Brain amyloid and cognition in Lewy body diseases§

Authors


  • Funding agencies: This work was supported by the Michael J. Fox Foundation for Parkinson's Research (to S.N.G. and J.H.G.), National Alzheimer's Coordinating Center Collaborative Project 5 U01 AG016976-11 (to S.N.G., K.A.J., and J.H.G.), the National Institute of Neurological Disorders and Stroke (to K.A.J.), the National Institute on Aging (to K.A.J.), the Alzheimer's Disease Association (to K.A.J.), and the Caja Madrid Foundation scholarship for postgraduate studies (to M.M.).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Many patients with PD develop PD with dementia (PDD), a syndrome that overlaps clinically and pathologically with dementia with Lewy bodies (DLB); PDD and DLB differ chiefly in the relative timing of dementia and parkinsonism. Brain amyloid deposition is an early feature of DLB and may account, in part, for its early dementia. We sought to confirm this hypothesis and also to determine whether amyloid accumulation contributes to cognitive impairment and dementia in the broad range of parkinsonian diseases. Twenty-nine cognitively healthy PD, 14 PD subjects with mild cognitive impairment (PD-MCI), 18 with DLB, 12 with PDD, and 85 healthy control subjects (HCS) underwent standardized neurologic and neuropsychological examinations and Pittsburgh compound B (PiB) imaging with PET. Apolipoprotein E (ApoE) genotypes were obtained in many patients. PiB retention was expressed as the distribution volume ratio using a cerebellar tissue reference. PiB retention was significantly higher in DLB than in any of the other diagnostic groups. PiB retention did not differ across PDD, PD-MCI, PD, and HCS. Amyloid burden increased with age and with the presence of the ApoE ε4 allele in all patient groups. Only in the DLB group was amyloid deposition associated with impaired cognition. DLB subjects have higher amyloid burden than subjects with PDD, PD-MCI, PD, or HCS; amyloid deposits are linked to cognitive impairment only in DLB. Early amyloid deposits in DLB relative to PDD may account for their difference in the timing of dementia and parkinsonism. © 2012 Movement Disorder Society

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