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Presence of Cerebral Amyloid Modulates Phenotype & Pattern of Neurodegeneration in Early Parkinson's Disease

McMillan, C; Wolk, D
 
2015-04-22
AAN: Washington, DC
Download Presentation: McMillan-AAN-2015.pdf
 
Abstract:
OBJECTIVE: To characterize cognitive, motor, imaging, and genetic phenotypes of early Parkinson's disease (ePD) patients based on CSF evidence of cerebral amyloidosis.

BACKGROUND:A significant proportion of PD patients develop dementia, many with amyloid pathology consistent with Alzheimer?s disease at autopsy. The frequency of cerebral amyloid and its relationship with disease phenotype in early stages of PD remain unclear.

DESIGN/METHODS:We evaluated 369 drug-naïve ePD patients. Data were obtained from the Parkinson?s Progression Markers Initiative (PPMI) database. CSF amyloid-beta levels were transformed using a previously reported linear regression procedure. A cutoff of >198 pg/mL was used to define amyloid-negative (PD-) and amyloid-positive (PD+) subgroups. Grey matter (GM) density from MRI was measured using ANTs. We compared groups using linear regressions.

RESULTS:We observed that 16.5% of ePD were PD+ and 84.5% were PD-. PD+ were significantly older than PD- (p<0.001) and had higher frequency of APOE e4 alleles (p=0.01). PD+ had reduced cognitive performance relative to PD- on symbol-digit matching (p=0.001), verbal category fluency (p=0.002), and delayed recall (p=0.015) tests, while recognition memory, visuospatial function, and general cognitive measures did not differ. PD+ tended to have more disruption of activities of daily living (p=0.033) and a trend towards greater motor impairment on the UPDRS-III (p=0.06). Most of these results remained when controlling for age and APOE. Imaging analysis in a subset of individuals (PD+=43; PD-=241) revealed overlapping GM atrophy relative to healthy controls in medial temporal, frontal, and brainstem structures. Direct comparisons revealed predominant reduced bilateral ventromedial prefrontal and superior frontal GM for PD+ relative to PD-, and subcortical GM reductions for PD- relative to PD+.

CONCLUSIONS:Evidence of cerebral amyloid in ePD yields a unique cognitive, motor, imaging, and genetic profile that should be considered when screening patients for trials involving disease-modifying agents.