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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 2 pathologies act synergistically to further potentiate the severity of parkinsonism beyond their separate effects.
Methods We used 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 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, Alzheimer disease 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 3 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) and 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 Parkinson disease were excluded. By 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.
Glossary
- AD=
- Alzheimer disease;
- CAA=
- cerebral amyloid angiopathy;
- CVD=
- cerebrovascular disease;
- IQR=
- interquartile range;
- LB=
- Lewy body;
- MAP=
- Memory and Aging Project;
- MARS=
- Minority Aging Research Study;
- PD=
- Parkinson disease;
- ROS=
- Religious Orders Study
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Peter Hedera, MD, PhD.
Editorial, page 290
- Received August 26, 2022.
- Accepted in final form April 21, 2023.
- © 2023 American Academy of Neurology
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