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Cerebrovascular disease pathology and parkinsonian signs in old age.

ABSTRACT: Mild motor symptoms including parkinsonian signs are common in old age, but their underlying neuropathology is unclear. We tested the hypothesis that cerebrovascular pathologies are related to parkinsonian signs.We studied brain autopsies from 418 deceased participants from the Religious Order Study, who underwent evaluation of parkinsonian signs with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. Brains were evaluated for macroscopic and microinfarcts and the severity of arteriolosclerosis. Regression analyses were used to examine the association of cerebrovascular pathologies with parkinsonian signs.More than 35% of cases (N=149) showed macroscopic infarcts. Almost 30% of cases without macroscopic infarcts showed pathologies not detected by conventional brain imaging: microinfarcts (N=33 [7.9%]), arteriolosclerosis (N=62 [14.8%]), or both (N=24 [5.7%]). Macroscopic infarcts, specifically multiple cortical and ?1 subcortical macroscopic infarcts, were related to higher global parkinsonian scores. The presence of multiple and cortical microinfarcts was associated with global parkinsonian score. Arteriolosclerosis was associated with global parkinsonian score, but this effect was attenuated and no longer significant after accounting for infarcts. Each of the 3 pathologies was separately associated with parkinsonian gait (macroscopic infarcts [estimate, 0.552; SE, 0.210; P=0.009]; microinfarcts [estimate, 0.424; SE, 0.213; P=0.047]; arteriolosclerosis [estimate, 0.191; SE, 0.056; P<0.001]). Further analyses showed that subcortical macroscopic and microinfarcts were specifically associated with the severity of parkinsonian gait.Cerebrovascular pathologies, including macroscopic infarcts, microinfarcts, and arteriolosclerosis, are common in older persons and may be unrecognized common etiologies of mild parkinsonian signs, especially parkinsonian gait, in old age.

SUBMITTER: Buchman AS

PROVIDER: S-EPMC3202031 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Cerebrovascular disease pathology and parkinsonian signs in old age.

Buchman Aron S AS Leurgans Sue E SE Nag Sukriti S Bennett David A DA Schneider Julie A JA

Stroke 20110901 11

<h4>Background and purpose</h4>Mild motor symptoms including parkinsonian signs are common in old age, but their underlying neuropathology is unclear. We tested the hypothesis that cerebrovascular pathologies are related to parkinsonian signs.<h4>Methods</h4>We studied brain autopsies from 418 deceased participants from the Religious Order Study, who underwent evaluation of parkinsonian signs with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. Brains wer ...[more]

PMID: 21885844

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Project description:Parkinsonian motor signs are common in the aging population and are associated with adverse health outcomes. Compared with Parkinson disease (PD), potential genetic risk factors for mild parkinsonian signs have been largely unexplored.To determine whether PD susceptibility loci are associated with parkinsonism or substantia nigra pathology in a large community-based cohort of older persons.Eighteen candidate single-nucleotide polymorphisms from PD genome-wide association studies were evaluated in a joint clinicopathologic cohort. Participants included 1698 individuals and a nested autopsy collection of 821 brains from the Religious Orders Study and the Rush Memory and Aging Project, 2 prospective community-based studies.The primary outcomes were a quantitative measure of global parkinsonism or component measures of bradykinesia, rigidity, tremor, and gait impairment that were based on the motor Unified Parkinson's Disease Rating Scale. In secondary analyses, we examined associations with additional quantitative motor traits and postmortem indices, including substantia nigra Lewy bodies and neuronal loss.Parkinson disease risk alleles in the MAPT (rs2942168; P?=?.0006) and CCDC62 (rs12817488; P?=?.004) loci were associated with global parkinsonism, and these associations remained after exclusion of patients with a PD diagnosis. Based on motor Unified Parkinson's Disease Rating Scale subscores, MAPT (P?=?.0002) and CCDC62 (P?=?.003) were predominantly associated with bradykinesia, and we further discovered associations between SREBF1 (rs11868035; P?=?.005) and gait impairment, SNCA (rs356220; P?=?.04) and rigidity, and GAK (rs1564282; P?=?.03) and tremor. In the autopsy cohort, only NMD3 (rs34016896; P?=?.03) was related to nigral neuronal loss, and no associations were detected with Lewy bodies.In addition to the established link to PD susceptibility, our results support a broader role for several loci in the development of parkinsonian motor signs and nigral pathology in older persons.

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Cerebrovascular disease pathology and parkinsonian signs in old age.

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Cerebrovascular disease pathology and parkinsonian signs in old age.

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