Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk of limitations in mobility.

Rationale Optimal secondary prevention of embolic stroke of undetermined source is not established. The current standard in these patients is acetylsalicylic acid, despite high prevalence of yet undetected paroxysmal atrial fibrillation. Aim The ATTICUS randomized trial is designed to determine whether the factor Xa inhibitor apixaban administered within 7 days after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of new ischemic lesions documented by brain magnetic resonance imaging within 12 months after index stroke. Design Prospective, randomized, blinded, parallel-group, open-label, German multicenter phase III trial in approximately 500 patients with embolic stroke of undetermined source. A key inclusion criterion is the presence or the planned implantation of an insertable cardiac monitor. Patients are 1:1 randomized to apixaban or acetylsalicylic acid and treated for a 12-month period. It is an event-driven trial aiming for core-lab adjudicated primary outcome events. Study outcomes The primary outcome is the occurrence of at least one new ischemic lesion identified by axial T2-weighted FLAIR magnetic resonance imaging and/or axial DWI magnetic resonance imaging at 12 months when compared with the baseline magnetic resonance imaging. Key secondary outcomes are the combination of recurrent ischemic strokes, hemorrhagic strokes, systemic embolism; combination of MACE including recurrent stroke, myocardial infarction, and cardiovascular death and combination of major and clinically relevant non-major bleeding defined according to ISTH, and change of cognitive function and quality of life (EQ-5D, Stroke Impact Scale). Discussion Embolic stroke of undetermined source is caused by embolic disease and associated with a high risk of recurrent ischemic strokes and clinically silent cerebral ischemic lesions. ATTICUS will investigate the impact of atrial fibrillation detected by insertable cardiac monitor and the effects of early anticoagulation with apixaban compared with antiplatelet therapy with acetylsalicylic acid on the incidence of new ischemic lesion after embolic stroke of undetermined source.

Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition. This suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting.

Background: Global age related white matter changes (ARWMC) are associated with progressive gait disturbances and falls, hypothesised to result from interruptions of cortico-subcortical circuits controlling balance, posture and locomotion. Methods: The location of ARWMC in a large cohort of elderly non-disabled individuals with reported falls was analysed, using the cross sectional data of the Leukoaraiosis and Disability (LADIS) study. Detailed anatomical distributions of ARWMC assessed by MRI studies were analysed with respect to falls and balance performance. Results: The severity of global ARWMC was significantly associated with a history of falls in the year prior to study inclusion (22.2% in the mild, 31.6% in the moderate and 37.3% in the severe ARWMC group according to the Fazekas scale; p = 0.002). Analysing the anatomical distribution of ARWMC, using the semiquantitative Scheltens scale, in multivariate analysis, periventricular (p = 0.006) and frontal deep (p = 0.033) ARWMC were independently associated with falls. Furthermore, logistic regression identified frontal deep (p = 0.003) ARWMC, but not basal ganglia and infratentorial hyperintensities, as significantly associated with balance disturbances. Conclusion: The association of frontal and periventricular ARWMC with falls supports the hypothesis that interruption of frontal subcortical motor circuits lead to balance disturbances and hence to an increased risk for falls in ARWMC.Changes in the cerebral white matter, also called leukoaraiosis, 1 are detected frequently on brain imaging of elderly persons and are known to be associated with several vascular risk factors.

Background and Purpose-We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. Methods-The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria. Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. Results-Six hundred thirty-nine subjects were included (74.1±5 years old, 55% women, 9.6±3.8 years of schooling, 64% physically active

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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.

Camptocormia, or "bent spine syndrome", may occur in various movement disorders such as primary dystonia or idiopathic Parkinson's disease (PD). Although deep brain stimulation (DBS) is an established treatment in refractory primary dystonia and advanced PD, few data are available on the effect of DBS on camptocormia comparing these two conditions. Seven patients (4 with dystonia, 3 with PD; mean age 60.3 years at surgery, range 39-73 years) with camptocormia were included in the study. Five patients underwent bilateral GPi DBS and two patients underwent bilateral STN DBS guided by CT-stereotactic surgery and microelectrode recording. Pre- and postoperative motor assessment included the BFM in the dystonia patients and the UPDRS in the PD patients. Severity of camptocormia was assessed by the BFM subscore for the trunk at the last available follow-up at a mean of 17.3 months (range 9-36 months). There were no surgical complications. In the four patients with dystonia there was a mean improvement of 53% in the BFM motor score (range 41-79%) and of 63% (range 50-67%) in the BFM subscore for the trunk at the last available follow-up (mean 14.3 months, range 9-18 months). In the three patients with camptocormia in PD who underwent bilateral STN DBS (2 patients) or pallidal DBS (1 patient), the PD symptoms improved markedly (mean improvement in the UPDRS motor subscore stimulation on/medication off 55%, range 49-61%), but there was no or only mild improvement of camptocormia in the two patients who underwent STN DBS, and only moderate improvement in the patient with GPi DBS at the last available follow-up (mean 21 months, range 12-36 months). GPi DBS is an effective treatment for camptocormia in dystonia. The response of camptocormia to chronic STN or GPi DBS in PD is more heterogenous. The latter may be due to a variety of causes and needs further clarification.