Characterizing mild cognitive impairment to predict incident dementia in adults with bipolar disorder: What should the benchmark be?

Objective: Although mild cognitive impairment (MCI) is generally considered a risk state for dementia, its prevalence and association with dementia are impacted by the number of tests and cut-points used to assess cognition and define "impairment," and sources of norms. Here, we investigate how these methodological variations impact estimates of incident dementia in adults with bipolar disorder (BD), a vulnerable population with pre-existing cognitive deficits and increased dementia risk. Method: Neuropsychological data from 148 adults with BD and 13,610 healthy controls (HC) were drawn from the National Alzheimer's Coordinating Center. BD participants' scores were standardized against published norms and again using regression-based norms generated from HC within the same catchment area as individual BD patients ("site-specific norms"), varying the number of within-domain tests (one vs. two) and the cut-points (-1 vs. -1.5 SD) used to operationalize MCI. Results: Site-specific norms were more sensitive to incident dementia (88.6%-94.3%) than published norms (74.3%-88.6%), but only when using a "single test" definition of impairment. Specificity (22.1%-74.3%), accuracy (37.8%-68.9%), and positive predictive values (26.1%-38.3%) were overall poor. Applying a "single test" definition of impairment resulted in better negative predictive values using site-specific (92.3%-93.3%) than published norms (83.6%-86.2%), and a substantial increase in relative risk of incident dementia relative to published norms. Conclusions: Neuropsychologists should define "impairment" as scores below -1.0 or -1.5 SD on at least two within-domain measures when using published norms to interpret cognitive performance in adults with BD.