The cardiovascular risk in Parkinson’s disease (PD) remains uncertain and controversial. Some studies suggest PD patients present an increased risk of cerebrovascular disease. We aimed to study the prevalence of neuroimaging cerebrovascular biomarkers in PD patients compared to controls, using an accurate and complete magnetic resonance (MR) imaging evaluation.
Material and Methods
Neuroimaging sub-study within a larger cross-sectional case–control study. An enriched subgroup of PD patients (≤10 years since diagnosis) with at least a moderate cardiovascular mortality risk based on a Systematic COronary Risk Evaluation (SCORE) was compared to community-based controls regarding neuroimaging biomarkers. Patients underwent a high-resolution T1-weighted MR imaging sequence at 3.0 T to visualize neuromelanin. A 3D SWI FFE, sagittal 3D T1-weighted, axial FLAIR and diffusion-weighted image sequences were obtained.
Results
The study included 47 patients, 24 with PD and 23 controls. PD patients presented a reduced area and signal intensity of the substantia nigra and locus coeruleus on neuromelanin-sensitive MR. The median SCORE was 5% in both groups. No significant differences regarding white matter hyperintensities (OR 4.84, 95% CI 0.50, 47.06), lacunes (OR 0.43, 95% CI 0.07, 2.63), microbleeds (OR 0.64, 95% CI 0.13, 3.26), or infarcts (0.95, 95% CI 0.12, 7.41) was found. The frequency of these neuroimaging biomarkers was very low in both groups.
Conclusion
The present study does not support an increased prevalence of neuroimaging cerebrovascular biomarkers in PD patients.
JainSGoldsteinDS. Cardiovascular dysautonomia in Parkinson disease: from pathophysiology to pathogenesis. Neurobiol Dis2012; 46(3): 572–580. DOI: 10.1016/j.nbd.2011.10.025.
2.
AlvesMCaldeiraDFerroJM, et al.Reply to letter: Does parkinson's disease increase the risk of cardiovascular events? A systematic review and meta-analysis. Eur J Neurol2020; 27(2): e12–296. DOI: 10.1111/ene.14076.
3.
AlvesMCaldeiraDRatoML, et al.Cardiovascular adverse events reported in placebo arm of randomized controlled trials in parkinson's disease. J Parkinsons Dis2020; 10(2): 641–651. DOI: 10.3233/JPD-191907.
4.
StaalsJMakinSDDoubalFN, et al. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology2014; 83: 1228–1234.
5.
UmotoMMiwaHAndoR, et al. White matter hyperintensities in patients with multiple system atrophy. Parkinsonism Relat Disord2012; 18(1): 17–20. DOI: 10.1016/j.parkreldis.2011.08.004.
6.
DalakerTOLarsenJPBergslandN, et al.Brain atrophy and white matter hyperintensities in early Parkinson's disease(a). Mov Disord2009; 24(15): 2233–2241. DOI: 10.1002/mds.22754.
7.
JonesJDTannerJJOkunM, et al.Are Parkinson's patients more vulnerable to the effects of cardiovascular risk: A neuroimaging and neuropsychological study. J Int Neuropsychol Soc2017; 23(04): 322–331. DOI: 10.1017/S1355617717000017.
8.
de SchipperLJHafkemeijerABoutsMJRJ, et al.Age- and disease-related cerebral white matter changes in patients with Parkinson's disease. Neurobiol Aging2019; 80: 203–209. DOI: 10.1016/j.neurobiolaging.2019.05.004.
9.
HanningUTeuberALangE, et al.White matter hyperintensities are not associated with cognitive decline in early Parkinson's disease: The DeNoPa cohort. Parkinsonism Relat Disord2019; 69: 61–67. DOI: 10.1016/j.parkreldis.2019.10.016.
10.
DebetteSSchillingSDuperronMG, et al.Clinical significance of magnetic resonance imaging markers of vascular brain injury: A systematic review and meta-analysis. JAMA Neurol2019; 76(1): 81–94. DOI: 10.1001/jamaneurol.2018.3122.
11.
MoroniFAmmiratiERoccaMA, et al.Cardiovascular disease and brain health: Focus on white matter hyperintensities. Int J Cardiol Heart Vasc2018; 19: 63–69. DOI: 10.1016/j.ijcha.2018.04.006.
12.
HughesAJDanielSEKilfordL, et al.Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry1992; 55(3): 181–184. DOI: 10.1136/jnnp.55.3.181.
13.
PiepoliMFPiepoliMFHoesAW, et al.2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol2016; 23(29): NP1–2381. DOI: 10.1093/eurheartj/ehw106.
14.
GregoireSMChaudharyUJBrownMM, et al.The microbleed anatomical rating scale (MARS): Reliability of a tool to map brain microbleeds. Neurology2009; 73(21): 1759–1766. DOI: 10.1212/WNL.0B013E3181C34A7D.
15.
PotterGMChappellFMMorrisZ, et al.Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability. Cerebrovasc Dis2015; 39(3–4): 224–231. DOI: 10.1159/000375153.
16.
SasakiMShibataETohyamaK, et al.Neuromelanin magnetic resonance imaging of locus ceruleus and substantia nigra in Parkinson's disease. Neuroreport2006; 17(11): 1215–1218. DOI: 10.1097/01.wnr.0000227984.84927.a7.
17.
PantoniLBasileAMPracucciG, et al.Impact of age-related cerebral white matter changes on the transition to disability - the LADIS study: rationale, design and methodology. Neuroepidemiology2005; 24(1–2): 51–62. DOI: 10.1159/000081050.
18.
EldholmRSPerssonKBarcaML, et al.Association between vascular comorbidity and progression of Alzheimer's disease: a two-year observational study in Norwegian memory clinics. BMC Geriatr2018; 18(1): 120–128. DOI: 10.1186/s12877-018-0813-4.
19.
Martí-FàbregasJMedrano-MartorellSMerinoE, et al. MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation. Neurology2019; 92(21): e2432–e2443. DOI: 10.1212/WNL.0000000000007532.
20.
GreenbergSMVernooijMWCordonnierC, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol2009; 8(2): 165–174. DOI: 10.1016/S1474-4422(09)70013-4.
21.
WahlundLOBarkhofFFazekasF, et al.A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke2001; 32(6): 1318–1322. DOI: 10.1161/01.str.32.6.1318.
22.
FazekasFChawlukJBAlaviA, et al.MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol1987; 149(2): 351–356. DOI: 10.2214/ajr.149.2.351.
23.
DoubalFNMaclullichAMJFergusonKJ, et al.Enlarged Perivascular Spaces on MRI Are a Feature of Cerebral Small Vessel Disease. Stroke2010; 41: 450–454. DOI: 10.1161/STROKEAHA.109.564914.
24.
ReimãoSPita LoboPNeutelD, et al.Quantitative analysis versus visual assessment of neuromelanin MR imaging for the diagnosis of Parkinson's disease. J Parkinsons Dis2015; 5(3): 561–567. DOI: 10.3233/JPD-150551.
25.
StaalsJBoothTMorrisZ, et al.Total MRI load of cerebral small vessel disease and cognitive ability in older people. Neurobiol Aging2015; 36(10): 2806–2811. DOI: 10.1016/j.neurobiolaging.2015.06.024.
26.
HuangYPChenLSYenMF, et al.Parkinson's disease is related to an increased risk of ischemic stroke-a population-based propensity score-matched follow-up study. PLoS One2013; 8(9): e68314. DOI: 10.1371/journal.pone.0068314.
27.
HongCTHuHHChanL, et al.Prevalent cerebrovascular and cardiovascular disease in people with Parkinson's disease: a meta-analysis. Clin Epidemiol2018; 10: 1147–1154. DOI: 10.2147/CLEP.S163493.
28.
PatelMCoutinhoCEmsleyHC. Prevalence of radiological and clinical cerebrovascular disease in idiopathic Parkinson's disease. Clin Neurol Neurosurg2011; 113(10): 830–834. DOI: 10.1016/j.clineuro.2011.05.014.
29.
ConroyRMPyöräläKFitzgeraldAP, et al.Estimation of ten-year risk of fatal cardiovascular disease in Europe: The SCORE project. Eur Heart J2003; 24(11): 987–1003. DOI: 10.1016/S0195-668X(03)00114-3.
30.
AndersonKMWilsonPWOdellPM, et al.An updated coronary risk profile. A statement for health professionals. Circulation1991; 83(1): 356–362. DOI: 10.1161/01.CIR.83.1.356.
31.
GoffDCLloyd-JonesDMBennettG, et al.2013ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 20132014; 129(25 Suppl. 1): S49–S73. DOI: 10.1161/01.cir.0000437741.48606.98.
