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Imaging amyloid deposition in Lewy body diseases

From Massachusetts General Hospital (S.N.G., E.M., J.A.B., J.J.L., D.R.E., T.S., A.J.F., B.T.H., J.H.G., K.A.J.), Boston; Harvard Medical School (S.N.G., D.M.R., J.J.L., D.R.E., B.T.H., J.H.G., K.A.J.), Boston; Brigham and Women’s Hospital (D.M.R., K.A.J.), Boston; Massachusetts Institute of Technology (J.J.L.), Cambridge; and University of Pittsburgh (W.E.K., C.A.M.), PA.

Address correspondence and reprint requests to Dr. Keith A. Johnson, Division of Nuclear Medicine and Molecular Imaging, 55 Fruit St., Boston, MA 02114; Massachusetts General Hospital, White 427, Boston, MA 02114 kajohnson{at}partners.org

Background: Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD).

Objectives: To determine whether amyloid deposition, as assessed by PET imaging with the β-amyloid–binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features.

Methods: Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio.

Results: Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function.

Conclusions: Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that β-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.

GLOSSARY: AAL = Automated Anatomic Labeling; AD = Alzheimer disease; ADRC = Alzheimer’s Disease Research Center; AMNART = American version of the National Adult Reading Test; ANCOVA = analysis of covariance; BDS = Blessed Dementia Scale; CAA = cerebral amyloid angiopathy; CDR = Clinical Dementia Rating; CDR-SB = Clinical Dementia Rating Sum of Boxes; DLB = dementia with Lewy bodies; DVR = distribution volume ratio; FCSRT = Cued Selective Reminding Test; FRSRT = Free Selective Reminding Test; H&Y = Hoehn and Yahr; MGH = Massachusetts General Hospital; MMSE = Mini-Mental State Examination; NC = normal control; NFT = neurofibrillary tangle; NPIQ = Neuropsychiatric Inventory Questionnaire; NS = not significant; PD = Parkinson disease; PDD = Parkinson disease dementia; PiB = Pittsburgh Compound B; ROI = region of interest; SPM2 = Statistical Parametric Mapping; UKPDSBRC = UK Parkinson’s Disease Society Brain Bank Research Center; UPDRS = United Parkinson’s Disease Rating Scale; WAIS-R = Wechsler Adult Intelligence Scale–Revised.

Supplemental data at www.neurology.org

Supported by grants from the Alzheimer’s Disease Research Center (ADRC) and Harvard Neurodiscovery Center (S.N.G., K.A.J.), Udall PD Center (P50-NS38372; J.H.G.), ADRC (P50-AG05134; J.H.G., K.A.J.), R21-NS060310 (S.N.G., J.H.G., K.A.J.), the Alzheimer Association (IIRG-06-26331; K.A.J.), R01 AG018402 (W.E.K., C.A.M.), R37 AG025516 (W.E.K., C.A.M.), P50 AG05133 (W.E.K., C.A.M.), 3R01AG027435-02S1 (K.A.J.), and P01 AG025204 (W.E.K., C.A.M.).

Disclosure: W.K. and C.A.M.: GE Healthcare holds a license agreement with the University of Pittsburgh based on the PiB technology described in this article. W.K. and C.A.M. are coinventors of PiB and, as such, have a financial interest in this license agreement. GE Healthcare provided no grant support for this study and had no role in the design or interpretation of results or preparation of this article. S.N.G., D.M.R., E.M., J.A.B., J.J.L., D.R.E., T.S., A.J.F., B.T.H., J.H.G., and K.A.J. have no disclosures.

Received February 21, 2008. Accepted in final form June 12, 2008.

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