Intra-Individual Variability in Alzheimer's Disease and Cognitive Aging: Definitions, Context, and Effect Sizes

BACKGROUND/AIMS To explore different definitions of intra-individual variability (IIV) to summarize performance on commonly utilized cognitive tests (Mini Mental State Exam; Clock Drawing Test); compare them and their potential to differentiate clinically-defined populations; and to examine their utility in predicting clinical change in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS Sample statistics were computed from ADNI cohorts with no cognitive diagnosis, a diagnosis of mild cognitive impairment (MCI), and a diagnosis of possible or probable Alzheimer's disease (AD). Nine different definitions of IIV were computed for each sample, and standardized effect sizes (Cohen's d) were computed for each of these definitions in 500 simulated replicates using scores on the Mini Mental State Exam and Clock Drawing Test. IIV was computed based on test items separately ('within test' IIV) and the two tests together ('across test' IIV). The best performing definition was then used to compute IIV for a third test, the Alzheimer's Disease Assessment Scale-Cognitive, and the simulations and effect sizes were again computed. All effect size estimates based on simulated data were compared to those computed based on the total scores in the observed data. Association between total score and IIV summaries of the tests and the Clinician's Dementia Rating were estimated to test the utility of IIV in predicting clinically meaningful changes in the cohorts over 12- and 24-month intervals. RESULTS ES estimates differed substantially depending on the definition of IIV and the test(s) on which IIV was based. IIV (coefficient of variation) summaries of MMSE and Clock-Drawing performed similarly to their total scores, the ADAS total performed better than its IIV summary. CONCLUSION IIV can be computed within (items) or across (totals) items on commonly-utilized cognitive tests, and may provide a useful additional summary measure of neuropsychological test performance.