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Abstract
Objective Mild parkinsonian signs (MPS) are an underappreciated neurologic condition in older adults; we assessed associations of MPS with measures of dopaminergic (catechol-O-methyltransferase [COMT] genotype, an indicator of synaptic dopamine levels) and vascular (white matter hyperintensities [WMH], an indicator of cerebral small vessel disease) factors.
Methods In a cohort of older adults (mean age 82.6 years [SD 2.6]; 58.0% female; 38.8% black), we assessed cross-sectional associations of WMH volume and COMT Val158Met (rs4680) genotype (n = 35 Met/Met, n = 180 Val carriers) with MPS by regression models adjusted for demographic and health characteristics. Interactions between WMH and COMT were assessed and analyses were repeated stratified by COMT genotype (Met/Met related to higher synaptic dopamine vs Val carriers related to lower synaptic dopamine).
Results MPS was present in 42.3% of our sample. WMH (odds ratio [OR] 1.16, confidence interval [CI] 1.05–1.27) but not COMT (Met/Met compared to Val carrier: OR 0.62, CI 0.27–1.42) was related to MPS. There was a significant interaction between WMH and COMT (p = 0.03). Stratified analyses reveled a strong association between WMH and MPS among COMT Val carriers (OR 1.23, CI 1.09–1.38), but not for Met/Met (OR 0.68, CI 0.45–1.02), independent of covariates.
Conclusions WMH had a direct relation with MPS. In contrast, COMT was not associated with MPS, but it did modify the effect of WMH on MPS. The dopaminergic system may provide compensation for the effects of WMH on MPS. These findings suggest that MPS has a vascular rather than dopaminergic origin in older adults, but both factors are important in MPS manifestation.
Glossary
- 3 MS=
- Modified Mini-Mental State Examination;
- BMI=
- body mass index;
- CI=
- confidence interval;
- COMT=
- catechol-O-methyltransferase;
- dlPFC=
- dorsolateral prefrontal cortex;
- DSST=
- Digit Symbol Substitution Test;
- FLAIR=
- fluid-attenuated inversion recovery;
- FOV=
- field of view;
- GM=
- gray matter;
- GMV=
- gray matter volume;
- HBP=
- Healthy Brain Project;
- Health ABC=
- Health Aging and Body Composition;
- MPS=
- mild parkinsonian signs;
- OR=
- odds ratio;
- PFC=
- prefrontal cortex;
- TE=
- echo time;
- TI=
- inversion time;
- TR=
- repetition time;
- WM=
- white matter;
- WMH=
- white matter hyperintensities
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.
- Received June 28, 2017.
- Accepted in final form October 4, 2017.
- Copyright © 2017 American Academy of Neurology
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