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Any strategy to reduce stroke burden involves crucial inputs from individuals (risk reduction, rapid recognition and response to symptoms onset) which imply a certain level of stroke knowledge. Health-related applications (apps) have been identified as a novel platform for dissemination of health information to the public. Only few apps about stroke are currently available with scientifically valid information, none of them are available in Italian. We developed the first and only Italian stroke app, ICTUS3R. We also pilot tested ICTUS3R in terms of its usage during the first 12 months following release (October 30, 2014). ICTUS3R was developed in collaboration with communication experts, stroke leaders and web producers. ICTUS3R was pilot tested in terms of number and distribution of downloads. Data about 1 year usage were anonymously collected from ICTUS 3R release on October 30, 2014. ICTUS3R includes a stroke screening tool, information how to react in case of suspected stroke, and information about risk factors including personal stroke risk calculator. ICTUS 3R web site was visited 36,242 times. Mean session duration was over 2 min. The 48 % of downloads were by individuals aged 25–44 years, 12 % by individuals ≥55 years. ICTUS3R downloads were distributed across all the Italian provinces, in varying proportions. The 4.3 % of downloads were done outside Italy. ICTUS3R can be an important contribution to stroke management and prevention, it proved to be well received for dissemination of stroke information among Italians. Its use could contribute to reduce stroke burden in Italy.

A possible definition of clinical, educational and organizing aspects of emergency neurology in Italy is reported in this position paper of Emergency Neurology Intersociety Group, created in 2008 among the two neurological Societies in Italy: Societa Italiana di Neurologia and Societa di Neuroscienze Ospedaliere. The aim of this Group has been the evaluation of the role of neurologist in the emergency setting of Italian hospitals, as well as of the description of different scenarios in which a ward dedicated to a semi-intensive care of neurological emergencies could have a role in the actual organization of academic or general hospitals in our Country. The actual great relevance of neurologist activity in the inpatients treatment, in fact, is actually misleaded as it is the considerable significance of neurological expertise, techniques and support in hospital care pathways also involving neurological manifestations throughout the course of other diseases. Finally, the possible contents of educational programs orienting neurological specialty towards a better comprehension and management of emergency neurological problems either in terms of specific formation or of techniques to be learned by emergency neurologist, are reported as a results of the Consensus Workshop hold in Castiglioncello (LI) in September 12th, 2009.

It is still debated whether cerebral autoregulation is preserved in patients presenting Shy-Drager syndrome (SD). In order to evaluate cerebral autoregulation in this disease the authors studied 5 patients with SD and 5 healthy control subjects by means of transcranial Doppler. Changes in mean flow velocity (MV) in the middle cerebral artery (MCA), as well as changes of the systemic mean arterial blood pressure (MBP) were measured at the same time during a tilt-table test. When the patients were tilted from the rest to the orthostatic position, MCA MV showed a rapid and significant decrease in all SD patients (−52.8%); the MCA MV values remained low during 10 minutes at 90°; control patients did not show similar changes (−6.9%), (P=0.0003). Although MBP values showed a considerable decrease during the test in SD patients (−31.0%), these changes never went below the cerebral autoregulation threshold. The authors’ data are suggestive of an impairment of cerebral autoregulation in SD patients.

Valenti R, Pescini F, Antonini S, Castellini G, Poggesi A, Bianchi S, Inzitari D, Pallanti S, Pantoni L. Major depression and bipolar disorders in CADASIL: a study using the DSM-IV semi-structured interview. Acta Neurol Scand: 2011: 124: 390–395. © 2011 John Wiley & Sons A/S. Objective – Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy characterized by migraine, cerebrovascular events, and cognitive impairment. Although recognized as a cardinal feature of the disease, psychiatric disturbances have rarely been the object of focused studies. We performed a structured evaluation of mood disorders in CADASIL. Materials and Methods – Twenty-three patients with CADASIL (five men and 18 women) were assessed by psychiatrists using the Structured Clinical Interview for the DSM-IV, clinician version. For the quantitative assessment of current mood disorder symptoms, the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Scale (YMRS) were used. Results – A lifetime depressive episode was recorded in 17/23 (73.9%) patients with CADASIL. Six (26.1%) patients with CADASIL reported a current depressive episode. A diagnosis of manic lifetime episode was made in 6 (26.1%) patients with CADASIL. The HRSD mean score in patients with current depression was 9.1 ± SD 8.1. The YMRS mean score was 14.2 ± SD 4.1 for manic CADASIL. Conclusion – This study confirms that mood disorders are frequent in CADASIL. The use of a structured psychiatric interview outlines a frequency of depression higher than that previously reported but also reveals a considerable frequency of bipolar disorders. If confirmed in larger series, these data suggest that a greater attention should be paid to the psychiatric aspects in CADASIL.

The outcome of stroke patients is complex and multidimensional. We evaluated the impact of acute-phase variables, including clinical state, complications, resource use and interventions, on 6-month survival after first-ever stroke, taking into account baseline conditions exerting a possible effect on outcome. As part of a National Research Program, we performed a prospective observational study of acute stroke patients in four Italian Regions. Consecutive patients admitted for a period of 3 months to the emergency rooms of participating hospitals were included. A total of 1030 patients were enrolled (median age 76.0 years, 52.1% males). At 6 months, 816 (79.2%) were alive, and 164 (15.9%) deceased. Survival status at the 6-month follow-up was missing for 50 (4.9%). Neurological state in the acute phase was significantly worse in patients deceased at 6 months, who showed also higher frequency of acute-phase complications. Cox regression analysis adjusted for demographics, pre-stroke function, baseline diseases and risk factors, indicated as significant predictors of 6-month death altered consciousness (HR, 1.70; 95% CI, 1.14-2.53), total anterior circulation infarct (HR, 2.13; 95% CI, 1.44-3.15), hyperthermia (HR, 1.70; 95% CI, 1.18-2.45), pneumonia (HR, 1.76; 95% CI, 1.18-2.61), heart failure (HR, 2.87; 95% CI, 1.34-6.13) and nasogastric feeding (HR, 2.35; 95% CI, 1.53-3.60), while antiplatelet therapy during acute phase (HR, 0.56; 95% CI, 0.39-0.79), and early mobilisation (HR, 0.55; 95% CI, 0.36-0.84) significantly increased 6-month survival. In a prospective observational study, stroke severity and some acute-phase complications, potentially modifiable, significantly increased the risk of 6-month death, independently of baseline variables. Early mobilisation positively affected survival, highlighting the role of early rehabilitation after stroke.

The authors investigated the relationship of metabolic syndrome (MetS) and its individual components with incident dementia in a prospective population-based study with a 3.5-year follow-up.A total of 2097 participants from a sample of 5632 subjects (65-84 years old) from the Italian Longitudinal Study on Ageing were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. Dementia, Alzheimer disease (AD) and vascular dementia (VaD) were classified using current published criteria.MetS subjects (N=918) compared with those without MetS (N=1179) had an increased risk for VaD (1.63% vs 0.85%, adjusted hazard ratio (HR) 3.71, 95% CI 1.40 to 9.83). After excluding 338 subjects with baseline undernutrition, MetS subjects compared with those without MetS had an elevated risk of VaD (adjusted HR, 3.82; 95% CI 1.32 to 11.06). Moreover, those with MetS and high inflammation had a still further higher risk of VaD (multivariate adjusted HR, 9.55; 95% CI 1.17 to 78.17) compared with those without MetS and high inflammation. On the other hand, those with MetS and low inflammation compared with those without MetS and low inflammation did not exhibit a significant increased risk of VaD (adjusted HR, 3.31, 95% CI 0.91 to 12.14). Finally, a synergistic MetS effect versus its individual component effects was verified on the risk of VaD.In our population, MetS subjects had an elevated risk of VaD that increased after excluding patients with baseline undernutrition and selecting MetS subjects with high inflammation.

Background and purpose: White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer’s disease (AD) and subcortical vascular dementia. Methods: Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid β, α- and β-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau181), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. Results: Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P

A limited number of studies suggested that in ischemic stroke patients, the number of bone marrow circulating progenitor cells (CPCs), either endothelial progenitor cells (EPCs) or CPCs, was negatively correlated with the number of infarcts as well as with the outcome. The aim of this study was to simultaneously measure CPCs and EPCs in the acute phase of ischemic stroke, and to establish whether a relationship exists with stroke severity and discharge outcome. In 67 (40 M; 27 F) ischemic stroke patients with a median age of 73 (21 to 91) years, the number of CPCs and EPCs was measured by flow cytometry and analyzed in relation to baseline NIH Stroke Scale score, ischemic stroke syndromes, and discharge outcome. Patients with partial anterior circulation syndrome showed a higher CPCs’ number with respect to patients with total anterior circulation syndrome. Moreover, a negative relationship between National Institutes of Health Stroke Scale score at the admission and CPCs number was observed. When the outcome was considered, patients discharged to home had a higher number of CPCs, but not of EPCs, compared with those moved to a rehabilitation unit. We report an association between the number of CPCs measured in the early phase after stroke presentation, neurologic severity, and discharge outcome.

Background and purpose: The safe implementation of thrombolysis in stroke-monitoring (SITS-MOST) study was an unique opportunity to test in Italy, where only few centres were expert in thrombolytic treatment before, safety and efficacy of i.v. alteplase within 3 h of ischaemic stroke outside the setting of clinical trials. Methods: In Italy to participate in the study the clinical centres had to possess organizational and structural characteristics certified by Regional Health Authorities. Results: Seventy-one centres were activated, 56 (79%) treated patients of which 41 (73%) had never used thrombolysis before the study. Globally, 586 patients were included. Baseline median National Institute of Health Stroke Scale of Italian patients was 13 vs. 12 in other European centres (P = 0.0001). Symptomatic intracerebral haemorrhage as per the NINDS/Cochrane definition, mortality and independence (modified Rankin Scale 0–2) rates at 3 months occurred respectively in 6.7% (95% CI: 4.8–9.1), 11.7% (9.2–14.6) and 51.6% (47.4–55.7) of Italian patients compared with 7.3% (6.7–8.0) (P = 0.56), 11.2% (10.4–12.1) (P = 0.75) and 55.1% (53.8–56.4) (P = 0.09) in the European patients and in 8.6% (40/65; 6.3–11.6), 17.3% (14.1–21.1) and 50.1% (44.5–54.7) of the patients treated in the pooled randomized controlled trials. Conclusions: The SITS-MOST study showed that in Italy i.v. alteplase is safe and effective in routine clinical use also in non-expert centres.

Purpose To explore the value of diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI) for the improved detection and quantification of cerebral tissue changes associated with ageing and white matter hyperintensities (WMH). Materials and Methods DWI (n = 340) and MTI (n = 177) were performed in nine centers of the multinational Leukoaraiosis And DISability (LADIS) study investigating the impact of WMH on 65- to 85-year-old individuals without prior disability. We assessed the apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) of normal appearing brain tissue (NABT) and within WMH and related them to subjects' age and WHM severity according to the Fazekas score. Results ADC and MTR values showed a significant inter-site variation, which was stronger for the MTR. After z-transformation multiple regression analysis revealed WMH severity and age as significant predictors of global ADC and MTR changes. Only lesional ADC, but not MTR was related to WMH severity. Conclusion ADC and MTR are both sensitive for age and WMH related changes in NABT. The ADC is more sensitive for tissue changes within WMH and appears to be more robust for multicenter settings. J. Magn. Reson. Imaging 2009;29:268–274. © 2009 Wiley-Liss, Inc.

Background: Subcortical ischemic vascular disease (SIVD) is a common, but often overlooked cause of vascular cognitive impairment. Diagnostic research criteria for SIVD are based on magnetic resonance imaging (MRI) findings including substantial white matter lesions (WML) and multiple lacunar infarcts. Empirical studies validating these imaging criteria are still few. The purpose of the study was to describe the clinical and cognitive characteristics of the MRI-defined SIVD in a mixed sample of functionally independent elderly subjects with WML. Methods: The subjects of the Leukoaraiosis and Disability (LADIS) study, aged 65–84 years, underwent comprehensive clinical and neuropsychological examinations, and brain MRI at the baseline assessment. The subjects meeting the SIVD imaging criteria (n = 89) were compared to the other subjects of the sample (n = 524). Results: SIVD was associated with lower education, hypertension and, independently, with obesity. The subjects with SIVD had more often motor impairment, a history of falls, and subtle impairment in activities of daily living, but they did not differ for depressive symptoms. SIVD subjects performed significantly inferiorly in tests of global cognitive function, psychomotor speed, attention and executive functions, verbal fluency, and working memory. Conclusion: In this population of nondisabled older adults with WML, SIVD was related to specific clinical and functional characteristics. Neuropsychological features included psychomotor slowing as well as deficits in attention and executive functions.

To assess, by using quantitative MRI metrics, structural and metabolic brain abnormalities in subjects with preclinical cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL).Brain MRI abnormalities have been occasionally reported in preclinical CADASIL subjects. However, very little is known as to when the brain tissue damage starts to accumulate, what brain regions are primarily involved and whether the brain damage is significant in subjects who have no overt clinical manifestations of the disease.Twelve subjects (mean age 40 years; range 26-55 years; males/females 6/6) with genetically proven CADASIL and no clinical signs of the disease underwent conventional MRI and proton MR spectroscopic imaging ((1)H-MRSI) to measure white matter (WM) lesion volume (LV), global and regional cerebral volumes, and WM levels of N-acetylaspartate (NAA) normalised to creatine (Cr). MR values were compared with those of 13 age- and sex-matched healthy controls.All preclinical CADASIL showed WM lesions (range 0.2 to 26 cm(3)). They were mostly distributed in the frontal and parietal regions, with the highest probability in the corona radiata. On (1)H-MRSI examination, NAA/Cr values were lower in preclinical CADASIL than in HC, particularly in the corona radiata (p0.01). Normalised brain and cortical volumes were also lower in preclinical CADASIL than in HC (p0.01), particularly in the frontal cortex.The pathological process occurring in CADASIL leads to damage of WM and neocortex much before the evidence of clinical symptoms. At this preclinical stage, this seems to take place prevalently in the frontal brain region.

OBJECTIVES: To investigate, in a cohort of nondisabled elderly people, the association between urinary complaints and severity of age-related white matter changes (ARWMC). DESIGN: Cross-sectional data analysis from a longitudinal multinational study. SETTING: The Leukoaraiosis And DISability Study, assessing ARWMC as an independent predictor of the transition from functional autonomy to disability in elderly subjects. PARTICIPANTS: Six hundred thirty-nine subjects (288 men, 351 women, mean age 74.1±5.0) with magnetic resonance imaging (MRI)-detected ARWMC of different severity. MEASUREMENTS: ARWMC severity was graded on MRI as mild, moderate, and severe (Fazekas scale). MRI assessment also included ARWMC volumetric analysis and the count of infarcts. Urinary complaints (nocturia, urinary frequency, urgency, incontinence) were recorded based on subjects' answers to four questions. RESULTS: In comparing the three ARWMC severity groups, there was a significant difference only in prevalence of urgency, with 16% of subjects in the mild severity group, 17% in the moderate severity group, and 25% in the severe group (P=.03). Adjusting for age, sex, lacunar and nonlacunar infarcts, diabetes mellitus, and use of diuretics, severe ARWMC retained an independent effect in the association with urinary urgency (odds ratio=1.74, 95% confidence interval=1.04–2.90, severe vs mild group). Subjects with urinary urgency also had higher ARWMC volumes (25.2, vs 20.4 mm3 in those without urinary urgency; P

Background and Purpose— We studied the natural course of white matter hyperintensities (WMH) and lacunes, the main MRI representatives of small vessel disease, over time and evaluated possible predictors for their development. Methods— Baseline and repeat MRI (3-year follow-up) were collected within the multicenter, multinational Leukoaraiosis and Disability study (n=396). Baseline WMH were scored on MRI by the Fazekas scale and the Scheltens scale. WMH progression was assessed using the modified Rotterdam Progression scale (absence/presence of progression in 9 brain regions). Baseline and new lacunes were counted per region. WMH and lacunes at baseline and vascular risk factors were evaluated as predictors of WMH progression and new lacunes. Results— WMH progressed (mean±SD=1.9±1.8) mostly in the subcortical white matter, where WMH was also most prevalent at baseline. The majority of new lacunes, which were found in 19% of the subjects (maximum=9), also appeared in the subcortical white matter, mainly of the frontal lobes, whereas most baseline lacunes were located in the basal ganglia. Baseline WMH and lacunes predicted both WMH progression and new lacunes. Furthermore, previous stroke, diabetes, and blood glucose were risk factors for WMH progression. Male sex, hypertension, systolic blood pressure, previous stroke, body mass index, high-density lipoprotein, and triglyceride levels were risk factors for new lacunes. Conclusion— WMH and lacunes progressed over time, predominantly in the subcortical white matter. Progression was observed especially in subjects with considerable WMH and lacunes at baseline. Moreover, the presence of vascular risk factors at baseline predicted WMH progression and new lacunes over a 3-year period.

Background and purpose: Age related white matter changes (ARWMC) are frequent in non-demented old subjects and are associated with impaired cognitive function. Our aim was to study the influence of vascular risk factors and ARWMC on the neuropsychological performance of an independent elderly population, to see if vascular risk factors impair cognition in addition to the effects of ARWMC. Methods: Independent subjects, aged 65-84 years, with any degree of ARWMC were assessed using a comprehensive neuropsychological battery including the Mini-Mental State Examination (MMSE), VADAS-Cog (Alzheimer's disease assessment scale) and the Stroop and Trail Making test. Vascular risk factors were recorded and ARWMC (measured by MRI) were graded into three classes. The impact of vascular risk factors and ARWMC on neuropsychological performance was assessed by linear regression analyses, with adjustment for age and education. Results: 638 patients (74.1 (5) years old, 55% women) were included. Patients with severe ARWMC performed significantly worse on global tests of cognition, executive functions, speed and motor control, attention, naming and visuoconstructional praxis. Diabetes interfered with tests of executive function, attention, speed and motor control, memory and naming. Arterial hypertension and stroke influenced executive functions and attention. The effect of these vascular risk factors was independent of the severity of ARWMC, age and education. Conclusion: ARWMC is related to worse performance in executive function, attention and speed. Diabetes, hypertension and previous stroke influenced neuropsychological performance, independently of the severity of ARWMC, stressing the need to control vascular risk factors in order to prevent cognitive decline in the elderly.

Information on subcortical ischaemic changes (SIC) in young hypertensive patients is scarce. We evaluated the frequency of SIC at magnetic resonance imaging (MRI), the possible effect on cognition of these patients, and the role of plasma markers known as indicators of endothelial and haemostatic activation. Inclusion criteria were age

BackgroundEvidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear.AimsTo investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders.MethodIn a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year.ResultsUsing logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (PConclusionsWhite matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life.

BACKGROUND AND PURPOSE: Cerebral white matter changes, termed leukoaraiosis (LA), appearing as areas of increased signal intensity in T2-weighted MR images, are common in elderly subjects, but the possible correlation of LA with cognitive or motor deficit has not been established. We hypothesized that histogram and voxel-based analyses of whole-brain mean diffusivity (MD) and fractional anisotropy (FA) maps calculated from diffusion tensor imaging (DTI) could be more sensitive tools than visual scales to investigate the clinical correlates of LA. MATERIALS AND METHODS: Thirty-six patients of the Leukoaraiosis and Disability Study were evaluated with fluid-attenuated inversion recovery for LA extension, T1-weighted images for volume, and DTI for MD and FA. The extent of LA was rated visually. The normalized total, gray, and white matter brain volumes were computed, as well as the 25th percentile, 50th percentile, kurtosis, and skewness of the MD and FA maps of the whole brain. Finally, voxel-based analysis on the maps of gray and white matter volume, MD, and FA was performed with SPM2 software. Correlation analyses between visual or computerized data and motor or neuropsychologic scale scores were performed using the Spearman rank test and the SPM2 software. RESULTS: The visual score correlated with some MD and FA histogram metrics (P < .01). However, only the 25th and 50th percentiles, kurtosis, and skewness of the MD and FA histograms correlated with motor or neuropsychologic deficits. Voxel-based analysis revealed a correlation (P < .05 corrected for multiple comparisons) between a large cluster of increased MD in the corpus callosum and pericallosal white matter and motor deficit. CONCLUSIONS: These results are consistent with the hypothesis that histogram and voxel-based analyses of the whole-brain MD and FA maps are more sensitive tools than the visual evaluation for clinical correlation in patients with LA.

Cognitive decline, particularly when executive functions are compromised, may worsen motor performance (MP) decline in the elderly population. We investigated whether a global test, a memory test, and an attention test predicted MP decline in older community-dwellers with normal baseline MP participating in the Italian Longitudinal Study on Aging (ILSA).One thousand fifty-two ILSA participants (71.2 +/- 4.8 years old, mean +/- standard deviation [SD], 67% men), with normal baseline MP were reassessed after 3 years using the same MP battery. Participants whose MP score reduction from baseline to follow-up was75 percentile were considered to be MP decliners. Global cognition, memory, and attention were assessed using the Mini-Mental State Examination (MMSE), the Babcock Story Recall Test (BSRT), and the Digit Cancellation Test (DCT), respectively. The baseline score on each test was examined as a potential predictor of decline in global MP or in single motor tasks.Baseline scores on the three cognitive tests were worse among the 166 MP decliners, compared with nondecliners. Participants in the lowest quartile of DCT had a2-fold higher adjusted risk of declining than did participants in the highest quartile (odds ratio = 2.47, 95% confidence interval, 1.29-4.74). Conversely, MMSE and BSRT scores no longer predicted MP decline after adjustment. Impaired attention strongly predicted the decline in attention-demanding tasks (tandem walking), but also affected routine tasks (walking).Impairment in a test measuring attention predicts MP decline among older community-dwellers with normal baseline MP. This finding is consistent with the hypothesis that attentional and executive dysfunction is a major determinant of mobility disability in elderly persons.

Objectives: To estimate prevalence and incidence of distal symmetric neuropathies (DSN) in the Italian elderly, and to evaluate the accuracy of our procedure to screen for DSN. Methods: In eight Italian municipalities, a population-based sample was directly evaluated both at baseline (1992) and after a 3-year follow-up. Cohort members who had died were studied. DSN diagnosis and subtyping were made according to specified diagnostic criteria. Results: Our screening procedure proved accurate (sensitivity 94.7%, specificity 70%, positive predictive value 18.9%), and provided an adjusted prevalence of 7.0 (95% CI, 6.9 to 7.0). Women outnumber men both in the oldest age groups and as a whole. Rates increase with increasing age in both genders. Among the 2,845 individuals re-screened at the follow-up and the 221 deceased subjects with reliable information, we identified 100 incident cases of DSN. Adjusted annual incidence rate (per 1,000 person-years) in the population 65 to 84 years of age is 7.9 (95% CI, 6.3 to 9.5), and for the nondiabetic DSN is 5.76 (95% CI, 4.3 to 7.3). Age significantly predicted the onset of DSN both in diabetic individuals (for every increasing year of age RR = 1.07; 95% CI, 1.01 to 1.14) and in the entire study population (RR = 1.05; 95% CI, 1.02 to 1.09). Conclusions: We provide the first population-based distal symmetric neuropathies incidence data, as well as prevalence rates from an unselected sample of Italian elderly. Distal symmetric neuropathies are an age-associated condition, but the frequency of diabetic distal symmetric neuropathies declines with age, coincident with an increase in nondiabetic cases.

Objectives: 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).Methods: 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.Results: 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.Conclusion: 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.

Dementia is one of the most disabling conditions in older people. Incidence of dementia steeply increases with age, doubling approximately every 5 years, and ranging from 4.0 per 1000 person-years in the group aged 65 to 69 years to 33.5 per 1000 person-years in the group aged 80 to 84 years.1 The most frequent type of dementia is Alzheimer’s disease (AD), followed by vascular dementia, a category encompassing different subtypes among which cerebral small vessel disease (SVD) and multi-infarct dementia are the most common.2 In both AD and vascular dementia, vascular risk factors play an important role, suggesting a possible favorable effect of treatment on the onset and progression of cognitive decline. Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation and ineffective atrial contraction and may be detected on ECG when distinct P waves are absent, and R–R intervals and atrial activity are irregular.3 AF is the most common arrhythmia encountered in clinical practice, and, similarly to dementia, its prevalence increases with age. Approximately 1% of AF patients are 7 days).3 Interest has emerged concerning the possible role of AF in relation to cognitive decline and dementia. More than 40 years ago, the term cardiogenic dementia had been introduced in support of a possible link between cardiac arrhythmias and cognitive impairment in elderly subjects.4 Only recently the relation between AF and cognitive impairment has become the object of investigations, reviews, and meta-analyses.5–11 …

Background Experimentally, metalloproteinases (MMPs) play a detrimental role related to the severity of ischemic brain lesions. Both MMPs activity and function in tissues reflect the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs). We aimed to evaluate the role of MMPs/TIMPs balance in the setting of rtPA-treated stroke patients. Methods Blood was taken before and 24-h after rtPA from 327 patients (mean age 68 years, median NIHSS 11) with acute ischemic stroke. Delta median values of each MMP/TIMP ratio [(post rtPA MMP/TIMP-baseline MMP/TIMP)/(baseline MMP/TIMP)] were analyzed related to symptomatic intracranial hemorrhage (sICH) according to NINDS criteria, relevant hemorrhagic transformation (HT) defined as confluent petechiae within the infarcted area or any parenchymal hemorrhage, stroke subtypes (according to Oxfordshire Community Stroke Project) and 3-month death. The net effect of each MMP/TIMP ratio was estimated by a logistic regression model including major clinical determinants of outcomes Results Adjusting for major clinical determinants, only increase in MMP9/TIMP1 and MMP9/TIMP2 ratios remained significantly associated with sICH (odds ratio [95% confidence interval], 1.67 [1.17–2.38], p = 0.005; 1.74 [1.21–2.49], p = 0.003, respectively). Only relative increase in MMP9/TIMP1 ratio proved significantly associated with relevant HT (odds ratio [95% confidence interval], 1.74 [1.17–2.57], p = 0.006) with a trend toward significance for MMP9/TIMP2 ratio (p = 0.007). Discussion Our data add substantial clinical evidence about the role of MMPs/TIMPs balance in rtPA-treated stroke patients. These results may serve to generate hypotheses on MMPs inhibitors to be administered together with rtPA in order to counteract its deleterious effect.

Objectives Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by NOTCH3 mutations. There are no clinical and neuroimaging findings pathognomonic of the disease. The aim of this paper was to provide a description of a group of NOTCH3-negative patients with a phenotype closely resembling that of CADASIL. Materials and methods We performed NOTCH3 analysis (exons 2-23) in 117 probands because of a clinician's suspicion of CADASIL. The CADASIL scale, a recently developed tool that allows to better select patients for NOTCH3 analysis, was retrospectively applied to NOTCH3-negative patients; the patient subgroup that scored higher than the screening cutoff for CADASIL was defined as CADASIL-like. Results Thirty-four CADASIL-like patients (mean age at onset 57.8 years [52.1–63.4], 50% males) were identified. Compared with 25 patients with CADASIL for clinical, familial, and neuroimaging features, only the following variables were significantly (α level

Vascular mild cognitive impairment (VMCI) is a disorder in which multimodal MRI can add significant value by combining diffusion tensor imaging (DTI) with brain morphometry. In this study we implemented and compared machine learning techniques for multimodal classification between 58 VMCI patients and 29 healthy subjects as well as for discrimination (within the VMCI group) between patients with different cognitive performances. For each subject, a cortical feature vector was constructed based on cortical parcellation and cortical and subcortical volumetric segmentation and a DTI feature vector was formed by combining descriptive statistical metrics related to the distribution of DTI invariants within white matter. We employed both a sequential minimal optimization and a functional tree classifier, using feature selection and 10-fold cross-validation, and compared their performances in monomodal and multimodal classification for both classification problems (healthy subjects vs VMCI and prediction of cognitive performance). While monomodal classification resulted in satisfactory performance in most cases, turning from monomodal to multimodal classification resulted in an improvement of the performance in the discrimination between VMCI patients with low cognitive performance and healthy subjects by up to 10% in sensitivity (leaving specificity unchanged). We therefore are able to confirm the usefulness of machine learning techniques in discriminating diseased states based on neuroimaging data.

Although a growing attention is being paid to acute ischemic stroke patients, the correlation between clinical outcome and infectious events in this population has been poorly investigated. 749 ischemic stroke (mean age 71 years old, males 56%) patients were enrolled in this prospective case-control study by 11 Italian Stroke Units. Demographic data, vascular risk factors, previous infections and post-stroke infections (PSIs) were recorded. Blood samples were collected and the enzyme-linked immunoassay was chosen to measure Chlamydia pneumoniae IgG and IgA plasma antibodies (antibody titers were classified with specific cut-off levels: IgA > 1:16 and IgG > 1:64). Early poor outcome was defined as mRS score >2 at discharge, while poor outcome at 6-month follow-up. Univariate and multivariate analyses were performed. Median NIHSS was 7, IgA and IgG antichlamydia pneumoniae seropositivities were observed in 308 (37.1%) and 207 (23.6%) patients, respectively. Multivariate analyses showed significant correlations between PSIs and NIHSS (RR: 1.06; 95% CI 1.02-1.09; p < 0.001) and PSIs and IgA antichlamydia pneumoniae seropositivity (RR: 3.84; 95% CI 2.53-5.84; p < 0.001). Significant disability was associated with baseline NIHSS (RR: 1.32; 95% CI 1.16-1.50; p < 0.001), IgA (RR: 2.67; 95% CI 1.06-6.70; p = 0.035) and IgG antichlamydia (RR: 5.75; 95% CI 1.83-18.03; p = 0.003) seropositivity and atrial fibrillation (RR: 2.58; 95% CI 1.81-3.67; p < 0.001). While previous infections were not associated with functional outcome, antichlamydia antibodies play a negative role in ischemic stroke patients. Preventive strategies may reduce the stroke burden and improve the clinical outcome.

i.v. Thrombolysis (IVT) is the most important achievement of the last 20 years in the field of ischemic stroke management. In Italy, the evidence that stroke units were effective per se in improving stroke outcome was not sufficient to favor their implementation. Only the approval of IVT boosted the activation of stroke units, which are now 170 centers widespread over the country. The numbers of treatments, however, are still limited, amounting in 2014 to approximately 4200 out of the 10 000 which should theoretically be performed each year. Too strict exclusion criteria and/or their too restrictive interpretation are two of the main causes of this substantial undertreatment. Hence, a critical reappraisal of these criteria was necessary. On the other hand, recent evidences on the potentialities of intra-arterial interventions made it mandatory to better define the role of these techniques in the chain of treatments for acute ischemic stroke. A panel of vascular neurologists (D. T., D. I., A. C., E. A., P. C., A. Z.) and of interventional neuro-radiologists (S. M., S. V., M. B.) collected the data through a systematic review of the available literature, searching electronic databases including PubMed, EMBase, OVID, and Cochrane Library, up to May 2015. Reference lists of the selected articles were also scrutinized. Each panelist was assigned individual sections, then the panel assessed the complete guidelines. Recommendations were formulated by integrating the principles of the Scottish Intercollegiate Guideline Network with the statistical considerations suggested by the Centre for EvidenceBased Medicine methodology (Table 1). When literature data and practice experience data were not available or not considered to be sufficient, no specific recommendation was made. Consensus was reached during face-to-face discussions. In case of disagreement, a majority decision was taken. Recommendations were then revised by a larger group of experts pertaining to the fields of trial methodology, vascular neurology, cardiology, emergency medicine, neurosurgery, vascular surgery, neuro-radiology, and rehabilitation (see Appendix S1), which in particular checked for the congruence between the grading and the source data.

The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) involves 11 European centers. It aims to assess the role of the age-related white matter changes as an independent factor in the transition to disability, and in cognitive performance of an independent elderly population. A comprehensive neuropsychological battery was constructed in order to harmonize the cognitive assessment across countries. Patients were evaluated at baseline and during the 3-year follow-up with the Mini-Mental State Examination, a modified version of the VADAS-Cog (Alzheimer’s Dementia Assessment Scale plus tests of Delayed recall, Symbol digit, Digit span, Maze, Digit cancellation and Verbal fluency), Trail making and Stroop test. Six hundred thirty-eight patients (mean age 74 ± 5 years; mean educational level 10 ± 4, F/M: 351/287) were included in this study. Neuropsychological data were analyzed test by test and also grouped in three compound measures (executive, memory and speed/motor control domains). Older subjects (>74 years) performed significantly worse than younger subjects on the ADAS-Mod and on the tests of memory (t631 = 3.25; p = 0.001), executive functions (t581 = 4.68; p = 0.001) and speed/motor control (t587 = 4.01; p = 0.001). Participants with higher educational level (>8 years of school) showed better performances on the compound measures for memory (t631 = 3.25; p = 0.001), executive functions (t581 = 4.68; p = 0.001) and speed/motor control (t587 = 4.01; p = 0.001). Using multiple regression analysis models to study the influence of demographic variables on cognitive performance, age and education remained important variables influencing test performance. In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance.

OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. PARTICIPANTS: 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. MEASUREMENTS: 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. RESULTS: 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

Background Information on determinants and prognosis of ischemic stroke subtypes is scarce. We aimed at evaluating risk factors, pathogenesis, treatment and outcome of different ischemic stroke subtypes. Methods In a European Concerted Action involving seven countries, ischemic stroke subtypes defined according to the Oxfordshire Community Stroke Project (OCSP) were evaluated for demographics, baseline risk factors, resource use, 3-month survival, disability (Barthel Index) and handicap (Rankin Scale). Results During the 12-month study period, cerebral infarction was diagnosed in 2740 patients with first-in-a-lifetime stroke (mean age 70.5 ± 12.4 years, 53.4% males). OCSP classification was achieved in 2472 (90.2%). Of these, 26.7% were total anterior circulation infarctions (TACI), 29.9% partial anterior circulation infarctions (PACI), 16.7% posterior circulation infarctions (POCI) and 26.7% lacunar infarctions (LACI). In multivariate analysis, atrial fibrillation was predictive of TACI (odds ratio [OR], 1.61; 95% CI, 1.28–2.03), hypertension (OR, 1.38; 95% CI, 1.16–1.65) and myocardial infarction (OR, 1.42; 95% CI, 1.08–1.86) predictive of PACI, hypertension (OR, 1.25; 95% CI, 1.04–1.50) predictive of LACI. A negative association was observed between TACI and hypertension (OR, 0.51; 95% CI, 0.42–0.61). Discharge home was 50% less probable in TACI and PACI than in LACI patients. As compared to LACI, TACI significantly increased the risk of 3-month death (OR, 5.73; 95% CI, 3.91–8.41), disability (OR, 3.27; 95% CI, 2.30–4.66) and handicap (OR, 2.71; 95% CI, 1.91–3.85). Conclusions Ischemic stroke subtypes have different risk factors profile, with consequences on pathogenesis and prognosis. Information on determinants of the clinical syndromes may impact on prevention and acute-phase interventions.

Background and Purpose— White matter hyperintensities (WMH) are associated with decline in cognition, gait, mood, and urinary continence. Associations may depend on the method used for measuring WMH. We investigated the ability of different WMH scoring methods to detect differences in WMH load between groups with and without symptoms. Methods— We used data of 618 independently living elderly with WMH collected in the Leukoaraiosis And DISability (LADIS) study. Subjects with and without symptoms of depression, gait disturbances, urinary incontinence, and memory decline were compared with respect to WMH load measured qualitatively using 3 widely used visual rating scales (Fazekas, Scheltens, and Age-Related White Matter Changes scales) and quantitatively with a semiautomated volumetric technique and an automatic lesion count. Statistical significance between groups was assessed with the χ 2 and Mann-Whitney tests. In addition, the punctate and confluent lesion type with comparable WMH volume were compared with respect to the clinical data using Student t test and χ 2 test. Direct comparison of visual ratings with volumetry was done using curve fitting. Results— Visual and volumetric assessment detected differences in WMH between groups with respect to gait disturbances and age. WMH volume measurement was more sensitive than visual scores with respect to memory symptoms. Number of lesions nor lesion type correlated with any of the clinical data. For all rating scales, a clear but nonlinear relationship was established with WMH volume. Conclusions— Visual rating scales display ceiling effects and poor discrimination of absolute lesion volumes. Consequently, they may be less sensitive in differentiating clinical groups.

OBJECTIVES: To examine risk and predictors of motor-performance (MP) decline targeting subjects performing normally at an initial observation. DESIGN: Cohort study. SETTING: A subsample of the Italian Longitudinal Study on Aging (aged 65-84). PARTICIPANTS: One thousand fifty-two subjects (mean age+/-standard deviation = 71+/-5, 69% men) with normal MP at baseline. MEASUREMENTS: Six tests (standing up from a chair, stepping up, tandem walk, standing on one leg, walking speed, and steps turning 180 degrees ) were used to assess MP at baseline and after 3 years. Baseline characteristics were potential predictors of MP decline. RESULTS: Of the 1,052 subjects performing normally at baseline, 166 (15.8%) had declined in MP at follow-up. Older age, female sex, lower education, symptoms of distal symmetrical neuropathy, cognitive impairment without dementia, parkinsonism, heart failure, anemia, depressive symptoms, worse Mini-Mental State Examination score, and lost activities of daily living and instrumental activities of daily living (IADLs) were significantly associated with MP decline in univariate comparisons. Older age (odds ratio (OR) = 3.84, 95% confidence interval (CI) = 2.14-6.88 comparing age classes > or =80 with 65-69), female sex (OR=1.50, 95% CI = 1.03-2.20), distal symmetric neuropathy (OR = 2.00, 95% CI = 1.03-3.87), depressive symptoms (OR = 1.85, 95% CI = 1.17-2.24), and baseline IADLs (OR = 1.22, 95% CI = 1.08-1.37 for each lost activity) independently predicted MP decline after regression analysis. CONCLUSION: In a population-based cohort of elderly people with normal MP, one-sixth declined in 3 years. Age, sex, distal symmetrical neuropathy, depressive symptoms, and baseline IADLs independently predicted this decline. Distal symmetrical neuropathy is underestimated in the clinical and epidemiological evaluation of motor decline in older people. Language: en

Background: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. Methods: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1 ± 5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. Results: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. Conclusions: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.

The authors describe the design and the general, ultrasonographic, neuropsychological methodology of an observational epidemiological population survey, named REMEMBER (Registry Evaluation Memory in Buttrio e Remanzacco) conducted in the northeast of Italy in a randomized stratified sample of 1,026 subjects (554 F and 472 M) aged 55–98 years. The study was planned as cross-sectional and longitudinal survey of cognitive impairment, cardiovascular risk factors, carotid atherosclerosis in a midlife and older Italian population sample. The objectives of the first phase are to assess the prevalence of the different types of dementia, the cognitive impairment non-dementia, the cardiovascular risk factors, the carotid intima-media thickness and arterial distensibility, and of depression. The conclusions of this study will make it possible to organize preventive and interventional strategies for these epidemic conditions.

Background and Purpose— To evaluate preliminarily efficacy and safety of intravenous tirofiban combined with mechanical clot disruption and urokinase in patients with stroke attributable to major cerebral artery occlusion. Methods— Eleven consecutive patients with stroke attributable to acute occlusion of a major cerebral artery were treated with an intravenous bolus injection of the platelet glycoprotein IIb/IIIa antagonist tirofiban combined with heparin and by endovascular procedures including mechanical thrombolysis and locally delivered urokinase. Of the 11 cases, 9 involved angioplasty and 2 only microcatheter and microguidewire manipulation. Results— There were 7 patients with internal carotid or middle cerebral artery occlusion treated within 6 hours and 4 patients with basilar artery occlusion treated within 12 hours of symptom onset. Median National Institutes of Health Stroke Scale (NIHSS) score on admission was 20. After the interventional procedure, vessel recanalization was partial (thrombolysis in myocardial infarction grade flow 2 [TIMI 2]) in 7 patients and absent or insufficient in 4 patients. Twenty-four hours after the procedure, all the patients but 1 improved substantially, and on control angiography, the occluded vessel was totally patent (TIMI 3) in 10 of the 11 patients. One patient with partial recanalization did not improve and died 3 months later from pulmonary embolism. Neither a symptomatic intracerebral hemorrhage nor systemic bleedings requiring blood transfusion occurred in any patient. At discharge, median NIHSS score was 2. The 3-month outcome was excellent in 8 patients (modified Rankin Scale [mRS] 0 to 1), good in 2 patients (mRS 2), and poor in 1 patient (mRS 6). Conclusions— The combination of intravenous tirofiban with intra-arterial mechanical clot disruption and urokinase may be successful in reopening an occluded major cerebral vessel without increasing the hemorrhagic risk and with good functional outcome. This strategy cannot be recommended as the systematic treatment of stroke attributable to major cerebral artery occlusion until tested in a controlled study design.

Cognitive impairment and gait disturbances are the most frequent clinical findings in patients with leukoaraiosis (LA). Corpus callosum (CC) atrophy has been associated with dementia in patients with LA, as well as with gait disturbances in patients with normal pressure hydrocephalus. We investigated, in patients with LA, the possible association between gait impairment and CC atrophy, taking into account cognitive deficits and the other brain lesions commonly present in these patients. Thirty patients (M:F=21:9; mean age 72.5+/-6.3 years) with gait disturbances and brain CT images consistent with LA underwent an assessment of gait and a cognitive assessment of global and selective functions. Magnetic resonance imaging (MRI) was used to measure thickness and area of the CC, total LA volume, lacunar infarcts and size of lateral ventricles. We examined the effect of every MRI change on each performance measure. Reduction of CC thickness, particularly that of the anterior segment, had a significant effect on severity of gait impairment, as measured using the gait scale's score. It was independent of any other brain changes revealed by MRI, including LA. An independent, significant association was also found between CC area and the Left Hand Praxis test results. In patients with LA, CC atrophy is associated with gait impairment independently of LA and other brain abnormalities usually present in these patients.

Background and Purpose— Evidence of drug efficacy in vascular dementia (VaD) is scanty. Therapeutic trials should address VaD subtypes. We studied the efficacy and safety of the calcium antagonist nimodipine in subcortical VaD. Methods— 242 patients defined as affected by subcortical VaD based on clinical (ICD-10) and computed tomography criteria were randomized to oral nimodipine 90 mg/d or placebo. Results— 230 patients (121 nimodipine, mean age 75.2±6.1; 109 placebo, 75.4±6.0) were valid for the intention-to-treat analysis. At 52 weeks, the Sandoz Clinical Assessment Geriatric scale 5-point variation (primary outcome measure) did not differ significantly between the 2 groups. However, patients on nimodipine performed better than placebo patients in lexical production ( P 2 P P Conclusions— Nimodipine may be of some benefit in subcortical VaD. Confirming previous results, the safety analysis of this study shows that in this high-risk population, nimodipine might protect against cardiovascular comorbidities.

Background and Purpose— On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease. Methods— Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more). Results— In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke. Conclusion— We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65–84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 ± 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Vascular dementia (VD) has not to be considered anymore as a univocal nosologic entity. Based on different types of lesions, distinct subtypes of vascular dementia may be identified, each caused by diverse pathophysiological mechanisms. Among these subtypes subcortical vascular dementia (SVD) may represent a well-defined entity in terms of pathophysiology, clinical features and neuroradiological aspects. The picture is characterized by history of arterial hypertension and other vascular risk factors, clinical symptoms and signs including, besides dementia, dysfunctions related to subcortical-frontal circuit damages, and extensive confluent or diffuse abnormalities in the subcortical brain white matter, small deep infarcts as revealed by computed tomographic (CT) or magnetic resonance imaging (MRI) scans. The homogeneity of this clinical-pathological picture is essential for the success of controlled clinical trials in the field of vascular dementia.

Objectives – To investigate the association of major lifestyle-related risk factors with the prevalent cases of Parkinson’s disease (PD) identified by the Italian Longitudinal Study on Aging. Methods – A total of 5632 individuals randomly selected from the population registers of eight centers were screened for parkinsonism using both a questionnaire and a neurologic examination.Screened positives underwent a structured clinical work-up for the diagnosis of parkinsonism and parkinsonism subtypes. Results – We identified 113 prevalent cases of PD.Age, male gender, and pesticide-use license were significantly related to PD.Heavy smoking was inversely related to PD.Age (OR ¼ 1.1; 95% CI, 1.06–1.15) and pesticide-use license (OR ¼ 3.7; 95% CI, 1.6–8.6) kept their significant correlation with the disease in the multivariate analysis to adjust for all the variables under investigation.Multivariate analyses were made for men and women separately: pesticide exposure was positively associated with PD only in men. Conclusions – Pesticide exposure might represent a candidate for environmental factors involved in PD.

Background and Purpose— The information on the existence of sex differences in management of stroke patients is scarce. We evaluated whether sex differences may influence clinical presentation, resource use, and outcome of stroke in a European multicenter study. Methods— In a European Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin Scale). Results— Overall, 2239 patients were males and 2260 females. Compared with males, female patients were significantly older (mean age 74.5±12.5 versus 69.2±12.1 years), more frequently institutionalized before stroke, and with a worse prestroke Rankin score (all values P P =0.007) and atrial fibrillation ( P P P P =0.001), swallowing problems ( P =0.005), and urinary incontinence ( P P P Conclusions— Sex-specific differences existed in a large European study of hospital admissions for acute stroke. Both medical and sociodemographic factors may significantly influence stroke outcome. Knowledge of these determinants may positively impact quality of care.

Background and Purpose— To provide further insight into the MRI assessment of age-related white matter changes (ARWMCs) with visual rating scales, 3 raters with different levels of experience tested the interrater agreement and comparability of 3 widely used rating scales in a cross-sectional and follow-up setting. Furthermore, the correlation between visual ratings and quantitative volumetric measurement was assessed. Methods— Three raters from different sites using 3 established rating scales (Manolio, Fazekas and Schmidt, Scheltens) evaluated 74 baseline and follow-up scans from 5 European centers. One investigator also rated baseline scans in a set of 255 participants of the Austrian Stroke Prevention Study (ASPS) and measured the volume of ARWMCs. Results— The interrater agreement for the baseline investigation was fair to good for all scales (κ values, 0.59 to 0.78). On the follow-up scans, all 3 raters depicted significant ARWMC progression; however, the direct interrater agreement for this task was poor (κ, 0.19 to 0.39). Comparison of the interrater reliability between the 3 scales revealed a statistical significant difference between the scale of Manolio and that of Fazekas and Schmidt for the baseline investigation ( z value, −2.9676; P =0.003), demonstrating better interrater agreement for the Fazekas and Schmidt scale. The rating results obtained with all 3 scales were highly correlated with each other (Spearman rank correlation, 0.712 to 0.806; P ≤0.01), and there was significant agreement between all 3 visual rating scales and the quantitative volumetric measurement of ARWMC (Kendall W , 0.37, 0.48, and 0.57; P Conclusions— Our data demonstrate that the 3 rating scales studied reflect the actual volume of ARWMCs well. The 2 scales that provide more detailed information on ARWMCs seemed preferential compared with the 1 that yields more global information. The visual assessment of ARWMC progression remains problematic and may require modifications or extensions of existing rating scales.

Carotid endarterectomy represents one of the main strategies for primary and secondary prevention of atherothrombotic ischemic stroke. ECST and NASCET studies on symptomatic carotid stenosis showed a significantly higher benefit of surgical compared to medical therapy to reduce the risk of ischemic stroke in case of severe stenosis, (over 70% in NASCET study and over 85% in ECST study) with a Number Needed to Treat, NNT, at 2 years of 8. For moderate stenosis (50–69% in the NASCET study) there was a smaller benefit (NNT = 20), while there was no benefit for stenosis < 50%. The ACAS study on asymptomatic carotid stenosis showed a higher benefit of surgical therapy for stenosis over 60% (NNT at 2 years of 67). The application of these results to clinical practice depends on the reproducibility of the same conditions mainly in terms of perioperative risk. Moreover, data on the natural history of asymptomatic carotid stenosis showed that only 50% of the ischemic events at follow-up were related to the stenosis itself. This could indicate that the real benefit of the surgical procedure could be less than that reported by the clinical trials. The plaque composition, to be evaluated by emerging ultrasonographic and magnetic resonance techniques, is assuming increasing relevance as a further criterion to establish the indication for the surgical procedure. At the moment, however, no evidence exists on this matter.

This article represents the update of ‘European Stroke Initiative Recommendations for Stroke Management’, first published in this Journal in 2000. The recommendations are endorsed by the 3 European societies which are represented in the European Stroke Initiative: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.

Background: Epidemiological data are essential to estimate the burden of stroke.We evaluated stroke incidence in older Italians and the effect of first-ever stroke on survival and activities of daily living (ADL). Methods: The analysis was performed in the Italian Longitudinal Study on Aging (ILSA) sample, consisting of 5,632 individuals aged 65–84. The ILSA aims at major cardiovascular and neurological age-associated diseases. The baseline survey was performed in 1992 to detect prevalent diseases. The longitudinal examination started on September 1995 aiming at incidence, function and survival. Results: Complete follow-up data were achieved for 77% of the baseline stroke-free cohort (4,164 persons; 50.9% males; mean age 74.5 ± 5.7 years). Incidence for first-ever stroke was 9.51 (95% CI: 7.75–11.27) per 1,000 person years and 12.99 (95% CI: 10.99–14.98) including recurrent stroke (total incidence). Crude mortality was 49.2% among first stroke patients and 15% among persons without stroke. The first-ever stroke mortality risk ratio, adjusted for demographics and comorbidity, was 2.40 (95% CI: 1.62–3.54). In survivors, impairment of at least one ADL was present in 67.6% of first-ever stroke patients vs. 31.6% of individuals without stroke. The comorbidity-adjusted OR was 2.63 (95% CI: 1.20–5.78) in the total cohort, and 4.00 (95% CI: 1.39–11.46) in individuals without disability at baseline. Conclusions: The ILSA provides the first data on stroke incidence in Italy on a national basis. Overall, 153,000 new cases can be expected annually in the Italian elderly population. First-ever stroke still has a strong effect on survival and function of older persons.

Background and Purpose: Data on stroke morbidity are lacking in southern Italy, an area with about 20 million inhabitants and a mean income lower than the rest of the country. Therefore a population-based stroke register was established to determine incidence and case fatality in the Province of Vibo Valentia, Calabria. Methods: The survey was conducted among the 179,186 residents. Standard definitions and multiple case-finding procedures were employed. All identified cases of first-ever stroke were followed at 28 days, 3 and 12 months. The registration started on January 1, 1996, and ended on December 31, 1996. Results: A total of 321 first-ever-in-a-lifetime strokes were identified. The crude annual incidence rate was 1.79 (95% CI 1.60–1.99) per 1,000 inhabitants. Rates age-standardized to the 1996 Italian population and to the standard European population were, respectively, 1.99 (95% CI 1.79–2.20) and 1.36 (95% CI 1.19–1.53) per 1,000 inhabitants. A subtype diagnosis was reached in 96% of patients. The crude annual incidence rates per 1,000 inhabitants were 1.31 for cerebral infarction, 0.35 for intracerebral hemorrhage, 0.06 for subarachnoid hemorrhage, and 0.07 for unspecified stroke. Overall case fatality was 23.7% at 28 days, 27.4% at 3 months and 40.2% at 12 months. Conclusions: This is the first prospective population-based stroke register established in southern Italy. Incidence and case fatality were comparable to those previously reported in northern and central Italy and other industrialized countries. Our estimates are useful for developing management services and allocating resources.