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

Ross J. Marriott; Kevin Murray; Leon Flicker; Graeme J. Hankey; Alvin M. Matsumoto; Girish Dwivedi; Leen Antonio; Osvaldo P. Almeida; Shalender Bhasin; Adrian S. Dobs; David J. Handelsman; Robin Haring; Terence W. O'Neill; Claes Ohlsson; Eric S. Orwoll; Dirk Vanderschueren; Gary A. Wittert; Frederick C.W. Wu; Bu B. Yeap

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, Kevin Murray, Leon Flicker, Graeme J. Hankey, Alvin M. Matsumoto, Girish Dwivedi, Leen Antonio, Osvaldo P. Almeida, Shalender Bhasin, Adrian S. Dobs, David J. Handelsman, Robin Haring, Terence W. O'Neill, Claes Ohlsson, Eric S. Orwoll, Dirk Vanderschueren, Gary A. Wittert, Frederick C.W. Wu, Bu B. Yeap

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28 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1907-1918
Number of pages	12
Journal	Alzheimer's and Dementia
Volume	18
Issue number	10
DOIs	https://doi.org/10.1002/alz.12529
Publication status	Accepted/In press - 3 Jan 2022
Externally published	Yes

ASJC Scopus subject areas

Clinical Neurology
Geriatrics and Gerontology
Psychiatry and Mental health
Cellular and Molecular Neuroscience
Health Policy
Developmental Neuroscience
Epidemiology

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10.1002/alz.12529

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Marriott, R. J., Murray, K., Flicker, L., Hankey, G. J., Matsumoto, A. M., Dwivedi, G., Antonio, L., Almeida, O. P., Bhasin, S., Dobs, A. S., Handelsman, D. J., Haring, R., O'Neill, T. W., Ohlsson, C., Orwoll, E. S., Vanderschueren, D., Wittert, G. A., Wu, F. C. W., & Yeap, B. B. (Accepted/In press). Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: the UK Biobank prospective cohort study. Alzheimer's and Dementia, 18(10), 1907-1918. https://doi.org/10.1002/alz.12529

@article{b0cc8be4d2db4a7687036c09c19d3407,

title = "Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: the UK Biobank prospective cohort study",

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.",

author = "Marriott, {Ross J.} and Kevin Murray and Leon Flicker and Hankey, {Graeme J.} and Matsumoto, {Alvin M.} and Girish Dwivedi and Leen Antonio and Almeida, {Osvaldo P.} and Shalender Bhasin and Dobs, {Adrian S.} and Handelsman, {David J.} and Robin Haring and O'Neill, {Terence W.} and Claes Ohlsson and Orwoll, {Eric S.} and Dirk Vanderschueren and Wittert, {Gary A.} and Wu, {Frederick C.W.} and Yeap, {Bu B.}",

note = "Funding Information: This work was supported by the Western Australian Health Translation Network and the Australian Government's Medical Research Future Fund via the Rapid Applied Research Translation program; and by a philanthropic donation from Lawley Pharmaceuticals to the University of Western Australia. The funding bodies had no role in the conduct of the research. Funding Information: BBY and RJM received funding support for the present manuscript from the Western Australian Health Translation Network and the Australian Government's Medical Research Future Fund, and via a philanthropic donation by Lawley Pharmaceuticals to the University of Western Australia. All other authors report no disclosures related to the present manuscript. A full list of disclosures unrelated to the present manuscript for all authors within the past 36 months is provided (Supplementary Material). ",

year = "2022",

month = jan,

day = "3",

doi = "10.1002/alz.12529",

language = "English",

volume = "18",

pages = "1907--1918",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc.",

number = "10",

}

Marriott, RJ, Murray, K, Flicker, L, Hankey, GJ, Matsumoto, AM, Dwivedi, G, Antonio, L, Almeida, OP, Bhasin, S, Dobs, AS, Handelsman, DJ, Haring, R, O'Neill, TW, Ohlsson, C, Orwoll, ES, Vanderschueren, D, Wittert, GA, Wu, FCW & Yeap, BB 2022, 'Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: the UK Biobank prospective cohort study', Alzheimer's and Dementia, vol. 18, no. 10, pp. 1907-1918. https://doi.org/10.1002/alz.12529

TY - JOUR

T1 - Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: the UK Biobank prospective cohort study

AU - Marriott, Ross J.

AU - Murray, Kevin

AU - Flicker, Leon

AU - Hankey, Graeme J.

AU - Matsumoto, Alvin M.

AU - Dwivedi, Girish

AU - Antonio, Leen

AU - Almeida, Osvaldo P.

AU - Bhasin, Shalender

AU - Dobs, Adrian S.

AU - Handelsman, David J.

AU - Haring, Robin

AU - O'Neill, Terence W.

AU - Ohlsson, Claes

AU - Orwoll, Eric S.

AU - Vanderschueren, Dirk

AU - Wittert, Gary A.

AU - Wu, Frederick C.W.

AU - Yeap, Bu B.

N1 - Funding Information: This work was supported by the Western Australian Health Translation Network and the Australian Government's Medical Research Future Fund via the Rapid Applied Research Translation program; and by a philanthropic donation from Lawley Pharmaceuticals to the University of Western Australia. The funding bodies had no role in the conduct of the research. Funding Information: BBY and RJM received funding support for the present manuscript from the Western Australian Health Translation Network and the Australian Government's Medical Research Future Fund, and via a philanthropic donation by Lawley Pharmaceuticals to the University of Western Australia. All other authors report no disclosures related to the present manuscript. A full list of disclosures unrelated to the present manuscript for all authors within the past 36 months is provided (Supplementary Material).

PY - 2022/1/3

Y1 - 2022/1/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85122155181&partnerID=8YFLogxK

U2 - 10.1002/alz.12529

DO - 10.1002/alz.12529

M3 - Article

AN - SCOPUS:85122155181

SN - 1552-5260

VL - 18

SP - 1907

EP - 1918

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 10

ER -

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

Abstract

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