Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings

Abstract

Background: Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods: We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research inperson cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results: A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95-0.99]), high education (OR = 1.64 [1.23-2.17]), male sex (OR = 1.56 [1.19-2.04]), and positive family history of dementia (OR = 1.66 [1.19-2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02-1.10]) and APOE ɛ4 allele carriership (OR = 2.99 [1.81-4.94]). These results were similar across prescreen settings.

Predicting amyloid status using self‐report information from an online research and recruitment registry: The Brain Health Registry

“…Other groups have explored the predictive abilities of self‐reported data; however, those studies used information collected in‐clinic. The discriminative abilities of our online models was comparable to previous in‐clinic prediction models, with AUCs from in‐clinic predictive models ranging from 0.51 to 0.70 34,35,46,47 . Comparisons to previous in‐clinic models are limited by the fact that these studies varied in: (1) the diagnostic groups included (CU, subjective memory concern, MCI, dementia, or combined diagnostic groups), (2) how the Aβ status was determined (PET or CSF), (3) the degree of validation (no validation, internal validation, and external validation), and (4) inclusion of specific self‐reported predictors.…”

NIA‐AA Alzheimer's Disease Framework: Clinical Characterization of Stages

“…These data suggest that ΔNBS may not be a useful element by which to classify individuals on the AD spectrum and raise questions about the appropriateness of this measure in the AD framework. In addition, NBS, such as depression, may actually improve over time making it a less reliable feature of AD 31 …”

“…In addition, NBS, such as depression, may actually improve over time making it a less reliable feature of AD. 31 …”

Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort

“…Exclusion criteria were the presence of conditions associated with neurodegeneration or affecting cognition, Clinical Dementia Rating (CDR) ≥1, contraindications to MRI or lumbar puncture, and cancer or history of cancer in the preceding 5 years. After obtaining written informed consent, a screening visit was conducted to check whether the study participants fulfilled these criteria, 18 , 19 and 144 participants were excluded (Figure S2 in supporting information). Demographic details were collected.…”