Diagnostic and Prognostic Accuracy of the Cogstate Brief Battery and Auditory Verbal Learning Test in Preclinical Alzheimer's Disease and Incident Mild Cognitive Impairment: Implications for Defining Subtle Objective Cognitive Impairment

Background: There are detectable cognitive differences in cognitively unimpaired (CU) individuals with preclinical Alzheimer's disease (AD). Objective: To determine whether cross-sectional performance on the Cogstate Brief Battery (CBB) and Auditory Verbal Learning Test (AVLT) could identify 1) CU participants with preclinical AD defined by neuroimaging biomarkers of amyloid and tau, and 2) incident mild cognitive impairment (MCI)/dementia. Method: CU participants age 50+ were eligible if they had 1) amyloid (A) and tau (T) imaging within two years of their baseline CBB or 2) at least one follow-up visit. AUROC analyses assessed the ability of measures to differentiate groups. We explored the frequency of cross-sectional subtle objective cognitive impairment (sOBJ) defined as performance <=-1 SD on CBB Learning/Working Memory Composite (Lrn/WM) or AVLT delayed recall using age-corrected normative data. Results: A+T+ (n = 33, mean age 79.5) and A+T- (n = 61, mean age 77.8) participants were older than A-T- participants (n = 146, mean age 66.3), and comparable on sex and education. Lrn/WM did not differentiate A+T+ or A+T- from A-T-participants. AVLT differentiated both A+T+ and A+T- from A-T- participants; 45% of A+T+ and 25% of A+T- participants met sOBJ criteria. The follow-up cohort included 150 CU individuals who converted to MCI/dementia and 450 age, sex, and education matched controls. Lrn/WM and AVLT differentiated between stable and converter CU participants. Conclusion: Among CU participants, AVLT helped differentiate A+T+ and A+T- from A-T- participants. The CBB did not differentiate biomarker subgroups, but showed potential for predicting incident MCI/dementia. Results inform future definitions of sOBJ.