Mild Cognitive Impairment in Late Middle Age in the Wisconsin Registry for Alzheimer's Prevention Study: Prevalence and Characteristics Using Robust and Standard Neuropsychological Normative Data

Objective: Detecting cognitive decline in presymptomatic Alzheimer's disease (AD) and early mild cognitive impairment (MCI) is challenging, but important for treatments targeting AD-related neurodegeneration. The current study aimed to investigate the utility and performance of internally developed robust norms and standard norms in identifying cognitive impairment in late middle-age (baseline age range = 36-68; M = 54). Method: Robust norms were developed for neuropsychological measures based on longitudinally confirmed cognitively normal (CN) participants (n = 476). Seven hundred and seventy-nine participants enriched for AD risk were classified as psychometric MCI (pMCI) or CN based on standard and robust norms and single-test versus multi-test criteria. Results: Prevalence of pMCI ranged from 3% to 49% depending on the classification scheme used. Those classified as pMCI using robust norms exhibited greater subjective cognitive complaints, diagnostic stability, and mild clinical symptoms at follow-up. Conclusions: Results suggest that identifying early clinically relevant cognitive decline in late middle-age is feasible using robust norms and multi-test criteria.