Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.
CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-β, are increasingly being used to define and stage Alzheimer’s disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer’s disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-β40 and amyloid-β42 were measured using the Simoa NF-light® and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer’s disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE ε4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer’s disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer’s disease dementia. A log2 higher baseline amyloid-β42 plasma level was associated with a lower risk of developing all-cause or Alzheimer’s disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47–0.78; P < 0.0001] and 0.59 (95% CI, 0.43–0.79; P = 0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38–1.83); P < 0.0001] or Alzheimer’s disease [adjusted HR 1.50 (95% CI, 1.26–1.78); P < 0.0001]. Combining the lowest quartile group of amyloid-β42 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3–40.4); P < 0.002] and with Alzheimer’s disease [adjusted HR 15.7 (95% CI, 2.1–117.4); P < 0.0001], compared to the highest quartile group of amyloid-β42 and lowest of NfL. Total-tau and amyloid-β40 levels were not associated with all-cause or Alzheimer’s disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer’s disease compared to those who remained dementia-free (P < 0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer’s disease diagnosis. Amyloid-β42 levels began to decrease in Alzheimer’s disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-β42 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer’s disease dementia. These data indicate that plasma NfL and amyloid-β42 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer’s disease dementia.
IMPORTANCE Retinal structures may serve as a biomarker for dementia, but longitudinal studies examining this link are lacking. OBJECTIVE To investigate the association of inner retinal layer thickness with prevalent and incident dementia in a general population of Dutch adults. DESIGN, SETTING, AND PARTICIPANTS From September 2007 to June 2012, participants from the prospective population-based Rotterdam Study who were 45 years and older and had gradable retinal optical coherence tomography images and at baseline were free from stroke, Parkinson disease, multiple sclerosis, glaucoma, macular degeneration, retinopathy, myopia, hyperopia, and optic disc pathology were included. They were followed up until January 1, 2015, for the onset of dementia. EXPOSURES Inner retinal layer thicknesses (ie, retinal nerve fiber layer [RNFL]) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses measured on optical coherence tomography images. MAIN OUTCOMES AND MEASURES Odds ratios and hazard ratios for incident dementia per SD decrease in retinal layer thickness adjusted for age, sex, education, and cardiovascular risk factors. RESULTS Of 5065 individuals eligible for optical coherence tomography scanning, 3289 (64.9%) (mean [SD] age 68.9 [9.9] years, 1879 [57%] women) were included in the analysis. Of these 3289 individuals, 41 (1.2%) already had dementia. Thinner GC-IPL was associated with prevalent dementia (odds ratio per SD decrease in GC-IPL, 1.37 [95% CI, 0.99-1.90]). No association was found of RNFL with prevalent dementia. During 14 674 person-years of follow-up (mean [SD], 4.5 [1.6] years), 86 individuals (2.6%) developed dementia of whom 68 (2.1%) had Alzheimer disease. Thinner RNFL at baseline was associated with an increased risk of developing dementia (hazard ratio per SD decrease in RNFL, 1.44 [95% CI, 1.19-1.75]), which was similar for Alzheimer disease (hazard ratio, 1.43 [95% CI, 1.15-1.78]). No association was found between GC-IPL thickness and incident dementia (hazard ratio, 1.13 [95% CI, 0.90-1.43]). CONCLUSIONS AND RELEVANCE Thinner RNFL is associated with an increased risk of dementia, including Alzheimer disease, suggesting that retinal neurodegeneration may serve as a preclinical biomarker for dementia.
Campbell, B. C. V. et al. (2018) Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data. Lancet Neurology, 17(1), pp. 47-53. (doi:10.1016/S1474-4422(17)30407-6) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/149670/ variables. An alternative approach using propensity-score stratification was also used. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models. Bias was assessed using the Cochrane tool.Findings: Of 1764 patients in 7 trials, 871 were allocated to endovascular thrombectomy. After exclusion of 74 patients (72 who did not undergo the procedure and 2 with missing data on anaesthetic strategy), 236/797 (30%) of endovascular patients were treated under GA. At baseline, GA patients were younger and had shorter time to randomisation but similar pre-treatment clinical severity compared to non-GA. Endovascular thrombectomy improved functional outcome at 3 months versus standard care in both GA (adjusted common odds ratio (cOR) 1·52, 95%CI 1·09-2·11, p=0·014) and non-GA (adjusted cOR 2·33, 95%CI 1·75-3·10, p<0·001) patients. However, outcomes were significantly better for those treated under non-GA versus GA (covariate-adjusted cOR 1·53, 95%CI 1·14-2·04, p=0·004; propensitystratified cOR 1·44 95%CI 1·08-1·92, p=0·012). The risk of bias and variability among studies was assessed to be low.Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons. Funding:The HERMES collaboration was funded by an unrestricted grant from Medtronic to the University of Calgary. Research in contextEvidence before this study between abolition of the thrombectomy treatment effect in MR CLEAN and no effect in THRACE. Three single-centre randomised trials of general anaesthesia versus conscious sedation found either no difference in functional outcome between groups or a slight benefit of general anaesthesia. Added value of this studyThese data from contemporary, high quality randomised trials form the largest study to date of the association between general anesthesia and the benefit of endovascular thrombectomy versus standard care. We used two different approaches to adjust for baseline imbalances (multivariable logistic regression and propensity-score stratification). We found that GA for endovascular thrombectomy, as practiced in contemporary clinical care across a wide range of expert centres during the rand...
The exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led to the discovery of genetic factors that play a role in the pathogenesis of dementia, including the apolipoprotein E (APOE) genotype and a large and still growing number of genetic variants. 1,2 Beyond the genetic architecture, several modifiable risk factors have been implicated in the development of dementia. 3 Prevention trials to halt or delay cognitive decline are increasingly recruiting older individuals who are genetically predisposed to dementia. However, it remains unclear whether targeted health and lifestyle interventions can attenuate or even offset this increased genetic risk. Here, we leverage long-term data on both genetic and modifiable factors from 6352 individuals aged 55 years and older within the population-based Rotterdam Study. In this study, we demonstrate that among individuals at low-and intermediate genetic risk, favorable Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
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