Most cited article - PubMed ID 22692677
Impairment of brain vessels may contribute to mortality in patients with Parkinson's disease
To determine whether systemic medical factors, such as vascular risk factors, metabolic and inflammatory markers contribute to cognitive decline in Parkinson's disease (PD); if confirmed to determine whether a clinically applicable risk factor model can predict the conversion from normal cognition (NC) to mild cognitive impairment (MCI). 58 patients who met the UK Brain Bank Criteria for PD underwent clinical and laboratory assessment at study entry; 47 patients were re-assessed after 2 years. Medical history, vascular risk (QRISK2), blood metabolic and inflammatory factors, brain vessel examinations, activity of daily living, and neuropsychological testing were performed. Forty patients had NC and 18 patients had MCI at baseline. Patients with MCI had higher level of interleukin 6, folic acid below normal range and higher L-dopa equivalent dose compared to cognitive normal patients at baseline. Patients with NC at baseline were classified into two groups: patients who remained cognitively normal (non-converters, n = 23) and patients who progressed to MCI (converters, n = 11). MCI converters were older at baseline and had higher QRISK2 than the non-converters. Patients with higher QRISK2, lower uric acid level and lower activity of daily living scale at baseline had a higher risk of converting from NC to MCI with a sensitivity of 72.2%, a specificity of 87%, and an overall accuracy of 82.4%. Systemic medical factors are associated with cognitive impairment in PD both cross-sectionally and longitudinally. A risk factor model predicting the decline from NC to MCI could be constructed.
- Keywords
- Cognitive impairment, Inflammation, Metabolic factors, Parkinson’s disease, Vascular risk factors,
- MeSH
- Cerebrovascular Disorders diagnosis epidemiology metabolism MeSH
- Cognitive Dysfunction diagnosis epidemiology metabolism MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Inflammation Mediators metabolism MeSH
- Metabolic Diseases diagnosis epidemiology metabolism MeSH
- Follow-Up Studies MeSH
- Parkinson Disease diagnosis epidemiology metabolism MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Inflammation Mediators MeSH
This expert working group report proposes an updated approach to subtype definition of vascular parkinsonism (VaP) based on a review of the existing literature. The persistent lack of consensus on clear terminology and inconsistent conceptual definition of VaP formed the impetus for the current expert recommendation report. The updated diagnostic approach intends to provide a comprehensive tool for clinical practice. The preamble for this initiative is that VaP can be diagnosed in individual patients with possible prognostic and therapeutic consequences and therefore should be recognized as a clinical entity. The diagnosis of VaP is based on the presence of clinical parkinsonism, with variable motor and non-motor signs that are corroborated by clinical, anatomic or imaging findings of cerebrovascular disease. Three VaP subtypes are presented: (1) The acute or subacute post-stroke VaP subtype presents with acute or subacute onset of parkinsonism, which is typically asymmetric and responds to dopaminergic drugs; (2) The more frequent insidious onset VaP subtype presents with progressive parkinsonism with prominent postural instability, gait impairment, corticospinal, cerebellar, pseudobulbar, cognitive and urinary symptoms and poor responsiveness to dopaminergic drugs. A higher-level gait disorder occurs frequently as a dominant manifestation in the clinical spectrum of insidious onset VaP, and (3) With the emergence of molecular imaging biomarkers in clinical practice, our diagnostic approach also allows for the recognition of mixed or overlapping syndromes of VaP with Parkinson's disease or other neurodegenerative parkinsonisms. Directions for future research are also discussed.
- Keywords
- Binswanger's disease, Cerebrovascular disease, Gait, Imaging, Vascular parkinsonism,
- MeSH
- Cerebrovascular Disorders classification complications diagnosis physiopathology MeSH
- Dementia classification diagnosis etiology physiopathology MeSH
- Diagnosis, Differential MeSH
- Cognitive Dysfunction classification diagnosis etiology physiopathology MeSH
- Humans MeSH
- Gait Disorders, Neurologic classification diagnosis etiology physiopathology MeSH
- Parkinsonian Disorders classification complications diagnosis physiopathology MeSH
- Review Literature as Topic MeSH
- Risk Factors MeSH
- Practice Guidelines as Topic * MeSH
- Syndrome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
INTRODUCTION: While progressive MRI brain changes characterize advanced Parkinson's disease (PD), little has been discovered about structural alterations in the earliest phase of the disease, i.e. in patients with motor symptoms and with normal cognition. Our study aimed to detect grey matter (GM) and white matter (WM) changes in PD patients without cognitive impairment. METHODS: Twenty PD patients and twenty-one healthy controls (HC) were tested for attention, executive function, working memory, and visuospatial and language domains. High-resolution T1-weighted and 60 directional diffusion-weighted 3T MRI images were acquired. The cortical, deep GM and WM volumes and density, as well as the diffusion properties of WM, were calculated. Analyses were repeated on data flipped to the side of the disease origin. RESULTS: PD patients did not show any significant differences from HC in cognitive functioning or in brain volumes. Decreased GM intensity was found in the left superior parietal lobe in the right (p<0.02) and left (p<0.01) flipped data. The analysis of original, un-flipped data demonstrated elevated axial diffusivity (p<0.01) in the superior and anterior corona radiata, internal capsule, and external capsule in the left hemisphere of PD relative to HC, while higher mean and radial diffusivity were discovered in the right (p<0.02 and p<0.03, respectively) and left (p<0.02 and p<0.02, respectively) in the fronto-temporal WM utilizing flipped data. CONCLUSIONS: PD patients without cognitive impairment and GM atrophy demonstrated widespread alterations of WM microstructure. Thus, WM impairment in PD might be a sensitive sign preceding the neuronal loss in associated GM regions.
- MeSH
- Atrophy MeSH
- White Matter diagnostic imaging pathology MeSH
- Adult MeSH
- Cognition MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Neuropsychological Tests MeSH
- Neuroimaging MeSH
- Parkinson Disease diagnostic imaging pathology psychology MeSH
- Disease Progression MeSH
- Gray Matter diagnostic imaging pathology MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
White matter lesions (WML) associated with cerebrovascular disease (CVD) may be observed on magnetic resonance imaging in Parkinson's disease (PD) patients. WML are an important factor contributing to postural, gait, and cognitive impairment in the elderly without PD and worsening the course of Alzheimer's disease (AD). Numerous articles are available on this topic. Whether WML modify and negatively influence the clinical symptoms, and course of PD is a subject of debate. The aim of this review is to examine the available literature on the contribution of WML to PD motor symptoms in relation to clinical characteristics and methods of assessing WML on MRI. After reviewing the database, we identified 19 studies reporting the relationship between WML and PD; ten studies focusing on the impact of WML on the cognitive status in PD were excluded. We analysed altogether nine studies reporting the relationship between WML and motor signs of PD. The review found association between WML severity and freezing of gait, less significant to responsiveness to dopaminergic treatment and postural instability; no negative impact on tremor and falls was observed. The impact of WML on bradykinesia and rigidity was inconsistent. Comorbid WML is associated with worsening axial motor performance, probably independently from the degree of nigrostriatal dopaminergic denervation in PD. Reducing the vascular risk factors that cause WML may be helpful in preventing the development of axial symptoms and ultimately in improving the quality of life of patients with PD. Given the lack of systematic studies, additional research in this field is needed.
- Keywords
- Cerebrovascular disease, Magnetic resonance imaging, Parkinson’s disease, White matter lesions,
- MeSH
- White Matter pathology MeSH
- Cerebrovascular Disorders complications MeSH
- Humans MeSH
- Gait Disorders, Neurologic etiology MeSH
- Parkinson Disease complications pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Objectives. The association between abnormal serum immunomarkers and mortality in 53 consecutive Parkinson's disease patients was studied. Materials and Methods. The plasma level of specific inflammatory cytokines was investigated: mannan-binding lectin (MBL), interleukin- (IL-) 6, and tumor necrosis factor-alpha (TNF-α). The baseline serum immunomarkers obtained from patients who died (n = 16) during a four-year follow-up period were compared with the data of patients who survived (n = 37). Results. The baseline level of IL-6 was significantly higher in the deceased patients than in the survivors. Elevated IL-6 levels and age were major independent contributors to disease mortality. Differences between other plasma cytokine level abnormalities were not significant. Conclusion. This study showed that IL-6 elevation may be a marker of increased mortality risk in Parkinson's disease patients. The inflammation may act in association with other factors and comorbidities in progressive neurodegenerative pathology.
- Publication type
- Journal Article MeSH