Biomarker-Integrated Digital Guidance for Early Alzheimer's Detection (BRIDGE-AD): A Nationwide Multicenter Study

Background: Cognitive impairment represents a spectrum of conditions affecting memory, reasoning, and daily functioning, with Alzheimer's disease (AD) constituting 60-80% of dementia cases globally. The worldwide burden of AD has reached 56.9 million cases, with projections indicating this will escalate dramatically due to population aging, particularly in low- and middle-income countries which will bear 65% of the economic burden by 2050.

The progression of AD typically involves a prolonged preclinical phase lasting 15-20 years before symptom onset. This extended window, coupled with the mild cognitive impairment stage, presents critical opportunities for early intervention. Contemporary diagnostic paradigms have shifted from symptom-based to pathology-driven criteria, enabling detection through biomarkers during asymptomatic phases. Community settings serve as ideal platforms for population-wide monitoring, where systematic screening combined with interventions like lifestyle modifications and cognitive training may also delay disease progression.

Current cognitive impairment screening systems face considerable challenges in terms of accuracy, efficiency, and scalability. Standard neuropsychological assessments are constrained by practice effects, subjective scoring, limited sensitivity to early cognitive changes, and the need for trained professionals. Emerging digital tools can improve testing efficiency and maintain high accuracy, offering benefits such as automated scoring and reduced reliance on specialized personnel. Meanwhile, predicting the future risk of dementia in cognitively normal individuals could enable personalized monitoring strategies. In the era of disease-modifying therapies, early detection of AD pathology is essential for initiating timely interventions. Therefore, there is an urgent need for accessible, scalable, and cost-effective screening approaches that can detect both cognitive symptoms and AD pathology, particularly in aging populations and resource-limited settings where the burden of dementia is growing most rapidly.

Our research proposes a stepwise screening approach. The first step involves rapid digital pre-screening of cognitive function through three components: the SCD-9 questionnaire to capture subjective cognitive complaints, a digital cognitive assessment to evaluate objective performance, and a predictive model to estimate future dementia risk in cognitively normal individuals. The second step confirms the presence of AD pathology using blood-based biomarkers, with a head-to-head comparison of multiple novel candidates to identify those with the greatest diagnostic utility.

Research Objective: Develop a screening and diagnostic pathway integrating digital cognitive tools and blood biomarkers for early detection of AD-related cognitive impairment in community populations.