Impact of Strategically Located White Matter Hyperintensities on Cognition in Memory Clinic Patients with Small Vessel Disease

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.

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Collateral Recruitment Is Impaired by Cerebral Small Vessel Disease

Stroke ◽

10.1161/strokeaha.119.027661 ◽

2020 ◽

Vol 51 (5) ◽

pp. 1404-1410 ◽

Cited By ~ 3

Author(s):

Michelle P. Lin ◽

Thomas G. Brott ◽

David S. Liebeskind ◽

James F. Meschia ◽

Kevin Sam ◽

...

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Cerebral Microbleeds ◽

Large Vessel ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Poor Recruitment

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.

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Adverse effects of pre-existing cerebral small vessel disease on cognitive improvement after carotid endarterectomy

International Journal of Stroke ◽

10.1177/1747493019874732 ◽

2019 ◽

Vol 15 (6) ◽

pp. 657-665 ◽

Cited By ~ 2

Author(s):

Jun Yoshida ◽

Fumio Yamashita ◽

Makoto Sasaki ◽

Kunihiro Yoshioka ◽

Shunrou Fujiwara ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Carotid Endarterectomy ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cognitive Improvement ◽

Vessel Disease

Background Although patients with improved cognition after carotid endarterectomy usually exhibit postoperative restoration of cerebral blood flow, less than half of patients with such cerebral blood flow change have postoperatively improved cognition. Cerebral small vessel disease on magnetic resonance imaging is associated with irreversible cognitive impairment. Aims The purpose of the present prospective study was to determine whether pre-existing cerebral small vessel disease affects cognitive improvement after carotid endarterectomy. Methods Brain MR imaging was performed preoperatively, and the number or grade of each cerebral small vessel disease was determined in 80 patients undergoing carotid endarterectomy for ipsilateral internal carotid artery stenosis (≥70%). The volume of white matter hyperintensities relative to the intracranial volume was also calculated. Brain perfusion single-photon emission computed tomography and neuropsychological testing were performed preoperatively and two months postoperatively. Based on these data, a postoperative increase in cerebral blood flow and postoperative improved cognition, respectively, were determined. Results Logistic regression analysis using the sequential backward elimination approach revealed that a postoperative increase in cerebral blood flow (95% confidence interval [CI], 10.74–3730.00; P = 0.0004) and the relative volume of white matter hyperintensities (95% CI, 0.01–0.63; P = 0.0314) were significantly associated with postoperative improved cognition. Although eight of nine patients with postoperative improved cognition exhibited both a relative volume of white matter hyperintensities <0.65% and a postoperative increase in cerebral blood flow, none of patients with a relative volume of white matter hyperintensities ≥0.65% had postoperative improved cognition regardless of any postoperative change in cerebral blood flow. Conclusion Pre-existing cerebral white matter hyperintensities on magnetic resonance imaging adversely affect cognitive improvement after carotid endarterectomy.

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Automated detection of white matter hyperintensities of all sizes in cerebral small vessel disease

Medical Physics ◽

10.1118/1.4966029 ◽

2016 ◽

Vol 43 (12) ◽

pp. 6246-6258 ◽

Cited By ~ 29

Author(s):

Mohsen Ghafoorian ◽

Nico Karssemeijer ◽

Inge W. M. van Uden ◽

Frank-Erik de Leeuw ◽

Tom Heskes ◽

...

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Automated Detection ◽

Small Vessel ◽

Vessel Disease

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Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness

Cerebrovascular Diseases Extra ◽

10.1159/000377710 ◽

2015 ◽

Vol 5 (2) ◽

pp. 41-51 ◽

Cited By ~ 21

Author(s):

Anna-Märta Gustavsson ◽

Erik Stomrud ◽

Kasim Abul-Kasim ◽

Lennart Minthon ◽

Peter M. Nilsson ◽

...

Keyword(s):

Cognitive Function ◽

White Matter ◽

Arterial Stiffness ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Microbleeds ◽

Small Vessel ◽

Cognitive Tests ◽

Vessel Disease ◽

Healthy Elderly

Background: Arterial stiffness reflects the ageing processes in the vascular system, and studies have shown an association between reduced cognitive function and cerebral small vessel disease. Small vessel disease can be visualized as white matter hyperintensities (WMH) and lacunar infarcts but also as cerebral microbleeds on brain magnetic resonance imaging (MRI). We aimed to investigate if arterial stiffness influences the presence of microbleeds, WMH and cognitive function in a population of cognitively healthy elderly. Methods: The study population is part of the Swedish BioFinder study and consisted of 208 individuals without any symptoms of cognitive impairment, who scored >27 points on the Mini-Mental State Examination. The participants (mean age, 72 years; 59% women) underwent MRI of the brain with visual rating of microbleeds and WMH. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV). Eight cognitive tests covering different cognitive domains were performed. Results: Microbleeds were detected in 12% and WMH in 31% of the participants. Mean (±standard deviation, SD) cfPWV was 10.0 (±2.0) m/s. There was no association between the presence of microbleeds and arterial stiffness. There was a positive association between arterial stiffness and WMH independent of age or sex (odds ratio, 1.58; 95% confidence interval, 1.04-2.40, p < 0.05), but the effect was attenuated when further adjustments for several cardiovascular risk factors were performed (p > 0.05). Cognitive performance was not associated with microbleeds, but individuals with WMH performed slightly worse than those without WMH on the Symbol Digit Modalities Test (mean ± SD, 35 ± 7.8 vs. 39 ± 8.1, p < 0.05). Linear regression revealed no direct associations between arterial stiffness and the results of the cognitive tests. Conclusions: Arterial stiffness was not associated with the presence of cerebral microbleeds or cognitive function in cognitively healthy elderly. However, arterial stiffness was related to the presence of WMH, but the association was attenuated when multiple adjustments were made. There was a weak negative association between WMH and performance in one specific test of attention. Longitudinal follow-up studies are needed to further assess the associations.

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Ventricular expansion, white matter hyperintensities, and global cognition in Alzheimer’s disease and normal aging

10.1101/2020.11.30.20240879 ◽

2020 ◽

Author(s):

Sabrina Adamo ◽

Joel Ramirez ◽

Melissa F. Holmes ◽

Fuqiang Gao ◽

Ljubica Zotovic ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Normal Aging ◽

Small Vessel ◽

Cognitive Test ◽

Vessel Disease ◽

Link Type

ABSTRACTBackgroundThe progression of Alzheimer’s Disease (AD) may be tracked by measuring the growth of the ventricular cerebrospinal fluid (vCSF) over time. AD is commonly comorbid with markers of cerebral small vessel disease (SVD), viewed on MRI as white matter hyperintensities (WMH). Larger WMH volumes are correlated with poorer cognitive test scores. Additionally, periventricular WMHs have a proposed relationship to the vCSF.PurposeThis study will examine ventricular expansion and its associations between periventricular/deep WMH and cognition in AD and normal aging.MethodsBaseline and 1-year follow-up data were collected from AD (n=117) and cognitively normal control (NCs; n=49) participants taking part in the Sunnybrook Dementia Study. MRI (1.5T) and scores from both the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS) were assessed at each time point. Volumetric data was generated using a semi-automated pipeline and each individual’s vCSF and WMHs were transformed to an intermediate space to determine volumetric growth. Regressions were used to determine relationships between vCSF growth measures, SVD burden, and cognition, accounting for demographics and individual interscan intervals.ResultsThe AD group displayed 14.6% annual ventricular growth as opposed to NC who had only 11.8% annual growth. AD showed significant growth in vCSF (p < 0.001), a trend toward greater pWMH growth (p = 0.06) and no difference in dWMH growth volumes compared to NC. vCSF growth was positively associated with pWMH (β = 0.32, p < 0.001) but not dWMH growth in AD while in NC it was associated with both pWMH (β = 0.48, p < 0.001) and dWMH growth (β = 0.35, p = 0.02). In AD, vCSF growth was associated with the both the MMSE (β = -0.30, p < 0.001) and the DRS (β = -0.31, p < 0.001) in separate models.ConclusionsThe findings from this study suggest that in just under 1.5 years, the significantly rapid ventricular expansion observed in AD may be closely related to periventricular small vessel disease. As vCSF growth rates are an important biomarker of AD neurodegeneration that corresponds with cognitive decline, future research should further explore atrophy associated with periventricular vasculopathy.Trial RegistrationClinicalTrials.gov, NCT01800214. Registered on 27 February 2013.

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Fibrinogen is an Independent Risk Factor for White Matter Hyperintensities in CADASIL but not in Sporadic Cerebral Small Vessel Disease Patients

Aging and Disease ◽

10.14336/ad.2020.1110 ◽

2021 ◽

Vol 12 (3) ◽

pp. 801

Author(s):

Xingfang Guo ◽

Bin Deng ◽

Lizi Zhong ◽

Fen Xie ◽

Qing Qiu ◽

...

Keyword(s):

Risk Factor ◽

White Matter ◽

Independent Risk Factor ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease

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Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

Brain Communications ◽

10.1093/braincomms/fcaa111 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Fanny Quandt ◽

Felix Fischer ◽

Julian Schröder ◽

Marlene Heinze ◽

Iris Lettow ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Functional Connectivity ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

White Matter Lesion ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Lesion Load ◽

Vessel Disease

Abstract Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.

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