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

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.

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

Translational Psychiatry ◽

10.1038/s41398-021-01495-4 ◽

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.

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

Aging ◽

10.18632/aging.101043 ◽

2016 ◽

Vol 8 (9) ◽

pp. 2039-2061 ◽

Cited By ~ 9

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

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

Scientific Reports ◽

10.1038/s41598-019-42534-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 11

Author(s):

Sarah McGrory ◽

Lucia Ballerini ◽

Fergus N. Doubal ◽

Julie Staals ◽

Mike Allerhand ◽

...

Keyword(s):

Birth Cohort ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Stroke Study ◽

Retinal Microvasculature ◽

Lothian Birth Cohort ◽

Mild Stroke

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Associations between total MRI-visible small vessel disease burden and domain-specific cognitive abilities in a community-dwelling older-age cohort

10.1101/2021.02.02.21250986 ◽

2021 ◽

Author(s):

OKL Hamilton ◽

SR Cox ◽

L Ballerini ◽

ME Bastin ◽

J Corley ◽

...

Keyword(s):

Cognitive Ability ◽

Processing Speed ◽

Verbal Memory ◽

Cognitive Abilities ◽

Small Vessel Disease ◽

Full Range ◽

Community Dwelling ◽

Small Vessel ◽

General Cognitive Ability ◽

Vessel Disease

AbstractCerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, however the precise nature of SVD-related cognitive deficits, and their associations with structural brain changes, remain unclear. We combined computational volumes and visually-rated MRI markers of SVD to quantify total SVD burden, using data from the Lothian Birth Cohort 1936 (n=540; age:72.6±0.7 years). We found negative associations between total SVD burden and general cognitive ability (standardised β: −0.363; 95%CI: [−0.49, −0.23]; p(FDR)<0.001), processing speed (−0.371 [−0.50, −0.24]; p(FDR)<0.001), verbal memory (−0.265; [−0.42, −0.11]; p(FDR)=0.002), and visuospatial ability (−0.170; [−0.32, −0.02]; p(FDR)=0.029). Only the association between SVD burden and processing speed remained after accounting for covariance with general cognitive ability (−0.325; [−0.61, −0.04]; p(FDR)=0.029). This suggests that SVD’s association with poorer processing speed is not driven by, but is independent of its association with poorer general cognitive ability. Tests of processing speed may be particularly sensitive to the cognitive impact of SVD, but all major cognitive domains should be tested to determine the full range of SVD-related cognitive characteristics.

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Cerebral small-vessel disease and decline in information processing speed, executive function and memory

Brain ◽

10.1093/brain/awh553 ◽

2005 ◽

Vol 128 (9) ◽

pp. 2034-2041 ◽

Cited By ~ 420

Author(s):

Niels D. Prins ◽

Ewoud J. van Dijk ◽

Tom den Heijer ◽

Sarah E. Vermeer ◽

Jellemer Jolles ◽

...

Keyword(s):

Information Processing ◽

Executive Function ◽

Processing Speed ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Information Processing Speed ◽

Vessel Disease

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Different cognitive profiles between mild cognitive impairment due to cerebral small vessel disease and mild cognitive impairment of Alzheimer’s disease origin

Journal of the International Neuropsychological Society ◽

10.1017/s1355617709990816 ◽

2009 ◽

Vol 15 (6) ◽

pp. 898-905 ◽

Cited By ~ 25

Author(s):

AIHONG ZHOU ◽

JIANPING JIA

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Processing Speed ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cognitive Domains ◽

Vessel Disease

AbstractControversy surrounds the differences of the cognitive profile between mild cognitive impairment resulting from cerebral small vessel disease (MCI-SVD) and mild cognitive impairment associated with prodromal Alzheimer’s disease (MCI-AD). The aim of this study was to explore and compare the cognitive features of MCI-SVD and MCI-AD. MCI-SVD patients (n = 56), MCI-AD patients (n = 30), and normal control subjects (n = 80) were comprehensively evaluated with neuropsychological tests covering five cognitive domains. The performance was compared between groups. Tests that discriminated between MCI-SVD and MCI-AD were identified. Multiple cognitive domains were impaired in MCI-SVD group, while memory and executive function were mainly impaired in MCI-AD group. Compared with MCI-SVD, MCI-AD patients performed relatively worse on memory tasks, but better on processing speed measures. The AVLT Long Delay Free Recall, Digit Symbol Test, and Stroop Test Part A (performance time) in combination categorized 91.1% of MCI-SVD patients and 86.7% of MCI-AD patients correctly. Current study suggested a nonspecific neuropsychological profile for MCI-SVD and a more specific cognitive pattern in MCI-AD. MCI-AD patients demonstrated greater memory impairment with relatively preserved mental processing speed compared with MCI-SVD patients. Tests tapping these two domains might be potentially useful for differentiating MCI-SVD and MCI-AD patients. (JINS, 2009, 15, 898–905.)

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Cognitive consequences of regression of cerebral small vessel disease

European Stroke Journal ◽

10.1177/2396987318820790 ◽

2018 ◽

Vol 4 (1) ◽

pp. 85-89 ◽

Cited By ~ 6

Author(s):

Esther MC van Leijsen ◽

Mayra I Bergkamp ◽

Ingeborg WM van Uden ◽

Sjacky Cooijmans ◽

Mohsen Ghafoorian ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Disease Markers ◽

Total Brain

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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Cerebral small vessel disease: Capillary pathways to stroke and cognitive decline

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15606723 ◽

2015 ◽

Vol 36 (2) ◽

pp. 302-325 ◽

Cited By ~ 102

Author(s):

Leif Østergaard ◽

Thorbjørn S Engedal ◽

Fiona Moreton ◽

Mikkel B Hansen ◽

Joanna M Wardlaw ◽

...

Keyword(s):

Cognitive Decline ◽

Capillary Flow ◽

Small Vessel Disease ◽

Genetic Disorders ◽

The Elderly ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vascular Pathology ◽

Vessel Disease ◽

Capillary Dysfunction

Cerebral small vessel disease (SVD) gives rise to one in five strokes worldwide and constitutes a major source of cognitive decline in the elderly. SVD is known to occur in relation to hypertension, diabetes, smoking, radiation therapy and in a range of inherited and genetic disorders, autoimmune disorders, connective tissue disorders, and infections. Until recently, changes in capillary patency and blood viscosity have received little attention in the aetiopathogenesis of SVD and the high risk of subsequent stroke and cognitive decline. Capillary flow patterns were, however, recently shown to limit the extraction efficacy of oxygen in tissue and capillary dysfunction therefore proposed as a source of stroke-like symptoms and neurodegeneration, even in the absence of physical flow-limiting vascular pathology. In this review, we examine whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD. We then discuss aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline.

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Superficial white matter microstructure affects processing speed in cerebral small vessel disease

10.1101/2021.12.30.474604 ◽

2022 ◽

Author(s):

Shuyue Wang ◽

Fan Zhang ◽

Peiyu Huang ◽

Hui Hong ◽

Yeerfan Jiaerken ◽

...

Keyword(s):

White Matter ◽

Processing Speed ◽

Diffusion Mri ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Large Contribution ◽

Vessel Disease ◽

White Matter Microstructure ◽

Patient Subgroups

White matter hyperintensities (WMH) are a typical feature of cerebral small vessel disease (CSVD). This condition contributes to about 50% of dementias worldwide, a massive health burden in aging. Microstructural alterations in the deep white matter (DWM) have been widely examined in CSVD. However, little is known about abnormalities in the superficial white matter (SWM) and their relevance for processing speed, the main cognitive deficit in CSVD. In this paper, 141 patients with CSVD were studied. Processing speed was assessed by the completion time of the Trail Making Test Part A. White matter abnormalities were assessed by WMH burden (lesion volume on T2-FLAIR) and diffusion MRI, including DTI and free-water (FW) imaging microstructure measures. The results of our study indicate that the superficial white matter may play a particularly important role in cognitive decline in CSVD. SWM imaging measures resulted in a large contribution to processing speed, despite a relatively small WMH burden in the SWM. SWM FW had the strongest association with processing speed among all imaging markers and, unlike the other diffusion MRI measures, significantly increased between two patient subgroups with the lowest WMH burdens (possibly representing early stages of disease). When comparing two patient subgroups with the highest WMH burdens, the involvement of WMH in the SWM was accompanied by significant differences in processing speed and white matter microstructure. Given significant effects of WMH volume and regional FW on processing speed, we performed a mediation analysis. SWM FW was found to fully mediate the association between WMH volume and processing speed, while no mediation effect of DWM FW was observed. Overall, our findings identify SWM abnormalities in CSVD and suggest that the SWM has an important contribution to processing speed. Results indicate that FW in the SWM is a sensitive marker of microstructural changes associated with cognition in CSVD. This study extends the current understanding of CSVD-related dysfunction and suggests that the SWM, as an understudied region, can be a potential target for monitoring pathophysiological processes in future research.

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