Social isolation is likely to be recommended for older adults due to COVID-19, with ongoing reduced clinical contact suggested for this population. This has increased the need for remote memory clinics, we therefore review the literature, current practices and guidelines on organizing such remote memory clinics, focusing on assessment of cognition, function and other relevant measurements, proposing a novel pathway based on three levels of complexity: simple telephone or video-based interviews and testing using available tests (Level 1), digitized and validated methods based on standard pen-and-paper tests and scales (Level 2), and finally fully digitized cognitive batteries and remote measurement technologies (RMTs, Level 3). Pros and cons of these strategies are discussed. Remotely collected data negates the need for frail patients or carers to commute to clinic and offers valuable insights into progression over time, as well as treatment responses to therapeutic interventions, providing a more realistic and contextualized environment for data-collection. Notwithstanding several challenges related to internet access, computer skills, limited evidence base and regulatory and data protection issues, digital biomarkers collected remotely have significant potential for diagnosis and symptom management in older adults and we propose a framework and pathway for how technologies can be implemented to support remote memory clinics. These platforms are also well-placed for administration of digital cognitive training and other interventions. The individual, societal and public/private costs of COVID-19 are high and will continue to rise for some time but the challenges the pandemic has placed on memory services also provides an opportunity to embrace novel approaches. Remote memory clinics' financial, logistical, clinical and practical benefits have been highlighted by COVID-19, supporting their use to not only be maintained when social distancing legislation is lifted but to be devoted extra resources and attention to ...
The neuropathological confirmation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles (NFT) remains the gold standard for a definitive diagnosis of Alzheimer's disease (AD). Nowadays, the in vivo diagnosis of AD is greatly aided by both cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Although highly accurate, their broad implementation is restricted by high cost, limited accessibility and invasiveness. We recently developed a high-performance, ultrasensitive immunoassay for the quantification of tau phosphorylated at threonine-181 (p-tau181) in plasma, which identifies AD pathophysiology with high accuracy. However, it remains unclear whether plasma p-tau181, measured years before the death, can predict the eventual neuropathological confirmation of AD, and successfully discriminates AD from non-AD dementia pathologies. We studied a unique cohort of 115 individuals with longitudinal blood collections with clinical evaluation at 8, 4 and 2 years prior to neuropathological assessment at death. The results demonstrate that plasma p-tau181 associates better with AD neuropathology and Braak staging than a clinical diagnosis 8 years before post-mortem. Moreover, while all patients had a diagnosis of AD dementia during life, plasma p-tau181 proved to discriminate AD from non-AD pathologies with high accuracy (AUC = 97.4%, 95% CI = 94.1-100%) even 8 years before death. Additionally, the longitudinal trajectory of plasma p-tau181 was assessed in all patients. We found that the main increases in plasma p-tau181 occurred between 8 and 4 years prior to death in patients with AD neuropathology and later plateauing. In contrast, non-AD pathologies and controls exhibited minor, albeit significant, increases in p-tau181 up until death. Overall, our study demonstrates that plasma p-tau181 is highly predictive and specific of AD neuropathology years before post-mortem examination. These data add further support for the use of plasma p-tau181 to aid clinical management in primary care and recruitment for clinical trials. ; Open access funding provided by University of Gothenburg. This study represents independent research partly funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. Tissue samples were supplied by The London Neurodegenerative Diseases Brain Bank, which receives funding from the UK Medical Research Council and as part of the Brains for Dementia Research programme, jointly funded by Alzheimer's Research UK and the Alzheimer's Society. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. TKK holds a postdoctoral fellowship from the BrightFocus Foundation (#A2020812F), and was further supported by the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensförbundet), the Agneta Prytz-Folkes and Gösta Folkes Foundation, Gamla Tjänarinnor, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Gun and Bertil Stohnes Foundation, and the Anna Lisa and Brother Björnsson's Foundation. MSC received funding from the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement no. 752310, and currently receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I). AH is funded by Research Centre for Mental Health and Biomedical Research Unit for Dementia. KB holds the Torsten Söderberg Professorship in Medicine and is supported by grants from the Swedish Research Council, the Swedish Alzheimer Foundation, and the Swedish Brain Foundation. AH is funded by Research Centre for Mental Health and Biomedical Research Unit for Dementia. KB holds the Torsten Söderberg Professorship in Medicine and is supported by grants from the Swedish Research Council, the Swedish Alzheimer Foundation, and the Swedish Brain Foundation. KB holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences, and is supported by the Swedish Research Council (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), and a grant (#ALFGBG-715986) from the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement. NJA is supported by the Wallenberg Centre for Molecular and Translational Medicine, the Swedish Alzheimer Foundation (Alzheimerfonden), the Swedish Dementia Foundation (Demensförbundet), and Hjärnfonden, Sweden.
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download ; A large fraction of genetic risk factors for Alzheimer's Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed a meta-analysis using GWAS results from 2,893 AD cases and 6,858 cognitively normal controls from Norway and 25,580 cases and 48,466 controls from the International Genomics of Alzheimer's Project (IGAP), denoted the discovery sample. Second, we selected the top hits (p < 1 × 10 ; Research Council of Norway (RCN) EU JPND Program ApGeM RCN Grant South-East Norway Health Authority Norwegian Health Association KG Jebsen Foundation European Union European Community PIAPP-GA-2011-286213 PsychDPC French National Foundation on Alzheimer's disease and related disorders LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Universite de Lille 2 Lille University Hospital Medical Research Council Alzheimer's Research UK Wellcome Trust German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) NIH/NIA NIA AGES NHLBI Icelandic Heart Association Erasmus Medical Center Erasmus University Alzheimer's Association
25 páginas, 6 figuras, 2 tablas ; Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. ; This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government's LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not ; Peer reviewed