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March 05, 2019; 92 (10) Article

Neural correlates of domain-specific cognitive decline

The ARIC-NCS Study

Andrea L.C. Schneider, Matthew L. Senjem, Aozhou Wu, Alden Gross, David S. Knopman, Jeffrey L. Gunter, Christopher G. Schwarz, Thomas H. Mosley, Rebecca F. Gottesman, A. Richey Sharrett, Clifford R. Jack
First published February 6, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007042
Andrea L.C. Schneider
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
MD, PhD
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Matthew L. Senjem
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
MS
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Aozhou Wu
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
MHS
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Alden Gross
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
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David S. Knopman
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
MD
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Jeffrey L. Gunter
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
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Christopher G. Schwarz
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
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Thomas H. Mosley
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
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Rebecca F. Gottesman
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
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A. Richey Sharrett
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
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Clifford R. Jack Jr
From the Department of Neurology (A.L.C.S., R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Radiology (M.L.S., J.L.G., C.G.S. C.R.J.), Information Technology (M.L.S., J.L.G.), and Neurology (D.S.K.), Mayo Clinic, Rochester, MN; Department of Epidemiology (A.W., A.G., R.F.G., A.R.S.), Johns Hopkins University Bloomberg School of Public Health; Johns Hopkins University Center on Aging and Health (A.G.), Baltimore, MD; and Department of Geriatrics (T.H.M.), University of Mississippi Medical Center, Jackson.
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Citation
Neural correlates of domain-specific cognitive decline
The ARIC-NCS Study
Andrea L.C. Schneider, Matthew L. Senjem, Aozhou Wu, Alden Gross, David S. Knopman, Jeffrey L. Gunter, Christopher G. Schwarz, Thomas H. Mosley, Rebecca F. Gottesman, A. Richey Sharrett, Clifford R. Jack
Neurology Mar 2019, 92 (10) e1051-e1063; DOI: 10.1212/WNL.0000000000007042

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Abstract

Objective To evaluate the association of cognitive declines in the domains of memory, language, and executive function with brain gray matter (GM) volume in old age.

Methods This was a prospective study of 1,846 participants in the Atherosclerosis Risk in Communities (ARIC) Study who underwent 3T brain MRI scans in 2011 to 2013. Participants were categorized by cognitive domain performance trajectory over the prior 20 years (cut point to define decline: 20th percentile). Associations between GM volume and cognitive declines were assessed at the voxel level with voxel-based morphometry and at the regional level with atlas-defined GM volumes of specific regions of interest.

Results Participants were an average age of 76 years; 60% were female; and 28% were black. Participants in the top 20th percentile for decline in the memory domain had smaller GM volumes in the medial temporal lobe (−3.3%, 95% confidence interval [CI] −4.6% to −2.1%), amygdala (−2.7%, 95% CI −4.1% to −1.3%), entorhinal cortex (−4.1%, 95% CI −6.0% to −2.2%), and hippocampus (−3.8%, 95% CI −5.2% to −2.4%) compared to participants who were in the lowest 80th percentile for decline in all domains. In contrast, among participants who were in the top 20th percentile for decline in the language or executive function domains, GM volumes were smaller in more brain regions.

Conclusions Declines in memory function were associated with brain volume loss in the medial temporal and hippocampal formations. Declines in language and executive function were associated with decreases in brain volumes across more noncontiguous brain regions.

Glossary

ARIC=
Atherosclerosis Risk in Communities;
CI=
confidence interval;
DSST=
Digit Symbol Substitution Test;
DWRT=
Delayed Word Recall Test;
GM=
gray matter;
MCALT=
Mayo Clinic Adult Lifespan Template;
MMSE=
Mini-Mental State Examination; WFT = Word Fluency Test

Footnotes

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

  • Received July 20, 2018.
  • Accepted in final form October 29, 2018.
  • © 2019 American Academy of Neurology
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