scholarly journals Retinal microvasculature and cerebral small vessel disease in the Lothian Birth Cohort 1936 and Mild Stroke Study

2018 ◽  
Author(s):  
Sarah McGrory ◽  
Lucia Ballerini ◽  
Fergus N. Doubal ◽  
Julie Staals ◽  
Mike Allerhand ◽  
...  
Keyword(s):  
Fractal Dimension ◽  
Birth Cohort ◽  
Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Retinal Vasculature ◽  
Vessel Disease ◽  
Stroke Study ◽  
Lothian Birth Cohort ◽  
Mild Stroke

ABSTRACTResearch has suggested that the retinal vasculature may act as a surrogate marker for diseased cerebral vessels. Retinal vascular parameters were measured using Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) software in two cohorts: (i) community-dwelling older subjects of the Lothian Birth Cohort 1936; and (ii) patients with recent minor ischaemic stroke of the Mild Stroke Study. Imaging markers of small vessel disease (SVD) (white matter hyperintensities [WMH] on structural MRI, visual scores and volume; perivascular spaces; lacunes and microbleeds), and vascular risk measures were assessed in both cohorts. We assessed associations between retinal and brain measurements using structural equation modelling and regression analysis. In the Lothian Birth Cohort 1936 arteriolar fractal dimension accounted for 4% of the variance in WMH load. In the Mild Stroke Study lower arteriolar fractal dimension was associated with deep WMH scores (odds ratio [OR] 0.53; 95% CI, 0.32-0.87). No other retinal measure was associated with SVD. Reduced fractal dimension, a measure of vascular complexity, is related to SVD imaging features in older people. The results provide some support for the use of the retinal vasculature in the study of brain microvascular disease.

scholarly journals Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936

Aging ◽  
2016 ◽  
Vol 8 (9) ◽  
pp. 2039-2061 ◽  
Author(s):  
Thalia S. Field ◽  
Fergus N. Doubal ◽  
Wendy Johnson ◽  
Ellen Backhouse ◽  
Caroline McHutchison ◽  
...  
Keyword(s):  
Birth Cohort ◽  
Early Life ◽  
Small Vessel Disease ◽  
Late Life ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Lothian Birth Cohort

scholarly journals Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3

2020 ◽  
pp. 239698732092961
Author(s):  
Una Clancy ◽  
Daniela Jaime Garcia ◽  
Michael S Stringer ◽  
Michael J Thrippleton ◽  
Maria C Valdés-Hernández ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Risk Factors ◽  
Magnetic Resonance ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Small Vessel ◽  
Resonance Imaging ◽  
Vessel Disease ◽  
Stroke Study ◽  
Mild Stroke

Background Cerebral small vessel disease is a major cause of dementia and stroke, visible on brain magnetic resonance imaging. Recent data suggest that small vessel disease lesions may be dynamic, damage extends into normal-appearing brain and microvascular dysfunctions include abnormal blood–brain barrier leakage, vasoreactivity and pulsatility, but much remains unknown regarding underlying pathophysiology, symptoms, clinical features and risk factors of small vessel disease. Patients and Methods: The Mild Stroke Study 3 is a prospective observational cohort study to identify risk factors for and clinical implications of small vessel disease progression and regression among up to 300 adults with non-disabling stroke. We perform detailed serial clinical, cognitive, lifestyle, physiological, retinal and brain magnetic resonance imaging assessments over one year; we assess cerebrovascular reactivity, blood flow, pulsatility and blood–brain barrier leakage on magnetic resonance imaging at baseline; we follow up to four years by post and phone. The study is registered ISRCTN 12113543. Summary Factors which influence direction and rate of change of small vessel disease lesions are poorly understood. We investigate the role of small vessel dysfunction using advanced serial neuroimaging in a deeply phenotyped cohort to increase understanding of the natural history of small vessel disease, identify those at highest risk of early disease progression or regression and uncover novel targets for small vessel disease prevention and therapy.

scholarly journals Cerebral small vessel disease burden and longitudinal cognitive decline from age 73 to 82: the Lothian Birth Cohort 1936

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
O. K. L. Hamilton ◽  
S. R. Cox ◽  
J. A. Okely ◽  
F. Conte ◽  
L. Ballerini ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Ability ◽  
Birth Cohort ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
General Cognitive Ability ◽  
Vessel Disease ◽  
Lothian Birth Cohort

AbstractSlowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.

scholarly journals Cerebral Small Vessel Disease Burden and Longitudinal Cognitive Decline from age 73 to 82: the Lothian Birth Cohort 1936

2021 ◽  
Author(s):  
Olivia KL Hamilton ◽  
Simon R Cox ◽  
Judy A Okely ◽  
Federica Conte ◽  
Lucia Ballerini ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Ability ◽  
Birth Cohort ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
General Cognitive Ability ◽  
Vessel Disease ◽  
Lothian Birth Cohort

Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD), however, it is unclear whether SVDs association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age:72.6±0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory, and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk, and childhood cognitive ability. In the fully-adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: -0.201; 95%CI: [-0.36, -0.04]; pFDR=0.022) and processing speed (-0.222; [-0.40, -0.04]; pFDR=0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVDs association with greater decline in general cognitive ability remained significant, prior to FDR correction (-0.222; [-0.39, -0.06]; p=0.008; pFDR=0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.

scholarly journals Cognitive heterogeneity among community-dwelling older adults with Cerebral Small Vessel Disease

2018 ◽  
Author(s):  
Ayan Dey ◽  
Vessela Stamenova ◽  
Agnes Bacopulos ◽  
Nivethika Jeyakumar ◽  
Gary R. Turner ◽  
...  
Keyword(s):  
White Matter ◽  
Subjective Experience ◽  
Small Vessel Disease ◽  
Neuropsychological Testing ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Vessel Disease ◽  
Age Related ◽  
Subjective Complaints

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities (WMHs). Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55-80 years old completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant WMH burden (~10 cubic cm). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed two CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioural heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective complaints that may be able to detect subtle effects of pathology not evident on standardized cognitive scores.

scholarly journals Association of cerebral small vessel disease burden with brain structure and cognitive and vascular risk trajectories in mid-to-late life

2021 ◽  
Author(s):  
Michelle G Jansen ◽  
Ludovica Griffanti ◽  
Clare E Mackay ◽  
Melis Anatürk ◽  
Luca Melazzini ◽  
...  
Keyword(s):  
Brain Structure ◽  
Small Vessel Disease ◽  
Late Life ◽  
Cognitive Status ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Vascular Risk ◽  
Linear Mixed Effects ◽  
Vessel Disease

We characterize the associations of total cerebral small vessel disease (SVD) burden with brain structure, trajectories of vascular risk factors, and cognitive functions in mid-to-late life. Participants were 623 community-dwelling adults from the Whitehall II Imaging Sub-study with multi-modal MRI (mean age 69.96 SD=5.18, 79% men). We used linear mixed-effects models to investigate associations of SVD burden with up to 25-year retrospective trajectories of vascular risk and cognitive performance. General linear modelling was used to investigate concurrent associations with grey matter (GM) density and white matter (WM) microstructure, and whether these associations were modified by cognitive status (Montreal Cognitive Assessment, MoCA). Severe SVD burden in older age was associated with higher mean arterial pressure throughout midlife (β=3.36, 95% CI [0.42—6.30]), and faster 25-year cognitive decline in letter fluency (β=-0.07, 95% CI [-0.13—-0.01]), and verbal reasoning (β=-0.05, 95% CI [-0.11—-0.001]). Moreover, SVD burden was related to lower GM volumes in 9.7% of total GM, and widespread WM microstructural decline (FWE-corrected p<0.05). The latter association was most pronounced in individuals with cognitive impairments on MoCA (F3,608=2.14, p=0.007). These findings highlight the importance of managing midlife vascular health to preserve brain structure and cognitive function in old age.

scholarly journals Disrupted Rest-Activity Rhythms and Cerebral Small Vessel Disease Pathology in Older Adults

Stroke ◽  
2021 ◽  
Author(s):  
Rosa Sommer ◽  
Lei Yu ◽  
Julie A. Schneider ◽  
David A. Bennett ◽  
Aron S. Buchman ◽  
...  
Keyword(s):  
Older Adults ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Activity Rhythms ◽  
Logistic Regression Models ◽  
Vessel Disease ◽  
Lower Amplitude ◽  
Rest Activity

Background and Purpose: The pathogenesis of cerebral small vessel disease remains incompletely understood. The relationship between circadian rhythm disturbances and histopathologic measures of cerebral small vessel disease has not been studied. We hypothesized that disrupted circadian rest-activity rhythms would be associated with a higher burden of cerebral small vessel disease pathology. Methods: We studied 561 community-dwelling older adults (mean age at death, 91.2, 27.4% male) from the Rush Memory and Aging Project. We used actigraphy to quantify several measures of 24-hour rest-activity rhythmicity, including interdaily stability, intradaily variability, and amplitude, and used ordinal logistic regression models to relate these measures to the severity of cerebral arteriolosclerosis, atherosclerosis, macroinfarcts, and microinfarcts, assessed at autopsy. Results: Lower interdaily stability was associated with a higher burden of arteriolosclerosis, higher intradaily variability was associated with a higher burden of atherosclerosis and subcortical infarcts, and lower amplitude was associated with a higher burden of arteriosclerosis, atherosclerosis and subcortical macroinfarcts. Moreover, the associations between interdaily stability and arteriolosclerosis and intradaily variability and subcortical infarcts were independent of cardiovascular risk factors, sleep fragmentation, and medical comorbidities. Conclusions: Disrupted rest-activity rhythms are associated with a greater burden of cerebral small vessel disease in older adults.

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