Alzheimer's Disease Biomarker Decision-Making among Patients with Mild Cognitive Impairment and Their Care Partners.

BACKGROUND: Alzheimer's disease (AD) biomarker tests can be ordered as part of the diagnostic workup of patients with mild cognitive impairment (MCI). Little is known about how patients with MCI and their care partners decide whether to pursue testing. OBJECTIVE: To examine factors that influence AD biomarker testing decisions among patients with MCI and their care partners. DESIGN: We performed structured research interviews with patients with MCI and their study partners to assess the importance of eight factors in the decision whether to undergo AD biomarker testing (6-point Likert scale; 1-extremely unimportant to 6-extremely important): cost, fear of testing procedures, learning if AD is the cause of cognitive problems, concern about health insurance, instructing future planning, informing treatment decisions, family members' opinions, and doctor recommendation. SETTING: Two researchers administered interviews with participants in-person (i.e., participant home, research center) or remotely (i.e., telephone, video-conference). PARTICIPANTS: We completed interviews with 65 patients with a diagnosis of MCI and 57 study partners, referred by dementia specialist clinicians from the University of California, Irvine health system. MEASUREMENTS: We used generalized estimating equations (GEE) to examine the mean importance of each factor among patients and study partners, and the mean difference in importance of each factor within dyads. RESULTS: One third of participants reported the patient had previously undergone AD biomarker testing. Fifty-five percent of patients and 65% of study partners who reported no previous testing indicated a desire for the patient to be tested. GEE analyses found that patients and study partners rated the following factors with highest importance: informing treatment decisions (mean score 5.29, 95% CI: 5.06, 5.52 for patients; mean score 5.56, 95% CI: 5.41, 5.72 for partners); doctor recommendation (4.94, 95% CI: 4.73, 5.15 for patients; 5.16, 95% CI: 4.97, 5.34 for partners); and instructing future planning (4.88, 95% CI: 4.59, 5.16 for patients; 5.11, 95% CI: 4.86, 5.35 for partners). High dyadic agreement was observed for all factors except fear of testing, which patients rated with lower importance than their study partners. CONCLUSIONS: Biomarker testing for AD in patients with MCI is a rapidly evolving practice and limited data exist on patient perspectives. In this study, most patients and their care partners were interested in testing to help inform treatment decisions and to plan for the future. Participants placed high importance on clinician recommendations for biomarker testing, highlighting the need for clear communication and education on the options, limitations, risks, and benefits of testing.

Cohort Effects in Alzheimer's Disease Trials: An Empirical Assessment Utilizing Data from the Alzheimer's Disease Cooperative Study.

BACKGROUND: Cohort effects in study populations can impact clinical trial conclusions and generalizability, particularly in trials with planned interim analyses. Long recruitment windows may exacerbate these risks in Alzheimer's disease (AD) trials. OBJECTIVES: To investigate the presence of cohort effects mild-to-moderate AD trials. DESIGN: Retrospective analysis using pooled participant-level data from nine randomized, placebo-controlled trials conducted by the Alzheimer's Disease Cooperative Study (ADCS). SETTING: Trials were multicenter studies conducted by an academic trial network. PARTICIPANTS: The trials enrolled participants with mild, mild-to-moderate, or moderate AD who were over age 50 and had mini mental state exam scores between 12 and 26. Interventions/Exposure: We defined a participant's site-standardized enrollment time as the number of days between their screening date and the first screening date among randomized participants at their site within their study. MAIN OUTCOME(S) AND MEASURE(S): Our primary outcome was the 12-month change in the AD assessment scale - cognitive subscale (ADAS-Cog). Secondary outcomes were participant demographics and time to study discontinuation. RESULTS: The pooled sample consisted of N=2,754 at baseline with N=2,191 participants completing a 12-month visit. We found no meaningful differences in the distributions of sex, race and ethnicity, age, years of education or baseline ADAS-Cog score across enrollment time. We found a significant association between enrollment time and 12-month change in ADAS-Cog, with participants enrolling 100 days later tending to experience an increase on the ADAS-Cog of 0.16 points greater (reflecting greater cognitive decline; 95% CI: (0.021, 0.294), p = 0.02), after controlling for potential confounding factors. CONCLUSION: We found minimal evidence of clinically relevant cohort effects in ADCS trials. Our results reinforce the original findings of these trials.