Vascular and dopaminergic contributors to mild parkinsonian signs in older adults

Neurology. 2018 Jan 16;90(3):e223-e229. doi: 10.1212/WNL.0000000000004842. Epub 2017 Dec 15.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Catechol O-Methyltransferase / genetics*
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Nuchal Cord
  • Organ Size
  • Parkinsonian Disorders / diagnostic imaging*
  • Parkinsonian Disorders / enzymology
  • Parkinsonian Disorders / epidemiology
  • Parkinsonian Disorders / genetics*
  • Severity of Illness Index
  • White Matter / diagnostic imaging*
  • White Matter / pathology


  • COMT protein, human
  • Catechol O-Methyltransferase