86 research outputs found
Levodopa-carbidopa intestinal gel in the treatment of patients with parkinson disease: Results of a 12-month open study
© 2017, Media Sphera. All rights reserved.Objective: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. Material and methods: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of âoffâ periods, âonâ periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D Đž EQ-VAS) dynamics, an analysis of patientâs diaries) were assessed throughout the whole study. Results: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of âoffâ periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of âonâ periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of âonâ periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. Conclusion: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction
Arterial hypertension and ÎČ-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study
Background: White matter hyperintensities (WMH) in subjects across the Alzheimerâs disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathologyânot just arterial hypertensionâimpacts WMH, which in turn adversely influences cognition. Here we seek to determine the effect of both hypertension and AÎČ positivity on WMH, and their impact on cognition. Methods: We analysed data from subjects with a low vascular profile and normal cognition (NC), subjective cognitive decline (SCD), and amnestic mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study (n = 375, median age 70.0 [IQR 66.0, 74.4] years; 178 female; NC/SCD/MCI 127/162/86). All subjects underwent a rich neuropsychological assessment. We focused on baseline memory and executive functionâderived from multiple neuropsychological tests using confirmatory factor analysisâ, baseline preclinical Alzheimerâs cognitive composite 5 (PACC5) scores, and changes in PACC5 scores over the course of three years (ÎPACC5). Results: Subjects with hypertension or AÎČ positivity presented the largest WMH volumes (pFDR < 0.05), with spatial overlap in the frontal (hypertension: 0.42 ± 0.17; AÎČ: 0.46 ± 0.18), occipital (hypertension: 0.50 ± 0.16; AÎČ: 0.50 ± 0.16), parietal lobes (hypertension: 0.57 ± 0.18; AÎČ: 0.56 ± 0.20), corona radiata (hypertension: 0.45 ± 0.17; AÎČ: 0.40 ± 0.13), optic radiation (hypertension: 0.39 ± 0.18; AÎČ: 0.74 ± 0.19), and splenium of the corpus callosum (hypertension: 0.36 ± 0.12; AÎČ: 0.28 ± 0.12). Elevated global and regional WMH volumes coincided with worse cognitive performance at baseline and over 3 years (pFDR < 0.05). AÎČ positivity was negatively associated with cognitive performance (direct effectâmemory: â 0.33 ± 0.08, pFDR < 0.001; executive: â 0.21 ± 0.08, pFDR < 0.001; PACC5: â 0.29 ± 0.09, pFDR = 0.006; ÎPACC5: â 0.34 ± 0.04, pFDR < 0.05). Splenial WMH mediated the relationship between hypertension and cognitive performance (indirect-only effectâmemory: â 0.05 ± 0.02, pFDR = 0.029; executive: â 0.04 ± 0.02, pFDR = 0.067; PACC5: â 0.05 ± 0.02, pFDR = 0.030; ÎPACC5: â 0.09 ± 0.03, pFDR = 0.043) and WMH in the optic radiation partially mediated that between AÎČ positivity and memory (indirect effectâmemory: â 0.05 ± 0.02, pFDR = 0.029). Conclusions: Posterior white matter is susceptible to hypertension and AÎČ accumulation. Posterior WMH mediate the association between these pathologies and cognitive dysfunction, making them a promising target to tackle the downstream damage related to the potentially interacting and potentiating effects of the two pathologies. Trial registration: German Clinical Trials Register (DRKS00007966, 04/05/2015)
Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer's Disease
© 2016 - IOS Press and the authors. All rights reserved.Alzheimer's disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-ÎČ plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging. In this study we have utilized a gene-expression array to screen blood and skin punch biopsy (fibroblasts, keratinocytes, and endothelial cells) for transcriptional differences that may lead to a greater understanding of AD as well as identify potential biomarkers. Our analysis identified 129 differentially expressed genes from blood of dementia cases when compared to healthy individuals, and four differentially expressed punch biopsy genes between AD subjects and controls. Additionally, we identified a set of genes in both tissue compartments that showed transcriptional variation in AD but were largely stable in controls. The translational products of these variable genes are involved in the maintenance of the Golgi structure, regulation of lipid metabolism, DNA repair, and chromatin remodeling. Our analysis potentially identifies specific genes in both tissue compartments that may ultimately lead to useful biomarkers and may provide new insight into the pathophysiology of AD
Gaussian Process-based prediction of memory performance and biomarker status in ageing and Alzheimer's disease-A systematic model evaluation
Resting-State Network Alterations Differ between Alzheimer's Disease Atrophy Subtypes
Several Alzheimer's disease (AD) atrophy subtypes were identified, but their brain network properties are unclear. We analyzed data from two independent datasets, including 166 participants (103Â AD/63 controls) from the DZNE-longitudinal cognitive impairment and dementia study and 151 participants (121Â AD/30 controls) from the AD neuroimaging initiative cohorts, aiming to identify differences between AD atrophy subtypes in resting-state functional magnetic resonance imaging intra-network connectivity (INC) and global and nodal network properties. Using a data-driven clustering approach, we identified four AD atrophy subtypes with differences in functional connectivity, accompanied by clinical and biomarker alterations, including a medio-temporal-predominant (S-MT), a limbic-predominant (S-L), a diffuse (S-D), and a mild-atrophy (S-MA) subtype. S-MT and S-D showed INC reduction in the default mode, dorsal attention, visual and limbic network, and a pronounced reduction of "global efficiency" and decrease of the "clustering coefficient" in parietal and temporal lobes. Despite severe atrophy in limbic areas, the S-L exhibited only marginal global network but substantial nodal network failure. S-MA, in contrast, showed limited impairment in clinical and cognitive scores but pronounced global network failure. Our results contribute toward a better understanding of heterogeneity in AD with the detection of distinct differences in functional connectivity networks accompanied by CSF biomarker and cognitive differences in AD subtypes
A comprehensive score reflecting memory-related fMRI activations and deactivations as potential biomarker for neurocognitive aging
Older adults and particularly those at risk for developing dementia typically show a
decline in episodic memory performance, which has been associated with altered
memory network activity detectable via functional magnetic resonance imaging
(fMRI). To quantify the degree of these alterations, a score has been developed as a
putative imaging biomarker for successful aging in memory for older adults (Functional Activity Deviations during Encoding, FADE; DĂŒzel et al., Hippocampus, 2011; 21:
803â814). Here, we introduce and validate a more comprehensive version of the
FADE score, termed FADE-SAME (Similarity of Activations during Memory Encoding),
which differs from the original FADE score by considering not only activations but
also deactivations in fMRI contrasts of stimulus novelty and successful encoding, and
by taking into account the variance of young adults' activations. We computed both
scores for novelty and subsequent memory contrasts in a cohort of 217 healthy
adults, including 106 young and 111 older participants, as well as a replication cohort
of 117 young subjects. We further tested the stability and generalizability of both
scores by controlling for different MR scanners and gender, as well as by using different data sets of young adults as reference samples. Both scores showed robust agegroup-related differences for the subsequent memory contrast, and the FADE-SAME
score additionally exhibited age-group-related differences for the novelty contrast.
Furthermore, both scores correlate with behavioral measures of cognitive aging,
namely memory performance. Taken together, our results suggest that single-value
scores of memory-related fMRI responses may constitute promising biomarkers for
quantifying neurocognitive aging
йДŃĐ°ĐżĐžŃ ĐŸŃŃĐ”ĐŸĐ°ŃŃŃĐžŃĐ° ĐșĐŸĐ»Đ”ĐœĐœŃŃ ŃŃŃŃĐ°ĐČĐŸĐČ Ń ŃĐŸŃĐșĐž Đ·ŃĐ”ĐœĐžŃ ĐŽĐŸĐșĐ°Đ·Đ°ŃДлŃĐœĐŸĐč ĐŒĐ”ĐŽĐžŃĐžĐœŃ: ĐŸĐ¶ĐžĐŽĐ°Đ”ĐŒŃĐ” ĐșŃĐ°ŃĐșĐŸŃŃĐŸŃĐœŃĐ”, ŃŃĐ”ĐŽĐœĐ”ŃŃĐŸŃĐœŃĐ” Đž ĐŽĐŸĐ»ĐłĐŸŃŃĐŸŃĐœŃĐ” ŃДзŃĐ»ŃŃĐ°ŃŃ ĐżŃĐžĐŒĐ”ĐœĐ”ĐœĐžŃ ŃĐ”ŃДпŃŃŃĐœĐŸĐłĐŸ ĐșŃĐžŃŃаллОŃĐ”ŃĐșĐŸĐłĐŸ глŃĐșĐŸĐ·Đ°ĐŒĐžĐœĐ° ŃŃĐ»ŃŃĐ°ŃĐ°
The need for effective drugs for the treatment of knee osteoarthritis (OA) is constantly growing. Current guidelines recommend the use of symptomatic slow acting drugs for osteoarthritis (SYSADOA) such as glucosamine (GCA) in this disease. Among various drugs containing GCA, high bioavailability and clinical efficacy have been shown only for prescription crystalline GCA sulfate (pGCAS) administration. Several meta-analyses and network meta-analyses have shown that efficacy of pGCAS 1500 mg once daily is superior to other GCA-based products (such as GCA hydrochloride with or without sodium sulfate) and the combination of GCA with chondroitin sulfate (CS) in terms of reducing the intensity of pain and improving the functional state. These studies confirmed the favorable safety profile of pGCAS, which was comparable to placebo in the incidence of adverse events. Pharmacoeconomic studies have also demonstrated greater cost-effectiveness of pGCAS compared to other GCA drugs.A group of Russian experts at a meeting of the advisory committee reviewed the evidence in favor of the use of pGCAS and evidence of its effectiveness in the treatment of knee OA in comparison with other products that include GCA, and the fixed combination of GCA with CS. Taking into account the results obtained, the use of pGCAS at a dose of 1500 mg once a day is recommended as a rational choice for the treatment of knee OA.ĐĐŸŃŃĐ”Đ±ĐœĐŸŃŃŃ ĐČ ŃŃŃĐ”ĐșŃĐžĐČĐœŃŃ
ĐżŃДпаŃĐ°ŃĐ°Ń
ĐŽĐ»Ń ŃĐ”ŃапОО ĐŸŃŃĐ”ĐŸĐ°ŃŃŃĐžŃĐ° (ĐĐ) ĐșĐŸĐ»Đ”ĐœĐœŃŃ
ŃŃŃŃĐ°ĐČĐŸĐČ (ĐĐĄ) ĐżĐŸŃŃĐŸŃĐœĐœĐŸ ŃĐ°ŃŃĐ°Đ”Ń. Đ ŃĐŸĐČŃĐ”ĐŒĐ”ĐœĐœŃŃ
ŃŃĐșĐŸĐČĐŸĐŽŃŃĐČĐ°Ń
ŃĐ”ĐșĐŸĐŒĐ”ĐœĐŽŃĐ”ŃŃŃ ĐżŃĐžĐŒĐ”ĐœŃŃŃ ĐżŃĐž ŃŃĐŸĐŒ Đ·Đ°Đ±ĐŸĐ»Đ”ĐČĐ°ĐœĐžĐž ŃĐžĐŒĐżŃĐŸĐŒĐ°ŃĐžŃĐ”ŃĐșОД ŃŃДЎŃŃĐČĐ° Đ·Đ°ĐŒĐ”ĐŽĐ»Đ”ĐœĐœĐŸĐłĐŸ ĐŽĐ”ĐčŃŃĐČĐžŃ (SYSADOA), ŃĐ°ĐșОД ĐșĐ°Đș глŃĐșĐŸĐ·Đ°ĐŒĐžĐœ (ĐĐĐ). ĐĄŃДЎО ŃазлОŃĐœŃŃ
лДĐșĐ°ŃŃŃĐČĐ”ĐœĐœŃŃ
ŃŃДЎŃŃĐČ, ŃĐŸĐŽĐ”ŃжаŃĐžŃ
ĐĐĐ, ĐČŃŃĐŸĐșĐ°Ń Đ±ĐžĐŸĐŽĐŸŃŃŃĐżĐœĐŸŃŃŃ Đž ĐșĐ»ĐžĐœĐžŃĐ”ŃĐșĐ°Ń ŃŃŃĐ”ĐșŃĐžĐČĐœĐŸŃŃŃ ĐŽĐŸĐșĐ°Đ·Đ°ĐœŃ ŃĐŸĐ»ŃĐșĐŸ ĐŽĐ»Ń ŃĐ”ŃДпŃŃŃĐœĐŸĐłĐŸ ĐșŃĐžŃŃаллОŃĐ”ŃĐșĐŸĐłĐŸ ĐĐĐ ŃŃĐ»ŃŃĐ°ŃĐ° (ŃĐĐĐĐĄ). Đ ĐœĐ”ŃĐșĐŸĐ»ŃĐșĐžŃ
ĐŒĐ”ŃĐ°Đ°ĐœĐ°Đ»ĐžĐ·Đ°Ń
Đž ŃĐ”ŃĐ”ĐČŃŃ
ĐŒĐ”ŃĐ°Đ°ĐœĐ°Đ»ĐžĐ·Đ°Ń
бŃĐ»ĐŸ ĐżĐŸĐșĐ°Đ·Đ°ĐœĐŸ, ŃŃĐŸ ŃĐĐĐĐĄ ĐČ ĐŽĐŸĐ·Đ” 1500 ĐŒĐł 1 ŃĐ°Đ· ĐČ ŃŃŃĐșĐž ĐżŃĐ”ĐČĐŸŃŃ
ĐŸĐŽĐžŃ ĐżĐŸ ŃŃŃĐ”ĐșŃĐžĐČĐœĐŸŃŃĐž ĐŽŃŃгОД ĐżŃĐŸĐŽŃĐșŃŃ ĐœĐ° ĐŸŃĐœĐŸĐČĐ” ĐĐĐ (ŃĐ°ĐșОД ĐșĐ°Đș ĐĐРгОЎŃĐŸŃ
Đ»ĐŸŃОЎ Ń ĐœĐ°ŃŃĐžŃ ŃŃĐ»ŃŃĐ°ŃĐŸĐŒ ОлО бДз ĐœĐ”ĐłĐŸ) Đž ĐșĐŸĐŒĐ±ĐžĐœĐ°ŃОО ĐĐĐ Ń Ń
ĐŸĐœĐŽŃĐŸĐžŃĐžĐœĐ° ŃŃĐ»ŃŃĐ°ŃĐŸĐŒ (Đ„ĐĄ) Ń ŃĐŸŃĐșĐž Đ·ŃĐ”ĐœĐžŃ ŃĐœĐžĐ¶Đ”ĐœĐžŃ ĐžĐœŃĐ”ĐœŃĐžĐČĐœĐŸŃŃĐž Đ±ĐŸĐ»Đž Đž ŃĐ»ŃŃŃĐ”ĐœĐžŃ ŃŃĐœĐșŃĐžĐŸĐœĐ°Đ»ŃĐœĐŸĐłĐŸ ŃĐŸŃŃĐŸŃĐœĐžŃ. Đ ŃŃĐžŃ
ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃŃ
бŃĐ» ĐżĐŸĐŽŃĐČĐ”ŃĐ¶ĐŽĐ”Đœ Đ±Đ»Đ°ĐłĐŸĐżŃĐžŃŃĐœŃĐč ĐżŃĐŸŃĐžĐ»Ń Đ±Đ”Đ·ĐŸĐżĐ°ŃĐœĐŸŃŃĐž ŃĐĐĐĐĄ, ĐșĐŸŃĐŸŃŃĐč ĐżĐŸ ŃĐ°ŃŃĐŸŃĐ” ŃĐ°Đ·ĐČĐžŃĐžŃ ĐœĐ”Đ¶Đ”Đ»Đ°ŃДлŃĐœŃŃ
ŃĐČĐ»Đ”ĐœĐžĐč бŃĐ» ŃĐŸĐżĐŸŃŃĐ°ĐČĐžĐŒ Ń ĐżĐ»Đ°ŃĐ”Đ±ĐŸ. ЀаŃĐŒĐ°ĐșĐŸŃĐșĐŸĐœĐŸĐŒĐžŃĐ”ŃĐșОД ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ ŃĐ°ĐșжД ĐżŃĐŸĐŽĐ”ĐŒĐŸĐœŃŃŃĐžŃĐŸĐČалО Đ±ĐŸĐ»ŃŃŃŃ ŃĐșĐŸĐœĐŸĐŒĐžŃĐ”ŃĐșŃŃ ŃŃŃĐ”ĐșŃĐžĐČĐœĐŸŃŃŃ ŃĐĐĐĐĄ ĐżĐŸ ŃŃĐ°ĐČĐœĐ”ĐœĐžŃ Ń ĐŽŃŃĐłĐžĐŒĐž лДĐșĐ°ŃŃŃĐČĐ”ĐœĐœŃĐŒĐž ŃŃДЎŃŃĐČĐ°ĐŒĐž ĐĐĐ.ĐŃŃппа ŃĐŸŃŃĐžĐčŃĐșĐžŃ
ŃĐșŃпДŃŃĐŸĐČ ĐœĐ° ŃĐŸĐČĐ”ŃĐ°ĐœĐžĐž ĐșĐŸĐœŃŃĐ»ŃŃĐ°ŃĐžĐČĐœĐŸĐłĐŸ ĐșĐŸĐŒĐžŃĐ”ŃĐ° ŃĐ°ŃŃĐŒĐŸŃŃДла ŃĐČОЎДŃДлŃŃŃĐČĐ° ĐČ ĐżĐŸĐ»ŃĐ·Ń ĐżŃĐžĐŒĐ”ĐœĐ”ĐœĐžŃ ŃĐĐĐĐĄ Đž ĐŽĐŸĐșĐ°Đ·Đ°ŃДлŃŃŃĐČĐ° Đ”ĐłĐŸ ŃŃŃĐ”ĐșŃĐžĐČĐœĐŸŃŃĐž ĐżŃĐž лДŃĐ”ĐœĐžĐž ĐĐ ĐĐĄ ĐČ ŃŃĐ°ĐČĐœĐ”ĐœĐžĐž Ń ĐŽŃŃĐłĐžĐŒĐž ĐżŃĐŸĐŽŃĐșŃĐ°ĐŒĐž, ĐČ ŃĐŸŃŃĐ°ĐČ ĐșĐŸŃĐŸŃŃŃ
ĐČŃ
ĐŸĐŽĐžŃ ĐĐĐ, Đž ŃĐžĐșŃĐžŃĐŸĐČĐ°ĐœĐœĐŸĐč ĐșĐŸĐŒĐ±ĐžĐœĐ°ŃОО ĐĐĐ Ń Đ„ĐĄ. ĐĄ ŃŃĐ”ŃĐŸĐŒ ĐżĐŸĐ»ŃŃĐ”ĐœĐœŃŃ
ŃДзŃĐ»ŃŃĐ°ŃĐŸĐČ ĐžŃĐżĐŸĐ»ŃĐ·ĐŸĐČĐ°ĐœĐžĐ” ŃĐĐĐĐĄ ĐČ ĐŽĐŸĐ·Đ” 1500 ĐŒĐł 1 ŃĐ°Đ· ĐČ ŃŃŃĐșĐž ŃĐ”ĐșĐŸĐŒĐ”ĐœĐŽĐŸĐČĐ°ĐœĐŸ ĐČ ĐșĐ°ŃĐ”ŃŃĐČĐ” ŃĐ°ŃĐžĐŸĐœĐ°Đ»ŃĐœĐŸĐłĐŸ ĐČŃĐ±ĐŸŃĐ° ĐŽĐ»Ń Đ»Đ”ŃĐ”ĐœĐžŃ ĐĐ ĐĐĄ
Arterial hypertension and ÎČ-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study
Background
White matter hyperintensities (WMH) in subjects across the Alzheimerâs disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathologyânot just arterial hypertensionâimpacts WMH, which in turn adversely influences cognition. Here we seek to determine the effect of both hypertension and AÎČ positivity on WMH, and their impact on cognition.
Methods
We analysed data from subjects with a low vascular profile and normal cognition (NC), subjective cognitive decline (SCD), and amnestic mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study (nâ=â375, median age 70.0 [IQR 66.0, 74.4] years; 178 female; NC/SCD/MCI 127/162/86). All subjects underwent a rich neuropsychological assessment. We focused on baseline memory and executive functionâderived from multiple neuropsychological tests using confirmatory factor analysisâ, baseline preclinical Alzheimerâs cognitive composite 5 (PACC5) scores, and changes in PACC5 scores over the course of three years (ÎPACC5).
Results
Subjects with hypertension or AÎČ positivity presented the largest WMH volumes (pFDRâ<â0.05), with spatial overlap in the frontal (hypertension: 0.42â±â0.17; AÎČ: 0.46â±â0.18), occipital (hypertension: 0.50â±â0.16; AÎČ: 0.50â±â0.16), parietal lobes (hypertension: 0.57â±â0.18; AÎČ: 0.56â±â0.20), corona radiata (hypertension: 0.45â±â0.17; AÎČ: 0.40â±â0.13), optic radiation (hypertension: 0.39â±â0.18; AÎČ: 0.74â±â0.19), and splenium of the corpus callosum (hypertension: 0.36â±â0.12; AÎČ: 0.28â±â0.12). Elevated global and regional WMH volumes coincided with worse cognitive performance at baseline and over 3 years (pFDRâ<â0.05). AÎČ positivity was negatively associated with cognitive performance (direct effectâmemory:âââ0.33â±â0.08, pFDRâ<â0.001; executive:âââ0.21â±â0.08, pFDRâ<â0.001; PACC5:âââ0.29â±â0.09, pFDRâ=â0.006; ÎPACC5:âââ0.34â±â0.04, pFDRâ<â0.05). Splenial WMH mediated the relationship between hypertension and cognitive performance (indirect-only effectâmemory:âââ0.05â±â0.02, pFDRâ=â0.029; executive:âââ0.04â±â0.02, pFDRâ=â0.067; PACC5:âââ0.05â±â0.02, pFDRâ=â0.030; ÎPACC5:âââ0.09â±â0.03, pFDRâ=â0.043) and WMH in the optic radiation partially mediated that between AÎČ positivity and memory (indirect effectâmemory:âââ0.05â±â0.02, pFDRâ=â0.029).
Conclusions
Posterior white matter is susceptible to hypertension and AÎČ accumulation. Posterior WMH mediate the association between these pathologies and cognitive dysfunction, making them a promising target to tackle the downstream damage related to the potentially interacting and potentiating effects of the two pathologies.
Trial registration
German Clinical Trials Register (DRKS00007966, 04/05/2015)
Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).
Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and â„1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (nâ=â5069) or prospectively (nâ=â5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (â€6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; pâ=â0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)
Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.
OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95%âCI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1âyear, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)
- âŠ