Marjolein Huijts

Accumulation of MRI Markers of Cerebral Small Vessel Disease is Associated with Decreased Cognitive Function. A Study in First-Ever Lacunar Stroke and Hypertensive Patients

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.

Cognitive impairment in heart failure: results from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) randomized trial.

Up 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.

Subjective Cognitive Failures in Patients With Hypertension Are Related to Cognitive Performance and Cerebral Microbleeds

Previous studies on the relationship between subjective cognitive failures (SCF) and objective cognitive function have shown inconsistent results. In addition, research on the association between SCF and imaging markers of cerebral small vessel disease is limited. We investigated whether SCF in patients with essential hypertension, who are at high risk of cerebral small vessel disease, are associated with objective cognitive function and magnetic resonance imaging manifestations of cerebral small vessel disease. We included 109 patients with hypertension who underwent extensive neuropsychological assessment, including questionnaires measuring SCF and symptoms of anxiety and depression. Brain magnetic resonance imaging was performed to rate the presence of lacunes, cerebral microbleeds, and perivascular spaces, as well as white matter hyperintensities volume. Results showed significant associations between SCF and objectively measured overall cognition (B=−0.02; 95% confidence interval=−0.03 to −0.005), memory (B=0.02; 95% confidence interval=−0.03 to −0.004), and information processing speed (B=−0.02; 95% confidence interval=−0.03 to −0.001) after adjustment for patient characteristics and vascular risk factors. In addition, SCF were associated with the presence of cerebral microbleeds (odds ratio=1.12; 95% confidence interval=1.02–1.23) after adjustment for patient characteristics and vascular risk factors but not with other imaging markers of cerebral small vessel disease. Our study demonstrates that attention for SCF in patients with hypertension is needed because these may point to lower objective cognitive function, which might be as a result of the presence of cerebral microbleeds. Accordingly, this study emphasizes that neuropsychological assessment and brain imaging need to be considered when patients with hypertension report SCF.

Basal ganglia enlarged perivascular spaces are linked to cognitive function in patients with cerebral small vessel disease.

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.

Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension

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.

Association of vitamin B12 deficiency with fatigue and depression after lacunar stroke.

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.

Endothelial Activation Is Associated With Cognitive Performance in Patients With Hypertension.

BACKGROUND Hypertension is associated with the occurrence of cognitive deficits and dementia, probably because hypertension is a major risk factor for the occurrence of brain damage as a result of cerebral small vessel disease (cSVD). Endothelial activation and inflammation have been suggested to play an important role in the pathogenesis of cSVD. We investigated if compound scores of endothelial activation or inflammation, based on several blood markers, are associated with cognitive performance 3 years later in patients with essential hypertension. METHODS At baseline, levels of blood markers of endothelial activation (soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), sP-selectin, and sE-selectin) and markers of inflammation (neopterin, C-reactive protein, and sICAM-1) were measured and transformed into compound scores using z-scores. In addition, a brain magnetic resonance imaging (MRI) was performed to determine the presence of cSVD-related MRI markers. Three years later, patients underwent a neuropsychological assessment to determine cognitive performance. RESULTS A total of 101 patients with hypertension were included in the present study. In multiple linear regression analyses with correction for demographics and MRI markers, the compound score of endothelial activation (B = -0.19, 95% confidence interval = -0.34 to -0.04, P = 0.014), but not of inflammation (B = -0.09, 95% confidence interval = -0.22 to 0.05, P = 0.198), was associated with worse cognitive performance. CONCLUSIONS Our results show that an overall measure of endothelial activation is associated with cognitive performance in patients with essential hypertension. This indicates that a process involving endothelial activation might play a role in the pathogenesis of cognitive problems in patients with hypertension.

Framingham Stroke Risk Profile is related to cerebral small vessel disease progression and lower cognitive performance in patients with hypertension

The Framingham Stroke Risk Profile (FSRP) was developed to predict clinical stroke. We investigated if FSRP is associated with more “silent” effects of cerebrovascular disease, namely progression of cerebral small vessel disease (cSVD)‐related brain damage and cognitive performance in hypertensive patients. Ninety patients with essential hypertension underwent a brain MRI scan and FSRP assessment at baseline, and a second brain MRI scan and neuropsychological assessment at 9‐year follow‐up. We visually rated progression of cSVD‐related MRI markers. FSRP was associated with progressive periventricular white matter hyperintensities (P = .017) and new microbleeds (P = .031), but not after correction for the FSRP age component. FSRP was associated with lower overall cognitive performance (P < .001) and this remained significant after correction for the FSRP age component. A vascular risk score might be useful in predicting progression of cSVD‐related brain damage or future cognitive performance in hypertensive patients. Age seems to be the most important component in FSRP.

MRI progression of cerebral small vessel disease and cognitive decline in patients with hypertension.

Objective: Hypertension is associated with cognitive deficits, probably because it is a major risk factor for the development of white matter hyperintensities (WMH), lacunes, and cerebral microbleeds, which are MRI markers of cerebral small vessel disease. Studies into associations between presence or progression of these MRI markers and cognitive decline in hypertensive patients are rare. We investigated the association of baseline presence and progression of MRI markers of cerebral small vessel disease with cognitive decline over 4 years in patients with hypertension. Methods: In this longitudinal study, hypertensive patients underwent neuropsychological assessments and brain MRI at baseline and after 4 years. Presence and progression of periventricular and subcortical WMH, lacunes, and cerebral microbleeds were visually rated. Results: In total, 128 hypertensive patients (90 patients with essential hypertension and 38 hypertensive lacunar stroke patients), mean age: 58.6 ± 12.2 years, were included. Progression of periventricular WMH was associated with cognitive decline in simple regression analysis (P = 0.001) and in multivariable analysis with correction for baseline WMH presence and potential confounders (P = 0.004). In this multivariable analysis, R2 of progression of periventricular WMH was 5.6%, whereas R2 of baseline presence of periventricular WMH was 0.6%. We did not find significant associations between baseline presence or progression of the other MRI markers and cognitive decline. Conclusion: In patients with hypertension, progression of periventricular WMH over 4 years is associated with cognitive decline, whereas we could not show an association between baseline periventricular WMH and cognitive decline. These results emphasize the importance of preventing progression of WMH in hypertensive patients.

Effects of vitamin B12 supplementation on cognition, depression, and fatigue in patients with lacunar stroke

We read the review by Moore et al . (2012), recently published in this journal, with great interest and compliment the authors for their thorough review of cognitive impairment and its relation to vitamin B12.