Severe Leukoaraiosis Research Articles

Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke

To evaluate whether the presence of leukoaraiosis or multiple lacunes is associated with symptomatic intracerebral hemorrhage (ICH) and 90-day outcome after thrombolytic treatment with tissue plasminogen activator (tPA). Data were from a Canadian national registry of thrombolyzed patients with ischemic stroke. A total of 820 scans were assessed, blind to clinical features, for the presence of severe vs no/moderate leukoaraiosis, and of multiple (>2) vs no/single lacunar infarcts. Logistic regression was used to determine if an independent interaction existed between the presence and degree of leukoaraiosis/lacunes and risk of symptomatic ICH, and to evaluate the predictive role of leukoaraiosis and lacunes in relation to 90-day outcome. An overall symptomatic ICH rate of 3.5% was observed. The rate of symptomatic ICH increased up to 10% in patients with severe leukoaraiosis and multiple lacunes. A significant association was observed between ICH risk and either severe leukoaraiosis (RR = 2.7 [95% CI 1.1 to 6.5]) or multiple lacunes (RR = 3.4 [95% CI 1.5 to 7.6]). Patients with multiple lacunes, but not leukoaraiosis, had higher mortality at 90 days compared to those with one or no lacunes (OR = 2.9, 95% CI 1.3 to 6.2, p = 0.008). No difference was observed in the good outcome rate among patients with and without leukoaraiosis or lacunes or both. The presence of small vessel disease on CT scan does not affect overall clinical outcome at 3 months in routine community use of tPA for ischemic stroke. A significant increase in the risk of symptomatic ICH is observed.

Chronic ischemic cerebral white matter disease is a risk factor for nonfocal neurologic injury after total aortic arch replacement

Leukoaraiosis (chronic ischemic white matter changes) on preoperative brain magnetic resonance imaging is common in patients having aortic arch surgery. This study sought to determine whether it is associated with adverse neurologic outcome in the postoperative period. Data were collected from a retrospective chart review of 142 patients in whom total aortic arch replacement was planned at the Cleveland Clinic between April 2000 and December 2004. All patients had preoperative brain magnetic resonance imaging evaluation. Leukoaraiosis severity was rated semiquantitatively using the Schelten's scale. Postoperative neurologic injuries were investigated by clinical examination and appropriate neuroimaging. They were stratified as type 1 (focal ischemic stroke) and type 2 (nonfocal neurocognitive changes, generalized seizures) injuries. The following were independent predictors of type 1 neurologic injury: age (odds ratio 1.06 [1.01-1.13], P = .02) and moderate to severe aortic atheroma (odds ratio 4.4 [1.4-9.7], P = .012). Total white matter scores (odds ratio 1.16 [1.06-1.27], P = .002) and higher preoperative hemoglobin A1c levels (odds ratio 1.8 [1.00-3.50], P = .05) were significantly associated with type 2 neurologic injuries. Survival was 96%, and 4.2% had persistent focal neurologic deficits at the time of hospital discharge. Leukoaraiosis is a significant independent predictor of nonfocal postoperative neurologic morbidity following aortic arch replacement surgery. Preoperative evaluation with magnetic resonance imaging allows identification of a patient subgroup at risk and implementation of strategies aimed at improving neurologic outcome.

Visual attention capacity after right hemisphere lesions

Recently there has been a growing interest in visual short-term memory (VSTM) including the neural basis of the function. Processing speed, another main aspect of visual attention capacity, has received less investigation. For both cognitive functions human lesion studies are sparse. We used a whole report experiment for estimation of these two parameters in 22 patients with right side stroke. Psychophysical performance was analyzed using Bundesen's [Bundesen, C. (1990). A theory of visual attention. Psychological Review, 97, 523–547] Theory of Visual Attention (TVA) and compared statistically to lesion location and size measured by MRI. Visual processing speed was impaired in the contralesional hemifield for most patients, but typically preserved ipsilesionally, even after large cortico-subcortical lesions. When bilateral deficits in processing speed occurred, they were related to damage in the right middle frontal gyrus or leukoaraiosis. The storage capacity of VSTM was also normal for most patients, but deficits were found after severe leukoaraiosis or large strokes extending deep into white matter. Thus, the study demonstrated the importance of white-matter connectivity for both VSTM capacity and ipsilesional processing speed. The study also showed that lesions in a large region of the right hemisphere, including the putamen, insula, and inferior frontal cortex, do not lead to general deficits in the capacity of visual attention.

Leukoaraiosis Is a Risk Factor for Symptomatic Intracerebral Hemorrhage After Thrombolysis for Acute Stroke

The aim of the study was to evaluate whether leukoaraiosis (LA) is a risk factor for symptomatic intracerebral hemorrhage (sICH) in patients treated with thrombolysis for acute stroke. In this retrospective, multicenter analysis, we evaluated data from acute anterior circulation stroke patients (n=449; <6 hours after symptom onset) treated with thrombolysis. All patients had received standard magnetic resonance imaging evaluation before thrombolysis, including a high-quality T2-weighted sequence. For the analysis, LA in the deep white matter was dichotomized into absent or mild versus moderate or severe (corresponding to Fazekas scores of 0 to 1 versus 2 to 3). The rate of sICH was significantly more frequent in patients with moderate to severe LA of the deep white matter (n=12 of 114; 10.5%) than in patients without relevant LA (n=13 of 335; 3.8%), corresponding to an odds ratio of 2.9 (95% CI, 1.29 to 6.59; P=0.015). In a logistic-regression analysis (including age, National Institutes of Health Stroke Scale score at presentation, and type of thrombolytic treatment), LA remained a significant independent risk factor (odds ratio, 2.9; P=0.03). LA of the deep white matter is an independent risk factor for sICH after thrombolytic treatment for acute stroke.

Leukoaraiosis Predicts Hidden Global Functioning Impairment in Nondisabled Older People: The LADIS (Leukoaraiosis and Disability in the Elderly) Study

To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age+/-standard deviation 74.1+/-5.0) with magnetic resonance imaging-detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified. Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning. At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score. Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.

Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke

Objective: To investigate whether the extent of white matter lesions (WML) on fluid attenuated inversion recovery (FLAIR) MRI sequences is an independent risk factor for recurrent stroke, and to document...

Intracranial arterial dolichoectasia and small‐vessel disease in stroke patients

Two studies found that stroke patients with intracranial arterial dolichoectasia (IADE) had lacunar infarction more often than the control subjects. The relation between IADE and other manifestations of small-vessel disease (multilacunar state, leukoaraiosis, and état criblé) was not investigated. The magnetic resonance images of 510 patients with brain infarction in the Etude du Profil Genetique de l'Infarctus Cerebral (GENIC) study were evaluated for the diagnosis of multilacunar infarction (>1 lacunar infarct), leukoaraiosis (assessed in periventricular and subcortical regions according to Scheltens and colleagues' scale, with severe leukoaraiosis defined as a score > 8), état criblé (using a semiquantitative score ranging from 0-8, with severe EC > 4), and IADE (using the consensus method). By comparison with stroke patients without IADE (n = 447), IADE(+) stroke patients (n = 63) had significantly more frequent multilacunar state (51 vs 33%), severe leukoaraiosis (34 vs 19%), and severe état criblé (32 vs 12%). After adjustment for potential confounding factors, the odds ratios (95% confidence interval) for the presence of IADE were 2.05 (1.08-3.87) for multilacunar state, 2.40 (1.11-5.20) for severe leukoaraiosis, and 3.60 (1.43-9.08) for severe état criblé. The factors significantly associated with état criblé were older age and a familial history of stroke. IADE in stroke patients was independently associated with parenchymal manifestations of small-vessel disease. These conditions may have in common underlying pathophysiological processes.

Association between subcortical vascular disease on CT and neuropathological findings.

Small vessel cerebrovascular disease (svCVD) causes cognitive impairment and predicts poorer outcomes in elderly persons. The demonstration of svCVD by structural imaging such as computed tomography (CT) is central to the clinical diagnosis but its accuracy is uncertain. The aim of this study was to assess the validity of CT to detect pathologically verified svCVD. Leukoaraiosis, patchy lesions, and lacunes were assessed separately in different cerebral regions on CT scans of 87 elderly persons with Mini-Mental State Examination scores between 0 and 30 enrolled in the OPTIMA project. We rated small vessel disease on pathology separately in the white matter and basal ganglia as absent/mild, moderate, and severe. The presence of microinfarcts was also noted. The severity of all types of CT lesions was associated with pathological findings. Subjects with absent/mild leukoaraiosis on CT decreased and those with severe leukoaraiosis increased with increasing severity of subcortical small vessel ratings on pathology (31, 18 and 0%; 17, 23 and 50%, respectively; p = 0.028). A similar association was present for patchy lesions (73, 59 and 17%; 7, 18 and 33%, respectively; p = 0.004) and lacune (83, 77 and 50%; 0, 4 and 17%, respectively; p = 0.023). Leukoaraiosis, patchy lesions, and lacunes on CT were associated also with microinfarcts on pathology (p < 0.05). The standardized assessment of svCVD on CT films at the time of the diagnosis correlates with small vessel disease on pathology at death.

Leukoaraiosis more than dementia is a predictor of stroke recurrence.

It has been suggested that poststroke dementia is associated with a higher risk of stroke recurrence. Leukoaraiosis, however, might be a confounding factor because it is a risk factor for stroke recurrence and cognitive decline. Our aim was to determine the influence of prestroke and poststroke dementia on the 3-year risk of stroke recurrence. We evaluated prestroke cognitive functions in 202 stroke patients >or=40 years of age using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), with a cutoff of 104 for the diagnosis of dementia. Patients were followed up for 3 years. Dementia was diagnosed on the basis of International Classification of Diseases, 10th revision, criteria in survivors who underwent a neurologist visit or from the IQCODE score in survivors who did not. The severity of leukoaraiosis was assessed with a visual rating scale on CT scans without contrast performed at the acute stage of stroke. At each follow-up contact, stroke recurrences were recorded. During 385 person-years of follow-up, a total of 29 patients developed 33 stroke recurrences, resulting in an incidence rate of 8.6 per 100 person-years. We did not find any influence of dementia on the risk of stroke recurrence. Leukoaraiosis, however, was a strong predictor of stroke recurrence within 3 years after stroke. Dementia was not a predictor of stroke recurrence, but leukoaraiosis was strongly associated with stroke recurrence. Special attention in the secondary prevention of stroke must be given to patients with leukoaraiosis with or without dementia.

Poststroke dementia: influence of hippocampal atrophy.

The prevalence of dementia is increased after stroke. Medial temporal lobe atrophy (MTLA) is associated with Alzheimer disease, and with prestroke dementia in patients who have had a stroke. To determine the influence of MTLA on the long-term risk of dementia after stroke, after excluding the patients who had prestroke dementia. The study was conducted in 144 consecutive patients who had a stroke, who were aged 40 years or older (66 women and 78 men; median age, 72 years), and who had an Informant Questionnaire on Cognitive Decline in the Elderly score lower than 104. On admission to the hospital all patients underwent a noncontrast computed tomographic scan including temporal lobe-positioned slices. A cut-off of 11.5 mm was used to differentiate patients with MTLA from those without MTLA. Patients were followed up with clinical and cognitive assessments over a 3-year period. Three years after stroke, 34 patients (23.6%) had developed new-onset dementia. The cumulative proportion of survivors without dementia was 57.6% in patients with MTLA and 80.8% in patients without MTLA (P =.02). The unadjusted relative risk of poststroke dementia associated with MTLA was 2.3 (95% confidence interval, 1.1-4.7). However, using the Cox proportional hazards model, MTLA did not seem to be an independent predictor of poststroke dementia. Independent predictors of poststroke dementia were increasing age, diabetes mellitus, severity of the clinical deficit at admission, and severity of leukoaraiosis on computed tomography. Patients who had a stroke and MTLA more frequently develop dementia than patients without MTLA, but our study does not suggest that MTLA independently contributes to dementia. A longer follow-up may be necessary to reevaluate the influence of MTLA.

Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis.

Patients with cerebral small vessel disease (SVD) can present as isolated lacunar infarction 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 prospective 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 samples. Patients were classified on brain imaging into two groups: isolated lacunar infarction (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 infarction 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.

Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke.

Prior ischemic stroke is a risk factor for intracerebral hemorrhage (ICH) in patients taking warfarin, but the mechanism is not known. This study investigates radiographic and clinical characteristics of patients with warfarin-related ICH following ischemic stroke. In this case-control study, the authors selected all patients with warfarin-related ICH and previous symptomatic ischemic stroke from a prospective cohort of consecutive patients with ICH. Control subjects were similarly aged patients with history of symptomatic stroke randomly chosen from an anticoagulant therapy unit. The 26 eligible ICH cases and 56 controls were compared for vascular risk factors, stroke characteristics, and extent of leukoaraiosis (graded in anterior and posterior brain regions on a validated scale of 0 to 4). The presence and severity of leukoaraiosis on CT scan correlated strongly with the occurrence of ICH. Leukoaraiosis was seen in 24 of 26 cases (92%) compared with 27 of 56 controls (48%), yielding an odds ratio of 12.9 (95% CI 2.8 to 59.8). Other clinical factors associated with ICH included an international normalized ratio >3.0, history of multiple previous strokes, and the presence of carotid artery stenosis. The relationship between leukoaraiosis and ICH persisted in multivariable analyses controlling for these risk factors as well as hypertension and diabetes mellitus. Leukoaraiosis is an independent risk factor for warfarin-related ICH in survivors of ischemic stroke, including those in the commonly employed range of anticoagulation.

Making anticoagulation safer.

The Smith et al. case-control study compared patients with warfarin-related intracerebral hemorrhage (ICH) and previous stroke vs age-matched poststroke patients on warfarin without ICH. The presence and severity of leukoaraiosis correlated strongly with ICH and was seen in 92% of ICH vs 48% of controls: odds ratio, 12.9. see following Commentary by Robert G. Hart, MD Oral anticoagulation with vitamin K antagonists has been prescribed for stroke prevention for over 50 years, but only during the past decade have the benefits and risks been defined by adequate randomized clinical trials. Bleeding is the major toxicity, and most fatal bleeds are ICH. Some 5,000 to 10,000 warfarin-associated ICHs occur yearly in the United States. Advanced patient age, anticoagulation intensity, and “cerebrovascular disease” are accepted risk factors for warfarin-associated ICH. Intensity of anticoagulation is the strongest, most consistent predictor, and targeting the lowest efficacious international normalized ratio is important. Recently, two novel predictors have been proposed in Neurology : APOE genotype (as a marker of cerebral amyloid angiopathy)1 and “leukoaraiosis” evident on cranial CT scanning in noncardioembolic brain ischemia. (Smith et al. in this issue and Gorter2). Although these novel predictors offer pathogenetic clues, neither has been sufficiently validated …

Pulse-wave encephalopathy: a comparative study of the hydrodynamics of leukoaraiosis and normal-pressure hydrocephalus.

There is a strong association between the occurrence of leukoaraiosis and normal-pressure hydrocephalus (NPH). Venous compression secondary to alterations in craniospinal compliance is implicated in the pathogenesis of NPH, and venous pathology has also been implicated in leukoaraiosis. The purpose of this paper is to compare and contrast the blood-flow and fluid-pulsatility characteristics of these conditions. I initially studied 18 subjects without pathology, with MRI flow-quantification studies of the cerebral arteries and veins, to define the range of normality. The main study involved 10 patients with idiopathic dementia but no leukoaraiosis who served as controls, 50 with idiopathic dementia with varying degrees of leukoaraiosis and 18 with NPH. I compared blood-flow volumes, vascular pulse-wave amplitudes and velocities. There was no significant difference in blood flow across the dementia patients. In patients with moderate leukoaraiosis, arterial pulsatility was 69%, cerebrospinal fluid (CSF) pulsation 104%, sagittal sinus pulsatility 48% and cortical vein pulsatility 34% higher than in demented patients without leukoaraiosis. Patients with NPH showed similar results with arterial pulsatility increased by 56% and sagittal sinus pulsatility by 70%. By contrast, the NPH patients' CSF pulse was 42% and the pulse wave delay at the sagittal sinus 50% less than in moderate leukoaraiosis. Thus, leukoaraiosis and NPH share increased arterial and sinus pulsatility. In leukoaraiosis cortical vein compliance is initially increased but in severe leukoaraiosis and NPH it is reduced.

Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes (leukoaraiosis) in patients with Alzheimer disease.

The pathogenesis of leukoaraiosis on computed tomographic (CT) scanning is unknown, but cerebrovascular risk factors for leukoaraiosis show overlap with those for Alzheimer disease (AD). To investigate the contribution of cerebrovascular risk factors, in particular plasma total homocysteine (tHcy), to leukoaraiosis in patients with AD and controls. Cross-sectional case-control study. Referral population to a hospital clinic and community volunteers from the Oxfordshire region in England seen between July 1, 1988, and July 1, 2000. One hundred thirty-seven AD cases (104 confirmed post mortem) and 277 controls matched for age (mean +/- SD, 73 +/- 8 years) and sex. Cerebrovascular risk factors and leukoaraiosis on CT scans of cases and controls; the odds ratio (OR) of having moderate to severe leukoaraiosis with higher levels of plasma tHcy and cerebrovascular risk factors such as age, sex, systolic blood pressure, smoking, diabetes mellitus, and apolipoprotein E epsilon4 genotype. Leukoaraiosis was more prevalent in AD cases. For a 5-micromol/L increase in tHcy levels, the OR for leukoaraiosis was 1.40 (95% confidence interval, 1.02-1.91) independent of other risk factors. The distribution pattern of leukoaraiosis was more marked in the deep white matter than in the periventricular area in individuals with elevated tHcy levels, particularly in patients with AD. Higher tHcy levels are an independent risk factor for moderate to severe leukoaraiosis in individuals with AD and of leukoaraiosis of the deep white matter in particular. The nature of the relationship between tHcy levels and leukoaraiosis in AD requires further longitudinal and intervention studies.

The coagulation-fibrinolysis system in patients with leukoaraiosis and Binswanger disease.

Hypercoagulability is observed in vascular dementia, including Binswanger disease. However, the correlation between hypercoagulability, leukoaraiosis, and dementia remains unclear. To examine how activation of the coagulation fibrinolysis correlates with leukoaraiosis and dementia. Thrombin-antithrombin complex (TAT), prothrombin fragment(1 + 2) (F1 + 2) and cross-linked D-dimer (XDP) were measured consecutively in 18 subjects without dementia and with leukoaraiosis, and in 29 subjects with subcortical vascular dementia and severe leukoaraiosis (Binswanger disease) at either stable or deteriorating stages. They were compared with 19 patients with old lacunar infarctions and 24 patients with other neurological diseases. We also examined the indices of cognitive impairment and brain atrophy. In each group, the ventricular area-cranial space area ratio was measured by an image analyzer. Patients with Binswanger disease who were exclusively at deteriorating stages showed increased TAT and XDP levels and an increased ventricular area-cranial space area ratio, as compared with the patients with other neurological diseases (P<.001). The index of cognitive impairment in patients at a deteriorating stage showed a decreasing trend vs that of patients in the stable stage. Among the variables that were significantly associated with a hypercoagulable condition (ie, age, scores on Mini-Mental State Examination or the Hasegawa Dementia Rating Scale, Revised [MMSE/HDRS], white matter lesions, ventricular area-cranial space area ratio, and C-reactive protein), age (odds ratio [OR], 2.82) and MMSE/HDSR scores (OR, 0.43) survived as predictors for coagulation activation, and C-reactive protein survived for fibrinolysis activation (OR, 4.63) in multivariate analysis. Hypercoagulability in a subgroup of patients with Binswanger disease and with more severe cognitive impairment and brain atrophy does not support a triggering role for a coagulation-fibrinolysis system, although it may contribute to worsening of neurological deficits.

Silent infarcts in stroke patients: patient characteristics and effect on 2-year outcome.

Although silent infarcts (SIs) are frequent in stroke patients, their clinical significance remains controversial, and their effect on stroke outcome remains unclear. This study evaluated the prevalence of SI on computed tomography, associated factors, and the effect on outcome in stroke patients. We studied 202 consecutive patients admitted for acute ischaemic or haemorrhagic stroke with clinical deficits lasting more than 24 h. Survivors were followed up for 24 months; no patient was lost to follow-up. Patients with Rankin scores of 2 or lower were considered separately. New vascular events were also recorded. Computed tomography showed that one-fourth of patients (52/202) had at least one SI; these were located in deep hemispheric areas in 46 patients, superficial hemispheric areas in 5, and the posterior fossa in 7. Logistic regression analysis showed the factors independently associated with SI to be severe leukoaraiosis (OR 1.71, 95% CI 1.26-2.31) and small-vessel occlusion as presumed cause of the index stroke (OR 2.66, 95% CI 1.22-5.79). SI did not affect vital or functional outcome or the occurrence of new vascular events within 2 years after stroke. Whether they affect cognitive outcome remains under evaluation over a longer follow-up period.

Does leukoaraiosis predict morbidity and mortality?

To determine whether leukoaraiosis predicts morbidity and mortality. Gait disturbance and leukoaraiosis both are common in the elderly. Gait disturbance predicts mortality. Leukoaraiosis may be a unifying factor to both gait disturbance and mortality. We followed 221 patients prospectively evaluated for severity of neurologic deficits by the National Institutes of Health (NIH) stroke scale and for leukoaraiosis in seven brain regions by CT, graded as absent (n = 119, 54%), mild (in at least one of seven brain regions; n = 54, 24%), or severe (present in all seven brain regions; n = 48, 22%). Pneumonia (n = 27, 12%), falls resulting in fracture requiring hospitalization (n = 7, 3%), and death (n = 38, 17%) were end points. Severe leukoaraiosis predicted death (Cox hazard ratio [HR] = 2.91; 95% CI = 1.5 - 5.6), pneumonia (HR = 5.1; 95% CI = 2.4 - 10.9), death from pneumonia (HR = 8.3; 95% CI = 1.5 - 46), and falls (HR = 6.8; 95% CI = 1.5 - 30). Severe leukoaraiosis predicted a combined end point of death, pneumonia, and falls (HR = 3.5; 95% CI = 2 - 6). Other predictors were NIH stroke scale score, age, smoking, diabetes, gait score, and referral diagnosis of either dementia or Parkinsonism. Severe leukoaraiosis remained a predictor after adjustment for these other factors (HR = 2.2; 95% CI = 1.2 - 3.9), but was borderline after adjusting for gait (HR = 1.96; 95% CI = 0.97 - 3.94; p = 0.061). The combination of severe leukoaraiosis and gait disturbance had the highest risk (HR = 4.4; 95% CI = 2.4 - 7.9). Severe leukoaraiosis predicts morbidity and mortality independently of preexisting neurologic deficits. The combination of leukoaraiosis and gait disturbance carries a poor prognosis.

Dementia with Leukoaraiosis: Clinical Differentiation by Temporoparietal Hypometabolism on 18FDG-PET Imaging

Patients with dementia and leukoaraiosis may have either Alzheimer’s disease (AD) with cerebrovascular changes or a form of vascular dementia (VaD). The presence or absence of the characteristic AD pattern of bilateral temporoparietal hypometabolism on ¹⁸FDG-PET was used to differentiate 30 patients with progressive dementia and severe leukoaraiosis. Compared to 18 patients with the typical AD pattern (group I), the remaining 12 (group II) had better recognition memory, and greater difficulty with sustained attention and serial reversals. Better recognition memory, confluent periventricular leukoaraiosis, and poorer sustained attention distinguished all group II patients from group I. Dementia patients with severe leukoaraiosis and bilateral temporoparietal hypometabolism may have predominant AD; those who lack this pattern and have confluent leukoaraiosis may have a greater contribution from VaD.

Correlation between computed tomography findings of leukoaraiosis and 24-hour blood pressure variability in elderly subjects

Leukoaraiosis (LA) has been defined as low attenuation areas involving only the periventricular white matter, in the mild form, and extending to the subcortical region in the severe form. This study evaluates, in elderly patients, if brain computed tomography (CT) evidence of LA significantly correlates with the findings of 24-hour, blood pressure monitoring. Sixtysix neurologically nondiseased elderly patients underwent CT examination of the brain and 24-hour ambulatory blood pressure monitoring. The patients were divided in two groups (patients with none-to-mild LA in group 1; patients with severe LA in group 2) based on CT findings evaluated at level of foramina of Monro, body of lateral ventricles, and frontoparietal white matter (centrum semiovale). CT findings were compared with main 24-hour ambulatory blood pressure monitoring results (systolic and diastolic blood pressure and heart rate values). Patients with severe LA showed a wider variability both in blood pressure and heart rate; in particular, major oscillations were found during the nighttime period. No significant 24-hour blood pressure variability was found in group 1. Increased blood pressure variability can play a role in the pathogenesis of LA.