Mild cognitive impairment and dementia are underrecognized in primary care, contributing to delayed diagnosis and limited access to care. Growing research has focused on improving cognitive evaluation in primary care, including the development of digital cognitive assessments (DCAs), which are emerging as scalable tools to expand access to testing and improve assessment accuracy. The Global CEO Initiative on Alzheimer's Disease convened a DCA Workgroup to develop expert recommendations for implementing supervised, in‐clinic DCAs within US clinical workflows. Intended for primary care healthcare professionals and relevant specialists, these recommendations outline implementation pathways that support recognition, diagnostic evaluation, and care planning across primary and specialty care. The recommendations define core implementation steps while allowing context‐specific adaptation and address operational, clinical, and structural facilitators and barriers to adoption. Integrating DCAs into clinical practice may improve timeliness of evaluation, enable earlier intervention, reduce specialty care bottlenecks, and promote more efficient use of healthcare resources.
P. Tariot, Darren R. Gitelman, Ishtar Govia et al.· Alzheimer's & Dementia· 0 citations
Importance
Blood-based biomarkers for Alzheimer disease, particularly plasma phosphorylated tau 217 (p-tau217), accurately reflect early Alzheimer disease brain pathology in cognitively unimpaired individuals, but estimates of absolute risk of progression to cognitive impairment across multiple cohorts are needed.
Objective
To estimate absolute risk of progression to cognitive impairment and rates of cognitive decline based on plasma p-tau217 across cognitively unimpaired older adults.
Design, Setting, and Participants
Longitudinal cohort study using harmonized data from 2684 cognitively unimpaired older adults (defined within cohort) across 6 observational and clinical trial cohorts based in North America, Japan, and Australia. The earliest enrollment was in 2004, with most recent follow-up in 2025.
Exposure
Baseline plasma p-tau217.
Main Outcomes and Measures
The primary outcome was time to progression to cognitive impairment (mild cognitive impairment, dementia, or 2 consecutive global Clinical Dementia Rating scores ≥0.5). The secondary outcome was longitudinal change on the latent Preclinical Alzheimer Cognitive Composite (PACC; higher values indicate better performance).
Results
Among the 2684 participants (median [IQR] age, 69.6 [66.2-74.2] years; 1697 [63%] female), there were 478 events of progression to cognitive impairment over a median follow-up of 5.4 years (maximum follow-up of 13.5 years). Each 1-SD increase in baseline p-tau217 level was associated with an increased risk of progression to cognitive impairment (hazard ratio, 1.38 [95% CI, 1.30-1.46]), and the association remained significant after adjustment, including β-amyloid positron emission tomography scan Centiloids (hazard ratio, 1.32 [95% CI, 1.24-1.41]). Participants with high (1.1-2.4 SD) and very high (>2.5 SD) baseline p-tau217 had 24% (95% CI, 20%-28%) and 38% (95% CI, 33%-43%) absolute risk of progression over 5 years, respectively, and risk was markedly higher over 10 years, although longer-term estimates were constrained by limited data. Elevated p-tau217 was also associated with faster cognitive decline based on change in latent PACC score. Among the overall sample, baseline latent PACC scores ranged from -0.8 to 2.7. The 5-year annualized decline for the very high p-tau217 group was -0.07 latent PACC units/y (95% CI, -0.10 to -0.05), relative to 0.03 units/y (95% CI, 0.02-0.04) in the low p-tau217 group.
Conclusions and Relevance
In a pooled sample of multiple selected cohorts of cognitively unimpaired older adults, higher plasma p-tau217 levels were consistently associated with increased risk of clinical progression and accelerated cognitive decline. By providing time-specific absolute risk estimates, these findings support the potential of p-tau217 for prognostic model development, with direct implications for future trial design. Further validation in unselected populations is needed to inform individual prognosis and clinical decision-making in cognitively unimpaired individuals.
R. Buckley, D. Townsend, C. Birkenbihl et al.· Journal of the American Medi...· 1 citation
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