Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

Lawrence, Andrew J.; Brookes, Rebecca L.; Zeestraten, Eva; Barrick, Thomas R.; Morris, Robin G.; Markus, Hugh S.

doi:10.1371/journal.pone.0135523

Cited by 49 publications

(45 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The result is in line with a recent study (Lawrence et al, 2015) in patients with lacunar stroke and leukoaraiosis, in which patients showed a significant decline in executive function, but not in other domains (processing speed, working memory, and global cognition).…”

Section: Discussionsupporting

confidence: 92%

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

Uiterwijk

Oostenbrugge

Huijts

et al. 2016

Front. Aging Neurosci.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

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

Uiterwijk

Oostenbrugge

Huijts

et al. 2016

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…A magnetic resonance imaging (MRI) substudy embedded in the same trial showed that homocysteine‐lowering therapy significantly reduced the progression of white matter hyperintensities (an MRI marker of small vessel disease) . Although it did not reduce cognitive decline in the same study, this may be because cognitive testing has been shown to be insensitive to detect changes over a 2‐ to 3‐year period in this cerebral small vessel disease . Furthermore, several case‐control studies have shown that elevated tHcy levels are a stronger risk factor for SVS than other ischemic stroke subtypes and that tHcy levels are higher in patients with cerebral small vessel disease than in healthy controls, although such studies only show associations and cannot exclude confounding.…”

mentioning

confidence: 95%

Homocysteine and small vessel stroke: A mendelian randomization analysis

Larsson

Traylor

Markus

2019

Annals of Neurology

Self Cite

View full text Add to dashboard Cite

Objective Trials of B vitamin therapy to lower blood total homocysteine (tHcy) levels for prevention of stroke are inconclusive. Secondary analyses of trial data and epidemiological studies suggest that tHcy levels may be particularly associated with small vessel stroke (SVS). We assessed whether circulating tHcy and B vitamin levels are selectively associated with SVS, but not other stroke subtypes, using Mendelian randomization. Methods We used summary statistics data for single‐nucleotide polymorphisms (SNPs) associated with tHcy (n = 18), folate (n = 3), vitamin B 6 (n = 1), and vitamin B 12 (n = 14) levels, and the corresponding data for stroke from the MEGASTROKE consortium (n = 16,952 subtyped ischemic stroke cases and 404,630 noncases). Results Genetically predicted tHcy was associated with SVS, with an odds ratio of 1.34 (95% confidence interval [CI], 1.13–1.58; p = 6.7 × 10 –4 ) per 1 standard deviation (SD) increase in genetically predicted tHcy levels, but was not associated with large artery or cardioembolic stroke. The association was mainly driven by SNPs at or near the MTHFR and MUT genes. The odds ratios of SVS per 1 SD increase in genetically predicted folate and vitamin B 6 levels were 0.49 (95% CI, 0.34–0.71; p = 1.3 × 10 –4 ) and 0.70 (95% CI, 0.52–0.94; p = 0.02), respectively. Genetically higher vitamin B 12 levels were not associated with any stroke subtype. Interpretation These findings suggest that any effect of homocysteine‐lowering treatment in preventing stroke will be confined to the SVS subtype. Whether genetic variants at or near the MTHFR and MUT genes influence SVS risk through pathways other than homocysteine levels and downstream effects require further investigation. Ann Neurol 2019;85:495–501

show abstract

“…These impairments characteristically involve cognitive flexibility, attention, and processing speed [3–5], with episodic memory relatively spared [6, 7]. Neuropsychiatric comorbidities, particularly depressive symptoms [8–10] are increasingly being linked to SVD.…”

Section: Introductionmentioning

confidence: 99%

Apathy, but not depression, is associated with executive dysfunction in cerebral small vessel disease

et al. 2017

Self Cite

View full text Add to dashboard Cite

ObjectiveTo determine the prevalence of apathy and depression in cerebral small vessel disease (SVD), and the relationships between both apathy and depression with cognition. To examine whether apathy is specifically related to impairment in executive functioning and processing speed.Methods196 patients with a clinical lacunar stroke and an anatomically corresponding lacunar infarct on MRI were compared to 300 stroke-free controls. Apathy and depression were measured using the Geriatric Depression Scale, and cognitive functioning was assessed using an SVD cognitive screening tool, the Brief Memory and Executive Test, which measures executive functioning/processing speed and memory/orientation. Path analysis and binary logistic regression were used to assess the relation between apathy, depression and cognitive impairment.Results31 participants with SVD (15.8%) met criteria for apathy only, 23 (11.8%) for both apathy and depression, and 2 (1.0%) for depression only. In the SVD group the presence of apathy was related to global cognition, and specifically to impaired executive functioning/processing speed, but not memory/orientation. The presence of depression was not related to global cognition, impaired executive functioning/processing speed or memory/orientation.ConclusionsApathy is a common feature of SVD and is associated with impaired executive functioning/processing speed suggesting the two may share biological mechanisms. Screening for apathy should be considered in SVD, and further work is required to develop and evaluate effective apathy treatment or management in SVD.

show abstract

Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

Cited by 49 publications

References 35 publications

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

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

Homocysteine and small vessel stroke: A mendelian randomization analysis

Apathy, but not depression, is associated with executive dysfunction in cerebral small vessel disease

Contact Info

Product

Resources

About