Endogenous Sex Hormones and Cognitive Function in Older Adults

Abstract

Estrogen and testosterone may influence cognition in older adults, but the relationship between sex hormones and cognitive function is complex. The aim of this systematic review is to examine the role of sex hormones in cognitive function among older adults. A comprehensive, electronic review of literature was performed. Inclusion criteria were original quantitative research, written in English, used human subjects with a mean age of ≥60 years, and published from January 1997 through May 2012. Findings were mixed, although potential patterns were identified. Estradiol levels were potentially associated with benefits to episodic memory, semantic memory, verbal memory, and verbal learning in females only. The association between testosterone and cognitive function was mixed in both genders. Mixed findings may have been influenced by methodological differences and future studies should include research designs with ample rigor, sufficiently powered samples, consistent cognitive measurements, and clear descriptions of handling and storage of biological specimens.

Keywords

sex hormones estrogen testosterone cognitive function older adults

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References

Aleman

de Vries

W. R.

Koppeschaar

H. P.

Osman-Dualeh

Verhaar

H. J.

Samson

M. M.

. . . de Haan

E. H.

(2001). Relationship between circulating levels of sex hormones and insulin-like growth factor-1 and fluid intelligence in older men. Experimental Aging Research, 27, 283-291.

Barrett-Connor

Goodman-Gruen

(1999). Cognitive function and endogenous sex hormones in older women. Journal of the American Geriatric Society, 47, 1289-1293.

Barrett-Connor

Goodman-Gruen

Patay

(1999). Endogenous sex hormones and cognitive function in older men. Journal of Clinical Endocrinology & Metabolism, 84, 3681-3685.

Bland

R. C.

Newman

S. C.

(2001). Mild dementia or cognitive impairment: The Modified Mini-Mental State Examination (3MS) as a screen for dementia. Canadian Journal of Psychiatry, 46, 506-510.

Brinton

R. D.

(2008). The healthy cell bias of estrogen action: Mitochondrial bioenergetics and neurological implications. Trends in Neurosciences, 31, 529-537. doi:10.1016/j.tins.2008.07.003

Burkitt

Widman

Saucier

D. M.

(2007). Evidence for the influence of testosterone in the performance of spatial navigation in a virtual water maze in women but not men. Hormones and Behavior, 51, 649-654. doi:10.1016/j.yhbeh.2007.03.007

Coker

Espeland

Rapp

Legault

Resnick

Hogan

. . . Shumaker

(2010). Postmenopausal hormone therapy and cognitive outcomes: The Women’s Health Initiative Memory Study (WHIMS). Journal of Steroid Biochemistry & Molecular Biology, 118, 304-310. doi:10.1016.j.jsbmb.2009.11.007

DeCarli

(2003). Mild cognitive impairment: Prevalence, prognosis, aetiology, and treatment. Lancet, 2, 15-21.

Drake

E. B.

Henderson

V. W.

Stanczyk

F. Z.

McCleary

C. A.

Brown

W. S.

Smith

C. A.

. . . Buckwalter

J. G.

(2000). Associations between circulating sex steroid hormones and cognition in normal elderly women. Neurology, 54, 599-602.

10.

Epel

E. S.

(2009). Psychological and metabolic stress: A recipe for accelerated cellular aging? Hormones, 8, 7-22.

11.

Folstein

M. F.

Folstein

S. E.

McHugh

P. R.

(1975). Mini-Mental State: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189-198.

12.

Fonda

S. J.

Bertrand

O’Donnell

Longcope

McKinlay

J. B.

(2005). Age, hormones, and cognitive functioning among middle-aged and elderly men: Cross-sectional evidence from the Massachusetts Male Aging Study. Journals of Gerontology: Medical Sciences, 60, 385-390.

13.

Gazdzinski

Kornak

Weiner

M. W.

Meyerhoff

D. J.

(2008). Body mass index and magnetic resonance markers of brain integrity in adults. Annals of Neurology, 63, 652-657. doi:10.1002/ana.21377

14.

Geerlings

M. I.

Strozyk

Masaki

Remaley

A. T.

Petrovich

Ross

G. W.

. . . Launer

L. J.

(2006). Endogenous sex hormones, cognitive decline, and future dementia in old men. Annals of Neurology, 60, 346-355. doi:10.1002/ana.20918

15.

Grady

Yaffee

Kristof

Lin

Richards

Barrett-Connor

(2002). Effect of postmenopausal hormone therapy on cognitive function: The heart and estrogen/progestin replacement study. American Journal of Medicine, 113, 543-548.

16.

Granger

D. A.

Johnson

S. B.

Szanton

S. L.

Out

Schumann

L. L.

(2012). Incorporating salivary biomarkers into nursing research: An overview and review of best practices. Biological Research for Nursing, 1, 1-10. doi:10.1177/1099800412443892

17.

Guyton

A. C.

Hall

J. E.

(2011). Textbook of medical physiology (12th ed.). Philadelphia, PA: Saunders.

18.

Hebert

L. E.

Scherr

P. A.

Bienas

J. L.

Bennett

D. A.

Evans

D. A.

(2003). Alzheimer disease in the US population: Prevalence estimates using the 2000 census. Archives of Neurology, 60, 1119-1122.

19.

Hogervorst

De Jager

Budge

Smith

D. A.

(2004). Serum levels of estradiol and testosterone and performance in different cognitive domains in healthy elderly men and women. Psychoneuroendocrinology, 29, 405-421. doi:10.1016/S0306-4530(03)00053-2

20.

Hogervorst

Matthews

F. E.

Brayne

(2010). Are optimal levels of testosterone associated with better cognitive function in healthy older women and men? Biochimica et Biophysica Acta, 1800, 1145-1152. doi:10.1016/j.bbagen.2009.12.009

21.

Holland

Bandelow

Hogervorst

(2011). Testosterone levels and cognition in elderly men: A review. Maturitas, 69, 322-337. doi:10.1016/j.maturitas.2011.05.012

22.

Hung

C. W.

Chen

Y. C.

Hsieh

W. L.

Chiou

S. H.

Kao

C. L.

(2010). Ageing and neurodegenerative diseases. Ageing Research Reviews, 9S, S36-S46. doi:10.1016/j.arr.2010.08.006

23.

Janowsky

J. S.

(2006). Thinking with your gonads: Testosterone and cognition. TRENDS in Cognitive Sciences, 10, 77-82. doi:10.1016/j.tics.2005.12.010

24.

Jiang

Mandrekar

Wilkinson

Cramer

Zelcer

Mann

. . . Landreth

G. E.

(1996). ApoE promotes the proteolytic degradation of Aβ. Neuron, 58, 681-693.

25.

Kaufman

J. M.

Vermeulen

(2005). The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocrine Reviews, 26, 833-876. doi:10.1210/er.2004-0013

26.

Kopp

Rosser

Wessel

(2008). Psychometric characteristics and practice effects of the Brunswick Trail Making Test. Perceptual & Motor Skills, 107, 707-733.

27.

LeBlanc

E. S.

Wang

P. Y.

Janowsky

J. S.

Neiss

M. B.

Fink

H. A.

Yaffee

. . . Orwoll

E. S.

(2010). Association between sex steroids and cognition in elderly men. Clinical Endocrinology, 72, 393-403. doi:10.1111/j.1365-2265.2009.03692.x

28.

Leranth

Petnehazy

MacLusky

N. J.

(2003). Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats. Journal of Neuroscience, 23, 1588-1592.

29.

Leranth

Prange-Kiel

Frick

K. M.

Horvath

T. L.

(2004). Low CA1 spine synaptic density is further reduced by castration in male non-human primates. Cerebral Cortex, 14, 503-510.

30.

Lessov-Schlaggar

C. N.

Reed

Swan

G. E.

Krasnow

R. E.

DeCarli

Marcus

Holloway

Wolf

Carmelli

(2005). Association of sex steroid hormones with brain morphology and cognition in elderly men. Neurology, 65, 1591-1596.

31.

Lewis

J. G.

(2006). Steroid analysis in saliva: A review. Clinical Biochemistry Reviews, 27, 139-146.

32.

Luboshitzky

Zabari

Shen-Orr

Herer

Lavie

(2001). Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men. Journal of Clinical Endocrinology & Metabolism, 86, 1134-1139. doi:10.1210/jc.86.3.1134

33.

MacLusky

N. J.

Bowlby

D. A.

Brown

T. J.

Peterson

R. E.

Hochberg

R. B.

(1997). Sex and the developing brain: Suppression of neuronal estrogen sensitivity by developmental androgen exposure. Neurochemical Research, 22, 1395-1414.

34.

Matousek

R. H.

Sherwin

B. B.

(2010). Sex steroid hormones and cognitive functioning in healthy, older men. Hormones and Behavior, 57, 352-359. doi:10.1016/j.yhbeh.2010.01.004

35.

McEwen

B. S.

Alves

S. E.

Bulloch

Weiland

N. G.

(1998). Clinically relevant basic science studies of gender differences and sex hormone effects. Psychopharmacology Bulletin, 34, 251-259.

36.

Moffat

S. D.

Zonderman

A. B.

Metter

E. J.

Blackman

M. R.

Harman

S. M.

Resnick

S. M.

(2002). Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. Journal of Clinical Endocrinology & Metabolism, 87, 5001-5007. doi:10.1210/jc.2002-020419

37.

Muller

Schupf

Manly

J. J.

Mayeux

Luchsinger

J. A.

(2010). Sex hormone binding globulin and incident Alzheimer’s disease in elderly men and women. Neurobiology of Aging, 31, 1758-1765.

38.

Muller

van den Beld

A. W.

Grobbee

D. E.

de Jong

F. H.

Lamberts

S. W.

(2009). Sex hormones and cognitive decline in elderly men. Psychoneuroendocrinology, 34, 27-31. doi:10.1016/j.psyneuen.2008.08.008

39.

National Center for Health Statistics. (2010). Older Americans 2010: Key indicators of well-being. Retrieved from www.agingstats.gov/agingstatsdotnet/Main_Site/Data/2010_Documents/Docs/OA_2010.pdf

40.

Perry

P. J.

Lund

B. C.

Arndt

Holman

Bever-Stille

K. A.

Paulsen

Demers

L. M.

(2001). Bioavailable testosterone as a correlate of cognition, psychological status, quality of life, and sexual function in aging: Implications for testosterone replacement therapy. Annals of Clinical Psychiatry, 13, 75-80.

41.

Phillips

G. B.

Yano

Stemmermann

G. N.

(1984). Decrease in serum estradiol values with storage. New England Journal of Medicine, 311, 1635.

42.

Rainbow

T. C.

Parsons

McEwen

B. S.

(1982). Sex-differences in rat brain oestrogen and progestin receptors. Nature, 300, 648-649.

43.

Ramsden

M. S.

Nyborg

A. C.

Murphy

M. P.

Chang

Stancyzk

F. Z.

Golde

T. E.

Pike

C. J.

(2003). Androgens modulate beta-amyloid levels in male rat brain. Journal of Neurochemistry, 87, 1052-1055.

44.

Ryan

Stanczyk

F. Z.

Dennerstein

Mack

W. J.

Clark

M. S.

Szoeke

Henderson

V. W.

(2011). Executive functions in recently postmenopausal women: Absence of strong association with serum gonadal steroids. Brain Research, 1379, 199-205. doi:10.1016/j.brainres.2010.10.093

45.

Ryan

Stanczyk

F. Z.

Dennerstein

Mack

W. J.

Clark

M. S.

Szoeke

. . . Henderson

V. W.

(2012). Hormone levels and cognitive function in postmenopausal midlife women. Neurobiology of Aging, 33, 617.e11-617.e22. doi:10.1016/j.neurobiolaging.2012.07.014

46.

Salimetrics

LLC.

(2012). Saliva collection and handling advice (3rd ed.). State College, PA: Author.

47.

Salthouse

(2011). Consequences of age-related cognitive declines. Annual Review of Psychology, 63, 5.1-5.6. doi:10.1146/annurev-psych-120710-100328

48.

Stern

(2009). Cognitive reserve. Neuropsychologia, 47, 2015-2028.

49.

Struble

L. M.

Sullivan

B. J.

(2011). Cognitive health in older adults. Nurse Practitioner, 36, 24-34.

50.

Teng

E. L.

Chui

H. C.

(1987). The Modified Mini-Mental State examination (3MS). Journal of Clinical Psychiatry, 48, 314-318.

51.

Thilers

P. P.

MacDonald

S. W.

Herlitz

(2006). The association between endogenous free testosterone and cognitive performance: A population-based study in 35 to 90 year-old men and women. Psychoneuroendocrinology, 31, 565-576. doi:10.1016/j.psyneuen.2005.12.005

52.

Van Strien

J. W.

Weber

R. F.

Burdoff

Bangma

(2009). Higher free testosterone level is associated with faster visual processing and more flanker interference in older men. Psychoneuroendocrinology, 64, 546-554. doi:10.1016/j.psyneuen.2008.10.020

53.

Vermeulen

Kaufman

Giagulli

(1996). Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. Journal of Clinical Endocrinology and Metabolism, 81, 1821-1826. doi:10.1210/jc.81.5.1821

54.

Wolf

O. T.

Kirschbaum

(2002). Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men. Hormones and Behavior, 41, 259-266. doi:10.1006.hbeh.2002.1770

55.

Yaffee

Barnes

Lindquist

Cauley

Simonsick

E. M.

Penninx

. . . Cummings

S. R.

(2007). Endogenous sex hormone levels and risk of cognitive decline in an older biracial cohort. Neurobiology of Aging, 28, 171-178. doi:10.1016/j.neurobiolaging.2006.10.004

56.

Yaffee

Grady

Pressman

Cummings

(1998). Serum estrogen levels, cognitive performance, and risk of cognitive decline in older community women. Journal of the American Geriatric Society, 46, 816-821.

57.

Yaffee

Lui

L. Y.

Grady

Cauley

Kramer

Cummings

S. R.

(2000). Cognitive decline in women in relation to non-protein-bound oestradiol concentrations. Lancet, 356, 708-712.

58.

Yaffee

Lui

L. Y.

Zmuda

Cauley

(2002). Sex hormones and cognitive function in older men. Journal of the American Geriatrics Society, 50, 707-712.

59.

Yeap

B. B.

Almeida

O. P.

Chubb

S. A.

Hankey

G. J.

Jamrozik

Flicker

(2008). Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The health in men study. Clinical Endocrinology, 68, 404-412. doi:10.1111/j.1365-2265.2007.03055.x

60.

Yonker

J. E.

Eriksson

Nilsson

L. G.

Herlitz

(2003). Sex differences in episodic memory: Minimal influence of estradiol. Brain and Cognition, 52, 231-238. doi:10.1016/S0278-2626(03)00074-5

61.

Zimmerman

M. E.

Lipton

R. B.

Santoro

McConnell

D. S.

Derby

C. A.

Katz

M. J.

Baigi

Saunders-Pullman

(2011). Endogenous estradiol is associated with verbal memory in nondemented older men. Brain and Cognition, 76, 158-165. doi:10.1016/j.bandc.2011.01.011