Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-25T05:12:44.813Z Has data issue: false hasContentIssue false

Depressive symptoms, antidepressant use, and future cognitive health in postmenopausal women: the Women's Health Initiative Memory Study

Published online by Cambridge University Press:  03 February 2012

Joseph S. Goveas*
Affiliation:
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Patricia E. Hogan
Affiliation:
Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Jane M. Kotchen
Affiliation:
Department of Population Health, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Jordan W. Smoller
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
Natalie L. Denburg
Affiliation:
Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa, USA
JoAnn E. Manson
Affiliation:
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
Aruna Tummala
Affiliation:
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
W. Jerry Mysiw
Affiliation:
Department of Physical Medicine and Rehabilitation, Ohio State University Medical Center, Columbus, Ohio, USA
Judith K. Ockene
Affiliation:
Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Nancy F. Woods
Affiliation:
Family and Child Nursing, University of Washington, Seattle, Washington, USA
Mark A. Espeland
Affiliation:
Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Sylvia Wassertheil-Smoller
Affiliation:
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York, USA
*
Correspondence should be addressed to: Joseph S. Goveas, MD, Assistant Professor, Department of Psychiatry and Behavioral Medicine Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. Phone: +414-955-8983; Fax: +414-955-6299. Email: [email protected].
Get access

Abstract

Background: Antidepressants are commonly prescribed medications in the elderly, but their relationship with incident mild cognitive impairment (MCI) and probable dementia is unknown.

Methods: The study cohort included 6,998 cognitively healthy, postmenopausal women, aged 65–79 years, who were enrolled in a hormone therapy clinical trial and had baseline depressive symptoms and antidepressant use history assessments at enrollment, and at least one postbaseline cognitive measurement. Participants were followed annually and the follow-up averaged 7.5 years for MCI and probable dementia outcomes. A central adjudication committee classified the presence of MCI and probable dementia based on extensive neuropsychiatric examination.

Results: Three hundred and eighty-three (5%) women were on antidepressants at baseline. Antidepressant use was associated with a 70% increased risk of MCI, after controlling for potential covariates including the degree of depressive symptom severity. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) were both associated with MCI (SSRIs: hazard ratios (HR), 1.78 [95% CI, 1.01–3.13]; TCAs: HR, 1.78 [95% CI, 0.99–3.21]). Depressed users (HR, 2.44 [95% CI, 1.24–4.80]), non-depressed users (HR, 1.79 [95% CI, 1.13–2.85]), and depressed non-users (HR, 1.62 [95% CI, 1.13–2.32]) had increased risk of incident MCI. Similarly, all three groups had increased risk of either MCI or dementia, relative to the control cohort.

Conclusions: Antidepressant use and different levels of depression severity were associated with subsequent cognitive impairment in a large cohort of postmenopausal women. Future research should examine the role of antidepressants in the depression–dementia relationship and determine if antidepressants can prevent incident MCI and dementia in individuals with late-life depression subtypes with different levels of severity.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aboukhatwa, M., Dosanjh, L. and Luo, Y. (2010). Antidepressants are a rational complementary therapy for the treatment of Alzheimer's disease. Molecular Neurodegenertion, 5, 10.CrossRefGoogle ScholarPubMed
Alexopoulos, G. S. (2005). Depression in the elderly. Lancet, 365, 19611970.CrossRefGoogle ScholarPubMed
Almeida, O. P., Alfonso, H., Hankey, G. J. and Flicker, L. (2010). Depression, antidepressant use and mortality in later life: the health in men study. PLoS One, 5, e11266.CrossRefGoogle ScholarPubMed
Bhalla, R. K. et al. (2009). Patterns of mild cognitive impairment after treatment of depression in the elderly. American Journal of Geriatric Psychiatry, 17, 308316.CrossRefGoogle ScholarPubMed
Borhani, N. O. et al. (1991). Systolic Hypertension in the Elderly Program (SHEP). Part 1: rationale and design. Hypertension, 17, II2II15.CrossRefGoogle ScholarPubMed
Butters, M. A. et al. (2008). Imaging Alzheimer pathology in late-life depression with PET and Pittsburgh Compound-B. Alzheimer Disease and Associated Disorders, 22, 261268.CrossRefGoogle ScholarPubMed
Coupland, C., Dhiman, P., Morriss, R., Arthur, A., Barton, G. and Hippisley-Cox, J. (2011). Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ, 343, d4551.CrossRefGoogle ScholarPubMed
Culang, M. E. et al. (2009). Change in cognitive functioning following acute antidepressant treatment in late-life depression. American Journal of Geriatric Psychiatry, 17, 881888.CrossRefGoogle ScholarPubMed
Goveas, J. S., Espeland, M. A., Woods, N. F., Wassertheil-Smoller, S. and Kotchen, J. M. (2011). Depressive symptoms and incidence of mild cognitive impairment and probable dementia in elderly women: the Women's Health Initiative Memory Study. Journal of the American Geriatric Society, 59, 5766.CrossRefGoogle ScholarPubMed
Haney, E. M., Warden, S. J. and Bliziotes, M. M. (2010). Effects of selective serotonin reuptake inhibitors on bone health in adults: time for recommendations about screening, prevention and management? Bone, 46, 1317.CrossRefGoogle Scholar
Hashioka, S., Mcgeer, P. L., Monji, A. and Kanba, S. (2009). Anti-inflammatory effects of antidepressants: possibilities for preventives against Alzheimer's disease. Central Nervous System Agents in Medicinal Chemistry, 9, 1219.CrossRefGoogle ScholarPubMed
Irie, F., Masaki, K. H., Petrovitch, H., Abbott, R. D., Ross, G. W., Taaffe, D. R. (2008). Apolipoprotein E epsilon4 allele genotype and the effect of depressive symptoms on the risk of dementia in men: the Honolulu-Asia Aging Study. Archives of General Psychiatry, 65, 906912.CrossRefGoogle ScholarPubMed
Knegtering, H., Eijck, M. and Huijsman, A. (1994). Effects of antidepressants on cognitive functioning of elderly patients. A review. Drugs and Aging, 5, 192199.CrossRefGoogle ScholarPubMed
Lee, J. S., Potter, G. G., Wagner, H. R., Welsh-Bohmer, K. A. and Steffens, D. C. (2007). Persistent mild cognitive impairment in geriatric depression. International Psychogeriatrics, 19, 125135.CrossRefGoogle ScholarPubMed
Mark, T. L., Joish, V. N., Hay, J. W., Sheehan, D. V., Johnston, S. S. and Cao, Z. (2011). Antidepressant use in geriatric populations: the burden of side effects and interactions and their impact on adherence and costs. American Journal of Geriatric Psychiatry, 19, 211221.CrossRefGoogle ScholarPubMed
Mossello, E., Boncinelli, M., Caleri, V., Cavallini, M. C., Palermo, E., Di Bari, M. (2008). Is antidepressant treatment associated with reduced cognitive decline in Alzheimer's disease? Dementia and Geriatric Cognitive Disorders, 25, 372379.CrossRefGoogle ScholarPubMed
Nelson, R. L. et al. (2007). Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice. Experimental Neurology, 205, 166176.CrossRefGoogle ScholarPubMed
Ownby, R. L., Crocco, E., Acevedo, A., John, V. and Loewenstein, D. (2006). Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Archives of General Psychiatry, 63, 530538.CrossRefGoogle ScholarPubMed
Rajji, T. K., Mulsant, B. H., Lotrich, F. E., Lokker, C. and Reynolds, C. F. III. (2008). Use of antidepressants in late-life depression. Drugs and Aging, 25, 841853.CrossRefGoogle ScholarPubMed
Ravaglia, G. et al. (2008). Prevalent depressive symptoms as a risk factor for conversion to mild cognitive impairment in an elderly Italian cohort. American Journal of Geriatric Psychiatry, 16, 834843.CrossRefGoogle Scholar
Reynolds, C. F. III et al. (2011). Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy. Archives of General Psychiatry, 68, 5160.CrossRefGoogle ScholarPubMed
Santarelli, L. et al. (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science, 301, 805809.CrossRefGoogle ScholarPubMed
Sapolsky, R. M. (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Archives of General Psychiatry, 57, 925935.CrossRefGoogle ScholarPubMed
Sheline, Y. I. et al. (2010). Support for the vascular depression hypothesis in late-life depression: results of a 2-site, prospective, antidepressant treatment trial. Archives of General Psychiatry, 67, 277285.CrossRefGoogle ScholarPubMed
Shumaker, S. A. et al. (1998). The Women's Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Controlled Clinical Trials, 19, 604621.CrossRefGoogle ScholarPubMed
Shumaker, S. A. et al. (2004). Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA, 291, 29472958.CrossRefGoogle ScholarPubMed
Smoller, J. W. et al. (2009). Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women's Health Initiative study. Archives of Internal Medicine, 169, 21282139.CrossRefGoogle ScholarPubMed
Steffens, D. C. et al. (2000). Hippocampal volume in geriatric depression. Biological Psychiatry, 48, 301309.CrossRefGoogle ScholarPubMed
Steffens, D. C. et al. (2004). Methodology and preliminary results from the neurocognitive outcomes of depression in the elderly study. Journal of Geriatric Psychiatry and Neurology, 17, 202211.CrossRefGoogle ScholarPubMed
Steffens, D. C. et al. (2006). Perspectives on depression, mild cognitive impairment, and cognitive decline. Archives of General Psychiatry, 63, 130138.CrossRefGoogle ScholarPubMed
Steffens, D. C., Chung, H., Krishnan, K. R., Longstreth, W. T. Jr., Carlson, M. and Burke, G. L. (2008). Antidepressant treatment and worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke, 39, 857862.CrossRefGoogle ScholarPubMed
Tuunainen, A., Langer, R. D., Klauber, M. R. and Kripke, D. F. (2001). Short version of the CES-D (Burnam screen) for depression in reference to the structured psychiatric interview. Psychiatry Research, 103, 261270.CrossRefGoogle Scholar
Weintraub, D. et al. (2010). Sertraline for the treatment of depression in Alzheimer disease: week-24 outcomes. American Journal of Geriatric Psychiatry, 18, 332340.CrossRefGoogle ScholarPubMed
Woolcott, J. C. et al. (2009). Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Archives of Internal Medicine, 169, 19521960.CrossRefGoogle ScholarPubMed
Wright, R. M. et al. (2009). Effect of central nervous system medication use on decline in cognition in community-dwelling older adults: findings from the Health, Aging And Body Composition Study. Journal of the American Geriatric Society, 57, 243250.CrossRefGoogle ScholarPubMed
Supplementary material: File

Goveas Supplementary Table

SUPPLEMENTAL TABLE. Scores on modified CERAD measures for MCI, Probable dementia, MCI/Probable dementia, Median (Min-Max).

Download Goveas Supplementary Table(File)
File 51.2 KB