The literature on Alzheimer’s disease (AD) provides little data about long-term cognitive course trajectories. We identify global cognitive outcome trajectories and associated predictor variables that may inform clinical research and care.

Data derived from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set were used to examine the cognitive course of persons with possible or probable AD, a Mini-Mental State Examination (MMSE) of ≥10, and complete annual assessments for 5 years.

Thirty-six Alzheimer’s Disease Research Centers.

Four hundred and fourteen persons.

We used a hybrid approach comprising qualitative analysis of MMSE trajectory graphs that were operationalized empirically and binary logistic regression analyses to assess 19 variables’ associations with each trajectory. MMSE scores of ±3 points or greater were considered clinically meaningful.

Five distinct cognitive trajectories were identified: fast decliners (32.6%), slow decliners (30.7%), zigzag stable (15.9%), stable (15.9%), and improvers (4.8%). The decliner groups had three subtypes: curvilinear, zigzag, and late decline. The fast decliners were associated with female gender, lower baseline MMSE scores, a shorter illness duration, or receiving a cognitive enhancer. An early MMSE decline of ≥3 points predicted a worse outcome. A higher rate of traumatic brain injury, the absence of an ApoE ϵ4 allele, and male gender were the strongest predictors of favorable outcomes.

Our hybrid approach revealed five distinct cognitive trajectories and a variegated pattern within the decliners and stable/improvers that was more consistent with real-world clinical experience than prior statistically modeled studies. Future investigations need to determine the consistency of the distribution of these categories across settings.