Vascular risk factors, white matter lesions and cognitive impairment in Parkinson’s disease: the PACOS longitudinal study

Abstract

Background Vascular risk factors (VRFs) may be associated with cognitive decline in early Parkinson's disease (PD) but results are inconclusive. The identification of modifiable risk factors is relevant for prevention and treatment. Methods Parkinson's disease (PD) patients of the PACOS cohort who underwent a baseline and follow-up neuropsychological evaluation were enrolled in the study. PD with Mild Cognitive Impairment (MCI) and dementia (PDD) were diagnosed according to the MDS criteria. A Baseline 1.5 T brain MRI was used to calculate the white matter lesions (WMLs) burden using the Wahlund visual scale. Laboratory data, presence of hypertension, diabetes and use of anti-hypertensive drugs were collected and the Framingham Risk (FR) score was calculated. VRFs predicting PD-MCI and PDD were evaluated using Cox proportional hazard regression model. Results Out of 139 enrolled patients, 84 (60.4%) were classified as normal cognition (NC) and 55 (39.6%) as MCI at baseline. At follow-up 28 (33.3%) PD-NC developed MCI and 4 (4.8%) PDD (follow-up time 23.5 ± 10.3 months). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD. At multivariate analysis among PD-NC a systolic blood pressure (SBP) > 140 mmHg was the stronger predictor of MCI (adjHR 4.04; 95% CI 1.41-11.3) while the presence of MCI at baseline (adj HR 7.55; 95% CI 1.76-32.3) and a severe WMLs burden (adj HR 2.80; 95% CI 0.86-9.04) were the strongest predictors of PDD, even if this latter association has a trend towards significance. Conclusion Hypertension represents the most important modifiable risk factor for PD-MCI in the PACOS cohort, increasing the risk of about four times.

The influence of white matter hyperintensity on cognitive impairment in Parkinson's disease

“…This finding needs further confirmation in larger prospective studies. Several following‐up studies 89,90 revealed that WMH on longitudinal changes may increase the risks for cognitive decline in PD. The greater baseline WMH burden showed, the more significantly cognitive decline in Parkinson's patients, suggesting baseline WMH burden could be the risk for future cognitive decline.…”

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

“…Parkinson's disease patients frequently suffer from mild cognitive impairment (MCI) (MoCA score more than 21 and less than 26) (Litvan et al, 2012), who are at higher risk of developing dementia compared to PD patients with normal cognition (PD-NC) (Kehagia et al, 2010). Several lines of evidence suggested the inflammatory risk factors (Trefoil Factor 3,neutrophils,lymphocytes,et al) in PD may modulate underlying neurodegeneration particularly in relation to dementia (Stojkovic et al, 2018;Zou et al, 2018;Nicoletti et al, 2020;Wang et al, 2020). It is promising to detect MRI-visible EPVS burden as a marker of cognitive decline in PD.…”

Genetic polymorphisms in the renin-angiotensin system and cognitive decline in Parkinson’s disease

“…We assume that polymorphisms in RAS genes may exert an indirect influence on cognitive decline in PD. Some studies revealed a correlation between white matter hyperintensities (WMH) seen in magnetic resonance imaging with dementia in PD [31][32][33]. Taylor et al [34] analysed polymorphisms in both angiotensin II receptors genes: A1166C (rs5186) in AGTR1 and C3123A (rs2148582) in AGTR2.…”