Neuropsychological Profiles and Trajectories in Preclinical Alzheimer's Disease

Objectives: The present study investigated the independent and synergistic effects of amyloid beta (A beta(1-42)) and phosphorylated tau (Ptau) pathologies on neuropsychological profiles and trajectories in cognitively normal older adults. Methods: Alzheimer's Disease Neuroimaging Initiative participants identified as cognitively normal at baseline underwent longitudinal assessment (N= 518; 0, 12, 24, 36 months), baseline lumbar puncture and follow-up cognitive exams. Cerebral spinal fluid (CSF) biomarker profiles (A beta-Ptau-, A beta+Ptau-, A beta-Ptau+, A beta+Ptau+) were compared on baseline profiles and trajectories for memory (Rey Auditory Verbal Learning Test), attention/executive function (Trail Making Test, A and B), language (Animal Fluency, Vegetable Fluency, Boston Naming Test) and processing speed (Digit Symbol) using multilevel models. Results: The A beta+Ptau+ group exhibited significantly worse baseline performance on tests of memory and executive function relative to the A beta-Ptau+ and A beta-Ptau- groups. The A beta+Ptau- group fell between the A beta+Ptau+ participants and the A beta-Ptau- and A beta-Ptau+ groups on all three cognitive domains and exhibited worse baseline executive function. The A beta-Ptau+ group performed worse than A beta-Ptau- participants on processing speed. Over 36-month follow-up, the A beta+Ptau+ group exhibited the greatest declines in memory and semantic fluency compared to all other groups. Conclusions: Cognitively normal older adults with both A beta and Ptau pathology exhibited the weakest profile, marked by the worst memory decline compared to the other groups. Other subtle changes in this group included declines in executive function and semantic fluency. Those with Ptau pathology alone showed slowed processing speed, and those with A beta pathology alone showed worse attention and executive function compared to biomarker negative participants.