Effects of Cerebrovascular and Lewy Body Pathology on Parkinsonian Signs in Community-Dwelling Older Adults

Abstract

Background and Objectives:The roles of Lewy body (LB) and separately of cerebrovascular disease (CVD) pathologies in the severity of parkinsonian signs are well recognized in old age. We investigated whether the two pathologies act synergistically to further potentiate the severity of parkinsonism beyond their separate effects.Methods:We employed postmortem data of decedents from 3 longitudinal community-based studies of aging who underwent annual clinical evaluation to assess parkinsonian signs using 26-items of the motor portion of a modified Unified Parkinson's Disease Rating Scale. A summary score was developed from each item score to construct a global parkinsonian score, with a higher score indicating more severe parkinsonism. A detailed neuropathologic evaluation was performed to identify LB, AD pathology, nigral neuronal loss, atherosclerosis, macroscopic infarcts, and other CVD pathologies (arteriolosclerosis, cerebral amyloid angiopathy, and microscopic infarcts). A series of regression models with terms for LB, CVD pathology, and the interaction of LB with CVD pathologies was fit for global parkinsonism proximate- to-death and for individual parkinsonian signs scores including, parkinsonian gait, rigidity, tremor, and bradykinesia.Results:In 1,753 participants (mean age at death=89 years; 68% women), LB was observed in 26% of participants and CVD pathologies were present in more than two thirds of participants. LB and three CVD pathologies (atherosclerosis, arteriolosclerosis, and macroscopic infarcts) were each independently associated with the severity of global parkinsonism proximate-to-death (LB: β=0.318, SE=0.08, p=<0.001, atherosclerosis: β=0.373, SE=0.079, p=<0.001, arteriolosclerosis: β=0.253, SE=0.078, p=0.001, macroscopic infarcts: β=0.333, SE=0.077, p=<0.001). A linear regression model adjusted for demographics, CVD, and neurodegenerative pathologies showed interaction between LB and macroscopic infarcts (β=0.463, SE=0.168, p=0.006), with LBs being associated with worse global parkinsonism when macroinfarcts are present. Similar interactions were found for atherosclerosis and LBs (β=0.371, SE=0.173, p=0.032) as well as for parkinsonian gait as the outcome (macroscopic infarcts: β=0.662, SE=0.239, p=0.005; atherosclerosis: β=0.509, SE=0.246, p=0.038). Findings were not affected when the 66 participants with a clinical diagnosis of PD were excluded. In contrast, there were no interactions between LB and other CVD pathologies or between atherosclerosis and macroscopic infarcts for global parkinsonism proximate-to-death.Discussion:These findings suggest that atherosclerosis and macroscopic infarcts interact with LB pathology to increase the severity of parkinsonism beyond their additive effects in older persons.

Substantia Nigra Pathology, Contact Sports Play, and Parkinsonism in Chronic Traumatic Encephalopathy

“…Parkinsonism is proposed to emerge secondary to disruption of nigrostriatal circuitry—in particular, impaired functioning or loss of substantia nigra (SN) dopaminergic neurons . Although parkinsonism is most commonly associated with α-synuclein accumulation in Lewy body disease (LBD), it is also observed in tauopathies, such as progressive supranuclear palsy and postencephalitic parkinsonism, and has been associated with cerebrovascular disease …”

“…[15][16][17][18] Although parkinsonism is most commonly associated with α-synuclein accumulation in Lewy body disease (LBD), it is also observed in tauopathies, such as progressive supranuclear palsy and postencephalitic parkinsonism, 19 and has been associated with cerebrovascular disease. [20][21][22][23][24] Some individuals who have sustained head injury exhibit motor dysfunction, 4,25 including parkinsonism 26,27 and Parkinson disease (PD). 28 Moderate to severe traumatic brain injury (TBI) is associated with an increased risk of parkinsonism 26,27 and Lewy body (LB) pathology, 12,29 and parkinsonism has been reported in approximately 30% of individuals older than 50 years diagnosed with CTE at autopsy.…”