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IntroductionWith emergence of disease-modifying therapies, efficient diagnostic pathways are critically needed to identify treatment candidates, evaluate disease severity, and support prognosis. A combination of plasma biomarkers and brief digital cognitive assessments could provide a scalable alternative to current diagnostic work-up.MethodsWe examined the accuracy of plasma biomarkers and a 10-minute supervised tablet-based cognitive assessment (Tablet-based Cognitive Assessment Tool Brain Health Assessment [TabCAT-BHA]) in predicting amyloid β positive (Aβ+) status on positron emission tomography (PET), concurrent disease severity, and functional decline in 309 older adults with subjective cognitive impairment (n = 49), mild cognitive impairment (n = 159), and dementia (n = 101).ResultsCombination of plasma pTau181, Aβ42/40, neurofilament light (NfL), and TabCAT-BHA was optimal for predicting Aβ-PET positivity (AUC = 0.962). Whereas NfL and TabCAT-BHA optimally predicted concurrent disease severity, combining these with pTau181 and glial fibrillary acidic protein was most accurate in predicting functional decline.DiscussionCombinations of plasma and digital cognitive markers show promise for scalable diagnosis and prognosis of ADRD.HighlightsThe need for cost-efficient diagnostic and prognostic markers of AD is urgent. Plasma and digital cognitive markers provide complementary diagnostic contributions. Combination of these markers holds promise for scalable diagnosis and prognosis. Future validation in community cohorts is needed to inform clinical implementation.

Backgroundβ-amyloid (Aβ) and tau positron emission tomography (PET) detect the pathological changes that define Alzheimer's disease (AD) in living people. Cognitive measures sensitive to Aβ and tau burden may help streamline identification of cases for confirmatory AD biomarker testing.MethodsWe examined the association of Brain Health Assessment (BHA) tablet-based cognitive measures with dichotomized Aβ -PET status using logistic regression models in individuals with mild cognitive impairment (MCI) or dementia (N = 140; 43 Aβ-, 97 Aβ+). We also investigated the relationship between the BHA tests and regional patterns of tau-PET signal using voxel-wise regression analyses in a subsample of 60 Aβ+ individuals with MCI or dementia.ResultsFavorites (associative memory), Match (executive functions and speed), and Everyday Cognition Scale scores were significantly associated with Aβ positivity (area under the curve [AUC] = 0.75 [95% CI 0.66-0.85]). We found significant associations with tau-PET signal in mesial temporal regions for Favorites, frontoparietal regions for Match, and occipitoparietal regions for Line Orientation (visuospatial skills) in a subsample of individuals with MCI and dementia.ConclusionThe BHA measures are significantly associated with both Aβ and regional tau in vivo imaging markers and could be used for the identification of patients with suspected AD pathology in clinical practice.

BackgroundRapid technological advances offer a possibility to develop cost-effective digital cognitive assessment tools. However, it is unclear whether these measures are suitable for application in populations from Low and middle-income countries (LMIC).ObjectiveTo examine the accuracy and validity of the Brain Health Assessment (BHA) in detecting cognitive impairment in a Cuban population.MethodsIn this cross-sectional study, 146 participants (cognitively healthy = 53, mild cognitive impairment (MCI) = 46, dementia = 47) were recruited at primary care and tertiary clinics. The main outcomes included: accuracy of the BHA and the Montreal Cognitive Assessment (MoCA) in discriminating between controls and cognitively impaired groups (MCI and dementia) and correlations between the BHA subtests of memory, executive functions, and visuospatial skills and criterion-standard paper-and-pencil tests in the same domains.ResultsThe BHA had an AUC of 0.95 (95% CI: 0.91-0.98) in discriminating between controls and cognitively impaired groups (MCI and dementia, combined) with 0.91 sensitivity at 0.85 specificity. In discriminating between control and MCI groups only, the BHA tests had an AUC of 0.94 (95% CI: 0.90-0.99) with 0.71 sensitivity at 0.85 specificity. Performance was superior to the MoCA across all diagnostic groups. Concurrent and discriminant validity analyses showed moderate to strong correlations between the BHA tests and standard paper-and-pencil measures in the same domain and weak correlations with standard measures in unrelated domains.ConclusionThe BHA has excellent performance characteristics in detecting cognitive impairment including dementia and MCI in a Hispanic population in Cuba and outperformed the MoCA. These results support potential application of digital cognitive assessment for older adults in LMIC.

IntroductionComposite scores based on psychometrically rigorous cognitive assessments are well suited for early diagnosis and disease monitoring.MethodsWe developed and cross-validated the Brain Health Assessment-Cognitive Score (BHA-CS), based on a brief computerized battery, in 451 cognitively normal (CN) and 399 cognitively impaired (mild cognitive impairment [MCI] or dementia) older adults. We investigated its long-term reliability and reliable change indices at longitudinal follow-up (N = 340), and the association with amyloid beta (Aβ) burden in the CN subgroup with Aβ positron emission tomography (N = 119).ResultsThe BHA-CS was accurate at detecting cognitive impairment and exhibited excellent long-term stability. Reliable decline over one year was detected in 75% of participants with dementia, 44% with MCI, and 3% of CN. Among CN, the Aβ-positive group showed worse longitudinal performance on the BHA-CS compared to the Aβ-negative group.DiscussionThe BHA-CS is sensitive to cognitive decline in preclinical and prodromal neurodegenerative disease.

Background/objectivesBrief cognitive screens lack the sensitivity to detect mild cognitive impairment (MCI) or support differential diagnoses. The objective of this study was to validate the 10-minute, tablet-based University of California, San Francisco (UCSF) Brain Health Assessment (BHA) to overcome these limitations.DesignCross-sectional.SettingUCSF Memory and Aging Center.ParticipantsOlder adults (N = 347) (neurologically healthy controls (n = 185), and individuals diagnosed with MCI (n = 99), dementia (n = 42), and as normal with concerns (n = 21)).MeasurementsThe BHA includes subtests of memory, executive function and speed, visuospatial skills, and language and an optional informant survey. Participants completed the Montreal Cognitive Assessment (MoCA) and criterion-standard neuropsychological tests. Standardized structural 3T brain magnetic resonance imaging was performed in 145 participants.ResultsAt a fixed 85% specificity rate, the BHA had 100% sensitivity to dementia and 84% to MCI; the MoCA had 75% sensitivity to dementia and 25% to MCI. The BHA had 83% sensitivity to MCI likely due to AD and 88% to MCI unlikely due to AD, and the MoCA had 58% sensitivity to MCI likely AD and 24% to MCI unlikely AD. The BHA subtests demonstrated moderate to high correlations with the criterion-standard tests from their respective cognitive domains. Memory test performance correlated with medial temporal lobe volumes; executive and speed with frontal, parietal, and basal ganglia volumes; and visuospatial with right parietal volumes.ConclusionThe BHA had excellent combined sensitivity and specificity to detect dementia and MCI, including MCI due to diverse etiologies. The subtests provide efficient, valid measures of neurocognition that are critical in making a differential diagnosis.

Objective Progressive word-finding difficulty is a primary cognitive complaint among healthy older adults and a symptom of pathological aging. Classic measures of visual confrontation naming, however, show ceiling effects among healthy older adults. To address the need for a naming test that is sensitive to subtle, age-related word-finding decline, we developed the Rapid Naming Test (RNT), a computerized, one-minute, speeded visual naming test. Method Functionally intact older (n = 145) and younger (n = 69) adults completed the RNT. Subsets of older adults also completed neuropsychological tests, a self-report scale of functional decline, amyloid-β PET imaging, and repeat RNT administration to determine test-retest reliability. Results RNT scores were normally distributed and exhibited good test-retest reliability. Younger adults performed better than older adults. Within older adults, lower scores were associated with older age. Higher scores correlated with measures of language, processing speed, and episodic learning and memory. Scores were not correlated with visuospatial or working memory tests. Worse performance was related to subjective language decline, even after controlling for a classic naming test and speed. The RNT was also negatively associated with amyloid-β burden. Conclusions The RNT appears to be a reliable test that is sensitive to subtle, age-related word-finding decline. Convergent and divergent validity are supported by its specific associations with measures relying on visual naming processes. Ecological validity is supported by its relationship with subjective real-world language difficulties. Lastly, worse performance was related to amyloid-β deposition, an Alzheimer's disease biomarker. This study represents a key step toward validating a novel, sensitive naming test in typically aging adults. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence of early cognitive changes associated with Alzheimer's disease (AD) biomarker burden. While changes in CSF phosphorylated tau (p‐tau) and Aβ42 levels have been shown to precede onset of clinical symptoms by 15‐20 years, preclinical cognitive changes remain poorly understood, particularly in multinational cohorts. In this study, we leveraged the data from the multisite European Prevention of Alzheimer's Dementia (EPAD) consortium (France, Netherlands, Spain, United Kingdom) to investigate cross‐sectional and longitudinal associations between cognitive performance and gold standard AD CSF biomarkers (p‐tau/Aβ42 ratio). Method: Participants were 811 clinically normal older adults (age: 65.1±6.8; education: 14.4±3.7; 57% female) who completed a battery of digital cognitive tests of working memory, inhibitory control, and associative memory (TabCAT, University of California San Francisco) in addition to CSF Aβ42 and p‐tau‐181 (Roche Elecsys®). Additionally, 114 of these participants completed both cognitive and biomarker studies at 1‐year follow‐up (age: 65.4±5.9; education: 13.2±3.5; 54% female). Cross‐sectional associations between p‐tau/Aβ42 ratio and cognitive performance were examined using multiple linear regression models, and longitudinal associations were examined using linear mixed effects models. All analyses covaried for age, sex, education, hippocampal volume, and APOE ε4 status. Longitudinal analyses additionally covaried for time since baseline. Result: At baseline, greater p‐tau/Aβ42 ratio was related to poorer performance on tasks of working memory (B=‐0.57, SE= 0.24, t=‐2.31, P=.02) and inhibitory control (B=‐0.45, SE=0.25, t=‐1.82, P=.06), but not on a task of associative memory (B=‐0.30, SE=0.26, t=‐1.13, P=.23). Longitudinal analyses showed that increases in p‐tau/Aβ42 ratio were significantly associated with decline in associative memory performance only (B=‐1.14, SE=0.52, t=‐2.20, P=.03). Conclusion: In summary, we found that greater AD biomarker burden was cross‐sectionally associated with poorer executive performance, while longitudinal increase in biomarker burden was related to greater decline in memory. Our findings contribute to the growing literature on the cognitive characteristics of preclinical AD and provide support for the hypothesis of an early impairment in attentional/executive processes, followed by a breakdown in memory functions as the pathological changes progress. A particular strength of our results is their potential generalizability in international cohorts and global studies of preclinical AD. [ABSTRACT FROM AUTHOR]

Introduction: Composite scores based on psychometrically rigorous cognitive assessments are well suited for early diagnosis and disease monitoring., Methods: We developed and cross-validated the Brain Health Assessment-Cognitive Score (BHA-CS), based on a brief computerized battery, in 451 cognitively normal (CN) and 399 cognitively impaired (mild cognitive impairment [MCI] or dementia) older adults. We investigated its long-term reliability and reliable change indices at longitudinal follow-up (N = 340), and the association with amyloid beta (Aβ) burden in the CN subgroup with Aβ positron emission tomography (N = 119)., Results: The BHA-CS was accurate at detecting cognitive impairment and exhibited excellent long-term stability. Reliable decline over one year was detected in 75% of participants with dementia, 44% with MCI, and 3% of CN. Among CN, the Aβ-positive group showed worse longitudinal performance on the BHA-CS compared to the Aβ-negative group., Discussion: The BHA-CS is sensitive to cognitive decline in preclinical and prodromal neurodegenerative disease., Competing Interests: No authors reported competing interests relevant to this study. Dr. La Joie has received research funding from the Alzheimer's Association. Dr. Rabinovici has received consulting fees or speaking honoraria from GE Healthcare, Axon Neurosciences, Merck, Eisai, Roche, and Genentech; grants from Avid Radiopharmaceuticals, Eli Lilly and Company, GE Healthcare, Life Molecular Imaging; and research funding from the National Institutes of Health (NIH), the Rainwater Charitable Foundation, and the Alzheimer's Association. Dr. Miller has received research funding from the NIH; serves as Medical Director for the John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation (ABF). Dr. Tomaszewski Farias has received research funding from the NIH. Dr. Kramer has received research funding from the NIH and the Larry L. Hillblom Foundation and royalties from Pearson Education, Inc. Dr. Rankin has received research funding from the NIH, Quest Diagnostics, the Rainwater Charitable Foundation, the Weill Family Foundation, and the Marcus Foundation. Dr. Possin has received research funding from the NIH, Quest Diagnostics, the Global Brain Health Institute, the Merck Foundation, and the Rainwater Charitable Foundation. No other disclosures were reported., (© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer's Association.)