Item-Level Investigation of Participant and Study Partner Report on the Cognitive Function Index from the A4 Study Screening Data.

BACKGROUND

Greater subjective cognitive changes on the Cognitive Function Index (CFI) was previously found to be associated with elevated amyloid (Aß) status in participants screening for the A4 Study, reported by study partners and the participants themselves. While the total score on the CFI related to amyloid for both sources respectively, potential differences in the specific types of cognitive changes reported by either participants or their study partners was not investigated.

OBJECTIVES

To determine the specific types of subjective cognitive changes endorsed by participants and their study partners that are associated with amyloid status in individuals screening for an AD prevention trial.

DESIGN, SETTING, PARTICIPANTS

Four thousand four hundred and eighty-six cognitively unimpaired (CDR=0; MMSE 25-30) participants (ages 65-85) screening for the A4 Study completed florbetapir (Aß) Positron Emission Tomography (PET) imaging. Participants were classified as elevated amyloid (Aß+; n=1323) or non-elevated amyloid (Aß-; n=3163).

MEASUREMENTS

Prior to amyloid PET imaging, subjective report of changes in cognitive functioning were measured using the CFI (15 item questionnaire; Yes/Maybe/No response options) and administered separately to both participants and their study partners (i.e., a family member or friend in regular contact with the participant). The impact of demographic factors on CFI report was investigated. For each item of the CFI, the relationship between Aß and CFI response was investigated using an ordinal mixed effects model for participant and study partner report.

RESULTS

Independent of Aß status, participants were more likely to report 'Yes' or 'Maybe' compared to the study partners for nearly all CFI items. Older age (r= 0.06, p<0.001) and lower education (r=-0.08, p<0.001) of the participant were associated with higher CFI. Highest coincident odds ratios related to Aß+ for both respondents included items assessing whether 'a substantial decline in memory' had occurred in the last year (ORsp= 1.35 [95% CI 1.11, 1.63]; ORp= 1.55 [95% CI 1.34, 1.79]) and whether the participant had 'seen a doctor about memory' (ORsp= 1.56 [95% CI 1.25, 1.95]; ORp =1.71 [95% CI 1.37, 2.12]). For two items, associations were significant for only study partner report; whether the participant 'Repeats questions' (ORsp = 1.30 [95% CI 1.07, 1.57]) and has 'trouble following the news' (ORsp= 1.46[95% CI 1.12, 1.91]). One question was significant only for participant report; 'trouble driving' (ORp= 1.25 [95% CI 1.04, 1.49]).

CONCLUSIONS

Elevated Aβ is associated with greater reporting of subjective cognitive changes as measured by the CFI in this cognitively unimpaired population. While participants were more likely than study partners to endorse change on most CFI items, unique CFI items were associated with elevated Aß for participants and their study partners, supporting the value of both sources of information in clinical trials.

Déclaration de conflit d'intérêts

R. Amariglio has nothing to disclose. J. Grill has nothing to disclose. D. Rentz has nothing to disclose. G Marshall reports personal fees and institutional support from Eisai Inc., institutional support from Eli Lilly and Company, Janssen Alzheimer Immunotherapy, Novartis, and Genentech, and personal fees from Grifols Shared Services North America, Inc, Pfizer outside the submitted work. R. Buckley has nothing to disclose. R. Yaari reports personal fees from Eli Lilly and Company during the conduct of the study. R. Raman reports grants from NIA, grants from Eli Lilly during the conduct of the study, grants from Janssen and grants from Eisai, outside the submitted work. CK. Sun reports grants from NIA and grants from Eli Lilly and Company during the conduct of the study. J. Sims he is an employee and stock holder of Eli Lilly and Company outside the submitted work. M. Donohue reports grants from NIH, grants and personal fees from Eli Lilly and Company during the conduct of the study, personal fees from Roche, personal fees from Biogen, personal fees from Neurotrack, other from Janssen, personal fees from Vivid Genomics outside the submitted work. P. Aisen reports grants from Janssen, grants from NIA, grants from FNIH, grants from Alzheimer’s Association, grants from Eisai, personal fees from Merck, personal fees from Biogen, personal fees from Roche, personal fees from Lundbeck, personal fees from Proclara, personal fees from Immunobrain Checkpoint outside the submitted work. K. Holdrige reports she is an employee and minor stockholder of Eli Lilly and Company. S Sikkes reports grants from Zon-MW OffRoad, grants from EU-JPND, institutional support from Lundbeck, Boehringer, and Toyama outside the submitted work. Dr. Gatchel reports grants from Alzheimer’s Association, grants from NIH/NIA, personal fees from Huron , grants from Merck , outside the submitted work.