Search

Aims/hypothesis: Accumulating evidence suggests an association between coronary heart disease and risk for cognitive impairment or dementia, but no study has systematically reviewed this association. Therefore, we summarized the available evidence on the association between coronary heart disease and risk for cognitive impairment or dementia., Methods: Medline, Embase, PsycINFO, and CINAHL were searched for all publications until 8th January 2016. Articles were included if they fulfilled the inclusion criteria: (1) myocardial infarction, angina pectoris or coronary heart disease (combination of both) as predictor variable; (2) cognition, cognitive impairment or dementia as outcome; (3) population-based study; (4) prospective (≥1 year follow-up), cross-sectional or case-control study design; (5) ≥100 participants; and (6) aged ≥45 years. Reference lists of publications and secondary literature were hand-searched for possible missing articles. Two reviewers independently screened all abstracts and extracted information from potential relevant full-text articles using a standardized data collection form. Study quality was assessed with the Newcastle-Ottawa Scale. We pooled estimates from the most fully adjusted model using random-effects meta-analysis., Results: We identified 6,132 abstracts, of which 24 studies were included. A meta-analysis of 10 prospective cohort studies showed that coronary heart disease was associated with increased risk of cognitive impairment or dementia (OR = 1.45, 95%CI = 1.21-1.74, p<0.001). Between-study heterogeneity was low (I2 = 25.7%, 95%CI = 0-64, p = 0.207). Similar significant associations were found in separate meta-analyses of prospective cohort studies for the individual predictors (myocardial infarction, angina pectoris). In contrast, meta-analyses of cross-sectional and case-control studies were inconclusive., Conclusion/interpretation: This meta-analysis suggests that coronary heart disease is prospectively associated with increased odds of developing cognitive impairment or dementia. Given the projected worldwide increase in the number of people affected by coronary heart disease and dementia, insight into causal mechanisms or common pathways underlying the heart-brain connection is needed.

Introduction: In acute ischemic stroke, imaging of the cranio-cervical vessels is essential for intra-arterial treatment selection. Fast, reliable and easy accessible imaging is necessary 24 hours a day, 7 days a week. Radiologists in training and non-expert readers often perform initial reviewing. In this pilot study, the potential benefit of adding 4Dimensional-CT Angiography (4D-CTA) to the patient selection protocol for intra-arterial therapy is investigated., Materials and Methods: Twenty-five datasets of prospectively recruited patients, eligible for intra-arterial treatment, were enrolled. Four radiologists-in-training consecutively reviewed CTA, CT-Perfusion and 4D-CTA (post-processed from CTP datasets) and scored: occlusion-presence and diagnostic certainty (scale 1-10). Time-to-diagnosis was registered., Results: Arterial occlusion was present in 8 patients. Accuracy improved from 88-92% after CTA and CTP assessment to 96-100% after 4D-CTA assessment (P-values >0,05). Mean diagnostic certainty improved from 7,2-8,6 to 8,8-9,3 (P-values all < 0,05). Mean time to diagnosis increased from 3, 5, 5 and 4 minutes after CTA to 9, 14, 12, and 10 minutes after 4D-CTA., Conclusion: 4D-CTA as an additive to regular CTA and CT-Perfusion in patients with acute ischemic stroke eligible for intra-arterial treatment shows a tendency to increase diagnostic accuracy and improves diagnostic certainty, when reviewed by radiologist in training, while only mildly prolonging time to diagnosis.

Background: In Parkinson's disease (PD), the complex relationship between motor symptoms, affective states, and contextual factors remains to be elucidated. The Experience Sampling Method provides (ESM) a novel approach to this issue. Using a mobile device with a special purpose application (app), motor symptoms, affective states and contextual factors are assessed repeatedly at random moments in the flow of daily life, yielding an intensive time series of symptoms and experience. The aim of this study was to study the feasibility of this method., Method: We studied the feasibility of a five-day period of ESM in PD and its ability to objectify diurnal fluctuations in motor symptom severity and their relation with affect and contextual factors in five PD patients with motor fluctuations., Results: Participants achieved a high compliance, with 84% of assessment moments completed without disturbance of daily activities. The utility of the device was rated 8 on a 10-point scale. We were able to capture extensive diurnal fluctuations that were not revealed by routine clinical assessment. In addition, we were able to detect clinically relevant associations between motor symptoms, emotional fluctuations and contextual factors at an intra-individual level., Conclusions: ESM represents a viable and novel approach to elucidate relationships between motor symptoms, affective states and contextual factors at the level of individual subjects. ESM holds promise for clinical practice and scientific research.

Introduction: Tissue plasminogen activator (tPA)-activity and plasminogen activator inhibitor type 1 (PAI-1) antigen are considered to be haemostasis-related markers of endothelial activation and relate to presence of cerebral white matter hyperintensities (WMH) as was earlier shown in a cross-sectional study. We investigated whether tPA-activity and PAI-1 levels are associated with WMH progression in a longitudinal study., Methods: In 127 first-ever lacunar stroke patients in whom baseline brain MRI and plasma levels of tPA-activity and PAI-1-antigen were available, we obtained a 2-year follow-up MRI. We assessed WMH progression by a visual WMH change scale. We determined the relationship between levels of tPA-activity and PAI-1 and WMH progression, by logistic regression analysis., Results: Plasma tPA-activity was associated with periventricular WMH progression (OR 2.36, 95% CI 1.01-5.49, with correction for age and sex and baseline presence of WMH), but not with deep or any (periventricular and/or deep) WMH progression. PAI-1 levels were lower in patients with WMH progression, but these results were not significant., Conclusion: We found a relationship between plasma tPA-activity and progression of periventricular WMH. More research is needed to determine whether there is a (direct) role of tPA in the development and progression of WMH.

Objectives: Perivascular spaces are associated with MRI markers of cerebral small vessel disease, including white matter hyperintensities. Although perivascular spaces are considered to be an early MRI marker of cerebral small vessel disease, it is unknown whether they are associated with further progression of MRI markers, especially white matter hyperintensities. We determined the association between perivascular spaces and progression of white matter hyperintensities after 2-year follow-up in lacunar stroke patients., Methods: In 118 lacunar stroke patients we obtained brain MRI and 24-hour ambulatory blood pressure measurements at baseline, and a follow-up brain MRI 2 years later. We visually graded perivascular spaces and white matter hyperintensities at baseline. Progression of white matter hyperintensities was assessed using a visual white matter hyperintensity change scale. Associations with white matter hyperintensity progression were tested with binary logistic regression analysis., Results: Extensive basal ganglia perivascular spaces were associated with progression of white matter hyperintensities (OR 4.29; 95% CI: 1.28-14.32; p<0.05), after adjustment for age, gender, 24-hour blood pressure and vascular risk factors. This association lost significance after additional adjustment for baseline white matter hyperintensities. Centrum semiovale perivascular spaces were not associated with progression of white matter hyperintensities., Conclusions: Our study shows that extensive basal ganglia perivascular spaces are associated with progression of white matter hyperintensities in cerebral small vessel disease. However, this association was not independent of baseline white matter hyperintensities. Therefore, presence of white matter hyperintensities at baseline remains an important determinant of further progression of white matter hyperintensities in cerebral small vessel disease.

In cross-sectional studies periventricular white matter lesions (WML) were related to low plasma levels of vitamin B12. Whether low vitamin B12 levels are also related to progression of WML is still unknown. We studied baseline vitamin B12 levels and its association with progression of WML over 2 years of follow-up in first-ever lacunar stroke patients. In 107 first-ever lacunar stroke patients in whom baseline brain MRI and vitamin B12 status were available, we obtained a follow-up brain MRI after 2 years. We assessed progression of periventricular WML (pWML) and deep WML (dWML) using a visual WML change scale. We studied the relationship between baseline levels of plasma vitamin B12 and progression of WML after 2 years of follow-up by binary logistic regression analyses. Vitamin B12 deficiency was more frequent in patients with progression of pWML compared to those without progression (41.9% and 19.7% respectively, p = 0.02). Corrected for sex and age, progression of pWML was associated with lower baseline levels of vitamin B12 (OR 1.42 per 50 unit decrease, 95% CI 1.00-1.92). Vitamin B12 levels were not associated with progression of dWML. In conclusion progression of pWML after 2 years of follow-up relates to low levels of vitamin B12 at baseline in first-ever lacunar stroke patients. Whether this population could benefit from vitamin B12 supplementation is unknown and requires further investigation.

Purpose: To investigate the natural history of carotid atherosclerosis in patients who experienced a TIA or ischemic stroke., Patients and Methods: Ninety-two TIA/stroke patients (57 men, mean age 67.7 ± 9.8 years) with ipsilateral <70% carotid stenosis underwent multisequence MRI of the plaque ipsilateral to the symptomatic side at baseline and after one year. For each plaque, several parameters were assessed at both time points., Results: Carotid lumen, wall and total vessel ( = carotid lumen and wall) volume did not significantly change. Forty-four patients had a plaque with a lipid-rich necrotic core (LRNC) at baseline, of which 34 also had a LRNC after one year. In three patients a LRNC appeared after one year. Thirty patients had a plaque with a thin and/or ruptured fibrous cap (FC) at both time points. In seven patients, FC status changed from thin and/or ruptured into thick and intact. In three patients, FC status changed from thick and intact into thin and/or ruptured. Twenty patients had intraplaque hemorrhage (IPH) at both time points. In four patients, IPH disappeared, whereas in three patients, new IPH appeared at follow-up., Conclusion: In TIA/stroke patients, carotid plaque morphology does not significantly change over a one-year period. IPH and FC status change in a minority of patients.

Background: In lacunar stroke patients vitamin B12 deficiency is often found and a relationship with the degree of periventricular white matter lesions (pWMLs) is suggested. Given the known relationships between WMLs and depression and between depression and fatigue after stroke, we studied both depression and fatigue in lacunar stroke patients with and without vitamin B12 deficiency., Methods: In 40 first-ever lacunar stroke patients vitamin B12 levels were determined and self-report questionnaires for fatigue and depression were completed three months after stroke., Results: Lacunar stroke patients with vitamin B12 deficiency (N = 13) reported significantly more fatigue (90.7 versus 59.4; p = .001) and depressive symptoms (6.62 versus 3.89; p<.05) than those without (N = 27). In regression analyses, vitamin B12 deficiency was significantly and independently associated with the presence of severe fatigue and clinically significant depression., Conclusions: Our preliminary results suggest a relationship between vitamin B12 deficiency and increased levels of fatigue and depression in lacunar stroke patients. If these findings could be replicated in a larger and general stroke sample, this would open treatment options and may improve quality of life after stroke.

Objective: To prospectively assess the relation between carotid plaque characteristics and the development of new cerebral white matter lesions (WMLs) at MRI., Methods: Fifty TIA/stroke patients with ipsilateral 30-69% carotid stenosis underwent MRI of the plaque at baseline. Total plaque volume and markers of vulnerability to thromboembolism (lipid-rich necrotic core [LRNC] volume, fibrous cap [FC] status, and presence of intraplaque hemorrhage [IPH]) were assessed. All patients also underwent brain MRI at baseline and after one year. Ipsilateral cerebral WMLs were quantified with a semiautomatic method., Results: Mean WML volume significantly increased over a one-year period (6.52 vs. 6.97 mm(3), P = 0.005). WML volume at baseline and WML progression did not significantly differ (P>0.05) between patients with 30-49% and patients with 50-69% stenosis. There was a significant correlation between total plaque volume and baseline ipsilateral WML volume (Spearman ρ = 0.393, P = 0.005). There was no significant correlation between total plaque volume and ipsilateral WML progression. There were no significant associations between LRNC volume and WML volume at baseline and WML progression. WML volume at baseline and WML progression did not significantly differ between patients with a thick and intact FC and patients with a thin and/or ruptured FC. WML volume at baseline and WML progression also did not significantly differ between patients with and without IPH., Conclusion: The results of this study indicate that carotid plaque burden is significantly associated with WML severity, but that there is no causal relationship between carotid plaque vulnerability and the occurrence of WMLs.

Background: Positive family history of stroke is an independent risk factor for lacunar stroke. However, the magnitude of familial aggregation of a certain disease is better evaluated by the genetic relative risk. This is calculated by dividing the prevalence of specific disease in family members of patients by the prevalence of this disease in the general population. In a cohort of lacunar stroke patients, who were subtyped clinically and radiologically, we determined the genetic relative risk of stroke., Methods: By questionnaire and additional interview, we obtained a complete first-degree family history of stroke. The prevalence of stroke in first-degree relatives of these lacunar stroke patients was compared to the self-reported prevalence of stroke in a Dutch community based cohort of elderly volunteers. Secondly, the influence of proband characteristics and family composition on parental and sibling history of stroke were evaluated., Principal Findings: We collected data of 1066 first-degree relatives of 195 lacunar stroke patients. Strokes occurred in 13.5% of first-degree relatives. The genetic relative risk was 2.94 (95%CI 2.45-3.53) for overall first-degree relatives, 4.52 (95%CI 3.61-5.65) for patients' parents and 2.10 (95%CI 1.63-2.69) for patients' siblings. Age of proband and proband status for hypertension influenced the chance of having a parent with a history of stroke whereas the likelihood of having a concordant sibling increased with sibship size., Conclusions: We found an increased genetic relative risk of stroke in first-degree relatives of patients with lacunar stroke. Our data warrant further genomic research in this well-defined high risk population for stroke.