RT Journal Article
SR Electronic
T1 Presence of cerebral amyloid modulates phenotype and pattern of neurodegeneration in early Parkinson's disease
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 1112
OP 1122
DO 10.1136/jnnp-2015-312690
VO 87
IS 10
A1 Corey T McMillan
A1 David A Wolk
YR 2016
UL http://jnnp.bmj.com/content/87/10/1112.abstract
AB Objective To evaluate the frequency of cerebral amyloid in early Parkinson's disease (ePD) and provide a multimodal assessment of the influence of cerebral amyloid on disease phenotype.Methods We performed a multicentre cohort study of the Parkinson's Progression Markers Initiative (PPMI), including 369 drug-naïve patients with ePD and 174 healthy controls (HC). Cerebrospinal fluid (CSF) amyloid-β levels were transformed using the linear regression procedure. A cut-off of >198 pg/mL was used to define amyloid-negative (PD−) and amyloid-positive (PD+) subgroups. Grey matter (GM) density and hippocampal volume from the MRI was measured using Advanced Normalisation Tools (ANTs). We compared demographic, genetic, CSF, behavioural, functional and imaging modalities across ePD− and ePD+ groups.Results We observed that 16.5% of ePD have CSF evidence of amyloidosis. PD+ was significantly older than PD−, had a higher frequency of APOE e4 alleles and all CSF measures (total-tau, phosphorylated-tau and α-synuclein) were reduced. PD+ had reduced cognitive performance relative to PD− on Symbol–Digit Matching, Verbal Category Fluency and Delayed Recall tests. Imaging analysis in a subset of individuals (PD+ =43; PD− =241) revealed overlapping GM atrophy relative to HC in medial temporal, frontal and brainstem structures. Direct comparisons revealed PD+ GM reductions predominantly located in the frontal cortex while PD− had GM reductions in subcortical structures. These observations remain when controlling for age and APOE e4 allele status.Conclusions Cerebral amyloid in ePD yields a unique phenotype across all measured modalities that is consistent with a synergistic interaction between α-synuclein and amyloid pathology. Amyloid status should be considered when screening these individuals for trials involving disease-modifying agents.