Subtle Cognitive Decline predicts progression to Mild Cognitive Impairment Above and Beyond Alzheimer’s Disease Risk Factors

Abstract

Early identification of those at risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is critical for early intervention. Recent work shows that subtle cognitive decline (SCD), operationally-defined using sensitive neuropsychological scores, predicts progression to MCI/AD and is associated with AD biomarkers. We aimed to determine whether SCD adds unique value in predicting progression to MCI/AD above and beyond other AD risk factors.547 cognitively unimpaired participants from the Alzheimer’s Disease Neuroimaging Initiative (359 without SCD; 188 with SCD) underwent neuropsychological testing and lumbar puncture. Participants were classified as SCD if they performed >1 SD below the demographically-adjusted mean on 1) two neuropsychological total scores in different cognitive domains, or 2) two memory test process scores (e.g., intrusion errors), or 3) one total score and one process score. Cox regressions examined whether SCD status predicted progression to MCI and AD within 5 years after adjusting for age, education, sex, MMSE, depressive symptoms, ischemia risk, apolipoprotein E genotype, and AD biomarker “positivity” based on the cerebrospinal fluid phosphorylated tau-to-β-amyloid ratio.SCD status predicted progression to MCI (HR = 2.74, 95% CI = 2.07-3.63, p