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Background: Computerised neuropsychological assessments (CNAs) are proposed as more accessible and culturally appropriate alternatives to traditional pencil‐and‐paper neuropsychological assessments (PnPAs) for diagnosing dementia in diverse populations. Whilst some PnPAs have demonstrated cultural and linguistic bias, research investigating the suitability of CNAs for culturally and linguistically diverse (CALD) individuals is limited, especially outside of the United States. Method: This study compared cognitive performance in a heterogenous sample of older Australian CALD English‐speakers and an L1 English‐speaking background (ESB) sample. Cross‐sectional data were drawn from the ongoing CogSCAN Study. Participants were 212 community‐dwelling individuals aged 60‐95 years without a dementia diagnosis (159 ESB/53 CALD). Participants completed a PnPA and/or CNAs, sessions were counterbalanced accordingly. CNA sessions involved two of four commercially‐available CNAs in a randomised order. Differences in the level and pattern of cognitive performance between groups on two CNAs (CANTAB/Cogstate) and a comprehensive PnPA in English, controlling for sociodemographic and health factors, are reported here. Selection of key variables for examination were based on previous findings (PnPA) and test developer recommendations (CNAs). Result: Sample characteristics are summarised in Table 1. CALD participants' cognitive performance on individual tests (Figure 1) was largely comparable to ESB participants on PnPA and each CNA. Significant differences between groups, after Bonferroni correction for multiple comparisons, were observed for the Boston Naming Test (PnPA; a language test widely criticised for use with CALD populations due to culturally biased stimuli) and Rapid Visual Information Processing (CANTAB; a test of attention/processing speed). Among participants who completed PnPA and Cogstate, a significant interaction between group and assessment type on global cognitive performance was observed; ESB participants outperformed CALD participants on PnPA, but not on Cogstate (Figure 2). No significant main effects or interaction were observed in PnPA versus CANTAB. Conclusion: These results showed fewer and smaller discrepancies across groups and assessment types than has been found in previous literature with other CALD samples, perhaps reflecting higher levels of English proficiency, acculturation, and education in English than previous cohorts. Work in progress is investigating the influence of linguistic and acculturation factors on cognitive performance in a larger and more diverse sample. [ABSTRACT FROM AUTHOR]

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD‐associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. Highlights: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages.Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration.Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia.Biomarkers of neuromodulatory integrity would be value‐creating for dementia care.Neuromodulatory nuclei present strategic prospects for disease‐modifying therapies. [ABSTRACT FROM AUTHOR]

Introduction: Human herpes simplex virus 1 (HSV1) is discussed to induce amyloid‐β (Aβ) accumulation and neurofibrillary tangles of hyperphosphorylated tau (pTau) in Alzheimer's disease (AD) in cell culture and animal models. Aβ appears to be virostatic. We investigated the association between intrathecal antibodies against HSV or cytomegalovirus (CMV) and cerebrospinal fluid (CSF) AD biomarkers. Methods: Aβ42/Aβ40 ratio, pTau, and tTau were measured in CSF of 117 patients with early AD positive for amyloid pathology (A+) and 30 healthy controls (A‐). CSF‐to‐serum anti‐HSV1/2‐IgG antibody indices (AI‐IgGHSV1/2) and CMV (AI‐IgGCMV) were determined by enzyme‐linked immunosorbent assay (ELISA). Results: Exclusively in HSV1‐seropositive AD, pTau was positively and significantly predicted by AI‐IgGHSV1/2 and negatively by the Aβ42/Aβ40 ratio in both univariate and multivariate regression analyses. Furthermore, a significant and negative interaction between the AI‐IgGHSV1/2 and Aβ42/Aβ40 ratio on pTau was found. Discussion: The results support the hypothesis that HSV infection contributes to AD. Highlights: HSV antibody index is positively associated with tau pathology in patients with AD.HSV antibody index is negatively associated with cerebral FDG metabolism.Amyloid modulates the association of HSV antibody index with CSF‐pTau.HSV in AD offers a pathophysiological model connecting tau and amyloid. [ABSTRACT FROM AUTHOR]

Background: Early and accurate diagnosis of Alzheimer's disease (AD) is critical to improve illness management and outcomes, making neuropsychological measures an essential tool for clinicians. Research has demonstrated that proactive semantic interference (PSI) and failure to recover from PSI (frPSI) are sensitive to cognitive changes in early mild cognitive impairment (MCI) and preclinical AD determined by Aβ load using PET (Loewenstein et al., 2018; Matias‐Guiu et al., 2017; Curiel et al., 2019). These novel constructs are assessed by the LASSI‐L (Crocco et al., 2018; Crocco et al., 2020). The aim of the current study was to compare a new computerized version of this measure, the LASSI‐BC, to the standard paper‐and‐pencil version of the test. Method: 110 cognitively unimpaired (CU) older adults and 79 older adults diagnosed with amnestic MCI (aMCI) were administered the paper‐and‐pencil form of the LASSI‐L, whereas 62 CU and 52 aMCI participants were administered the LASSI‐BC. Their performance was compared to assess the validity of the LASSI‐BC to discriminate between different diagnostic groups. Result: To assess the validity of the computerized version, both the aMCI and CU groups were compared using χ2 test for categorical variables and ANOVA for continuous variables, with adjustment for covariates such as degree of initial learning, sex, education, and language of evaluation. The performance of CU and aMCI groups using either form was relatively commensurate. Notably, sensitivity and specificity of measures of PSI and frPSI on both versions were calculated to assess diagnostic validity, yielding the following Results Sensitivity of 86.5%, Specificity of 88.1%, and Overall Classification of 87.4% for the LASSI‐BC relative to a Sensitivity of 65.0%, Specificity of 83.6%, and Overall Classification of 75.8% obtained for the paper‐and‐pencil LASSI‐L. Conclusion: The LASSI‐BC displayed exceptionally high diagnostic validity which was comparable to the well‐established LASSI‐L. Notably, the advantages of the LASSI‐BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built‐in audio recording of responses. These findings support the LASSI‐BC, a novel computerized assessment, as an exceptional tool for the early identification of individuals at risk of progressing to dementia. [ABSTRACT FROM AUTHOR]

Background: The HABS‐HD study is an epidemiological study of aging in diverse populations and began transitioning from entirely paper‐based charting to electronic data capture (EDC) in 2018. As the study evolved, the team realized that neuropsychological testing, scoring, and quality review consumed many resources and much staff time. This abstract aims to describe how the HABS‐HD study moved from paper‐based capture of neuropsychological data to EDC with a small data team. Method: The HABS‐HD staff recognized the time commitment for scoring and reviewing scores for the neuropsychological assessment, which created a delay between a participant completing the study and the research diagnosis. Senior research assistants worked with internal developers to create an EDC for the neuropsychological assessment. The data core is small and consists of a director, an assistant director, two developers, two data entry personnel, and a clinician. Specific components were completed on paper to prevent an increase in equipment cost and maintain methodological consistency. These components were reviewed post‐assessment, and a senior research assistant directly entered the scores into the EDC. Result: The EDC neuropsychological assessment was tested before going live. The team adapted data capture from the older method into the EDC. The new system allows the research director to obtain statistics of individual testers and provide more training as needed. It also permits more senior personnel to review the paper components and enter them directly into the EDC, which improves throughput. Conclusion: Smaller data core teams can transition larger projects from paper methods to EDC. The change does not need to be entirely paper or electronic, but investigators should evaluate which methodologies function best for their populations. Finally, communication between the personnel capturing the data, reviewing the quality of the capture, and writing the EDC software is essential. [ABSTRACT FROM AUTHOR]

Background: It is crucial to develop non‐pharmacological interventions to help people with dementia. Among different types of non‐pharmaceutical interventions for dementia, art therapy interventions have been shown helpful for improving patients' physiological and mental states, in particular their cognitive performances, cognitive functionalities, including emotional states, verbal fluency, and behavioral reactions. We use Interactive Drawing Therapy (IDT), proposed by Russell Withers, as an art therapeutic method for people with dementia and to explore the method's effectiveness, we suggest developing a vocal assessment method. Method: We will recruit participants with mild AD and individuals without dementia and divide them into two groups, an experimental group that will attend the IDT sessions and a control group that won't be offered the IDT sessions. All participants will attend two picture description sessions while they describe the cookie theft picture or the picnic scene. For the experimental group, we will offer attending two IDT sessions between two picture description sessions. During the first IDT session, the art therapist helps participants draw their thoughts about what he is doing during the day and describe their feelings. During the second IDT session, the art therapist shows one of the pictures, "Man changing the bulb" or "The Cat in the Tree," and asks them to describe the picture with drawing and writing words. We collect speeches of participants during picture description and IDT sessions. The cognitive status of each participant will be measured using the Mini‐mental state examination (MMSE) test. Result: We will aim to develop a binary classifier to distinguish patients with improved verbal fluency from patients without any enhancements in verbal fluency. It can be a part of a vocal assessment method to assess improvements in verbal fluency of patients attending IDT sessions which will be designed by combing the picture description. We also expect that such IDT sessions can enhance the verbal fluency of patients with dementia. Conclusion: This study will promise to develop a vocal system to discover the effectiveness of IDT for peoplewith dementia. As a part of this study we aim to identify linguistic and acoustic features that might change during the IDT sessions. [ABSTRACT FROM AUTHOR]

Background: There is an unmet need for a minimally invasive clinical test using samples collected by medical staff or by self‐collection to screen persons at risk for Alzheimer's disease (AD) for initial diagnosis as well as for monitoring progression. Addressing this need is even more challenging for underserved and rural populations. Currently, use of whole blood has required venipuncture and RNA extraction. None‐the‐less, AD gene expression signatures using RNA extracted from whole blood have been reported by a number of groups. We have developed a direct, extraction‐free TempO‐Seq® assay of gene expression using blood from a finger prick spotted on filter paper. This novel method is perhaps the simplest and least invasive method of obtaining a blood sample and performing a test that can be used to identify a diagnostic Alzheimer's signature. Method: The targeted sequencing of the whole transcriptome via the TempO‐Seq® gene expression assay (Yeakley, PLosOne doi.org/10.1371/journal.pone.0178302) was adapted to utilize blood spotted on filter paper. Samples were obtained under an IRB‐approved protocol from normal volunteers and patients clinically diagnosed with AD or Parkinson's disease (PD). Result: A protocol that eliminated interference by components of whole blood with enzymes used in molecular biology assays was successfully implemented. This permitted a TempO‐Seq assay to be carried out without extraction of RNA from the filter paper blood spots. Highly expressed genes were attenuated to increase the sensitivity with which AD biomarker genes could be measured. The shelf‐life of blood spotted filter paper stored at room temperature was greater than 6 months. AD, PD, and normal control blood samples were assayed and a proposed gene expression signature for AD was identified. Conclusion: Use of a simple gene expression‐based assay of blood from a finger prick spotted on filter paper to diagnose AD is feasible. The spotted blood sample is stable for months at room temperature, permitting self‐collection or assisted collection and mailing of samples for testing. [ABSTRACT FROM AUTHOR]

Background: Cognitive intervention is accepted as a potential therapy to prevent the incident dementia. It was found that computerized cognitive training might be effective for older adults with mild cognitive impairment (MCI) in previous studies. We aimed to find the effect of multidomain cognitive training using tablet computer on the cognitive and psychological function in patients with MCI. Method: Participants in training group (n = 15) conducted a multidomain cognitive training program using table computer and those in control group (n = 13) conducted an educational book reading twice a week for eight weeks. They were evaluated of their cognitive and psychiatric function before and after the program. The differences of the pre‐ and post‐ scores were compared between training and control groups. Result: Participants in training group showed improvement in cognitive domains such as language (p = 0.012), memory (p = 0.050), and frontal executive function (p = 0.017), and psychiatric symptoms such as apathy (p = 0.001) and quality of life (p = 0.035) after the training. Control group participants showed improvements in frontal executive function (p = 0.013), positive affect (p = 0.019), apathy (p = 0.022) and mild behavioral impairment score (p = 0.049). Between group comparison of the pre‐ and post‐training difference showed significant improvement in training group compared to control group in memory (p = 0.020), frontal executive function (p = 0.024), positive affect (p = 0.037), apathy (p = 0.048), and quality of life (p = 0.047). Conclusion: We found the effect of multidomain cognitive training using tablet computer in cognitive domain including memory and executive function, positive affect, apathy, and quality of life in MCI patients. Tablet computer cognitive training may be effective in multidomain cognitive training with transfer effect in the prodromal stage of dementia. Future trials with larger sample size and various devices would find the effect of the computerized cognitive training. [ABSTRACT FROM AUTHOR]

Background Cerebrospinal fluid (CSF) biomarkers β-amyloid 1-42 (Aβ 1-42 ), also expressed as Aβ 1-42 :Aβ 1-40 ratio, T-tau, and P-tau 181P , have proven diagnostic accuracy for mild cognitive impairment and Alzheimer's disease (AD). How to use, interpret, and disclose biomarker results drives the need for standardization. Methods Previous Alzheimer's Biomarkers Standardization Initiative meetings discussed preanalytical issues affecting Aβ 1-42 and tau in CSF. This second round of consensus meetings focused on issues related to clinical use of AD CSF biomarkers. Results Consensus was reached that lumbar puncture for AD CSF biomarker analysis be considered as a routine clinical test in patients with early-onset dementia, at the prodromal stage or with atypical AD. Moreover, consensus was reached on which biomarkers to use, how results should be interpreted, and potential confounding factors. Conclusions Changes in Aβ 1-42 , T-tau, and P-tau 181P allow diagnosis of AD in its prodromal stage. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Background: Numerous studies show that the cerebrospinal fluid biomarkers total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181P), and amyloid-β (1-42) (Aβ1–42) have high diagnostic accuracy for Alzheimer’s disease. Variability in concentrations for Aβ1–42, T-tau, and P-tau181P drives the need for standardization. Methods: Key issues were identified and discussed before the first meeting of the members of the Alzheimer’s Biomarkers Standardization Initiative (ABSI). Subsequent ABSI consensus meetings focused on preanalytical issues. Results: Consensus was reached on preanalytical issues such as the effects of fasting, different tube types, centrifugation, time and temperature before storage, storage temperature, repeated freeze/thaw cycles, and length of storage on concentrations of Aβ1–42, T-tau, and P-tau181P in cerebrospinal fluid. Conclusions: The consensus reached on preanalytical issues and the recommendations put forward during the ABSI consensus meetings are presented in this paper. [Copyright &y& Elsevier]

Abstract: Background: In the earliest clinical stages of Alzheimer’s disease (AD) when symptoms are mild, clinical diagnosis can be difficult. AD pathology most likely precedes symptoms. Biomarkers can serve as early diagnostic indicators or as markers of preclinical pathologic change. Candidate biomarkers derived from structural and functional neuroimaging and those measured in cerebrospinal fluid (CSF) and plasma show the greatest promise. Unbiased exploratory approaches, eg, proteomics or cortical thickness analysis, could yield novel biomarkers. The objective of this article was to review recent progress in selected imaging and neurochemical biomarkers for early diagnosis, classification, progression, and prediction of AD. Methods: We performed a survey of recent research, focusing on core biomarker candidates in AD. Results: A number of in vivo neurochemistry and neuroimaging techniques, which can reliably assess aspects of physiology, pathology, chemistry, and neuroanatomy, hold promise as biomarkers. These neurobiologic measures appear to relate closely to pathophysiologic, neuropathologic, and clinical data, such as hyperphosphorylation of tau, amyloid beta (Aβ) metabolism, lipid peroxidation, pattern and rate of atrophy, loss of neuronal integrity, functional and cognitive decline, as well as risk of future decline. Current advances in the neuroimaging of mediotemporal, neocortical, and subcortical areas of the brain of mild cognitive impairment (MCI) and AD subjects are presented. CSF levels of Aβ42, tau, and hyperphosphorylated tau protein (p-tau) can distinguish subjects with MCI who are likely to progress to AD. They also show preclinical alterations that predict later development of early AD symptoms. Studies on plasma Aβ are not entirely consistent, but recent findings suggest that decreased plasma Aβ42 relative to Aβ40 might increase the risk of AD. Increased production of Aβ in aging is suggested by elevation of BACE1 protein and enzyme activity in the brain and CSF of subjects with MCI. CSF tau and p-tau are increased in MCI as well and show predictive value. Other biomarkers might indicate components of a cascade initiated by Aβ, such as oxidative stress or inflammation. These merit further study in MCI and earlier. Conclusions: A number of neuroimaging candidate markers are promising, such as hippocampus and entorhinal cortex volumes, basal forebrain nuclei, cortical thickness, deformation-based and voxel-based morphometry, structural and effective connectivity by using diffusion tensor imaging, tractography, and functional magnetic resonance imaging. CSF Aβ42, BACE1, total tau, and p-tau are substantially altered in MCI and clinical AD. Other interesting novel marker candidates derived from blood are being currently proposed (phase I). Biomarker discovery through proteomic approaches requires further research. Large-scale international controlled multicenter trials (such as the U.S., European, Australian, and Japanese Alzheimer’s Disease Neuroimaging Initiative and the German Dementia Network) are engaged in phase III development of the core feasible imaging and CSF biomarker candidates in AD. Biomarkers are in the process of implementation as primary outcome variables into regulatory guideline documents regarding study design and approval for compounds claiming disease modification. [Copyright &y& Elsevier]

Background: Cognitive training refers to cognitive exercises with inherent challenges that target enhance performance in specific cognitive domain. There has been number of studies reported positive outcome of cognitive training in persons with Alzheimer's disease. In this study, we newly designed set of paper‐based cognitive training program, "Gipum‐seo" which consists of different levels of difficulty using predesigned exercises and evaluated its efficacy of cognitive enhancement on patients with early stage of Alzheimer's disease. Method: Forty participants who are diagnosed with early stage of Alzheimer's dementia participated in this study. To test the efficacy of paper‐based cognitive training programs to cognition, all patients were randomly allocated to either an intervention group (n=20) or a control group (n=20). The intervention group regularly received 24 sessions of paper‐based cognitive training, over a 12 week period. Neuropsychological examinations were conducted before and after this training period. Result: After 12 weeks, the intervention group showed a significant change in Korean version of the Mini‐Mental State Examination (25.90±3.8), compared to the control group (23.7±2.8) (p=0.04). Also, there was significant improvement in language, attention and executive function for the training group, as compared with controls. Conclusion: Paper‐based cognitive training might have beneficial effects on the general cognitive functions in early stage of Alzheimer's dementia. [ABSTRACT FROM AUTHOR]

Background: Cognitive training refers to cognitive exercises with inherent challenges that target enhance performance in specific cognitive domain. There has been number of studies reported positive outcome of cognitive training in persons with Alzheimer's disease. In this study, we newly designed set of paper‐based cognitive training program, "Gipum‐seo" which consists of different levels of difficulty using predesigned exercises and evaluated its efficacy of cognitive enhancement on patients with early stage of Alzheimer's disease. Method: Forty participants who are diagnosed with early stage of Alzheimer's dementia participated in this study. To test the efficacy of paper‐based cognitive training programs to cognition, all patients were randomly allocated to either an intervention group (n=20) or a control group (n=20). The intervention group regularly received 24 sessions of paper‐based cognitive training, over a 12 week period. Neuropsychological examinations were conducted before and after this training period. Result: After 12 weeks, the intervention group showed a significant change in Korean version of the Mini‐Mental State Examination (25.90±3.8), compared to the control group (23.7±2.8) (p=0.04). Also, there was significant improvement in language, attention and executive function for the training group, as compared with controls. Conclusion: Paper‐based cognitive training might have beneficial effects on the general cognitive functions in early stage of Alzheimer's dementia. [ABSTRACT FROM AUTHOR]

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [ 18 F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; (6) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Multimodal methods incorporating APOE status and longitudinal MRI proved most highly predictive of future decline. Refinements of clinical tests used as outcome measures such as clinical dementia rating-sum of boxes further reduced sample sizes; (7) the pioneering of genome-wide association studies that leverage quantitative imaging and biomarker phenotypes, including longitudinal data, to confirm recently identified loci, CR1, CLU , and PICALM and to identify novel AD risk loci; (8) worldwide impact through the establishment of ADNI-like programs in Japan, Australia, Argentina, Taiwan, China, Korea, Europe, and Italy; (9) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker and clinical data to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (10) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. [ABSTRACT FROM AUTHOR]

Abstract: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates for the detection of AD in its preclinical stages; (5) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities, whereas MRI measures of change were shown to be the most efficient outcome measures; (6) the confirmation of the AD risk loci CLU, CR1, and PICALM and the identification of novel candidate risk loci; (7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia, and Australia; (8) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (9) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. The ADNI study was extended by a 2-year Grand Opportunities grant in 2009 and a renewal of ADNI (ADNI-2) in October 2010 through to 2016, with enrollment of an additional 550 participants. [Copyright &y& Elsevier]

Abstract: The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates for the detection of AD in its preclinical stages; (5) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities, whereas MRI measures of change were shown to be the most efficient outcome measures; (6) the confirmation of the AD risk loci CLU, CR1, and PICALM and the identification of novel candidate risk loci; (7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia, and Australia; (8) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (9) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. The ADNI study was extended by a 2-year Grand Opportunities grant in 2009 and a renewal of ADNI (ADNI-2) in October 2010 through to 2016, with enrollment of an additional 550 participants. [Copyright &y& Elsevier]

Ongoing assessment of patients with Alzheimer's disease (AD) in postapproval studies is important for mapping disease progression and evaluating real‐world treatment effectiveness and safety. However, interpreting outcomes in the real world is challenging owing to variation in data collected across centers and specialties and greater heterogeneity of patients compared with trial participants. Here, we share considerations for observational postapproval studies designed to collect harmonized longitudinal data from individuals with mild cognitive impairment or mild dementia stage of disease who receive therapies targeting the underlying pathological processes of AD in routine practice. This paper considers key study design parameters, including proposed aims and objectives, study populations, approaches to data collection, and measures of cognition, functional abilities, neuropsychiatric status, quality of life, health economics, safety, and drug utilization. Postapproval studies that capture these considerations will be important to provide standardized data on AD treatment effectiveness and safety in real‐world settings. [ABSTRACT FROM AUTHOR]

Background: Tools for web‐based testing to detect cognitive impairment are still underdeveloped in Thailand. Our aim was to generate a web‐based instrument to assess cognitive and functional abilities and to explore its ability for diagnosis of dementia and MCI. Method: We have developed a web application for cognitive and functional assessment to detect cognitive impairment. We hoped that subjects or family members could use this web‐based tests at home as self‐screening. These web‐based tests included an electronic version of the Thai Mental State Examination (e‐TMSE), a clock drawing test, a category verbal fluency test, a short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and Thai activities of daily living scale (Thai ADL). Correlations, receiver operator curves (ROCs), sensitivity, and specificity were analyzed using SPSS (version 18). Result: A total of 198 participants (69% female, mean age 66.7 ± 10 years). 57.1% had education of more than 6 years. Forty‐four were Major Neurocognitive Disorder, fifty‐eight were Mild Neurocognitive Disorder (MCI), and ninety‐six were normal controls. The e‐TMSE correlated with both paper‐pencil based TMSE(r = 0.80,p<0.001) as well as clock drawing test (r = 0.470 p<0.001). There were also statistically significant high correlations between digital and paper & pencil tests (e.g, category verbal fluency test, A short form of the IQCODE, and ADL). For diagnosis of dementia, e‐TMSE achieved an AUC of 0.84 (95% bootstrapped CI [0.78, 0.90]. The cut‐off score ≤23 offered sensitivity and specificity of 88.6% and 70.1% respectively. For diagnosis of dementia with the combination of 5 e‐tests, the AUC was 0.832 (p<0.001), while for MCI diagnosis, the AUC was 0.615 (p = 0.013). The area under the ROC of the IQCODE combined with ADL scale test was 0.907 (p<0.001). Conclusion: We demonstrated that our web application that included: e‐TMSE, clock drawing test, category verbal fluency test, IQCODE and Thai‐ADL scale showed good correlation between digital vs paper‐pencil tests. Individual e‐test and combination of them can offer self screening for MCI and dementia. [ABSTRACT FROM AUTHOR]

Background: Early screening of mild cognitive impairment (MCI) is crucial for the elderly to access formal diagnosis and intervention of Alzheimer's Disease (AD) and related dementias (ADRD) at early stages. Owing to the rapid development of artificial intelligence (AI) and voice recognition technology, the detection method using speech patterns as digital biomarkers collected by digital consumer devices can accommodate a huge demand for early and large‐scale detection. We here reported the design and development of the Shanghai Cognitive Screening (SCS) mini‐program, the first intelligent voice recognition‐based cognitive assessment WeChat mini‐program in China. Method: The SCS mini‐program was developed based on the cognitive paradigm and classic pencil‐and‐paper neuropsychological assessments (e.g. Montreal cognitive assessment basic [MoCA‐B]). Through Automatic Speech Recognition (ASR), users speak to complete tasks including Naming, Immediate Recall, Delayed Recall, Symbol Digit Modalities Test (SDMT), Delayed RecallII, and Recognition (Figure 1). The acoustic, phonetics, and linguistic speech pattern variables would also be extracted and processed as digital biomarkers. The SCS intelligent prediction model enrolls speech pattern digital biomarkers, individual task scores, and time use variables with age, gender, and education level as linking variables, which enables to grade the user's global cognitive function and individual cognitive domains (Figure 2). Result: After completing all tasks in the SCS, users can immediately read the comprehensive results which are divided into 4 categories corresponding to 4 grading intervals: "healthy" (cognitively normal), "low risk" (suspected SCD), "medium‐high risk" (suspected MCI), and "high risk" (suspected AD). We also use a radar chart with scores of cognitive domains (i.e., memory, attention, visual perception, language, and executive functions), a memory trend graph (i.e., immediate and delayed recalls), an attention persistence graph, and related advice in the automatically generated report (Figure 3). Conclusion: The SCS mini‐program is more efficient and economical compared to traditional paper‐based cognitive assessments. It is suitable for clinical cognitive assessment, remote self‐rating, and community screening for MCI and dementias among Chinese older adults and other ADRD high‐risk groups. Clinical trials are yet to be conducted to validate the accuracy and diagnostic value of the SCS WeChat mini‐program. [ABSTRACT FROM AUTHOR]

Background: Early screening of mild cognitive impairment (MCI) is crucial for the elderly to access formal diagnosis and intervention of Alzheimer's Disease (AD) and related dementias (ADRD) at early stages. Owing to the rapid development of artificial intelligence (AI) and voice recognition technology, the detection method using speech patterns as digital biomarkers collected by digital consumer devices can accommodate a huge demand for early and large‐scale detection. We here reported the design and development of the Shanghai Cognitive Screening (SCS) mini‐program, the first intelligent voice recognition‐based cognitive assessment WeChat mini‐program in China. Method: The SCS mini‐program was developed based on the cognitive paradigm and classic pencil‐and‐paper neuropsychological assessments (e.g. Montreal cognitive assessment basic [MoCA‐B]). Through Automatic Speech Recognition (ASR), users speak to complete tasks including Naming, Immediate Recall, Delayed Recall, Symbol Digit Modalities Test (SDMT), Delayed RecallII, and Recognition (Figure 1). The acoustic, phonetics, and linguistic speech pattern variables would also be extracted and processed as digital biomarkers. The SCS intelligent prediction model enrolls speech pattern digital biomarkers, individual task scores, and time use variables with age, gender, and education level as linking variables, which enables to grade the user's global cognitive function and individual cognitive domains (Figure 2). Result: After completing all tasks in the SCS, users can immediately read the comprehensive results which are divided into 4 categories corresponding to 4 grading intervals: "healthy" (cognitively normal), "low risk" (suspected SCD), "medium‐high risk" (suspected MCI), and "high risk" (suspected AD). We also use a radar chart with scores of cognitive domains (i.e., memory, attention, visual perception, language, and executive functions), a memory trend graph (i.e., immediate and delayed recalls), an attention persistence graph, and related advice in the automatically generated report (Figure 3). Conclusion: The SCS mini‐program is more efficient and economical compared to traditional paper‐based cognitive assessments. It is suitable for clinical cognitive assessment, remote self‐rating, and community screening for MCI and dementias among Chinese older adults and other ADRD high‐risk groups. Clinical trials are yet to be conducted to validate the accuracy and diagnostic value of the SCS WeChat mini‐program. [ABSTRACT FROM AUTHOR]

Background: Frailty is a multidimensional construct that represents an age‐related reduction in physiologic reserve and resistance to stressors. Health‐related quality of life was found to be significantly low for the frail older adults. Method: VOS viewer is a program that graphically represents them through bibliometric analysis. Using the Web of Science data and VOS viewer program, we analyzed frail older adults and quality of life. We identified and incorporated 194 publications. We searched all years the data from 2012 to 2021 using the keywords: TITLE ((frail OR frailty OR feeble) AND (qol OR "quality of life" OR "life satisfaction" OR satisfaction OR "well‐being" OR "subjective life")) AND DOCTYPE (ar) AND PUBYEAR 2012‐2021 LANGUAGE (English). Result: Looking at the trend of changes in the number of published documents from 2012 to 2021, it showed an increase of 337.5% (Figure 1). The most research was included 74 and 27 cases in Geriatrics Gerontology (Figure 2). A total of 188 papers on the QoL for the frail older adults were published in 110 journals (Table 1). Australia and the United States published the largest number of papers with 29 (15.10%) (Figure 3). Studies on the quality of life of the frail older adults were conducted by researchers belonging to 434 institutions. Maastricht University, University Groningen, and Erasmus University published the largest number of papers with 6 each (Figure 4). A total of 909 keywords were searched in 188 papers, and the top 100 keywords were selected based on the frequency. There were 6 clusters and Based on the TLS and the top 5 keywords were health (49 times), mobility (41 times), disability (37 times), prevalence (37 times), and adults (33 times) (Figure 5). Conclusion: Research on the QoL and the frail older adults is increasing. For preventive treatment for the frail older adults, which determines the quality of life, it is necessary to focus on research topics on this. [ABSTRACT FROM AUTHOR]

Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public‐health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public‐domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor. Highlights: A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research.Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field. [ABSTRACT FROM AUTHOR]

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice. [ABSTRACT FROM AUTHOR]

Recent advancements in the artificial intelligence (AI) domain have revolutionized the early detection of cognitive impairments associated with dementia. This has motivated clinicians to use AI‐powered dementia detection systems, particularly systems developed based on individuals' and patients' speech and language, for a quick and accurate identification of patients with dementia. This paper reviews articles about developing assessment tools using machine learning and deep learning algorithms trained by vocal and textual datasets. [ABSTRACT FROM AUTHOR]

Background: With the recent increase in the older adults population, interest in successful aging is increasing. Aging anxiety, a psychological mechanism that affects successful aging, refers to the inability to feel stable due to worry or fear in old age, which negatively affects the older adult's feelings of depression and quality of life. According to a study on successful aging and aging anxiety, it was recently reported that aging anxiety can be prevented by realizing healthy aging through lifestyle intervention. To date, studies analyzing aging anxiety and lifestyle from a macro perspective are insufficient. To compensate for these limitations, bibliographic analysis methods that derive the characteristics of academic literature from bibliographic information are used. Since it is essential to understand research trends from a macroscopic point of view at a time when the need for research on aging anxiety and lifestyle is emphasized, in this study, the flow of research on aging anxiety and lifestyle is identified to prepare basic data for future research. Method: Among the bibliographic analysis methods, first a citation analysis method that identifies the association based on the number of citations. Second a simultaneous appearance word analysis method that identifies the association based on the number of keywords appeared was used. VOSviewer was used to cluster and chart the analyzed information. Result: The frequency of published papers by year showed a gradual increase until 2017 and a rapid increase from 2018. In the field of research paper study, research was most actively conducted in the field of psychiatry. In the citation analysis, the United States, Australia, and the United Kingdom showed high correlation with each other, and as a result of conducting simultaneous word analysis on major keywords, words with high association with 'aging anxiety' were found to be 'depression'. Conclusion: This study is meaningful in that it grasped the flow of aging anxiety and lifestyle research from a macroscopic point of view using a bibliographic analysis method. Based on this, it is expected to understand the importance of lifestyle from the preventive point of view of aging and to be used as basic data for intervention and related education. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The development of biomarkers for Alzheimer's disease (AD) has allowed researchers to increase sample homogeneity and test candidate treatments earlier in the disease. The integration of biomarker "screening" criteria should be met with a parallel implementation of standardized methods to disclose biomarker testing results to research participants; however, the extent to which protocolized disclosure occurs in trials is unknown. METHODS: We reviewed the literature to identify prodromal AD trials published in the past 10 years. From these, we quantified the frequency of biomarker disclosure reporting and the depth of descriptions provided. RESULTS: Of 30 published trials using positron emission tomography or cerebrospinal fluid‐based amyloid positivity as an eligibility criterion, only one mentioned disclosure, with no details on methods. DISCUSSION: Possible reasons for and implications of this information gap are discussed. Recommendations are provided for trialists considering biomarker screening as part of intervention trials focused on prodromal AD. HIGHLIGHTS: Few prodromal Alzheimer's disease (AD) trial papers discuss biomarker disclosure.Disclosure has implications for participants, family members, and trial success.Disclosure must be consistently integrated and reported in prodromal AD trials.Best practice guidelines and training resources for disclosure are needed. [ABSTRACT FROM AUTHOR]

Introduction: The projected growth of Alzheimer's disease (AD) and AD‐related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. Methods: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. Results: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. Discussion: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. Highlights: Ecological systems theory links structural/social determinants to AD/ADRD.Structural/social determinants accrue and interact over the life course to impact AD/ADRD.Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws).Most macro‐level determinants have been understudied in the AD/ADRD literature. [ABSTRACT FROM AUTHOR]

Background: Currently, there is a search for timely care and intervention on patients with dementia, which have reasonable costs and allow the sustainability and efficiency of national health and social care systems (Livingston et al., 2017). Cognitive interventions delivered in the patient's home can be an excellent alternative, due to their feasibility(Jang et al., 2021) and accessibility (Rai et al., 2021) to the intervention. The aim of this paper is to describe the evidence on cognitive intervention performed at home for patients with MCI and mild dementia. To describe its characteristics and outcomes, and to address its feasibility and usability. Method: A systematic review was performed using the PRISMA recommendations. We reviewed 190 records from four databases: PubMed, CINAHL, Web of Science, and PsycInfo.The quality of the studies was assessed using the tool "Assessment (mERA) checklist7" (World Health Organization, 2016) Result: Ten papers were included. With a mean quality score of 0.76/1 (91.7% agreement). The sample contains (N = 777) patients (MA 75.9). 80% have an education >7 years. 87.1% have a diagnosis of mild dementia. There are (N = 628) caregivers (MA 64.8). Seventy percent (n = 440) are women. Positive results were found in: 71% of studies that looked for results on cognition. 66% of the studies that looked for results on mood and behavioral symptoms. 83% of studies that looked for results on functionality/quality of life. 100% of the studies that looked feasibility, and 75% of the studies that looked for results on the caregiver. Conclusion: Cognitive intervention in the home of patients with MCI and early dementia showed positive results at a cognitive, emotional and behavioral levels. Likewise, in the caregiving relationship, emotional health and quality of life of caregivers. The use of assistive technologies in the home has some benefits over face‐to‐face care. Outcome‐cost ratio can be a cost‐effective solution for the sustainability and efficiency of national health and social care systems. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline is a self‐reported experience of declining cognitive function showing normal performance in cognitive assessments, which is a known risk factor for dementia. Recent studies highlight the importance of nonpharmacological multidomain interventions that can target multiple risk factors of dementia in older adults. We investigated the efficacy of the Silvia program, a mobile‐based multidomain intervention, to improve cognitive function and health‐related outcomes of older adults with a high risk of dementia. Additionally, we compared its effects to a conventional paper‐based multidomain program on various health indicators related to risk factors of dementia. Method: This prospective randomized controlled trial involved 77 older adults with a high risk of dementia recruited from the Dementia Prevention and Management Center in Gwangju, South Korea during May to October 2022. Participants were randomly assigned to either the mobile‐ or paper‐based group. Interventions were administered for 12 weeks, where pre‐ and post‐assessments were conducted. Result: The Korean version of the Repeatable Battery for the Assessment of Neuropsychological status (K‐RBANS) total score did not show significant differences between groups. The mobile group showed better improvement in K‐PRMQ scores and PSS scores than the paper group. Differences within groups showed that mobile‐based interventions significantly improved the Korean version of the prospective and retrospective memory questionnaire (K‐PRMQ), State‐Trait Anxiety Inventory‐X‐1 (STAI‐X‐1), Perceived Stress Scale (PSS), and e EuroQoL 5‐Dimension 5‐Level (EQ‐5D‐5L) scores, while paper‐based interventions significantly improved PSS, and EQ‐5D‐5L scores. Conclusion: The Silvia program was more effective than paper‐based intervention in improving self‐reported memory failures, stress, anxiety, and health‐related quality of life. However, longer periods of administration for more than 12 weeks may be needed to achieve significant improvements in cognitive function by objective measures [ABSTRACT FROM AUTHOR]

Background: A core outcome set (COS) is a minimum set of health outcomes to be measured for a given condition. COS can be developed for specific populations, interventions, or settings, so several COS may exist for a condition e.g., dementia. Comparison of the outcomes and measurement tools informs which outcomes should be considered by stakeholders when assessing quality of care. Method: COS developed for people living with any type of dementia were identified through the COMET database1 and handsearching references of eligible papers. Data was extracted on COS scope (population, intervention), stakeholders, development methods, and the outcomes and tools recommended within each COS. Recommended outcomes were classified against COMET's taxonomy2 and tools were grouped by outcome across COS. Result: Ten papers outlining 14 COS were identified (Table 1). Nine included people living with dementia, carers or care organisations in the consensus process. Eleven specified use for a disease stage or intervention. Eleven COS were for research use, one for routine care, and two for both settings. 87 outcomes covering a range of domains were recommended (Table 2). Function/Activities of Daily Living, Cognition, Patient behaviour/ neuropsychiatric symptoms, QoL, and Family Carer QoL were all recommended by at least four COS. Eight COS included recommendations of how to measure the outcomes, but tools differed across the COS. Conclusion: Multiple COS for dementia have been identified. Most of these have been developed for research, specific interventions, or stages of dementia. Although the majority involved people with dementia or their carers, further quality assessment is needed. Evaluation of recommended outcomes and quality of COS development is required where multiple COS exist, or COS scope does not directly match the proposed area of application. This information can be used by stakeholders from the intended setting to select or ratify the most pertinent outcomes instead of creating additional COS. 1https://www.comet‐initiative.org/ 2Dodd S et al. A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery. J Clin Epidemiol. 2018;96:84‐92. [ABSTRACT FROM AUTHOR]

Background: Most people with clinical dementia have at least two other conditions. This co‐occurrence of multiple conditions, known as multimorbidity, is associated with worse quality of life, increased mortality and greater healthcare costs. However, there is limited research on the bidirectional interaction of physical multimorbidity and all‐cause dementia. We aimed to review and summarize key themes in this area, especially in the context of recent pharmacological advances. Method: We searched PubMed and Google Scholar, updating the search strategy of a 2014 review of comorbidity and dementia. We added new key words reflecting recent trends in Alzheimer's disease research, including: "amyloid", "biomarker" and "disease‐modifying". We searched the resulting papers' references and citations and generated a narrative review of the literature grouped by research methodology. Result: Several key themes emerged from the published literature. Epidemiological studies confirmed that most people with dementia have multimorbidity. They additionally identified multimorbidity as a risk factor for dementia or cognitive impairment and found it to be associated with dementia progression and worse quality of life. Studies on the association between multimorbidity and biomarkers of neurodegeneration were either negative or found an inverse relationship. People with multimorbidity were found to be significantly under‐represented in clinical trials, especially those of dementia drugs. Qualitative research on healthcare delivery highlighted the importance of family carers and communication between providers, and a review of care coordination interventions identified important factors that optimize transitions of care. There was also recognition of the need to address racial and ethnic disparities in people with multimorbidity and dementia. Several papers called for a comprehensive understanding of dementia in relation to the whole person and society. Conclusion: Having multiple conditions alongside dementia poses challenges for patients, caregivers and clinicians. Multimorbidity is an important consideration for those designing representative clinical trials, and it may be more difficult to treat dementia in people with several comorbid conditions. This work highlights the need for specific research into the relative contributions of multimorbidity and other person‐centered characteristics on clinically meaningful outcomes. In the context of new and costly therapies, this will inform equitable allocation of research and healthcare resources. [ABSTRACT FROM AUTHOR]

Background: Computerized cognitive tests are critical in the screening of preclinical Alzheimer's Disease (AD) given their ability to be conducted remotely at low cost. Here, we explore whether machine‐learning derived composites of remote cognitive tests can improve sensitivity when detecting brain amyloid (Aβ) accumulation in cognitively normal (CN) cohorts than traditional pen‐and‐paper alternatives. Method: Based on the CogState Brief Battery tests in CN individuals from the A4 dataset (n = 4230, Aβ‐ = 3094), we construct a data‐driven composite, denoted the Remote Empirical Cognitive composite for Alzheimer's Disease (RECAD), designed to be sensitive to Aβ‐PET positivity. Specifically, the composite uses a random feature elimination logistic regression to identify a subset of predictive tests. We construct and evaluate the model using 10 repeat, 5‐fold cross‐validation in the A4 baseline data. We conduct temporal validation with the A4 second visit and external validation using CN participants from the ADNI (n = 389, Aβ‐ = 143), comparing against the pen‐and‐paper‐based PACC composite and previous computerized composites CBB and C3. Result: RECAD includes three accuracy scores (Identification, One‐Back and One‐card) and one reaction time (Detection). In cross‐validation in the A4 baseline, RECAD show a significantly higher ability to discriminate Aβ status [mean Cohen's d = 0.26] than PACC [mean d = 0.25, t‐test p<0.001] and computerized composites CBB [median d = 0.13, p<0.001] and C3 [mean d = 0.18, p<0.001]. RECAD significantly improves beyond C3 in the A4 second visit (z‐test p<0.001). Moreover, these trends are replicated in the ADNI at baseline (RECAD d = 0.215, PACC d = 0.061) and 24 months (RECAD d = 0.295, PACC d = ‐0.026) but the small sample and effect size limits our ability to demonstrate statistical significance. Conclusion: RECAD, as a machine‐learning derived composite of remotely conducted cognitive tests, shows a comparable or better sensitivity to the established pen‐and‐paper composite test when screening for Aβ+ among CN cohorts. While effect sizes are small, conducting such remote tests repeatedly may be a useful pre‐screening for downstream biofluid evaluation. [ABSTRACT FROM AUTHOR]

Background: Target product profiles (TPP) were first defined by industry and supported by FDA to address user needs and guide communication in all phases of drug development. However, heterogeneity in practical use hurdles uptake in academic research. Our study aims to facilitate uptake by outlining a reference template to be adapted to dementia research. Methods: We conducted a systematic review to extract structural characteristics, along with differences and commonalities across TPPs used in different product development (e.g., drugs vs diagnostics). We included data from peer‐reviewed publications on TPPs content (i.e., developing, revising, or mentioning a TPP), product type (drug, diagnostics, vaccine, medical device, other), disease category (infectious, non‐infectious diseases), specific disease, TPP features of the target profile, and levels of compliance for each feature. Results: 327 of 1297 identified records were eligible for full‐text review. Preliminary data extraction from 20 papers shows that: Content: 45% (n = 9) developed a new TPP, 10% (n = 2) revised a predefined TPP; 45% only mentioned TPPs (n = 9). Product: of the nine papers that developed a new TPP, 77.8% (n = 7) were for drug and 22.2% (n = 2) for diagnostics development. Disease category: 70% (n = 14) used TPPs in infectious diseases while 30% (n = 6) were in non‐infectious diseases. So far, no publication reported using TPPs in dementia. TPP features for different product types from the 11 publications that developed or revised TPPs: 39 features were extracted from TPPs for diagnostic development, 11 of which (28%) were in common. We extracted 35 features from TPPs for drug development, 9 of which (27.5%) were in common. Levels of compliance ranged between one (n = 5, 45.5%) to two (n = 5, 45.5%) levels, corresponding to conservative and optimistic levels. One (9%) did not report targeted levels of compliance. Conclusion: TPPs are not frequently used by academic researchers. Despite being a useful tool enhancing product development, its considerable heterogeneity in structure renders its adaptation challenging. Completing data extraction and comparing the outcome with opinion leader's assessment and formal guidance (e.g., from WHO) will facilitate drawing a comprehensive picture of common TPP features to derive a consistent and comprehensive template and facilitate its use in academic dementia research. [ABSTRACT FROM AUTHOR]

The MarkVCID consortium was formed under cooperative agreements with the National Institute of Neurologic Diseases and Stroke (NINDS) and National Institute on Aging (NIA) in 2016 with the goals of developing and validating biomarkers for the cerebral small vessel diseases associated with the vascular contributions to cognitive impairment and dementia (VCID). Rigorously validated biomarkers have consistently been identified as crucial for multicenter studies to identify effective strategies to prevent and treat VCID, specifically to detect increased VCID risk, diagnose the presence of small vessel disease and its subtypes, assess prognosis for disease progression or response to treatment, demonstrate target engagement or mechanism of action for candidate interventions, and monitor disease progression during treatment. The seven project sites and central coordinating center comprising MarkVCID, working with NINDS and NIA, identified a panel of 11 candidate fluid‐ and neuroimaging‐based biomarker kits and established harmonized multicenter study protocols (see companion paper "MarkVCID cerebral small vessel consortium: I. Enrollment, clinical, fluid protocols" for full details). Here we describe the MarkVCID neuroimaging protocols with specific focus on validating their application to future multicenter trials. MarkVCID procedures for participant enrollment; clinical and cognitive evaluation; and collection, handling, and instrumental validation of fluid samples are described in detail in a companion paper. Magnetic resonance imaging (MRI) has long served as the neuroimaging modality of choice for cerebral small vessel disease and VCID because of its sensitivity to a wide range of brain properties, including small structural lesions, connectivity, and cerebrovascular physiology. Despite MRI's widespread use in the VCID field, there have been relatively scant data validating the repeatability and reproducibility of MRI‐based biomarkers across raters, scanner types, and time intervals (collectively defined as instrumental validity). The MRI protocols described here address the core MRI sequences for assessing cerebral small vessel disease in future research studies, specific sequence parameters for use across various research scanner types, and rigorous procedures for determining instrumental validity. Another candidate neuroimaging modality considered by MarkVCID is optical coherence tomography angiography (OCTA), a non‐invasive technique for directly visualizing retinal capillaries as a marker of the cerebral capillaries. OCTA has theoretical promise as a unique opportunity to visualize small vessels derived from the cerebral circulation, but at a considerably earlier stage of development than MRI. The additional OCTA protocols described here address procedures for determining OCTA instrumental validity, evaluating sources of variability such as pupil dilation, and handling data to maintain participant privacy. MRI protocol and instrumental validationThe core sequences selected for the MarkVCID MRI protocol are three‐dimensional T1‐weighted multi‐echo magnetization‐prepared rapid‐acquisition‐of‐gradient‐echo (ME‐MPRAGE), three‐dimensional T2‐weighted fast spin echo fluid‐attenuated‐inversion‐recovery (FLAIR), two‐dimensional diffusion‐weighted spin‐echo echo‐planar imaging (DWI), three‐dimensional T2*‐weighted multi‐echo gradient echo (3D‐GRE), three‐dimensional T2‐weighted fast spin‐echo imaging (T2w), and two‐dimensional T2*‐weighted gradient echo echo‐planar blood‐oxygenation‐level‐dependent imaging with brief periods of CO2 inhalation (BOLD‐CVR). Harmonized parameters for each of these core sequences were developed for four 3 Tesla MRI scanner models in widespread use at academic medical centers.MarkVCID project sites are trained and certified for their instantiation of the consortium MRI protocols. Sites are required to perform image quality checks every 2 months using the Alzheimer's Disease Neuroimaging Initiative phantom.Instrumental validation for MarkVCID MRI‐based biomarkers is operationally defined as inter‐rater reliability, test‐retest repeatability, and inter‐scanner reproducibility. Assessments of these instrumental properties are performed on individuals representing a range of cerebral small vessel disease from mild to severe.Inter‐rater reliability is determined by distribution of an independent dataset of MRI scans to each analysis site. Test‐retest repeatability is determined by repeat MRI scans performed on individual participants on a single MRI scanner after a short (1‐ to 14‐day) interval. Inter‐scanner reproducibility is determined by repeat MRI scans performed on individuals performed across four MRI scanner models. OCTA protocol and instrumental validationThe MarkVCID OCTA protocol uses a commercially available, Food and Drug Administration‐approved OCTA apparatus. Imaging is performed on one dilated and one undilated eye to assess the need for dilation. Scans are performed in quadruplicate. MarkVCID project sites participating in OCTA validation are trained and certified by this biomarker's lead investigator.Inter‐rater reliability for OCTA is assessed by distribution of OCTA datasets to each analysis site. Test‐retest repeatability is assessed by repeat OCTA imaging on individuals on the same day as their baseline OCTA and a different‐day repeat session after a short (1‐ to 14‐day) interval.Methods were developed to allow the OCTA data to be de‐identified by the sites before transmission to the central data management system. The MarkVCID neuroimaging protocols, like the other MarkVCID procedures, are designed to allow translation to multicenter trials and as a template for outside groups to generate directly comparable neuroimaging data. The MarkVCID neuroimaging protocols are available to the biomedical community and intended to be shared. In addition to the instrumental validation procedures described here, each of the neuroimaging MarkVCID kits will undergo biological validation to determine its ability to measure important aspects of VCID such as cognitive function. The analytic methods for the neuroimaging‐based kits and the results of these validation studies will be published separately. The results will ultimately determine the neuroimaging kits' potential usefulness for multicenter interventional trials in small vessel disease–related VCID. [ABSTRACT FROM AUTHOR]

Background: Experimental, clinical, and genetic epidemiological studies continue clarifying important aspects of Alzheimer's disease (AD) pathological development. Despite this progress the genetic mechanisms of AD regulation remain unclear. One problem that may contribute to slowing further progress in better understanding of these mechanisms deals with difficulties in replication of the results of genetic association studies. To overcome this problem the idea of using a gene‐based analysis in which all common variation within a candidate gene is considered jointly has been suggested. In this paper we investigate to what extent the use of gene‐based analyses resolves the non‐replication problem. Method: We performed gene‐level and meta‐analysis association studies for two cohorts: Cardiovascular Heart Study (CHS) and Framingham (FRAM) using Alzheimer's disease as a primary outcome. To support our findings, we also performed meta‐analysis following gene‐enrichment study for both cohorts. Analysis was performed separately for males and females and for both sexes. Additional covariates were age, smoking. Gene‐level analysis was performed with fastBAT and enrichment analysis with ClusterProfiler on KEGG database. Result: Our analysis identified a list of highly significant genes, such as TOMM40, APOC1 (all with FDR‐adjusted p‐value < 0.05) and pathways, such as Cholesterol metabolism, Fluid shear stress and atherosclerosis, Proteoglycans in cancer, Lipid and atherosclerosis showed statistically significant associations (FDR‐adjusted p‐value < 0.05) in both datasets and sexes. Meta‐analysis revealed TOMM40 (p‐value = 2.35E‐16), APOC1 (p‐value 4.46E‐13), ENSG00000259648 (p‐value = 8.88E‐06), PEX7 (p‐value = 4.40E‐05), ENSG00000287274 (p‐value = 5.38E‐05) genes for men and women combined; men exclusively revealed ENSG00000259648, TOMM40, and APOC1 (p‐value<1.75E‐05) and women TOMM40 and APOC1 (p‐value<6E‐08). Gene‐enrichment meta‐analysis revealed NOD‐like receptor signaling pathway (adjusted p‐value 3.23E‐07), Lipid and atherosclerosis (p‐value = 5.93E‐05), Yersinia (p‐value = 1.17E‐04) for men and women combined; for men only the pathways are Lipid and atherosclerosis (p‐value = 3.61E‐03), TGF‐beta signaling pathway (p‐value = 3.61E‐03), AGE‐RAGE signaling pathway in diabetic complications (p‐value = 5.18E‐03); and for women Cholesterol metabolism (p‐value = 3.49E‐07), Fatty acid degradation (p‐value = 1.04E‐06), PPAR signaling pathway (p‐value = 1.23E‐05). Conclusion: In this work we were able to identify statistically significant genes and pathways showed replication across the studies and are potentially useful for uncovering genetic mechanisms of AD. However, other things such as genetic heterogeneity may influence disease developing and needed further exploration. [ABSTRACT FROM AUTHOR]

Background: One of the great challenges facing clinical trial recruitment is to have a representative sample reflective of the diversity of the US population. While racial and ethnic minorities compromise 39% of the United States population, they only account for 2%‐16% of clinical trial participants.1 The aim of the FOCUS study was to collect cognitive testing data from a diverse population and develop normative ranges for Cognivue, the first FDA‐cleared computerized cognitive assessment device based on modern cognitive neuroscience. Cognivue Thrive provides a 5‐minute cognitive screen while Cognivue Clarity provides a 10‐minute comprehensive assessment, allowing both physicians and non‐physician clinicians to objectively and quantitatively access brain health beyond traditional paper and pencil cognitive tests. Method: Cognivue partnered with Velocity Clinical Research to lead the recruitment efforts for the FOCUS study. The enrollment goal included an objective to enroll a group resembling the racial, ethnic, gender, and educational makeup recorded in the 2020 U.S. census data. Study subjects were recruited through local community outreach, participant referrals, and advertising. Recruitment was stopped once goals for specific sub‐groups were reached, to model real‐world outcomes. Cognivue Thrive and Clarity were administered to assess scoring and normative ranges and compared against performance on other neuropsychological test batteries within the diverse study cohort. Result: The Cognivue/Velocity partnership resulted in recruitment of more than 1,500 subjects from 14 sites in 11 states with a mean age of 50.2±16.3y (range 18‐89), 59.2% female, and 51.8% with 12 years or less of education. Over 28% of subjects identified their race as Black or African American, American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, or other non‐white, and over 12% of participants identified as Hispanic or Latino. Conclusion: Working in collaboration with Velocity, a clinical research partner with study sites throughout the United States, Cognivue was able to reach a 37% research participation rate of historically underserved and underrepresented populations in the national FOCUS study. 1Clin Pharmacol Ther. 2015 Mar;97(3):263‐73. https://doi.org/10.1002/cpt.61. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is the second most common neurodegenerative disease and affects the lives of people around the world. Approximately 30% to 40% of people with Parkinson's disease also develop cognitive symptoms. Most notably impairments are observed in executive function, visuospatial abilities and memory are observed. An effective alternative to treat these symptoms is cognitive rehabilitation, but there are still too few publications presenting cognitive rehabilitation protocols for this population. The aim of the present study was to develop a rehabilitation protocol focused on cognitive symptoms in people with Parkinson's disease. Methods: A free search was conducted for publications on the topic of cognitive rehabilitation for people with Parkinson's disease and cognitive symptoms. From the reading of these studies, a set of exercises aimed at training executive functions, visuospatial skills and memory was then developed. Result: The elaborated protocol includes nine sessions of 60 minutes each. It should be used by appropriately trained healthcare professionals. The protocol consists of activities using paper and pencil, as essential materials, which means low application costs. The protocol includes activities aimed at training visuospatial skills (Figure 1), memory (Figure 2) and executive functions (working memory, reasoning, mental flexibility, problem solving and planning) (Figure 3) with an increasing level of difficulty. Conclusion: This study presents the formulation and scientific dissemination of a protocol that is easy to use, inexpensive and effective in the rehabilitation of these individuals. References: Aarsland, D., Batzu, L., Halliday, G. M., Geurtsen, G. J., Ballard, C., Ray Chaudhuri, K., & Weintraub, D. (2021). Parkinson disease‐associated cognitive impairment. Nature Reviews. Disease Primers, 7(1), 47. https://doi.org/10.1038/s41572‐021‐00280‐3 Balestrino, R., & Schapira, A. H. V. (2020). Parkinson disease. European Journal of Neurology, 27(1), 27‐42. https://doi.org/10.1111/ene.14108 [ABSTRACT FROM AUTHOR]

Background: The LEAD Guide (Life‐Planning in Early Alzheimer's and Other Dementias)1 is a validated paper‐based dementia‐focused advance care planning (ACP) guide that addresses changes in cognition and goals of care along the ADRD continuum, preparing surrogate decision‐makers for loss of the care recipient's decisional abilities. Achieving agreement on decision elements of ACP in care partner (CP)/care recipient (CR) dyads may reduce ambiguity, increase CP confidence, and assure that preferences and values are honored. Using multiple approaches, we developed a working definition of ACP concordance amongst ADRD dyads. Method: Using the LEAD Guide as the foundation we developed the pilot LEAD Intervention, a community‐based NIH Stage‐1 behavioral intervention.2 This 9‐month study guided CP/CR dyads through a dementia‐focused ACP process that integrates a digital version of the LEAD Guide with ACP educational modules delivered through a web‐based platform. Dyads had the option of recording their care conversation. To understand the process of achieving dyadic consensus in elements of ACP, we conducted a scoping review of the literature and a qualitative analysis of recorded interviews. Result: Of 61 eligible dyads, 41 completed the LEAD intervention; 7 in‐depth recordings were obtained. Our scoping review of 6,788 manuscripts identified no operational definitions of ACP concordance, 35 that revealed essential elements of successful discussion processes and only one that characterized essential qualities of CPs. Using descriptive analysis,3 seven themes illustrating agreement on ACP issues were discerned: Respect/Regard for each other; use of Clarifying Processes; Conveying Health Care Scenarios to justify wishes; Affirmation of Understanding; Recognizing Uncertainty; Humor and Expression of Positive Emotions; and Trust. Notably, all seven dyads voiced confidence that they "finished the discussion successfully," meaning reaching a state of concordance. Conclusion: Our synthesis of the research literature and our qualitative findings suggests that a working definition of ACP decision concordance is when the caregiver understands the patient's values that inform the preferences and choices of the patient, understands those choices and preferences and the rationale for the choices and preferences, and expresses a willingness to accomplish the patient's wishes to the best of their ability. This definition contributes to research clarity in ACP investigations. [ABSTRACT FROM AUTHOR]

Background: Promoting habitual physical activity (HPA; e.g. walking) may help decelerate dependency and disability in people with dementia (PwD). HPA refers to any movement the skeletal muscles make which requires energy expenditure, including daily tasks (e.g. gardening/housework). Research regarding physical activity in PwD mainly focuses on exercise‐based activities, which may not be feasible for people with chronic health conditions or frailty, or who cannot afford or travel to exercise classes. Promoting participation in HPA may be an inclusive, accessible strategy to support PwD to remain physically active and mobile. PwD participate in less HPA than recommended and disease‐specific factors (e.g. cognition) do not sufficiently explain this. In healthy ageing, HPA participation is associated with multiple socio‐ecological factors (e.g. psychosocial wellbeing/social support/environment) but this has not been explored in dementia. The ActivDem study aims to identify key socio‐ecological influences on HPA change over time in community‐dwellers with dementia. Figure 1 presents ActivDem's core objectives. Method: PwD and their carers will be recruited from the ongoing cohort study, DETERMIND, they will participate in a continuous seven‐day HPA assessment. This involves wearing an inertial measurement unit on their lower back at baseline and one‐year follow up. Digital mobility outcomes relating to volume (e.g. steps per day), pattern (e.g. mean ambulatory bout length), and variability (i.e. of bout length) will be derived via validated algorithms. PwD will also complete the LASA Physical Activity Questionnaire and Falls Efficacy Scale. Carers will complete the Dementia Management Strategies Scale. Demographic, clinical and psychosocial characteristics and information on care support will be assessed as part of the DETERMIND study (1). Result: Longitudinal statistical methods will identify key predictors of HPA change in PwD, and examine the relationship between HPA and independence Conclusion: The ActivDem study will identify key socio‐ecological predictors of HPA change, these will inform key interventional components to support PwD to remain physically active and mobile following diagnosis of dementia. References 1. Farina et al., 2020. DETERMinants of quality of life, care and costs, and consequences of INequalities in people with Dementia and their carers (DETERMIND): A protocol paper. Int. J. Geriatr. [ABSTRACT FROM AUTHOR]

Background: Mobile, valid and engaging cognitive assessments are essential for detecting and tracking change in research participants and patients at risk for Alzheimer's Disease and Related Dementias (ADRDs). This pilot study aims to determine the feasibility and generalizability of at‐home, app‐based cognitive assessments included in the mobile cognitive app performance platform (mCAPP), to detect cognitive changes associated with aging and preclinical AD. Method: The mCAPP includes three gamified tasks (Figure 1): (1) a "concentration" memory task that includes learning and matching hidden card pairs with increasing memory load, pattern separation features (lure vs. non‐lure), and spatial memory (2) a stroop‐like task ("brick drop") with speeded word and color identification and response inhibition components and (3) a digit‐symbol coding‐like task ("space imposters") with increasing pairs and incidental learning components. Participants completed the NACC UDS3 and additional paper and pencil tests. Participants used the mCAPP at home for two weeks. Participants included sixty older adults (73% female; age = 71.9±4.6, education = 16.6±2.4; 50% White, 48% Black/African American, 2% Multiracial) without cognitive impairment enrolled in the Penn ADRC cohort. Result: Participants played 12±5.1 sessions over two weeks for 11.5±2.8 min/session, with 68% playing more than the assigned sessions. Almost all participants (98%) used a smartphone and 62% played games on their phone. Usability rating was 6.3±0.8 (1‐7 scale) and most participants reported task difficulty was just right (70%‐95%). 68% reported preferring mobile device based cognitive assessment to standard in‐person cognitive batteries. All tasks showed lower performance with increasing cognitive load (p's<.05). Age and education correlated with both mCAPP and traditional cognitive measures. Concentration performance correlated with UDS3 memory measures and the PACC overall (p's<.05), however when examined by self‐identified racial group, relationships remained significant in White participants, but not in Black/African American participants (Figure 2). Brick drop performance correlated with the Stroop task (p<.05) and space imposters performance correlated with the Digit Symbol Substitution Test (p<.001) within all groups. Conclusion: This pilot study shows app usability for at‐home use in a diverse cohort of older adults. Performance across measures indicate initial reliability and validity of mCAPP with attention needed to differences in performance across participants with diverse sociodemographic backgrounds. [ABSTRACT FROM AUTHOR]

Background: Early screening for mild cognitive impairment (MCI) is the key method to prevent and delay dementia. Digital screening tools are more efficient than traditional paper‐and‐pencil cognitive assessments, and gamified versions would promote engagement and completion rates. We introduced here the design and development of the Game‐based Cognitive Assessment ‐ 3 Minute Version (G3) WeChat mini‐program for MCI screening in Chinese older adults. Method: G3 is a battery of three one‐minute digital games built within the WeChat platform. Developed based on the cognitive paradigm and classic neuropsychological tests such as Trail Making Test (TMT), the Silhouettes test, the Brief Visuospatial Memory Test‐Revised (BVMT‐R) test, and California Card Sorting Tests (CCST), the G3 mini‐games, "Number Ordering", "Species Sorting", and "Gold finding" would measure the computational and executive function, abstractive function and visual perception, memory, and attention, respectively. In each game, the difficulty will be automatically adjusted according to performance. G3 integrates users' game scores, age, gender, and education levels, to generate a comprehensive assessment of cognitive function with results of the six cognitive domains (Figure 2). Result: As of August 31, 2022, more than 11 million users have completed G3 tests, 85.38% of them are aged under 40, and 2.05% of them are aged over 60 (Figure 3). Although people in all age groups have desired to know their cognitive function, the number of users decreased as people aged. Among users aged 40‐70, more females than males participated in G3 games, indicating middle‐aged and older women paid more attention to cognitive function. Among users over 45 years old, those of lower education levels (primary school or no education), middle levels (middle or high school), and university degrees accounted for 2.93%, 32.4%, and 59.65% respectively. The completion rate of users aged over 45 is 92.28%, and those over 80 years exceeded 86%. Conclusion: The G3 was a battery of three novel 1‐minute game‐based digital cognitive tests. The process is simple, efficient, and interesting. It is a promising tool for self‐administering, advancing large‐scale community screening, and social education for MCI in Chinese older adults, warranting further clinical trials to validate its feasibility, sensitivity, and diagnostic value. [ABSTRACT FROM AUTHOR]