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January 01, 2013; 80 (1) Article

Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia

Stephen N. Gomperts, Joseph J. Locascio, Dorene Rentz, Andrea Santarlasci, Marta Marquie, Keith A. Johnson, John H. Growdon
First published December 12, 2012, DOI: https://doi.org/10.1212/WNL.0b013e31827b1a07
Stephen N. Gomperts
From the Departments of Neurology (S.N.G., J.J.L., D.R., A.S., M.M., K.A.J., J.H.G.) and Radiology (K.A.J.), Massachusetts General Hospital, Boston; and Autonomous University of Barcelona–Medicine Doctoral Studies (M.M.), Barcelona, Spain.
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Joseph J. Locascio
From the Departments of Neurology (S.N.G., J.J.L., D.R., A.S., M.M., K.A.J., J.H.G.) and Radiology (K.A.J.), Massachusetts General Hospital, Boston; and Autonomous University of Barcelona–Medicine Doctoral Studies (M.M.), Barcelona, Spain.
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Dorene Rentz
From the Departments of Neurology (S.N.G., J.J.L., D.R., A.S., M.M., K.A.J., J.H.G.) and Radiology (K.A.J.), Massachusetts General Hospital, Boston; and Autonomous University of Barcelona–Medicine Doctoral Studies (M.M.), Barcelona, Spain.
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Andrea Santarlasci
From the Departments of Neurology (S.N.G., J.J.L., D.R., A.S., M.M., K.A.J., J.H.G.) and Radiology (K.A.J.), Massachusetts General Hospital, Boston; and Autonomous University of Barcelona–Medicine Doctoral Studies (M.M.), Barcelona, Spain.
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Marta Marquie
From the Departments of Neurology (S.N.G., J.J.L., D.R., A.S., M.M., K.A.J., J.H.G.) and Radiology (K.A.J.), Massachusetts General Hospital, Boston; and Autonomous University of Barcelona–Medicine Doctoral Studies (M.M.), Barcelona, Spain.
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Keith A. Johnson
From the Departments of Neurology (S.N.G., J.J.L., D.R., A.S., M.M., K.A.J., J.H.G.) and Radiology (K.A.J.), Massachusetts General Hospital, Boston; and Autonomous University of Barcelona–Medicine Doctoral Studies (M.M.), Barcelona, Spain.
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John H. Growdon
From the Departments of Neurology (S.N.G., J.J.L., D.R., A.S., M.M., K.A.J., J.H.G.) and Radiology (K.A.J.), Massachusetts General Hospital, Boston; and Autonomous University of Barcelona–Medicine Doctoral Studies (M.M.), Barcelona, Spain.
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Citation
Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia
Stephen N. Gomperts, Joseph J. Locascio, Dorene Rentz, Andrea Santarlasci, Marta Marquie, Keith A. Johnson, John H. Growdon
Neurology Jan 2013, 80 (1) 85-91; DOI: 10.1212/WNL.0b013e31827b1a07

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ABSTRACT

Objective: To determine whether amyloid burden, as indexed by Pittsburgh compound B (PiB) retention, identifies patients with Parkinson disease with mild cognitive impairment (PD-MCI) compared to those with normal cognition (PD-nl). A related aim is to determine whether amyloid burden predicts cognitive decline in a cohort of subjects with PD without dementia.

Methods: In this prospective cohort study, we examined 46 subjects with PD without dementia, of whom 35 had normal cognition and 11 met criteria for PD-MCI at study baseline. All subjects underwent standardized neurologic and neuropsychological examinations and PiB PET at baseline, and clinical examinations were conducted annually for up to 5 years.

Results: At baseline, precuneus PiB retention did not distinguish PD-MCI from PD-nl. Subjects with PD-MCI declined more rapidly than PD-nl subjects on cognitive tests of memory, executive function, and activation retrieval. Of the 35 PD-nl subjects, 8 progressed to PD-MCI and 1 to dementia; of the 11 PD-MCI subjects, 5 converted to dementia. Both higher PiB retention and a diagnosis of PD-MCI predicted a greater hazard of conversion to a more severe diagnosis. Baseline PiB retention predicted worsening in executive function over time. The APOE ε4 allele also related to worsening in executive function, as well as visuospatial function, activation retrieval, and performance on the Mini-Mental State Examination. In contrast to its relation to cognitive decline, PiB retention did not affect progression of motor impairment.

Conclusions: At baseline measurements, amyloid burden does not distinguish between cognitively impaired and unimpaired subjects with PD without dementia, but our data suggest that amyloid contributes to cognitive, but not motor, decline over time.

GLOSSARY

AD=
Alzheimer disease;
CDR=
Clinical Dementia Rating;
CDR-SB=
Clinical Dementia Rating sum of boxes;
CI=
confidence interval;
DVR=
distribution volume ratio;
H&Y=
Hoehn & Yahr;
MCI=
mild cognitive impairment;
MMSE=
Mini-Mental State Examination;
NP=
neuropsychological;
PD=
Parkinson disease;
PD-MCI=
Parkinson disease with mild cognitive impairment;
PD-nl=
Parkinson disease with normal cognition;
PDD=
Parkinson disease dementia;
PiB=
Pittsburgh compound B;
UPDRS=
Unified Parkinson’s Disease Rating Scale;
WAIS-R=
Wechsler Adult Intelligence Scale–Revised;
WMS-R=
Wechsler Memory 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 March 20, 2012.
  • Accepted August 13, 2012.
  • © 2012 American Academy of Neurology
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