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Earlier diagnosis of Alzheimer’s disease (AD) requires biomarkers sensitive to the structural and functional changes associated with the disease. While considerable progress has been made in the development of structural biomarkers, functional biomarkers of early cognitive change are still needed. We present Fastball, a new EEG method for the passive, objective and implicit measurement of recognition memory, that requires no behavioural response or comprehension of the task. Younger adults (aged M=24 SD=6), older adults (aged M=74 SD=4) and AD patients aged M=79 SD=10), (n=20 per group) completed the Fastball task, lasting just under three minutes. The task required the passive viewing of rapidly presented images and assessed their spontaneous ability to differentiate between images on the basis of previous exposure, i.e. old/new. Participants were not instructed to attend to previously seen images and provided no behavioural response. Following the Fastball task, they completed a cued recall task to measure their explicit recognition of previously seen stimuli. AD patients showed significantly impaired recognition memory compared to healthy older adult controls in the Fastball task (p

© 2019 The Authors Understanding the ecological traits which predispose species to local or global extinction allows for more effective pre-emptive conservation management interventions. Insect population declines are a major facet of the global biodiversity crisis, yet even in Europe they remain poorly understood. Here we identify traits linked to population trends in ‘common and widespread’ UK moths. Population trend data from the Rothamsted Research Insect Survey spanning 40 years was subject to classification and regression models to identify common traits among species experiencing a significant change in occurrence. Our final model had an accuracy of 76% and managed to predict declining species on 90% of occasions, but was less successful with increasing species. By far the most powerful predictor associated for declines was moth wingspan with large species declining more frequently. Preference for woody or herbaceous larval food sources, nocturnal photoperiod activity, and richness of habitats occupied also proved to be significantly associated with decline. Our results suggest that ecological traits can be reliably used to predict declines in moths, and that this model could be used for Data Deficient species, of which there are many.

Next-generation genetic sequencing (NGS) technologies facilitate the screening of multiple genes linked to neurodegenerative dementia, but there is little guidance available about their use in clinical practice. Guidelines on which patients would most profit from testing, and information on the likelihood of discovery of a causal variant in a clinical syndrome, are conspicuously absent from the literature, mostly for a lack of large-scale studies. We applied a validated NGS dementia panel to 3241 patients with dementia and healthy aged controls; 13,152 variants were classified by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6% of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and family history each strongly predict the likelihood of finding a DV, but healthcare setting and gender did not. DVs were frequently found in genes not usually associated with the clinical syndrome. Patients recruited from primary referral centres were compared to those seen at higher-level research centres and a national clinical neurogenetic laboratory; rates of discovery were comparable, making selection bias unlikely and the results generalizable to clinical practice. We estimated penetrance of DVs using large-scale online genomic population databases and found 71 with evidence of reduced penetrance. Two DVs in the same patient were found more frequently than expected. These publicly-available data should provide a basis for informed counselling and clinical decision making.

© 2016 Greenan et al.Background: Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia. Methods/Design: This is a randomised controlled trial of calcium channel blockade with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks. Discussion: There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions. Trial registration: Current Controlled Trials ISRCTN31208535. Registered on 7 March 2014.

Next-generation genetic sequencing (NGS) technologies facilitate the screening of multiple genes linked to neurodegenerative dementia, but there is little guidance available about their use in clinical practice. Guidelines on which patients would most profit from testing, and information on the likelihood of discovery of a causal variant in a clinical syndrome, are conspicuously absent from the literature, mostly for a lack of large-scale studies. We applied a validated NGS dementia panel to 3241 patients with dementia and healthy aged controls; 13,152 variants were classified by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6% of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and family history each strongly predict the likelihood of finding a DV, but healthcare setting and gender did not. DVs were frequently found in genes not usually associated with the clinical syndrome. Patients recruited from primary referral centres were compared to those seen at higher-level research centres and a national clinical neurogenetic laboratory; rates of discovery were comparable, making selection bias unlikely and the results generalizable to clinical practice. We estimated penetrance of DVs using large-scale online genomic population databases and found 71 with evidence of reduced penetrance. Two DVs in the same patient were found more frequently than expected. These publicly-available data should provide a basis for informed counselling and clinical decision making.