Brain amyloid and cognition in Lewy body diseases.
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.
Massachusetts General Hospital, 15 Parkman Street, Boston, MA 02114,USA.
Stephen N
SN
Gomperts
Joseph J
JJ
Locascio
Marta
M
Marquie
Andrea L
AL
Santarlasci
Dorene M
DM
Rentz
Jacqueline
J
Maye
Keith A
KA
Johnson
John H
JH
Growdon
D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism; D000978:Antiparkinson Agents / Q000627:therapeutic use; D053318:Apolipoprotein E3 / Q000235:genetics; D003071:Cognition; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D020961:Lewy Body Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*; D008297:Male; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000378:metabolism / Q000523:psychology; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000378:metabolism
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D000978:Antiparkinson Agents; D053318:Apolipoprotein E3; D013844:Thiazoles; D007980:Levodopa