REAL AD-Validation of a realistic screening approach for early Alzheimer's disease

Abstract

Early diagnosis is crucial to treatment success. This is especially relevant for Alzheimer's disease (AD), with its protracted preclinical phase. Most health care systems do not have the resources to conduct large-scale AD screenings in middle-aged individuals in need of novel AD treatment options and early, accurate diagnosis. Recent developments in blood-based biomarkers and remote cognitive testing offer novel, cost-effective, and scalable methods to detect cognitive and biomarker changes that may indicate early AD. In research cohorts, promising results have been reported, but these modalities have not been validated in population-based settings. The validation of a realistic screening approach for early Alzheimer's disease (REAL AD) study aims to validate the diagnostic and prognostic performance of the combined use of blood-based biomarkers and remote cognitive testing as a screening approach for early AD employing an existing health care infrastructure (the Swedish Västra Götaland Region Primary Healthcare). REAL AD aims to provide a concrete, individualized diagnostic framework, which could significantly improve AD prognosis. HIGHLIGHTS: In Sweden, most Alzheimer's disease (AD) diagnoses are made in primary care, where access to AD biomarkers is almost non-existent. Most health care systems have limited resources for the screening of middle-aged adults for early evidence of AD pathology. Blood-based biomarkers and remote cognitive testing offer novel, cost-effective, and scalable methods for detecting cognitive and biomarker changes that may indicate early AD. The REAL AD study aims to validate the diagnostic and prognostic performance of blood-based biomarkers and remote cognitive testing as a screening approach for early AD in an existing primary health care infrastructure in the Västra Götaland Region in Sweden. Studies such as REAL AD will play a vital role in helping to move the field toward concrete implementation of biomarkers in AD diagnostic workup at all care levels, eventually providing more comprehensive treatments options for the large and growing AD population, and for those at risk.

Keywords: Alzheimer's disease; blood‐based biomarkers; digital biomarker; primary care; screening.

FIGURE 1

Overview of the screening study design. Each of the four steps in the screening study encompasses multiple data collection points: baseline, 18‐, 27‐, and 36‐month follow‐up for steps 1 (questionnaires about basic health, demographic, and lifestyle information) and 2 (remote cognitive testing), as well as the optional questionnaires on lifestyle factors, baseline and 18 months for step 3 (blood sampling).

FIGURE 2

Map of the Västra Götaland Region (VGR) primary care centers involved in REAL AD. Location of the VGR in Sweden and distribution of public primary care centers taking part in REAL AD across the region.

FIGURE 3

Overview of the overall study design including the validation sub‐study. After the baseline screening phase has been completed (top panel), participants will be recruited to the validation sub‐study (bottom panel) and undergo the following examinations at baseline and on a follow‐up occasion 48 months later: Neuropsychological testing, blood and CSF sampling, clinical assessment, structural and functional MRI, as well as tau PET using [¹⁸F]RO948.