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The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, pre-diagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease.UK Biobank data were extracted. Cognitive and functional measures in individuals who subsequently developed Alzheimer's disease (AD), Parkinson disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, or multiple system atrophy were compared against individuals without neurodegenerative diagnoses. The same measures were regressed against time to diagnosis, after adjusting for the effects of age.There was evidence for pre-diagnostic cognitive impairment and decline with time, particularly in AD. Pre-diagnostic functional impairment and decline were observed in multiple diseases.The scale and longitudinal follow-up of UK Biobank participants provides evidence for cognitive and functional decline years before symptoms become obvious in multiple neurodegenerative diseases. Identifying pre-diagnostic functional and cognitive changes could improve selection for preventive and early disease-modifying treatment trials.

The increasing availability of large high-dimensional data from experimental medicine, population-based and clinical cohorts, clinical trials, and electronic health records has the potential to transform dementia research. Our ability to make best use of this rich data will depend on utilisation of advanced machine learning and artificial intelligence (AI) techniques and collaboration across disciplinary and geographic boundaries.The Deep Dementia Phenotyping (DEMON) Network launched in 2019Membership on 4th February 2022 comprised 1,321 individuals from 61 countries across 6 continents (see Figure). Areas of expertise include dementia research (904; 68%), data science (692; 52%), clinical practice (244; 18%), industry (162; 12%), and regulation (26; 2%). Individual membership is free, and regular knowledge transfer events are provided including a monthly seminar series, talks and workshops, training, networking, and early career development. Each Working Group meets monthly, with multiple grants, reviews, and original research articles in progress. Eight state of the science position papers are in preparation, resulting from a Symposium held in April 2021. In January 2022, 110 early career researchers participated in the Network's flagship event 'NEUROHACK', a 4-day competitive global hackathon, with pilot grants awarded to those generating the most innovative solutions.The DEMON Network is a rapidly growing global platform for innovation that is supporting the global dementia research community to collaborate. Find out more at demondementia.com.

© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Introduction: Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy. Methods: Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling. Results: Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions. Discussion: Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD., This work is co‐funded by the UK Medical Research Council (MR/M023664/1), the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant and the Bluefield Project, as well as a JPND grant “GENFI‐prox” (by DLR/BMBF to MS, joined with JDR, JvS, MO, BB and CG). MM is supported by the Cambridge Trust & Sidney Sussex College Scholarship. PSJ is supported by the Cambridge Centre for Parkinson Plus. KAT is supported by the British Academy Postdoctoral Fellowship (KAT: PF160048) and Guarantors of Brain (KAT: 101149). TR is supported by the Cambridge Centre for Parkinson Plus and Cambridge Biomedical Resource Centre. RAK is supported by Medical Research Council (RAK: SUAG/047/G101400). JBR reports grants from the NIHR Cambridge Biomedical research centre, Wellcome Trust (103838), and Medical Research Council (SUAG051/G101400; MR/T033371/1); personal fees from Asceneuron, WAVE, Astex, and Biogen; and grants from Janssen, AZ Medimmune, and Eli Lilly, outside the submitted work. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS‐JF‐19a‐004‐517), and by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK.