Simple MRI score aids prediction of dementia in cerebral small vessel disease.
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ABSTRACT: Objective
To determine whether a simple small vessel disease (SVD) score, which uses information available on rapid visual assessment of clinical MRI scans, predicts risk of cognitive decline and dementia, above that provided by simple clinical measures.Methods
Three prospective longitudinal cohort studies (SCANS [St George's Cognition and Neuroimaging in Stroke], RUN DMC [Radboud University Nijmegen Diffusion Imaging and Magnetic Resonance Imaging Cohort], and the ASPS [Austrian Stroke Prevention Study]), which covered a range of SVD severity from mild and asymptomatic to severe and symptomatic, were included. In all studies, MRI was performed at baseline, cognitive tests repeated during follow-up, and progression to dementia recorded prospectively. Outcome measures were cognitive decline and onset of dementia during follow-up. We determined whether the SVD score predicted risk of cognitive decline and future dementia. We also determined whether using the score to select a group of patients with more severe disease would reduce sample sizes for clinical intervention trials.Results
In a pooled analysis of all 3 cohorts, the score improved prediction of dementia (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.81-0.89) compared with that from clinical risk factors alone (AUC, 0.76; 95% CI, 0.71-0.81). Predictive performance was higher in patients with more severe SVD. Power calculations showed selecting patients with a higher score reduced sample sizes required for hypothetical clinical trials by 40%-66% depending on the outcome measure used.Conclusions
A simple SVD score, easily obtainable from clinical MRI scans and therefore applicable in routine clinical practice, aided prediction of future dementia risk.
SUBMITTER: Amin Al Olama A
PROVIDER: S-EPMC7274929 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To determine whether MRI markers, including diffusion tensor imaging (DTI), can predict cognitive decline and dementia in patients with cerebral small vessel disease (SVD).In the prospective St George's Cognition and Neuroimaging in Stroke study, multimodal MRI was performed annually for 3 years and cognitive assessments annually for 5 years in a cohort of 99 patients with SVD, defined as symptomatic lacunar stroke and confluent white matter hyperintensities (WMH). Progression to dementia was determined in all patients. Progression of WMH, brain volume, lacunes, cerebral microbleeds, and a DTI measure (the normalized peak height of the mean diffusivity histogram distribution) as a marker of white matter microstructural damage were determined.Over 5 years of follow-up, 18 patients (18.2%) progressed to dementia. A significant change in all MRI markers, representing deterioration, was observed. The presence of new lacunes, and rate of increase in white matter microstructural damage on DTI, correlated with both decline in executive function and global functioning. Growth of WMH and deterioration of white matter microstructure on DTI predicted progression to dementia. A model including change in MRI variables together with their baseline values correctly classified progression to dementia with a C statistic of 0.85.This longitudinal prospective study provides evidence that change in MRI measures including DTI, over time durations during which cognitive change is not detectable, predicts cognitive decline and progression to dementia. It supports the use of MRI measures, including DTI, as useful surrogate biomarkers to monitor disease and assess therapeutic interventions.
| S-EPMC5664300 | biostudies-literature
Project description:Sporadic cerebral small vessel disease is an important cause of vascular dementia, a syndrome of cognitive impairment together with vascular brain damage. At post-mortem pure vascular dementia is rare, with evidence of co-existing Alzheimer's disease pathology in 95% of cases. This work used MRI to characterize structural abnormalities during the preclinical phase of vascular dementia in symptomatic small vessel disease. 121 subjects were recruited into the St George's Cognition and Neuroimaging in Stroke study and followed up longitudinally for five years. Over this period 22 individuals converted to dementia. Using voxel-based morphometry, we found structural abnormalities present at baseline in those with preclinical dementia, with reduced grey matter density in the left striatum and hippocampus, and more white matter hyperintensities in the frontal white-matter. The lacunar data revealed that some of these abnormalities may be due to lesions within the striatum and centrum semiovale. Using support vector machines, future dementia could be best predicted using hippocampal and striatal Jacobian determinant data, achieving a balanced classification accuracy of 73%. Using cluster ward linkage we identified four anatomical subtypes. Successful predictions were restricted to groups with lower levels of vascular damage. The subgroup that could not be predicted were younger, further from conversion, had the highest levels of vascular damage, with milder cognitive impairment at baseline but more rapid deterioration in processing speed and executive function, consistent with a primary vascular dementia. In contrast, the remaining groups had decreasing levels of vascular damage and increasing memory impairment consistent with progressively more Alzheimer's-like pathology. Voxel-wise rates of hippocampal atrophy supported these distinctions, with the vascular group closely resembling the non-dementing cohort, whereas the Alzheimer's like group demonstrated global hippocampal atrophy. This work reveals distinct anatomical endophenotypes in preclinical vascular dementia, forming a spectrum between vascular and Alzheimer's like pathology. The latter group can be identified using baseline MRI, with 73% converting within 5?years. It was not possible to predict the vascular dominant dementia subgroup, however 19% of negative predictions with high levels of vascular disease would ultimately develop dementia. It may be that techniques more sensitive to white matter damage, such as diffusion weighted imaging, may prove more useful for this vascular dominant subgroup in the future. This work provides a way to accurately stratify patients using a baseline MRI scan, and has utility in future clinical trials designed to slow or prevent the onset of dementia in these high-risk cohorts.
| S-EPMC6039843 | biostudies-other
Project description:BackgroundCerebral small vessel disease is the most common pathology underlying vascular dementia. In small vessel disease, diffusion tensor imaging is more sensitive to white matter damage and better predicts dementia risk than conventional magnetic resonance imaging sequences, such as T1 and fluid attenuation inversion recovery, but diffusion tensor imaging takes longer to acquire and is not routinely available in clinical practice. As diffusion tensor imaging-derived scalar maps-fractional anisotropy (FA) and mean diffusivity (MD)-are frequently used in clinical settings, one solution is to synthesize FA/MD from T1 images.MethodsWe developed a deep learning model to synthesize FA/MD from T1. The training data set consisted of 4998 participants with the highest white matter hyperintensity volumes in the UK Biobank. Four external validations data sets with small vessel disease were included: SCANS (St George's Cognition and Neuroimaging in Stroke; n=120), RUN DMC (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort; n=502), PRESERVE (Blood Pressure in Established Cerebral Small Vessel Disease; n=105), and NETWORKS (n=26), along with 1000 normal controls from the UK Biobank.ResultsThe synthetic maps resembled ground-truth maps (structural similarity index >0.89 for MD maps and >0.80 for FA maps across all external validation data sets except for SCANS). The prediction accuracy of dementia using whole-brain median MD from the synthetic maps is comparable to the ground truth (SCANS ground-truth c-index, 0.822 and synthetic, 0.821; RUN DMC ground truth, 0.816 and synthetic, 0.812) and better than white matter hyperintensity volume (SCANS, 0.534; RUN DMC, 0.710).ConclusionsWe have developed a fast and generalizable method to synthesize FA/MD maps from T1 to improve the prediction accuracy of dementia in small vessel disease when diffusion tensor imaging data have not been acquired.
| S-EPMC11346716 | biostudies-literature
Project description: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.
| S-EPMC5149514 | biostudies-literature
Project description:Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype.
| S-EPMC6683288 | biostudies-literature
Project description:A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B?-insensitive R? measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R? and R?* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24?30 h and (iv) one month. Absolute and blood-normalised changes in R? and R?* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R? measurements were accurate across a wide range of values. R? (p < 0.05) and R?* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24?30 h. R?* returned to baseline at one month. Blood-normalised R? and R?* changes post-infusion and at 24?30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R?* than for R? mapping. R? and R?* changes were correlated at 24?30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R?* appears to be more sensitive to USPIO than R?. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak.
| S-EPMC6387454 | biostudies-literature
Project description:Even with postmortem pathological examination, only limited information is provided of the foci of in vivo clinical information. Cerebral small vessel disease, which is associated with ageing, dementia and stroke, highlights the difficulty in arriving at a definitive diagnosis of the lesions detected on in vivo radiological examination. We performed a radiological-pathological comparative study using ex vivo MRI to examine small cerebral lesions. Four patients with small vessel disease lesions detected on in vivo MRI were studied. Exact pathological findings of in vivo MRI-detected lesions were revealed. The ischaemic lesion after 17 days from onset showed positivity for peroxiredoxin, cluster of differentiation 204 and glial fibrillary acidic protein, indicating sterile inflammation and neuroprotective reaction. Cortical microinfarcts beneath the cortical superficial siderosis were associated with inflammation from the superficial layer in a patient with cerebral amyloid angiopathy; in this patient, a bilinear track-like appearance of the cortical superficial siderosis on the ex vivo MRI was compatible with iron deposition on the pia matter and within cortical layers II-III. An in vivo MRI-detected cerebral microbleed was revealed to be heterogeneous. An in vivo MRI-detected cerebral microbleed was revealed to be a venous angioma. Furthermore, a neuropathologically confirmed embolic cerebral microbleed was firstly detected using this method. Our results suggest that in vivo MRI-detected lobar cerebral microbleeds can be caused by non-cerebral amyloid angiopathy aetiologies, such as microembolism and venous angioma. Venous angioma and embolic microbleeds may mimic cerebral amyloid angiopathy markers on in vivo MRI. To clarify the clinical importance of these lesions, we should investigate their rate and frequency in a large cohort of healthy individuals and patients with cardiac risk factors. Thus, we provide evidence that ex vivo micro-MRI improves the clinical diagnosis of small vessel diseases.
| S-EPMC8111066 | biostudies-literature
Project description:ObjectiveOur aim was to investigate the relationship of carotid structure and function with MRI markers of cerebral ischemic small-vessel disease.MethodsThe study comprised 1,800 participants (aged 72.5 ± 4.1 years, 59.4% women) from the 3C-Dijon Study, a population-based, prospective cohort study, who had undergone quantitative brain MRI and carotid ultrasound. We used multivariable logistic and linear regression adjusted for age, sex, and vascular risk factors.ResultsPresence of carotid plaque and increasing carotid lumen diameter (but not common carotid artery intima-media thickness) were associated with higher prevalence of lacunar infarcts: odds ratio (OR) = 1.60 (95% confidence interval [CI]: 1.09-2.35), p = 0.02 and OR = 1.24 (95% CI: 1.02-1.50), p = 0.03 (by SD increase). Carotid plaque was also associated with large white matter hyperintensity volume (WMHV) (age-specific top quartile of WMHV distribution): OR = 1.32 (95% CI: 1.04-1.67), p = 0.02, independently of vascular risk factors. Increasing Young elastic modulus and higher circumferential wall stress, reflecting augmented carotid stiffness, were associated with increasing WMHV (effect estimate [?] ± standard error: 0.0003 ± 0.0001, p = 0.024; ? ± standard error: 0.005 ± 0.002, p = 0.008). Large WMHV was also associated with increasing Young elastic modulus (OR = 1.22 [95% CI: 1.04-1.42], p = 0.01) and with decreasing distensibility coefficient (OR = 0.83 [95% CI: 0.69-0.99], p = 0.04), independently of vascular risk factors. Associations of carotid lumen diameter with lacunar infarcts and of carotid stiffness markers with WMHV were independent of carotid plaque.ConclusionsIn addition to and independently of carotid plaque, increasing carotid lumen diameter and markers of carotid stiffness were associated with increasing prevalence of lacunar infarcts and increasing WMHV, respectively.
| S-EPMC3590057 | biostudies-literature
Project description:Background and Purpose: The association of retinal microvascular abnormalities with the total cerebral small vessel disease (cSVD) burden found on brain MRI has not been determined. In the present study, we examined whether the retinopathy score could predict the total cSVD burden in ischemic stroke/transient ischemic attack (TIA) patients. A simple practical diagnostic tool may help identify candidates for MRI screening. Methods: We consecutively collected clinical data including retinal photography and cerebral MRI of ischemic stroke/TIA patients from August 2016 to August 2017 at our stroke center. The retinopathy score was assessed by the Keith-Wagener-Barker grading system for analyzing retinal microvascular abnormalities. To evaluate the total cSVD burden, the total cSVD score was assessed by awarding one point for the presence of each marker of cSVD on MRI. The clinical characteristics and retinopathy score were analyzed across patients for each total cSVD score. The association between the retinopathy score and the total cSVD score was analyzed. Results: Among the 263 enrolled patients, the frequency of hypertension in patients with a total cSVD score of 2, 3, or 4 was higher than that in patients with a score of 0 (69.5, 71.7, and 89.2% vs. 45.2% respectively, all P < 0.05). The retinopathy score was related to the total cSVD score (r = 0.687, P < 0.001). Adjusted multivariate ordinal regression showed that the retinopathy score was independently correlated with the total cSVD score (odds ratio [OR], 4.18; 95% confidence interval [CI], 3.07-5.70) after adjustment for age, history of hypertension, previous stroke/TIA and current smoking. The c statistics were 0.30 (95% CI, 0.24-0.37; P < 0.05), 0.46 (95% CI, 0.39-0.53; P = 0.303), 0.79 (95% CI, 0.72-0.86; P < 0.001), and 0.81 (95% CI, 0.74-0.88; P < 0.001) for predicting the total cSVD score of 1, 2, 3, and 4 respectively. Conclusions: These results suggest that retinal microvascular abnormalities have predictive value for severe total cSVD burden in ischemic stroke/TIA patients.
| S-EPMC7177024 | biostudies-literature
Project description:Cerebral small vessel disease (SVD) is among the most frequent causes of both stroke and dementia. There is a growing list of genes known to be implicated in Mendelian forms of SVD. Also, genome-wide association studies have identified common variants at a number of genetic loci that are associated with manifestations of SVD, among them loci for white matter hyperintensities, small vessel stroke, and deep intracerebral hemorrhage. Driven by these discoveries and new animal models substantial progress has been made in elucidating the molecular, cellular, and physiologic mechanisms underlying SVD. A major theme emerging from these studies is the extracellular matrix (ECM). Recent findings include a role of structural constituents of the ECM such as type IV collagens in hereditary and sporadic SVD, the sequestration of proteins with a known role in ECM maintenance into aggregates of NOTCH3, and altered signaling through molecules known to interact with the ECM. Here, we review recent progress in the identification of genes involved in SVD and discuss mechanistic concepts with a particular focus on the ECM.
| S-EPMC4758558 | biostudies-literature