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, thi

Demographics and mean scores for lacunar stroke patients with and without vitamin B12 deficiency.

<p>*NIHSS scores were only available for 9 (with vitamin B12 deficiency) and 15 (without deficiency) patients.</p

Logistic regression analyses on the presence of severe fatigue.

<p>Model 1: univariate analysis. Model 2: multivariate analysis with adjustments for age and the presence of severe pWMLs.</p

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, R-2 of progression of periventricular WMH was 5.6%, whereas R-2 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

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

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