Scalable plasma and digital cognitive markers for diagnosis and prognosis of Alzheimer's disease and related dementias.

INTRODUCTION: With 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. METHODS: We 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 ß positive (Aß+) 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). RESULTS: Combination of plasma pTau181, Aß42/40, neurofilament light (NfL), and TabCAT-BHA was optimal for predicting Aß-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. DISCUSSION: Combinations of plasma and digital cognitive markers show promise for scalable diagnosis and prognosis of ADRD. HIGHLIGHTS: The 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.

Facilitators and Barriers to Dementia Assessment and Diagnosis: Perspectives From Dementia Experts Within a Global Health Context.

Objectives: Dementia poses one of the greatest global health challenges, affecting 50 million people worldwide. With 10 million new cases each year, dementia is a growing burden, particularly in low- and middle-income countries (LMIC). This study aimed to identify the facilitators and barriers to providing quality dementia assessment and care in LMICs from a global health perspective. Methods/Design: A qualitative semi-structured interview study with 20 dementia expert healthcare providers from 19 countries. To be included, providers had to: practice dementia assessment or care in LMICs where the population over age 60 is projected to more than double by 2050 and be recognized as a leading dementia expert in the region based on position, research publications, and/or policy leadership. Interviews were analyzed by a multidisciplinary team of researchers using thematic analysis. Results: Barriers to dementia assessment and care included stigma about dementia, poor patient engagement in and access to healthcare, inadequate linguistic and cultural validation, limited dementia capable workforce, competing healthcare system priorities, and insufficient health financing. Facilitators included the rise in dementia awareness campaigns, dementia training for general practitioners, availability of family support and family caregivers, and national and international collaborations including coordinated policy efforts and involvement in international research initiatives. Conclusions: Findings from this study provide insights for prioritizing dementia assessment and care capacity-building in LMICs as a global health priority and for tailored public health approaches to strengthen dementia assessment and care at the individual, community, national, and multi-national levels.

Detecting Alzheimer's disease biomarkers with a brief tablet-based cognitive battery: sensitivity to Aß and tau PET.

BACKGROUND: ß-amyloid (Aß) and tau positron emission tomography (PET) detect the pathological changes that define Alzheimer's disease (AD) in living people. Cognitive measures sensitive to Aß and tau burden may help streamline identification of cases for confirmatory AD biomarker testing. METHODS: We examined the association of Brain Health Assessment (BHA) tablet-based cognitive measures with dichotomized Aß -PET status using logistic regression models in individuals with mild cognitive impairment (MCI) or dementia (N = 140; 43 Aß-, 97 Aß+). 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 Aß+ individuals with MCI or dementia. RESULTS: Favorites (associative memory), Match (executive functions and speed), and Everyday Cognition Scale scores were significantly associated with Aß 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. CONCLUSION: The BHA measures are significantly associated with both Aß and regional tau in vivo imaging markers and could be used for the identification of patients with suspected AD pathology in clinical practice.

Global Perspectives on Brief Cognitive Assessments for Dementia Diagnosis.

BACKGROUND: Timely diagnosis of dementia is a global healthcare priority, particularly in low to middle income countries where rapid increases in older adult populations are expected. OBJECTIVE: To investigate global perspectives on the role of brief cognitive assessments (BCAs) in dementia diagnosis, strengths and limitations of existing measures, and future directions and needs. METHODS: This is a qualitative study of 18 dementia experts from different areas of the world. Participants were selected using purposeful sampling based on the following criteria: 1) practicing in countries with projected growth of older adult population of over 100%by 2050; 2) expertise in dementia diagnosis and treatment; 3) involvement in clinical practice and training; and 4) recognition as a national dementia expert based on leadership positions within healthcare system, research, and/or policy work. Participants were individually interviewed in their language of choice over secure videoconference sessions. Interviews were analyzed by a multidisciplinary team using theme identification approach. RESULTS: Four domains with subthemes emerged illustrating participants' perspectives: 1) strengths of BCAs; 2) limitations of BCAs; 3) needs related to the use of BCAs; and 4) characteristics of an ideal BCA. While most experts agreed that BCAs were important and useful for dementia diagnosis, the themes emphasized the need for development and validation of novel measures that are sensitive, psychometrically sound, and culturally appropriate. CONCLUSION: BCAs are important for guiding diagnosis and care for dementia patients. Findings provide a roadmap for novel BCA development to assist in diagnostic decision making for clinicians serving a rapidly growing and diverse dementia population.

BHA-CS: A novel cognitive composite for Alzheimer's disease and related disorders.

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 (Aß) burden in the CN subgroup with Aß 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 Aß-positive group showed worse longitudinal performance on the BHA-CS compared to the Aß-negative group. DISCUSSION: The BHA-CS is sensitive to cognitive decline in preclinical and prodromal neurodegenerative disease.