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Objective: Neuropsychological assessment through VideoTeleConferencing (VTC) can help improve access to diagnostic and follow-up care in memory clinics. This study investigated the stability of performance on VTC assessment in relation to in-person assessment using a test-retest design and explored user experiences of VTC assessment. Materials and Methods: Thirty-one patients (62 ± 6.7 years, 45% female, 58% Subjective Cognitive Decline, 42% Mild Cognitive Impairment/dementia diagnosis) were included from the Amsterdam Dementia Cohort between August 2020 and February 2021. Patients underwent a face-to-face neuropsychological assessment followed by a VTC assessment using the same test protocol within 4 months. Reliability coefficients were calculated using intraclass correlation coefficients (ICC). For each test, the proportion of clinically relevant differences in performances between assessment modalities was calculated. User experiences of patients and neuropsychologists were assessed with questionnaires (User Satisfaction and Ease of use [USE] questionnaire and System Usability Scale [SUS]). Neuropsychologists also participated in a focus group. Results: ICC values were moderate to excellent (0.63-0.93) for all test measures in the total sample. On all tests, most patients did not show clinically relevant performance differences between modalities. Patients and neuropsychologists reported overall positive VTC system usability, although neuropsychologists indicated in the focus group that patients without cognitive impairment required less training for the system and were more independent. Conclusion: VTC assessment showed adequate to excellent test-retest reliability for a broad range of neuropsychological tests commonly used in practice. Assessment through VTC may be a user friendly method in the memory clinic, especially to monitor individuals at risk for future cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Blood‐based biomarkers can provide a non‐invasive and accessible way to identify neurodegenerative diseases before the clinical onset of dementia. Our study aimed to examine whether levels of phosphorylated‐tau‐181 (pTau181), amyloid beta1‐42/1‐40 (Aβ42/40), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are associated with risk of developing dementia in a memory clinic population of individuals with either subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Method: From the Amsterdam Dementia Cohort we included 311 individuals with SCD (age 61±9 years, n=128 (41%) female, MMSE 29±1) and 252 with MCI (age 65±7 years, n=89 (35%) female, MMSE 27±2), who had annual follow‐up visits for re‐evaluation of diagnosis (average follow‐up duration: 2.7±1.7 years.) Baseline plasma biomarkers were measured using Simoa and the associations of the Z‐transformed biomarker concentrations with incident dementia were evaluated using Cox regression models adjusted for age, sex, baseline diagnosis and the interaction between baseline diagnosis (SCD/MCI) and the biomarker concentration. The markers were first evaluated individually and then simultaneously in a combined model. We stratified results for baseline diagnosis when the biomarker*diagnosis interaction was significant. Result: During follow‐up, 94 individuals developed dementia (14 with SCD, 80 with MCI at baseline, 86 Alzheimer's Disease, 8 other forms of dementia; average time to progression: 2.8±1.8 years). We found an interaction between baseline diagnosis and NfL for incident dementia (p=0.03). No other interactions were found. In the total set, both high baseline pTau181 (hazard ratio (HR)=3.4 (95%CI: 1.3–9.0); figure 1A), and high baseline GFAP (HR=5.5 (95%CI: 1.6–18.6); figure 1B) were associated with increased risk of dementia, but the association with Aβ42/40 was not significant (HR=0.4 (95%CI: 0.2–1.1)). NfL had no significant association with increased dementia incident risk in both SCD subset (HR=1.8, (95%CI: 0.9‐3.6)) and the MCI subset (HR= 1.3, (95%CI: 1.0–1.6)). When we simultaneously entered all biomarkers, pTau181 and GFAP remained significantly associated with incident dementia (table 1.) Conclusion: Our results suggest that plasma GFAP and pTau181 have prognostic value to predict dementia in individuals presenting at a memory clinic. [ABSTRACT FROM AUTHOR]

Background: Clinical implementation of novel blood‐based biomarkers for Alzheimer's disease (AD) will aid in accurate, less‐invasive diagnosis. However, variation in blood handling may affect the accuracy of biomarker's measurement. Establishing standardized operating procedures (SOPs) to mitigate these effects is essential for implementing novel blood‐based biomarkers into clinical use. We aim to provide an evidence‐based SOP specific for AD blood‐based biomarkers by studying the effects of multiple pre‐analytical variations in blood samples from AD and healthy controls (HCs). Here, we show the first results obtained, addressing the effect of biomarker's adsorption to lab plastics, during sample processing. Method: Blood samples are being withdrawn from 150 volunteers (AD and HCs) and treated according to one of ten pre‐analytical experimental protocols. Several aliquots per sample are being obtained, to be shared and analyzed among labs, focusing on labs with novel P‐tau plasma tests. Preliminary results are acquired for the effect of 1x, 2x and 4x tube transfers in fresh polypropylene tubes with fresh pipet tips at every transfer, compared to no tube transfer, as a reference condition. Sample analysis was performed on Simoa using the Simoa neurology 4‐plex E assay (Aβ1‐42, Aβ1‐40, GFAP, NfL), and the P‐tau181 V2 assay. A variation in the median value of one of the measured biomarkers of at least 10% from the reference condition was regarded as a significant change. Result: Formally, medians of all tube transfers for all biomarkers measured (Aβ1‐42, Aβ1‐40, GFAP, NfL and Ptau‐181), stayed within the predefined range, for both AD and HC. However, the levels of Aβ1‐42 and Aβ1‐40 showed an obvious tendency to decrease at the 4th tube transfer. For Aβ1‐40, levels in HCs were more affected compared to those in AD (median 92%; AD: median = 95%). For Aβ1‐42, both AD and HCs showed a similar decrease (median: 91% and 93%). This decrease is not so apparent with the Aβ1‐42/Aβ1‐40 ratio. Conclusion: In line with the results, 4 tube transfers or less should have no influence on the accuracy of the measured biomarkers. For Aβ peptide measurements, using the Aβ1‐42/Aβ1‐40 ratio appears to stabilize the effect of tube transfer. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic poses enormous social challenges, especially during lockdown. Recently, the second lockdown started in the Netherlands. We aimed to investigate and compare the psychosocial effects of corona measures during lockdown in memory clinic (pre‐)dementia patients and their caregivers. Method: During second lockdown, n=137 symptomatic patients (age=67.7±6.54, 36.5%F, MMSE = 24.4±4.7; n=82 dementia, n=55 MCI), n=244 cognitively normal (age=63.6±7.56, 38.9%F, MMSE = 28.8±1.18; SCD) and n=198 caregivers of Alzheimer Center Amsterdam completed a survey on psychosocial effects of corona. Questions related to loneliness, worries for faster cognitive decline, psychological and behavioral problems. In a subset of patients (n=169) and caregivers (n=38) we were able to compare their answers to answers on a similar survey completed during first lockdown (May 2020). Result: In total, n=17 (4.5%) patients [n=3 (2.2%) symptomatic, n=14 (5.7%) cognitively normal] and n=8 (4%) caregivers reported a positive test result for COVID‐19. Over one‐third of caregivers reported worries for faster cognitive decline [n=76 (38%)] and behavioral problems [n=70 (35%)] in patients. Feelings of loneliness were experienced by n=23 (17%) symptomatic patients, n=44 (18%) cognitively normal and n=50 (25%) caregivers. One quarter of patients [n=78 (25%)] reported more depressive feelings during lockdown [n=27 (20%) symptomatic, n=51 (21%) cognitively normal]. More feelings of fatigue were reported by n=23 (17%) symptomatic patients, n=46 (19%) cognitively normal, and n=67 (34%) caregivers. Comparing results to those obtained during the first lockdown, feelings of loneliness [Χ2=26.4, p<.001 in patients, Χ2=10.3, p<.001 in caregivers] and anxiety [Χ2=25.9, p<.001 in patients, Χ2=6.69, p=.010 in caregivers] increased. During second lockdown, less feelings of apathy [Χ2=13.0, p<.001], but more depressive feelings [Χ2=27.6, p<.001] were reported in patients compared to first lockdown. Caregivers were more worried for memory decline in patients during second lockdown [Χ2=4.09, p=.043]. Conclusion: Compared to first lockdown, feelings of loneliness, anxiety, worries for faster cognitive decline and depressive feelings increased in second lockdown. A noticeable part of (pre‐)dementia patients and caregivers report feelings of loneliness, worries for faster cognitive decline, psychological and behavioral problems in second lockdown. These psychosocial effects are more frequently reported by caregivers than patients. [ABSTRACT FROM AUTHOR]

Introduction: We investigated relationships among genetic determinants of Alzheimer's disease (AD), amyloid/tau/neurodegenaration (ATN) biomarkers, and risk of dementia., Methods: We studied cognitively normal individuals with subjective cognitive decline (SCD) from the Amsterdam Dementia Cohort and SCIENCe project. We examined associations between genetic variants and ATN biomarkers, and evaluated their predictive value for incident dementia. A polygenic risk score (PRS) was calculated based on 39 genetic variants. The APOE gene was not included in the PRS and was analyzed separately., Results: The PRS and APOE ε4 were associated with amyloid-positive ATN profiles, and APOE ε4 additionally with isolated increased tau (A-T+N-). A high PRS and APOE ε4 separately predicted AD dementia. Combined, a high PRS increased while a low PRS attenuated the risk associated with ε4 carriers., Discussion: Genetic variants beyond APOE are clinically relevant and contribute to the pathophysiology of AD. In the future, a PRS might be used in individualized risk profiling., Competing Interests: Jarith L. Ebenau, Sven J. van der Lee, Marc Hulsman, Niccolò Tesi, Iris E. Jansen, Inge M.W. Verberk, and Mardou van Leeuwenstijn report no conflicts of interest. Charlotte E. Teunissen serves on the advisory board of Roche; performed contract research or received grants from AC‐Immune, ADxNeurosciences, Boehringer, Brainstorm Therapeutics, Celgene, EIP Pharma, PeopleBio, Vivoryon, Roche, Toyama Fujifilm, Esai, and Probiodrug; and received lecture fees from Biogen and Axon Neurosciences. Her research is supported by the European Commission (Marie Curie International Training Network, and JPND), Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, Alzheimer Association. CT is recipient of ABOARD, which is a public–private partnership receiving funding from ZonMW and Health∼Holland, Topsector Life Sciences & Health. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes‐Strijbis fonds. CT has a collaboration contract with ADx Neurosciences and Quanterix. CT is editor at Alzheimer's Research & Therapy, Neurology: Neuroimmunology & Neuroinflammation and Medidact Neurology, and edited a volume in the series Neuromethods (Springer). Frederik Barkhof is a consultant for Biogen‐Idec, Bayer‐Schering, Merck‐Serono, Roche, NovartisIXICO, and Combinostics; has received sponsoring from European Commission‐Horizon 2020, National Institute for Health Research‐University College London Hospitals Biomedical Research Centre, TEVA, Novartis, and Biogen; and serves on the editorial boards of Radiology, Brain, Neuroradiology, Multiple Sclerosis Journal, and Neurology. Niels D. Prins is consultant to Boehringer Ingelheim, Aribio, and Amylyx. He is co‐PI of a study with Fuji Film Toyama Chemical. He serves on the DSMB of Abbvie's M15‐566 trial. NP has received a speaker fee from Biogen. Payments were made to his company. He is CEO and co‐owner of the Brain Research Center, the Netherlands. Philip Scheltens has acquired grant support (for the institution) from Biogen. In the past two years, he has received consultancy/speaker fees (paid to the institution) from Probiodrug Biogen, EIP Pharma, Merck AG. Henne Holstege received funding from Aegon, Health ∼ Holland, Hans und Ilse Breuer Stiftung, JPND research, 100‐plus enabling, and Alzheimer Nederland. All funding is paid to her institution. Bart N.M. van Berckel has received funding from ZonMW, the Netherlands Organization of Scientific Research, the Centre of Translational Molecular Imaging, and Avid Radiopharmaceuticals. All funding is paid to his institution. Wiesje M. van der Flier Research programs have been funded by ZonMW, NWO, EU‐FP7, EU‐JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes‐Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA Inc, Boehringer Ingelheim, Life‐MI, AVID, Roche BV, Fujifilm, Combinostics. WF holds the Pasman chair. WF has performed contract research for Biogen MA Inc and Boehringer Ingelheim. WF has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai, and WebMD Neurology (Medscape). WF is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WF is associate editor at Alzheimer's Research & Therapy. All funding is paid to her institution., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)