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April 09, 2013; 80 (15) Article

Cognitive trajectories associated with β-amyloid deposition in the oldest-old without dementia

Beth E. Snitz, Lisa A. Weissfeld, Oscar L. Lopez, Lewis H. Kuller, Judith Saxton, Dilrukshika M. Singhabahu, William E. Klunk, Chester A. Mathis, Julie C. Price, Diane G. Ives, Ann D. Cohen, Eric McDade, Steven T. DeKosky
First published March 20, 2013, DOI: https://doi.org/10.1212/WNL.0b013e31828c2fc8
Beth E. Snitz
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Lisa A. Weissfeld
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Oscar L. Lopez
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Lewis H. Kuller
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Judith Saxton
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Dilrukshika M. Singhabahu
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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William E. Klunk
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Chester A. Mathis
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Julie C. Price
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Diane G. Ives
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Ann D. Cohen
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Eric McDade
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Steven T. DeKosky
From the Departments of Neurology (B.E.S., O.L.L., J.S., E.M.), Biostatistics (L.A.W., D.M.S.), Epidemiology (L.H.K., D.G.I.), Psychiatry (W.E.K., A.D.C.), and Radiology (C.A.M., J.C.P.), University of Pittsburgh, Pittsburgh, PA; and School of Medicine (S.T.D.), University of Virginia, Charlottesville.
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Citation
Cognitive trajectories associated with β-amyloid deposition in the oldest-old without dementia
Beth E. Snitz, Lisa A. Weissfeld, Oscar L. Lopez, Lewis H. Kuller, Judith Saxton, Dilrukshika M. Singhabahu, William E. Klunk, Chester A. Mathis, Julie C. Price, Diane G. Ives, Ann D. Cohen, Eric McDade, Steven T. DeKosky
Neurology Apr 2013, 80 (15) 1378-1384; DOI: 10.1212/WNL.0b013e31828c2fc8

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Abstract

Objective: To determine whether a high prevalence (55%) of Aβ deposition in a cohort of individuals remaining dementia-free into their 9th and 10th decades is associated with cognitive decline prior to imaging.

Methods: A total of 194 participants (mean age 85.5 years, range 82–95) who completed the Ginkgo Evaluation of Memory Study (GEMS) and remained dementia-free subsequently completed Pittsburgh compound B–PET imaging. We examined cross-sectional associations between Aβ status and performance on a broad neuropsychological test battery completed at GEMS entry 7–9 years prior to neuroimaging. We also longitudinally examined cognition over annual evaluations using linear mixed models.

Results: At GEMS screening (2000–2002), participants who were Aβ-positive in 2009 had lower performance on the Stroop test (p < 0.01) and Raven's Progressive Matrices (p = 0.05), with trend level difference for Block Design (p = 0.07). Longitudinal analyses showed significant slope differences for immediate and delayed recall of the Rey-Osterrieth figure, semantic fluency, and Trail-Making Test parts A and B, indicating greater performance decline prior to neuroimaging for Aβ-positive relative to Aβ-negative participants (ps < 0.05).

Conclusions: Highly prevalent Aβ deposition in oldest-older adults is associated with cognitive decline in visual memory, semantic fluency, and psychomotor speed beginning 7–9 years prior to neuroimaging. Mean differences in nonmemory domains, primarily executive functions, between Aβ-status groups may be detectable 7–9 years before neuroimaging.

GLOSSARY

AD=
Alzheimer disease;
BNT=
Boston Naming Test;
CDR=
Clinical Dementia Rating;
CES-D=
Center for Epidemiologic Studies Depression scale;
CI=
confidence interval;
CVLT=
California Verbal Learning Test;
GEMS=
Ginkgo Evaluation of Memory Study;
MCI=
mild cognitive impairment;
PiB=
Pittsburgh compound B;
R-O=
Rey-Osterrieth;
ROI=
regions of interest;
SUV=
standardized uptake value;
SUVR=
SUV ratio;
WAIS-R=
Wechsler Adult Intelligence Scale–Revised

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 www.neurology.org

  • Received October 18, 2012.
  • Accepted in final form January 10, 2013.
  • © 2013 American Academy of Neurology
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