Objectives

Preclinical Alzheimer's disease (AD) clinical trials screen cognitively unimpaired older adults for biomarker criteria and disclose their results. We examined whether participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease Study with "elevated" and "not elevated" amyloid differed in scores on the "Views and Perceptions of Amyloid Imaging" questionnaire. We hypothesized that, prior to disclosure, those with elevated amyloid would score higher than those with not elevated amyloid. We also quantified how responses changed after result disclosure.

Methods

We assessed data from 4327 individuals who completed the questionnaire at screening visit 1 and after amyloid disclosure. We used linear regression models to assess the relationship between questionnaire category scores and amyloid status. We also quantified the relationship between category score changes and amyloid status.

Results

Overall, participants scored altruism and contribution to research as the strongest motivations for undergoing amyloid imaging. Those with elevated amyloid scored 0.23 points higher in the Perceived Risk category, on average, than those who had not elevated amyloid prior to disclosure; this effect attenuated towards zero after adjusting for Cognitive Function Instrument score. After disclosure, participants with elevated amyloid demonstrated less within-subject change in Perceived Risk, on average, compared to those with similar pre-disclosure scores who had not elevated amyloid, while demonstrating greater changes in the altruism and planning categories.

Interpretation

Altruism and learning disease risk motivated enrollment in this preclinical AD trial. Participants with elevated amyloid differed from their not elevated counterparts in their perceptions of amyloid imaging, even before undergoing the procedure.

Background

Preclinical Alzheimer's disease (AD) clinical trials require participants to enroll with a study partner, a person who can attend visits and report changes in the participant's cognitive ability. Whether study partners, compared to participants themselves, provide added information about participant cognition in preclinical AD trials is an open question. We tested the hypothesis that study partners provide meaningful information related to participant cognition cross-sectionally and longitudinally, and assessed whether amyloid status modified observed effects.

Methods

We assessed participant and study partner Everyday Cognition (ECog) scores and participant Alzheimer's Disease Assessment Scale 13-item cognitive subscale (ADAS13) data from 335 cognitively normal participant-partner dyads in the AD Neuroimaging Initiative. We used random forest and linear mixed effects (LME) models to predict ADAS13 scores as a function of participant and/or study partner ECog scores over time. LME models were adjusted for potential confounding factors, including APOE4 status, amyloid status, baseline age, years of education, and sex. Random forest models were split into the above factors, as well as race/ethnicity and other available neuropsychological battery test scores.

Results

In random forest models predicting ADAS13 12 months from baseline, we observed no difference in the estimated mean variable importance (eMVI) associated with baseline study partner ECog compared to the baseline participant ECog (eMVI = 0.15, 95%CB 0.13, 0.16 for partner; eMVI = 0.15, 95%CB 0.14, 0.16 for participant). In models predicting ADAS13 48 months after baseline, the eMVI associated with baseline study partner ECog was slightly lower than that associated with baseline participant ECog (eMVI = 0.21, 95%CB 0.20, 0.22 for partner; eMVI = 0.24, 95%CB 0.22, 0.25 for participant). In cross-sectional models, study partner eMVI was twice as large as participant eMVI at 12 months (eMVI = 0.20, 95%CB 0.19, 0.21 for partner; eMVI = 0.09, 95%CB 0.09, 0.10 for participant) and three times as large at 48 months (eMVI = 0.38, 95%CB 0.36, 0.39 for partner; eMVI = 0.13, 95%CB 0.12, 0.14 for participant). We did not observe qualitative differences by amyloid status.

Conclusions

While baseline participant reports reasonably predict subsequent cognitive change, informants perform better at cross-sectionally recognizing cognitive status as observation time grows. The study partner requirement may be essential to ensure trial data integrity, especially in longer trials.

Introduction

The apolipoprotein E (APOE) gene is the strongest known genetic risk factor for sporadic Alzheimer disease (AD). APOE can be used as an enrichment strategy or inclusion criterion for AD prevention trials. Personal genomics companies market direct-to-consumer (DTC) genetic tests, including APOE. We assessed DTC APOE testing usage among enrollees of the University of California Irvine Consent-to-Contact Registry, an online recruitment registry, and attitudes toward using this information in clinical trial recruitment.

Methods

We emailed links to an electronic survey to registry enrollees age 50 years or older. We assessed participants' use of DTC services, willingness to learn APOE status, and willingness to share genetic information. Logistic regression models assessed relationships between DTC testing usage and demographic characteristics, and with willingness to share results to assist trial recruitment.

Results

Among 1312 responders (57% response rate), few (7%) had used DTC testing for APOE. Non-Hispanic Asian enrollees were 93% less likely to have used DTC testing, compared with non-Hispanic Whites [95% confidence interval: (0.01, 0.67)]. Willingness to share APOE information for study recruitment was >90% for both users and nonusers.

Conclusions

Matching participants to trials on the basis of DTC APOE information may be an effective way to streamline AD prevention trial recruitment.