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Sökning: WFRF:(Poggesi A)

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21.
  • Baezner, H, et al. (författare)
  • Association of gait and balance disorders with age-related white matter changes: the LADIS study.
  • 2008
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 70:12, s. 935-42
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers are evaluating the role of age-related white matter changes (ARWMC) as an independent determinant of the transition to disability in the elderly (65 to 84 years). We aimed at determining the influence of ARWMC on different objective measures of gait and balance. METHODS: Six hundred thirty-nine nondisabled individuals were prospectively enrolled and are being followed-up for 3 years. Subjects are graded in three standardized categories of ARWMC (mild, moderate, and severe) according to central MRI reading. Quantitative tests of gait and balance include the Short Physical Performance Battery (SPPB; range: 0 [poor] to 12 [normal]), a timed 8-m walk, and a timed single leg stance test. RESULTS: In cross-sectional analysis, deficiencies in gait and balance performance were correlated with the severity of ARWMC (SPPB: 10.2 +/- 2.1 in the mild, 9.9 +/- 2.0 in the moderate, 8.9 +/- 2.6 in the severe group; p < 0.001). Walking speed correlated with the severity of ARWMC (1.24 +/- 0.28 m/second in the mild, 1.18 +/- 0.32 m/second in the moderate, and 1.09 +/- 0.31 m/second in the severe group; p < 0.001). Balance was best in individuals with mild ARWMC (single leg stance time: 18.9 +/- 10.8 seconds) compared with moderate and severe ARWMC (16.4 +/- 10.8 and 13.6 +/- 11.2 seconds) (p < 0.001). Physically inactive individuals had a higher risk of a pathologic SPPB score (moderate vs mild ARWMC: odds ratio 1.60, 95% CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to 2.80). CONCLUSIONS: 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.
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22.
  • Blahak, C, et al. (författare)
  • Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study.
  • 2009
  • Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:6, s. 608-13
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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23.
  • Gouw, Alida A, et al. (författare)
  • Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study.
  • 2008
  • Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628. ; 39:5, s. 1414-20
  • Tidskriftsartikel (refereegranskat)abstract
    • 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. CONCLUSIONS: 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.
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24.
  • Kreisel, S. H., et al. (författare)
  • Deterioration of Gait and Balance over Time: The Effects of Age-Related White Matter Change - The LADIS Study
  • 2013
  • Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 35:6, s. 544-553
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cross-sectional studies have shown an association between the severity of age-related white matter change (ARWMC) and lower body motor function. However, the association between prevalent ARWMC and incident deterioration of balance and gait remains insufficiently investigated. This study investigates if the degree of prevalent ARWMC has a differential effect on lower body motor function as it changes over time, hypothesizing that individuals with more severe baseline white matter pathology experience greater clinical deterioration independent of potential confounders. This is of clinical relevance: given the increasing use of neuroimaging, incidental white matter pathology is common; being able to delineate natural trajectories of balance and gait function given ARWMC may improve patient advice and help optimize allocation of care. Methods: 639 non-disabled elderly individuals with prevalent ARWMC (grading of severity of ARWMC using the Fazekas scale) were followed up yearly for 3 years, as part of the Leukoaraiosis and Disability Study. The primary outcome variable, reflecting the temporal course of gait and balance function, was the change of scores on the Short Physical Performance Battery (SPPB) over time versus the severity of ARWMC. We used linear mixed modelling to analyse change over time. Explorative analysis was carried out investigating the effect of age on potential deterioration of gait and balance function. We used propensity scores to adjust for multiple confounders that affect both the exposure (i. e. ARWMC) and outcome. Results: Subjects' lower body motor function deteriorated by 2.6% per year. However, after adjustment for baseline motor impairment and potential confounders, only subjects with moderate [-0.22 points per year on the SPPB (equals -2.3%); 95% CI -0.35 to -0.09, p < 0.001] or severe [-0.46 points per year (equals -4.7%); 95% CI -0.63 to -0.28, p < 0.0001] ARWMC show a loss of function. Age shows differential effects: relatively younger elderly subjects have similar temporal dynamics in SPPB change independent of their individual degree of ARWMC severity; however, subjects with severe ARWMC and who are older than 75.9 years deteriorate significantly more rapidly than their counterparts with only mild or moderate white matter pathology. Conclusion: Only moderate and severe ARWMC is independently associated -on average -with a deterioration of gait and balance. Albeit the possibility of unmeasured confounding and other methodological constraints, there is nonetheless evidence of large interindividual variability: some subjects with moderate or severe ARWMC stay stable over time or even show improvement. Furthermore, there is explorative analysis showing that younger elderly subjects may be able to better compensate even severe ARWMC. These individuals' gait and balance function stays relatively stable over time, whereas their older counterparts deteriorate significantly. This may point towards a threshold effect given ARWMC.
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25.
  • Poggesi, A, et al. (författare)
  • 2001–2011: a decade of the LADIS (Leukoaraiosis And DISability) Study: what have we learned about white matter changes and small-vessel disease?
  • 2011
  • Ingår i: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 32:6, s. 577-588
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the last 20 years, evidence about the clinical correlates of cerebral white matter changes (WMC; also called leukoaraiosis) has been accumulating. WMC are now listed among the neuroimaging expressions of cerebral small-vessel disease and are no longer considered an innocuous finding because they are associated, in cross-sectional surveys, with various disturbances and, in follow-up studies, with poor prognosis. The Leukoaraiosis And DISability (LADIS) study has contributed substantially to this body of knowledge. LADIS is a European multicenter collaboration that was started in 2001 with the aim of assessing the independent role of WMC in predicting disability in subjects aged 65–84. The main results of the LADIS study have been released in 2009 with the demonstration that severe WMC more than double the risk of transition from an autonomous to a dependent status after 3 years of follow-up. The LADIS study has also contributed more focused substudies assessing the possible role of WMC in the decline of cognitive and motor performances, depressive symptoms associated with aging and cerebrovascular diseases, urinary disturbances, and also the role of other brain lesions (lacunar infarcts, cerebral atrophy, and corpus callosum morphology). The LADIS study provides a good example of harmonization of instruments (MRI protocol, clinical, neuropsychological, and functional scales) within an international collaboration. Currently, the LADIS study is providing data about the natural history of WMC. In this paper, we review the background and the main results of the LADIS study. This review puts forward some considerations for future studies in the field.
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26.
  • Russu, A., et al. (författare)
  • Joint Modeling of Efficacy, Dropout, and Tolerability in Flexible-Dose Trials : A Case Study in Depression
  • 2012
  • Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 91:5, s. 863-871
  • Tidskriftsartikel (refereegranskat)abstract
    • Many difficulties may arise during the modeling of the time course of Hamilton Rating Scale for Depression (HAM D) scores in clinical trials for the evaluation of antidepressant drugs: (i) flexible designs, used to increase the chance of selecting more efficacious doses, (ii) dropout events, and (iii) adverse effects related to the experimental compound. It is crucial to take into account all these factors when designing an appropriate model of the HAM D time course and to obtain a realistic description of the dropout process. In this work, we propose an integrated approach to the modeling of a double-blind, flexible-dose, placebo-controlled, phase II depression trial that comprises response, tolerability, and dropout. We investigate three different dropout mechanisms in terms of informativeness. Goodness of fit is quantitatively assessed with respect to response (HAM D score) and dropout data. We show that dropout is a complex phenomenon that may be influenced by HAM D evolution, dose changes, and occurrence of drug-related adverse effects.
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