Background: White matter lesions (WMLs), asymptomatic lacunar infarcts, brain microbleeds (BMBs), and enlarged perivascular spaces (EPVS) have been identified as silent lesions due to cerebral small vessel disease (cSVD). All these markers have been individually linked to cognitive functioning, but are also strongly correlated with each other. The combined effect of these markers on cognitive function has never been studied and would possibly provide more useful information on the effect on cognitive function.Methods: Brain MRI and extensive neuropsychological assessment were performed in 189 patients at risk for cSVD (112 hypertensive patients and 77 first-ever lacunar stroke patients). We rated the presence of any asymptomatic lacunar infarct, extensive WMLs, any deep BMB, and moderate to extensive EPVS in the basal ganglia. The presence of each marker was summed to an ordinal score between 0 and 4. Associations with domains of cognitive function (memory, executive function, information processing speed, and overall cognition) were analyzed with correlation analyses.Results: Correlation analyses revealed significant associations between accumulating cSVD burden and decreased performance on all cognitive domains (all p ≤ 0.001). Results remained significant for information processing speed (r = −0.181, p = 0.013) and overall cognition (r = −0.178, p = 0.017), after correction for age and sex. Testing of trend using linear regression analyses revealed the same results.Discussion: We tested a new approach to capture total brain damage resulting from cSVD and found that accumulation of MRI burden of cSVD is associated with decreased performance on tests of information processing speed and overall cognition, implying that accumulating brain damage is accompanied by worse cognitive functioning.

Objectives: Hypertension is a major risk factor for white matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces, which are MRI markers of cerebral small vessel disease (SVD). Studies have shown associations between these individual MRI markers and cognitive functioning and decline. Recently, a “total SVD score” was proposed in which the different MRI markers were combined into one measure of SVD, to capture total SVD-related brain damage. We investigated if this SVD score was associated with cognitive decline over 4 years in patients with hypertension.Methods: In this longitudinal cohort study, 130 hypertensive patients (91 patients with uncomplicated hypertension and 39 hypertensive patients with a lacunar stroke) were included. They underwent a neuropsychological assessment at baseline and after 4 years. The presence of WMH, lacunes, cerebral microbleeds, and perivascular spaces were rated on baseline MRI. Presence of each individual marker was added to calculate the total SVD score (range 0–4) in each patient.Results: Uncorrected linear regression analyses showed associations between SVD score and decline in overall cognition (p = 0.017), executive functioning (p < 0.001) and information processing speed (p = 0.037), but not with memory (p = 0.911). The association between SVD score and decline in overall cognition and executive function remained significant after adjustment for age, sex, education, anxiety and depression score, potential vascular risk factors, patient group, and baseline cognitive performance.Conclusion: Our study shows that a total SVD score can predict cognitive decline, specifically in executive function, over 4 years in hypertensive patients. This emphasizes the importance of considering total brain damage due to SVD.

Enlarged perivascular spaces (EPVS) are a feature of cerebral small vessel disease (cSVD) and have been related to cSVD severity. A higher number of EPVS were related to decreased cognition in healthy elderly, but this has never been investigated in patients at high risk of cSVD. We included 189 patients with a high risk of cSVD (hypertensive patients and lacunar stroke patients). Patients underwent brain MRI and extensive neuropsychological assessment. EPVS were rated in the basal ganglia (BG) and centrum semiovale (CSO). Correlation analyses between EPVS and cognitive domains were adjusted for white matter lesions (WMLs), age, sex and symptomatic stroke. Negative correlations were found between EPVS in the BG and all cognitive domains, independent of WMLs. After correction for age, results remained significant for information processing speed (IPS) only. No independent correlation was found between EPVS in the CSO and cognition. We demonstrated that more BG EPVS were associated with a decrease in IPS, independent of age and WMLs. This emphasizes that specifically EPVS in the BG are associated with cSVD, and with cSVD-related decreases in cognition.

AimsUp to 50% of patients with heart failure (HF) may suffer from severe cognitive impairment (SCI), but longitudinal studies are sparse, and effects of changes in HF severity on cognitive function are unknown. Therefore, we assessed the prevalence of SCI in HF patients, its relationship with HF severity, its effects on morbidity and mortality, and the relationship between changes in HF severity and cognitive function. Methods and resultsWe included 611 patients from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) and assessed cognitive function [Hodkinson Abbreviated Mental Test (AMT)] in relation to severity of HF (NYHA class, NT-proBNP) at baseline and 18 months (n ¼ 382) and effects on hospitalization-free survival and mortality. SCI (i.e. AMT score ≤7) was present in 9.2% of patients at baseline, but only 20% of them had a diagnosis of dementia. Prevalence of SCI remained stable during follow-up. SCI was present at baseline more often in NYHA IV patients compared with NYHA II [odds ratio 2.94; 95% confidence interval (CI) 1.15-7.51, P ¼ 0.025], but it was not related to NT-proBNP levels. SCI was related to higher mortality (hazard ratio 1.53, 95% CI 1.02-2.30, P ¼ 0.04), but not hospitalization-free survival. Changes in HF severity were not significantly related to changes in cognitive function. ConclusionSCI is a frequent, but often unrecognized finding in HF patients, but the influence of HF severity and its changes on cognitive function were less than hypothesized. Trial registration ISRCTN43596477--