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| 12. |
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| 13. |
- Alves, G., et al.
(författare)
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CSF A beta(42) predicts early-onset dementia in Parkinson disease
- 2014
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 82:20, s. 1784-1790
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To test in vivo the proposal from clinicopathologic studies that -amyloid (A) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF A and related measures as early prognostic biomarkers of dementia in an incident PD cohort.Methods:We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of A42, A40, and A38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of A42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria.Results:CSF levels of A42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p = 0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other markers. Low A42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (85%), with hazard ratios of 9.9 (95% confidence interval 2.3-43.5, p = 0.002) for A42(ECL) <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for A42(ELISA) <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. A42 reductions tended to precede the onset of PD-MCI that progressed to dementia.Conclusions:These in vivo data support the role of A pathology in the etiology and highlight the potential utility of CSF A42 as an early prognostic biomarker of dementia associated with PD.
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| 14. |
- Andersen, Peter M.
(författare)
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Is all ALS genetic?
- 2017
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 89:3, s. 220-221
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Arenaza-Urquijo, E. M., et al.
(författare)
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Association of years to parent's sporadic onset and risk factors with neural integrity and Alzheimer biomarkers
- 2020
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 95:15, s. E2065-E2074
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the hypothesis that proximity to parental age at onset (AAO) in sporadic Alzheimer disease (AD) is associated with greater AD and neural injury biomarker alterations during midlife and to assess the role of nonmodifiable and modifiable factors. Methods This observational study included 290 cognitively unimpaired (CU) participants with a family history (FH) of clinically diagnosed sporadic AD (age 49-73 years) from the Alzheimer's and Families (ALFA) study. [F-18]flutemetamol-PET standardized uptake value ratios, CSF beta-amyloid(42/40) ratio, and phosphorylated tau were used as AD biomarkers. Hippocampal volumes and CSF total tau were used as neural injury biomarkers. Mental and vascular health proxies were calculated. In multiple regression models, we assessed the effect of proximity to parental AAO and its interaction with age on AD and neural injury biomarkers. Then, we evaluated the effects of FH load (number of parents affected), sex, APOE epsilon 4, education, and vascular and mental health. Results Proximity to parental AAO was associated with beta-amyloid, but not with neural injury biomarkers, and interacted with sex and age, showing that women and older participants had increased beta-amyloid. FH load and APOE epsilon 4 showed independent contributions to beta-amyloid load. Education and vascular and mental health proxies were not associated with AD biomarkers. However, lower mental health proxies were associated with decreased hippocampal volumes with age. Conclusion The identification of the earliest biomarker changes and modifiable factors to be targeted in early interventions is crucial for AD prevention. Proximity to parental AAO may offer a timeline for detection of incipient beta-amyloid changes in women. In risk-enriched middle-aged cohorts, mental health may be a target for early interventions.
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| 16. |
- Arnoldussen, Ilse A. C., et al.
(författare)
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Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study
- 2019
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Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 93:9, s. e864-e878
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Adiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC).METHODS: RUN DMC participants were followed up for 9 years (2006-2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes.RESULTS: Cross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men.CONCLUSIONS: Anthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.
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| 17. |
- Aronsson, Mattias, et al.
(författare)
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Cost-effectiveness of endovascular thrombectomy in patients with acute ischemic stroke.
- 2016
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Ingår i: Neurology. - : American Academy of neurology. - 0028-3878 .- 1526-632X. ; 86:11, s. 1053-9
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To evaluate the cost-effectiveness of adding endovascular thrombectomy to standard care in patients with acute ischemic stroke.Methods:The cost-effectiveness analysis of endovascular thrombectomy in patients with acute ischemic stroke was based on a decision-analytic Markov model. Primary outcomes from ESCAPE, Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA), Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT), and Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) along with data from published studies and registries were used in this analysis. We used a health care payer perspective and a lifelong time horizon to estimate costs and effects.Results:The model showed that adding thrombectomy with stent retrievers to guideline-based care (including IV thrombolysis) resulted in a gain of 0.40 life-years and 0.99 quality-adjusted life-years along with a cost savings of approximately $221 per patient. The sensitivity analysis showed that the results were not sensitive to changes in uncertain parameters or assumptions.Conclusions:Adding endovascular treatment to standard care resulted in substantial clinical benefits at low costs. The results were consistent throughout irrespective of whether data from ESCAPE, EXTEND-IA, MR CLEAN, REVASCAT, or SWIFT PRIME were used in this model.
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| 18. |
- Aziz, N. A., et al.
(författare)
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Weight loss in Huntington disease increases with higher CAG repeat number
- 2008
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 71:19, s. 1506-1513
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number. Methods: In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD. Results: In patients with HD, mean body mass index decreased with -0.15 units per year (p < 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length. Conclusions: Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics. Neurology (R) 2008;71:1506-1513
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| 19. |
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| 20. |
- Baezner, H, et al.
(författare)
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Association of gait and balance disorders with age-related white matter changes: the LADIS study.
- 2008
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 70:12, s. 935-42
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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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