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

Abstract

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.

Episodic Memory Impairment Mediates the Loss of Awareness in Mild Cognitive Impairment

“…That is, although models in the CN and the Dementia groups did not show significant effects, neither direct nor indirect, significant partial mediations were observed in the MCI group with EM. To begin with, increased discordance between the informant's and participant's complaints have already been observed in the literature, using raw complaint scores (Amariglio et al, 2021) as well as awareness indices as in our study (Folstein et al, 1975;Cacciamani et al, 2017Cacciamani et al, , 2020Hanseeuw et al, 2020;Vannini et al, 2020). In our study, only the MCI group demonstrated a significant relationship between amyloidosis, cognition and awareness, with EM partially mediating the relationship between amyloid and awareness.…”

Instrumental activities of daily living, amyloid, and cognition in cognitively normal older adults screening for the A4 Study

“…Prior studies in CN participants have shown associations between amyloid burden and objective and subjective cognitive function 23–26 but only limited evidence for a relationship with IADL difficulties 16,17 . The current analyses demonstrated an association among IADL, amyloid burden, objective cognition, and subjective cognitive concerns.…”

The use of subjective cognitive complaints for detecting mild cognitive impairment in older adults across cultural and linguistic groups: A comparison of the Cognitive Function Instrument to the Montreal Cognitive Assessment

“…52 Greater reporting of CFI items was found to be associated with elevated amyloid levels in the brain. 53 The CFI demonstrated a similar effect size between amyloid beta groups as that of detailed neuropsychological testing in a recent study. 54 In the current study, we sought to build upon previous findings that SCC, measured by the CFI, was associated with concurrent and longitudinal cognitive performance in older adults without dementia 51,55 and aimed to examine the CFI's utility as a potential screening tool for MCI.…”