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Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease

Daniel Weintraub, Nicole Dietz, John E. Duda, David A. Wolk, Jimit Doshi, Sharon X. Xie, Christos Davatzikos, Christopher M. Clark, Andrew Siderowf
DOI: http://dx.doi.org/10.1093/brain/awr277 First published online: 22 November 2011

Summary

Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (β = −0.31, P = 0.007), including in non-demented patients (β = −0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal–temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline in Parkinson's disease.

  • Alzheimer's disease
  • dementia
  • mild cognitive impairment
  • Parkinson's disease
  • neurodegeneration
  • Abbreviations
    DRS
    Dementia Rating Scale
    RAVENS
    Regional Analysis of Volumes Examined in Normalized Space
    SPARE-AD
    Spatial Pattern of Atrophy for Recognition of Alzheimer's Disease; UPDRS = Unified Parkinson's Disease Rating Scale
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