***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Cerebral autosomal dominant arteriopathy with subcortical infa rcts and leucoencephalopathy ( CADASIL ) is a hereditary arteriopathy caused by mutations of the Notch3 gene . The risk factors for cerebral microhaemorrhages ( CM ) , their relationship to other MRI lesions in the disease and their potential clinical impact have not been previously defined . Our purpose was to examine the frequency , number and location of microhaemorrhages in a multicentre cohort study , defining predisposing factors and associated radiographic markers in CADASIL patients . We collected clinical data from 147 consecutive patients enrolled in an ongoing prospect i ve cohort study .  Degree of neurological disability and cognitive impairment were assessed by st and ardized scales . T(1)-weighted , FLAIR and T2 * -weighted gradient-echo ( GE ) MRI sequences were performed . Volume and location of lacunar infa rcts and white matter hyperintensity ( WMH ) were assessed . Number and location of CM were recorded . CM were present in 35 % patients , most commonly occurring in the thalamus , brainstem and basal ganglia . The location of CM qualitatively differed from areas of lacunar infa rct ion and WMH . There was a significant association between the presence of CM and a history of hypertension ( P = 0.005 ) , systolic blood pressure ( SBP ) ( P = 0.014 ) , haemoglobin A1c ( HbA1c ) ( P = 0.004 ) and the volume of lacunar infa rcts ( P = 0.010 ) and WMHs ( P = 0.046 ) . The number of CM was independently associated with SBP ( P = 0.005 ) , the diagnosis of hypertension ( P = 0.0004 ) , volume of WMH ( P = 0.0005 ) and lacunar infa rcts ( P = 0.004 ) . In contrast , no association was found between blood pressure or HbA1c and the load of WMH or lacunar infa rcts . The presence of CM was independently associated with increased modified Rankin scores . CM are independently associated with blood pressure and HbA1c as well as with lacunar infa rct and WMH volume in CADASIL . Both the vascular risk factors and regional distribution of CM appear distinct from those associated with other MRI markers , suggesting a distinct pathological process . These lesions have a potential clinical impact in CADASIL . These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease Background —The prevalence of white matter hyperintensities ( WMHs ) detected on cerebral MRI is associated with hypertension , but it is not known whether blood pressure lowering can arrest their progression . We report here the results of an MRI sub study of PROGRESS ( Perindopril Protection Against Recurrent Stroke Study ) , a r and omized trial of blood pressure lowering in subjects with cerebrovascular disease . Methods and Results —The sub study comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months ( SD=6.0 months ) . At the first MRI , WMHs were grade d with a visual rating scale from A ( no WMH ) to D ( severe WMH ) . Participants were assigned to a combination of perindopril plus indapamide ( or their placebos ; 58 % ) or to single therapy with perindopril ( or placebo ) . At the time of the second MRI , the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure . Twenty-four subjects ( 12.5 % ) developed new WMHs at follow-up . The risk of new WMH was reduced by 43 % ( 95 % CI −7 % to 89 % ) in the active treatment group compared with the placebo group ( P=0.17 ) . The mean total volume of new WMHs was significantly reduced in the active treatment group ( 0.4 mm3 [ SE=0.8 ] ) compared with the placebo group ( 2.0 mm3 [ SE=0.7 ] ; P=0.012 ) . This difference was greatest for patients with severe WMH at entry , 0.0 mm3 ( SE=0 ) in the active treatment group versus 7.6 mm3 ( SE=1.0 ) in the placebo group ( P<0.0001 ) . Conclusions —These results indicate that an active blood pressure – lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease Cerebral white matter lesions ( WMLs ) have been associated with cognitive dysfunction . Whether periventricular or subcortical WMLs relate differently to cognitive function is still uncertain . In addition , it is unclear whether WMLs are related to specific cognitive domains such as memory or psychomotor speed . We examined the relationship between periventricular and subcortical WMLs and cognitive functioning in 1,077 elderly subjects r and omly sample d from the general population . Quantification of WMLs was assessed by means of an extensive rating scale on 1.5‐T magnetic resonance imaging scans . Cognitive function was assessed by using multiple neuropsychological tests from which we constructed compound scores for psychomotor speed , memory performance , and global cognitive function . When analyzed separately , both periventricular and subcortical WMLs were related to all neuropsychological measures . When periventricular WMLs were analyzed conditional on subcortical WMLs and vice versa , the relationship between periventricular WMLs and global cognitive function remained unaltered whereas the relationship with subcortical WMLs disappeared . Subjects with most severe periventricular WMLs performed nearly 1 SD below average on tasks involving psychomotor speed , and more than 0.5 SD below average for global cognitive function . Tasks that involve speed of cognitive processes appear to be more affected by WMLs than memory tasks . Ann Neurol 2000;47:145–151 Background and Purpose We investigated the hypothesis that patients with one or more asymptomatic lacunar infa rcts and those with only one symptomatic lacunar infa rct represent two clinical ly distinct lacunar infa rct entities . Methods In a prospect i ve series of 100 lacunar infa rct patients , univariate and multivariate logistic regression analysis was performed on clinical features , vascular risk factors , and leukoaraiosis between patients with and without asymptomatic lacunar infa rcts . Results Patients with asymptomatic lacunar infa rcts had hypertension significantly more often ( 71 % versus 43 % ; [ crude ] odds ratio , 3.31 ; 95 % confidence intervals , 1.16 - 9.43 ; p<0.05 ) and had leukoaraiosis significantly more often ( 71 % versus 19 % ; [ crude ] odds ratio , 10.67 ; 95 % confidence intervals , 3.81 - 32.10 ; p < 0.001 ) than those with only a symptomatic lacunar infa rct . After multivariate logistic regression analysis , only leukoaraiosis was significantly associated with the presence of asymptomatic lacunar infa rcts . The asymptomatic lacunar infa rcts differed in location , involved vascular territory , and volume from the symptomatic infa rcts . Conclusions Two distinct lacunar infa rct entities might be broadly distinguished during life : lacunar infa rct patients with a single , symptomatic lacunar infa rct , and patients with multiple lacunar infa rcts and a high frequency of hypertension and leukoaraiosis , in which the underlying small-vessel vasculopathy might be different Background and Purpose — Gradient-echo T2 * -weighted MRI is uniquely sensitive to detect silent , old hemosiderin deposits , but the clinical significance of such “ microbleeds ” remains to be determined . Therefore , we investigated the incidence and the number of microbleeds among different stroke subtypes and the correlation with stroke recurrence and the severity of leukoaraiosis . Methods — This study consisted of 213 patients ( 73.5±9.1 years old , 104 men and 109 women ) , who were classified according to stroke subtypes into atherothrombotic infa rct ion ( 24 patients ) , cardioembolic infa rct ion ( 23 patients ) , lacunar infa rct ion ( 66 patients ) , intracerebral hemorrhage ( 35 patients ) , and control ( 65 patients ) groups .  Gradient-echo T2 * -weighted MRI was performed with a 1.5 T system , and asymptomatic microbleeds were located and counted . Results — The incidence and the number of microbleeds were significantly greater in patients with intracerebral hemorrhage ( 71.4 % and 9.1±13.8 , respectively ) and lacunar infa rct ion ( 62.1 % and 7.4±16.1 ) compared with patients with cardioembolic infa rct ion ( 30.4 % and 2.5±5.6 ) , atherothrombotic infa rct ion ( 20.8 % and 0.63±1.53 ) , and controls ( 7.7 % and 0.09±0.34 ) . There was a correlation between the number of microbleeds and the severity of periventricular hyperintensity ( r = 0.626 , P < 0.0001 ) . There was also a correlation between the number of microbleeds and the number of intracerebral hemorrhages ( r = 0.689 , P < 0.0001 ) or lacunar infa rct ions ( r = 0.514 , P < 0.0001 ) . The locations of microbleeds were subcortical white matter ( 31.8 % ) , thalamus ( 24.8 % ) , basal ganglia ( 19.8 % ) , brain stem ( 12.0 % ) , and cerebellum ( 11.7 % ) . Conclusions — The findings suggest that microbleeds on T2 * -weighted MRI are an indicator of advanced small artery disease of the brain with an increased risk for bleeding . This result should be taken into consideration when treating patients with stroke , and further studies are required Patients with cerebral small vessel disease ( SVD ) can present as isolated lacunar infa rct ion or with diffuse white matter changes , with the imaging appearance of leukoaraiosis . Endothelial dysfunction , which can lead to breakdown of the blood-brain barrier , impaired cerebral autoregulation and prothrombotic changes , is believed to be important in mediating disease . Circulating levels of intercellular adhesion molecule 1 ( ICAM1 ) , thrombomodulin ( TM ) , tissue factor ( TF ) and tissue factor pathway inhibitor ( TFPI ) are markers of endothelial activation and damage , and may provide insights into disease pathogenesis or differences between phenotypes . We therefore measured these markers in a prospect i ve series of patients with lacunar stroke . One hundred and ten white Caucasian patients with previous lacunar stroke and 50 community control subjects were studied .  Markers of endothelial function were measured on venous blood sample s. Patients were classified on brain imaging into two groups : isolated lacunar infa rct ion  ( n = 47 ) and ischaemic leukoaraiosis , defined as a clinical lacunar stroke and leukoaraiosis on brain imaging ( n = 63 ) . The number of lacunes and severity of leukoaraiosis were also scored on MRI . ICAM1 , TM and TFPI were elevated in cerebral SVD subjects compared with controls ( P < or= 0.006 ) . The ischaemic leukoaraiosis group had a different endothelial marker profile , with lower levels of TFPI ( P = 0.01 ) and a higher TF/TFPI ratio ( P = 0.01 ) compared with the isolated lacunar infa rct ion group . TM levels were associated with the number of lacunes ( P = 0.008 ) and the leukoaraiosis score ( P = 0.03 ) , but TF levels and the TF/TFPI ratio were associated only with the extent of leukoaraiosis ( P < or= 0.02 ) . These results suggest that there is evidence of chronic endothelial dysfunction in cerebral SVD , and endothelial prothrombotic changes may be important in mediating the ischaemic leukoaraiosis phenotype . Therapies which help to stabilize the endothelium may have a role in this group of patients Background and Purpose — Most previous studies addressed the cognitive impact of lacunar infa rcts using radiologic correlations that are known to correlate poorly with neuropathological data . Moreover , absence of systematic bilateral assessment of vascular lesions and masking effects of Alzheimer disease pathology and macrovascular lesions may explain discrepancies among previous reports . To define the relative contribution of silent lacunes to cognitive decline , we performed a detailed analysis of lacunar and microvascular pathology in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions . Methods — Cognitive status was assessed prospect ively using the  Clinical Dementia Rating  ( CDR ) scale ; neuropathological evaluation included Aβ-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes ; statistical analysis included multivariate models controlling for age , amyloid deposits , and microvascular pathology . Results — Thalamic and basal ganglia lacunes were negatively associated with CDR scores ; cortical microin 
    Output:
    
Longitudinal studies have demonstrated detectable progression of lesion load over short time periods , and weak correlations with cognition .
Stronger correlations with cognition have been found with diffusion tensor imaging , which is more sensitive to white matter tract structure , supporting a role for disconnection in the pathogenesis of cognitive impairment .
Brain volume also consistently correlates with cognition in asymptomatic small vessel disease , sporadic small vessel disease , and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infa rcts and Leukoencephalopathy .
The greater sensitivity of diffusion tensor imaging parameters and brain volume to change , and the stronger correlation of these parameters with cognition , suggest that they may be more powerful surrogates .