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August 19, 2014; 83 (8) Article

Clinical-pathologic study of depressive symptoms and cognitive decline in old age

Robert S. Wilson, Ana W. Capuano, Patricia A. Boyle, George M. Hoganson, Loren P. Hizel, Raj C. Shah, Sukriti Nag, Julie A. Schneider, Steven E. Arnold, David A. Bennett
First published July 30, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000715
Robert S. Wilson
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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Ana W. Capuano
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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Patricia A. Boyle
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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George M. Hoganson
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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Loren P. Hizel
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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Raj C. Shah
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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Sukriti Nag
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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Julie A. Schneider
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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Steven E. Arnold
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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David A. Bennett
From the Rush Alzheimer's Disease Center (R.S.W., A.W.C., P.A.B., G.M.H., L.P.H., R.C.S., S.N., J.A.S., D.A.B.) and Departments of Behavioral Sciences (R.S.W., P.A.B.), Neurological Sciences (R.S.W., A.W.C., J.A.S., D.A.B.), Pathology (S.N., J.A.S.), and Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Departments of Psychiatry and Neurology (S.E.A.), University of Pennsylvania, Philadelphia.
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Citation
Clinical-pathologic study of depressive symptoms and cognitive decline in old age
Robert S. Wilson, Ana W. Capuano, Patricia A. Boyle, George M. Hoganson, Loren P. Hizel, Raj C. Shah, Sukriti Nag, Julie A. Schneider, Steven E. Arnold, David A. Bennett
Neurology Aug 2014, 83 (8) 702-709; DOI: 10.1212/WNL.0000000000000715

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Abstract

Objective: To clarify the relationship between depressive symptoms and the clinical and neuropathologic manifestations of dementia.

Methods: In a clinical-pathologic cohort study, 1,764 older persons without cognitive impairment at enrollment completed annual clinical evaluations for a mean of 7.8 years. The evaluations included assessment of depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) and cognitive function (battery of 17 performance tests). A total of 582 individuals died during follow-up and underwent a uniform neuropathologic examination to quantify β-amyloid plaques and tau tangle density in multiple brain regions and identify neocortical Lewy bodies, hippocampal sclerosis, and gross and microscopic cerebral infarcts.

Results: Level of depressive symptoms slightly increased during follow-up. Incident mild cognitive impairment (52.2%) was associated with higher level of depressive symptoms before the diagnosis but not with change in symptoms after the diagnosis; incident dementia (17.9%) was associated with higher symptom level before dementia onset and with more rapid decline in symptoms after dementia onset. None of the neuropathologic markers was related to level of depressive symptoms or change in symptoms over time. In a mixed-effects model adjusted for the neuropathologic markers, higher level of depressive symptoms averaged over evaluations was associated with more rapid global cognitive decline, accounting for 4.4% of the variability in decline not attributable to the neuropathologic markers. Depressive symptoms did not modify the association of the neuropathologic markers with cognitive decline.

Conclusion: In old age, depressive symptoms have an association with cognitive decline that is independent of the neuropathologic hallmarks of dementia.

GLOSSARY

MCI=
mild cognitive impairment

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received February 6, 2014.
  • Accepted in final form May 17, 2014.
  • © 2014 American Academy of Neurology
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Letters: Rapid online correspondence

  • Prevention of cognitive decline in old age by antidepressant treatment?
    • Hagen Kunte, Neurologist and Psychiatrist, Charit? - Universit?tsmedizin Berlinhagen.kunte@charite.de
    • Golo Kronenberg, Berlin, Germany; Rainer Hellweg, Berlin, Germany
    Submitted October 16, 2014
  • Re:Prevention of cognitive decline in old age by antidepressant treatment?
    • Robert S. Wilson, Professor, Rush University Medical Center, Chicago, ILrwilson@rush.edu
    Submitted October 16, 2014
  • Depressive symptoms and cognitive decline in aging: is sleep a possible modulator?
    • Andre C. Boin, Universidade Federal de Sao Pauloandre.c.boin@gmail.com
    • Camila Hirotsu, Sao Paulo, Brazil, Monica Levy Andersen, Sao Paulo, Brazil and Sergio Tufik, Sao Paulo, Brazil
    Submitted September 08, 2014
  • Re:Prevention of cognitive decline in old age by antidepressant treatment?
    • Donald R. Royall, Professor of Psychiatry, University of Texas Health Science Center at San Antonioroyall@uthscsa.edu
    Submitted August 26, 2014
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