Depressive symptoms in mild cognitive impairment predict greater atrophy in alzheimer's disease-related regions

Grace J. Lee; Po H. Lu; Xue Hua; Suh Lee; Stephanie Wu; Ken Nguyen; Edmond Teng; Alex D. Leow; Clifford R. Jack; Arthur W. Toga; Michael W. Weiner; George Bartzokis; Paul M. Thompson

doi:10.1016/j.biopsych.2011.12.024

Depressive symptoms in mild cognitive impairment predict greater atrophy in alzheimer's disease-related regions

Grace J. Lee, Po H. Lu, Xue Hua, Suh Lee, Stephanie Wu, Ken Nguyen, Edmond Teng, Alex D. Leow, Clifford R. Jack, Arthur W. Toga, Michael W. Weiner, George Bartzokis, Paul M. Thompson

Research output: Contribution to journal › Article › peer-review

139 Scopus citations

Abstract

Background: Depression has been associated with higher conversion rates from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and may be a marker of prodromal AD that can be used to identify individuals with MCI who are most likely to progress to AD. Thus, we examined the neuroanatomical changes associated with depressive symptoms in MCI. Methods: Two-hundred forty-three MCI subjects from the Alzheimer's Disease Neuroimaging Initiative who had brain magnetic resonance imaging scans at baseline and 2-year follow-up were classified into depressed (n = 44), nondepressed with other neuropsychiatric symptoms (n = 93), and no-symptom (NOSYMP; n = 106) groups based on the Neuropsychiatric Inventory Questionnaire. Tensor-based morphometry was used to create individual three-dimensional maps of 2-year brain changes that were compared between groups. Results: Depressed subjects had more frontal (p =.024), parietal (p =.030), and temporal (p =.038) white matter atrophy than NOSYMP subjects. Those whose depressive symptoms persisted over 2 years also had higher conversion to AD and more decline on measures of global cognition, language, and executive functioning compared with stable NOSYMP subjects. Nondepressed with other neuropsychiatric symptoms and NOSYMP groups exhibited no differences in rates of atrophy. Conclusions: Depressive symptoms were associated with greater atrophy in AD-affected regions, increased cognitive decline, and higher rates of conversion to AD. Depression in individuals with MCI may be associated with underlying neuropathological changes, including prodromal AD, and may be a potentially useful clinical marker in identifying MCI patients who are most likely to progress to AD.

Original language	English
Pages (from-to)	814-821
Number of pages	8
Journal	Biological Psychiatry
Volume	71
Issue number	9
DOIs	https://doi.org/10.1016/j.biopsych.2011.12.024
State	Published - 1 May 2012
Externally published	Yes

Keywords

Alzheimer's disease
depression
mild cognitive impairment
neuropsychiatric symptoms
tensor-based morphometry
white matter

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10.1016/j.biopsych.2011.12.024

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@article{aae6f3bbd17c40959de4c527cbc70fdd,

title = "Depressive symptoms in mild cognitive impairment predict greater atrophy in alzheimer's disease-related regions",

abstract = "Background: Depression has been associated with higher conversion rates from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and may be a marker of prodromal AD that can be used to identify individuals with MCI who are most likely to progress to AD. Thus, we examined the neuroanatomical changes associated with depressive symptoms in MCI. Methods: Two-hundred forty-three MCI subjects from the Alzheimer's Disease Neuroimaging Initiative who had brain magnetic resonance imaging scans at baseline and 2-year follow-up were classified into depressed (n = 44), nondepressed with other neuropsychiatric symptoms (n = 93), and no-symptom (NOSYMP; n = 106) groups based on the Neuropsychiatric Inventory Questionnaire. Tensor-based morphometry was used to create individual three-dimensional maps of 2-year brain changes that were compared between groups. Results: Depressed subjects had more frontal (p =.024), parietal (p =.030), and temporal (p =.038) white matter atrophy than NOSYMP subjects. Those whose depressive symptoms persisted over 2 years also had higher conversion to AD and more decline on measures of global cognition, language, and executive functioning compared with stable NOSYMP subjects. Nondepressed with other neuropsychiatric symptoms and NOSYMP groups exhibited no differences in rates of atrophy. Conclusions: Depressive symptoms were associated with greater atrophy in AD-affected regions, increased cognitive decline, and higher rates of conversion to AD. Depression in individuals with MCI may be associated with underlying neuropathological changes, including prodromal AD, and may be a potentially useful clinical marker in identifying MCI patients who are most likely to progress to AD.",

keywords = "Alzheimer's disease, depression, mild cognitive impairment, neuropsychiatric symptoms, tensor-based morphometry, white matter",

author = "Lee, {Grace J.} and Lu, {Po H.} and Xue Hua and Suh Lee and Stephanie Wu and Ken Nguyen and Edmond Teng and Leow, {Alex D.} and Jack, {Clifford R.} and Toga, {Arthur W.} and Weiner, {Michael W.} and George Bartzokis and Thompson, {Paul M.}",

note = "Funding Information: Dr. Weiner serves on scientific advisory boards for Bayer Schering Pharma; Eli Lilly and Company; CoMentis, Inc.; Neurochem Inc; Eisai Inc.; Avid Radiopharmaceuticals Inc.; Aegis Therapies; Genentech, Inc.; Allergan, Inc.; Lippincott Williams & Wilkins; Bristol-Myers Squibb; Forest Laboratories, Inc.; Pfizer Inc; McKinsey & Company; Mitsubishi Tanabe Pharma Corporation; and Novartis; has received funding for travel from Nestl{\'e} and Kenes International and to attend conferences not funded by industry; serves on the editorial board of Alzheimer's & Dementia; has received honoraria from the Rotman Research Institute and BOLT International; serves as a consultant for Elan Corporation; receives research support from Merck & Co. and Radiopharmaceuticals Inc.; and holds stock in Synarc and Elan Corporation. Funding Information: Dr. Toga received a speaker honorarium from St. Jude Children's Hospital; serves in an editorial capacity for NeuroImage, InSight, The Cerebellum, Neuroimaging, Neuroinformatics, Anatomy & Embryology, Current Medical Imaging Reviews, Biology Image Library, Biomedical Computation Review, Brain Structure and Function, and Journal of Neural Regeneration Research; has served on scientific and/or external advisory boards for Wellcome Trust, Allen Institute for Brain Science, University of Texas at Austin, Oklahoma IDeA Network for Biomedical Research Excellence, Takeda Global Research & Development Center, and the University of Pittsburgh; and has received/receives research support from an Academic Excellence Grant– SUN Microsystems and from High-Q Foundation and the National Multiple Sclerosis Society . ",

year = "2012",

month = may,

day = "1",

doi = "10.1016/j.biopsych.2011.12.024",

language = "English",

volume = "71",

pages = "814--821",

journal = "Biological Psychiatry",

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TY - JOUR

T1 - Depressive symptoms in mild cognitive impairment predict greater atrophy in alzheimer's disease-related regions

AU - Lee, Grace J.

AU - Lu, Po H.

AU - Hua, Xue

AU - Lee, Suh

AU - Wu, Stephanie

AU - Nguyen, Ken

AU - Teng, Edmond

AU - Leow, Alex D.

AU - Jack, Clifford R.

AU - Toga, Arthur W.

AU - Weiner, Michael W.

AU - Bartzokis, George

AU - Thompson, Paul M.

N1 - Funding Information: Dr. Weiner serves on scientific advisory boards for Bayer Schering Pharma; Eli Lilly and Company; CoMentis, Inc.; Neurochem Inc; Eisai Inc.; Avid Radiopharmaceuticals Inc.; Aegis Therapies; Genentech, Inc.; Allergan, Inc.; Lippincott Williams & Wilkins; Bristol-Myers Squibb; Forest Laboratories, Inc.; Pfizer Inc; McKinsey & Company; Mitsubishi Tanabe Pharma Corporation; and Novartis; has received funding for travel from Nestlé and Kenes International and to attend conferences not funded by industry; serves on the editorial board of Alzheimer's & Dementia; has received honoraria from the Rotman Research Institute and BOLT International; serves as a consultant for Elan Corporation; receives research support from Merck & Co. and Radiopharmaceuticals Inc.; and holds stock in Synarc and Elan Corporation. Funding Information: Dr. Toga received a speaker honorarium from St. Jude Children's Hospital; serves in an editorial capacity for NeuroImage, InSight, The Cerebellum, Neuroimaging, Neuroinformatics, Anatomy & Embryology, Current Medical Imaging Reviews, Biology Image Library, Biomedical Computation Review, Brain Structure and Function, and Journal of Neural Regeneration Research; has served on scientific and/or external advisory boards for Wellcome Trust, Allen Institute for Brain Science, University of Texas at Austin, Oklahoma IDeA Network for Biomedical Research Excellence, Takeda Global Research & Development Center, and the University of Pittsburgh; and has received/receives research support from an Academic Excellence Grant– SUN Microsystems and from High-Q Foundation and the National Multiple Sclerosis Society .

PY - 2012/5/1

Y1 - 2012/5/1

N2 - Background: Depression has been associated with higher conversion rates from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and may be a marker of prodromal AD that can be used to identify individuals with MCI who are most likely to progress to AD. Thus, we examined the neuroanatomical changes associated with depressive symptoms in MCI. Methods: Two-hundred forty-three MCI subjects from the Alzheimer's Disease Neuroimaging Initiative who had brain magnetic resonance imaging scans at baseline and 2-year follow-up were classified into depressed (n = 44), nondepressed with other neuropsychiatric symptoms (n = 93), and no-symptom (NOSYMP; n = 106) groups based on the Neuropsychiatric Inventory Questionnaire. Tensor-based morphometry was used to create individual three-dimensional maps of 2-year brain changes that were compared between groups. Results: Depressed subjects had more frontal (p =.024), parietal (p =.030), and temporal (p =.038) white matter atrophy than NOSYMP subjects. Those whose depressive symptoms persisted over 2 years also had higher conversion to AD and more decline on measures of global cognition, language, and executive functioning compared with stable NOSYMP subjects. Nondepressed with other neuropsychiatric symptoms and NOSYMP groups exhibited no differences in rates of atrophy. Conclusions: Depressive symptoms were associated with greater atrophy in AD-affected regions, increased cognitive decline, and higher rates of conversion to AD. Depression in individuals with MCI may be associated with underlying neuropathological changes, including prodromal AD, and may be a potentially useful clinical marker in identifying MCI patients who are most likely to progress to AD.

AB - Background: Depression has been associated with higher conversion rates from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and may be a marker of prodromal AD that can be used to identify individuals with MCI who are most likely to progress to AD. Thus, we examined the neuroanatomical changes associated with depressive symptoms in MCI. Methods: Two-hundred forty-three MCI subjects from the Alzheimer's Disease Neuroimaging Initiative who had brain magnetic resonance imaging scans at baseline and 2-year follow-up were classified into depressed (n = 44), nondepressed with other neuropsychiatric symptoms (n = 93), and no-symptom (NOSYMP; n = 106) groups based on the Neuropsychiatric Inventory Questionnaire. Tensor-based morphometry was used to create individual three-dimensional maps of 2-year brain changes that were compared between groups. Results: Depressed subjects had more frontal (p =.024), parietal (p =.030), and temporal (p =.038) white matter atrophy than NOSYMP subjects. Those whose depressive symptoms persisted over 2 years also had higher conversion to AD and more decline on measures of global cognition, language, and executive functioning compared with stable NOSYMP subjects. Nondepressed with other neuropsychiatric symptoms and NOSYMP groups exhibited no differences in rates of atrophy. Conclusions: Depressive symptoms were associated with greater atrophy in AD-affected regions, increased cognitive decline, and higher rates of conversion to AD. Depression in individuals with MCI may be associated with underlying neuropathological changes, including prodromal AD, and may be a potentially useful clinical marker in identifying MCI patients who are most likely to progress to AD.

KW - Alzheimer's disease

KW - depression

KW - mild cognitive impairment

KW - neuropsychiatric symptoms

KW - tensor-based morphometry

KW - white matter

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U2 - 10.1016/j.biopsych.2011.12.024

DO - 10.1016/j.biopsych.2011.12.024

M3 - Article

C2 - 22322105

AN - SCOPUS:84862776747

SN - 0006-3223

VL - 71

SP - 814

EP - 821

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 9

ER -

Depressive symptoms in mild cognitive impairment predict greater atrophy in alzheimer's disease-related regions

Abstract

Keywords

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