 10.1002/alz.12529

Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study

Ross J Marriott et al. Alzheimers Dement. 2022 Oct.

. 2022 Oct;18(10):1907-1918.

doi: 10.1002/alz.12529. Epub 2022 Jan 3.

Authors

Affiliations

¹ School of Population and Global Health, University of Western Australia, Perth, Australia.
² Medical School, University of Western Australia, Perth, Australia.
³ Western Australian Centre for Healthy Ageing, University of Western Australia, Perth, Australia.
⁴ Department of Medicine, University of Washington School of Medicine, Seattle, USA.
⁵ Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, USA.
⁶ Harry Perkins Institute of Medical Research, Fiona Stanley Hospital, Perth, Australia.
⁷ Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
⁸ Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
⁹ Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, USA.
¹⁰ ANZAC Research Institute, University of Sydney, Sydney, Australia.
¹¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
¹² European University of Applied Sciences, Faculty of Applied Public Health, Rostock, Germany.
¹³ Centre for Epidemiology Versus Arthritis, University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK.
¹⁴ Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁵ Region Vastra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁶ Oregon Health and Science University, Portland, USA.
¹⁷ Freemasons Centre for Men's Health and Wellbeing, School of Medicine, University of Adelaide, Adelaide, Australia.
¹⁸ Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, UK.
¹⁹ Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.

PMID: 34978125
DOI: 10.1002/alz.12529

Abstract

Introduction: The association of testosterone concentrations with dementia risk remains uncertain. We examined associations of serum testosterone and sex hormone-binding globulin (SHBG) with incidence of dementia and Alzheimer's disease.

Methods: Serum total testosterone and SHBG were measured by immunoassay. The incidence of dementia and Alzheimer's disease (AD) was recorded. Cox proportional hazards regression was adjusted for age and other variables.

Results: In 159,411 community-dwelling men (median age 61, followed for 7 years), 826 developed dementia, including 288 from AD. Lower total testosterone was associated with a higher incidence of dementia (overall trend: P = .001, lowest vs highest quintile: hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.13-1.81), and AD (P = .017, HR = 1.80, CI = 1.21-2.66). Lower SHBG was associated with a lower incidence of dementia (P < .001, HR = 0.66, CI = 0.51-0.85) and AD (P = .012, HR = 0.53, CI = 0.34-0.84).

Discussion: Lower total testosterone and higher SHBG are independently associated with incident dementia and AD in older men. Additional research is needed to determine causality.

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References

REFERENCES

1. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet commission. Lancet. 2020;396:413-446.
1. Camacho EM, Huhtaniemi IT, O'Neill TW, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol. 2013;168:445-455.
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1. Moffat SD, Zonderman AB, Metter EJ, et al. Free testosterone and risk for Alzheimer disease in older men. Neurology. 2004;62:188-193.

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Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study

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Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study

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