Memory, executive, and multidomain subtle cognitive impairment: clinical and biomarker findings

Jon B Toledo; Maria Bjerke; Kewei Chen; Martin Rozycki; Clifford R Jack Jr; Michael W Weiner; Steven E Arnold; Eric M Reiman; Christos Davatzikos; Leslie M Shaw; John Q Trojanowski; Alzheimer's Disease Neuroimaging Initiative

doi:10.1212/WNL.0000000000001738

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Memory, executive, and multidomain subtle cognitive impairment: clinical and biomarker findings

Journal article

Open access

Peer reviewed

Memory, executive, and multidomain subtle cognitive impairment: clinical and biomarker findings

Jon B Toledo, Maria Bjerke, Kewei Chen, Martin Rozycki, Clifford R Jack Jr, Michael W Weiner, Steven E Arnold, Eric M Reiman, Christos Davatzikos, Leslie M Shaw, …

Neurology, Vol.85(2), pp.144-153

07/14/2015

DOI: 10.1212/WNL.0000000000001738

PMCID: PMC4515043

PMID: 26085606

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Abstract

We studied the biomarker signatures and prognoses of 3 different subtle cognitive impairment (SCI) groups (executive, memory, and multidomain) as well as the subjective memory complaints (SMC) group. We studied 522 healthy controls in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cutoffs for executive, memory, and multidomain SCI were defined using participants who remained cognitively normal (CN) for 7 years. CSF Alzheimer disease (AD) biomarkers, composite and region-of-interest (ROI) MRI, and fluorodeoxyglucose-PET measures were compared in these participants. Using a stringent cutoff (fifth percentile), 27.6% of the ADNI participants were classified as SCI. Most single ROI or global-based measures were not sensitive to detect differences between groups. Only MRI-SPARE-AD (Spatial Pattern of Abnormalities for Recognition of Early AD), a quantitative MRI pattern-based global index, showed differences between all groups, excluding the executive SCI group. Atrophy patterns differed in memory SCI and SMC. The CN and the SMC groups presented a similar distribution of preclinical dementia stages. Fifty percent of the participants with executive, memory, and multidomain SCI progressed to mild cognitive impairment or dementia at 7, 5, and 2 years, respectively. Our results indicate that (1) the different SCI categories have different clinical prognoses and biomarker signatures, (2) longitudinally followed CN subjects are needed to establish clinical cutoffs, (3) subjects with SMC show a frontal pattern of brain atrophy, and (4) pattern-based analyses outperform commonly used single ROI-based neuroimaging biomarkers and are needed to detect initial stages of cognitive impairment.

Magnetic Resonance Imaging

Humans

Cognition Disorders - pathology

Male

Positron-Emission Tomography

Cognitive Dysfunction - pathology

Disease Progression

Alzheimer Disease - pathology

Multimodal Imaging

Aged, 80 and over

Brain - pathology

Female

Aged

Biomarkers - cerebrospinal fluid

Executive Function

Memory Disorders - pathology

Details

Title: Subtitle: Memory, executive, and multidomain subtle cognitive impairment: clinical and biomarker findings
Creators: Jon B Toledo - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Maria Bjerke - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Kewei Chen - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Martin Rozycki - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Clifford R Jack Jr - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Michael W Weiner - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Steven E Arnold - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Eric M Reiman - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Christos Davatzikos - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
Leslie M Shaw - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco
John Q Trojanowski - From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco. trojanow@mail.med.upenn.edu
Alzheimer's Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Neurology, Vol.85(2), pp.144-153
DOI: 10.1212/WNL.0000000000001738
PMID: 26085606
PMCID: PMC4515043
NLM abbreviation: Neurology
ISSN: 0028-3878
eISSN: 1526-632X
Publisher: United States
Grant note: P30 AG062421 / NIA NIH HHS R01AG043392 / NIA NIH HHS P01 AG032953 / NIA NIH HHS U01-AG06786 / NIA NIH HHS P30 AG010124 / NIA NIH HHS U01DK057135 / NIDDK NIH HHS P30 AG013846 / NIA NIH HHS P01 AG017586 / NIA NIH HHS U01 AG024904 / NIA NIH HHS P30AG10124 / NIA NIH HHS P50 AG005134 / NIA NIH HHS R01DA025201 / NIDA NIH HHS R01AG039478 / NIA NIH HHS R01 AG37551 / NIA NIH HHS P50 NS053488 / NINDS NIH HHS U01-AG024904 / NIA NIH HHS R01 AG041851 / NIA NIH HHS R01-AG011378 / NIA NIH HHS U01AG024904 / NIA NIH HHS U01-HL096917 / NHLBI NIH HHS
Language: English
Date published: 07/14/2015
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051787002771

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