Empirically Defining Trajectories of Late-Life Cognitive and Functional Decline and Classifying Potential Trajectory Class Membership (P4.092)

OBJECTIVE: Define cognitive and functional decline trajectories using Growth Mixture Modeling (GMM) and determine predictors of potential class membership using Classification and Regression Trees (CART). BACKGROUND: Considerable variability exists in rate of cognitive and functional decline in Alzheimer’s Disease (AD), impeding forecasting an individual’s clinical course. Early prediction of clinical trajectory will permit maximizing care planning and potentially delay decline. DESIGN/METHODS: Subjects were elderly healthy controls (HC, n=325), persons with early mild cognitive impairment (EMCI, n=279), late MCI (LMCI, n=372), or AD dementia (n=216) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-1/GO/2), using first-available β-amyloid measurement ([ 11 C]PiB or [ 18 F]florbetapir PET SUVR, or cerebrospinal fluid Aβ 1-42 ) as baseline plus up to 24 months assessments using Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog 13 ) and Functional Activities Questionnaire (FAQ). GMM was conducted jointly on ADAS-Cog 13 and FAQ. Using baseline variables (e.g.; diagnosis, demographics, co-morbidities, FAQ, amyloid and APOE4 status) CART predicted likely class membership. RESULTS: GMM identified 3 trajectory classes: C1 (n=162, 13.6[percnt]) with highest baseline FAQ and ADAS-Cog 13 , and similar rates of cognitive and functional worsening; C2 (n=211, 17.7[percnt]) with intermediate baseline FAQ and ADAS-Cog 13 , but steeper functional than cognitive decline; C3 (n=819, 68.7[percnt]) with lowest baseline FAQ and ADAS-Cog 13 and minimal changes over time. C3 was least likely to be amyloid or APOE4 positive and most likely to involve HCs or EMCI cases. CART yielded 2 decision nodes for likely class membership: FAQ蠅13.5 for C1 (n=115, 9.6[percnt]), then either 4.5蠅FAQ<13.5 for C2 (n=241, 11.8[percnt]) or FAQ<4.5 for C3 (n=836; 70.1[percnt]). CONCLUSIONS: The higher the baseline FAQ and ADAS-Cog 13 scores, the more rapidly the class progressed, regardless of baseline diagnosis. Amyloid and APOE4 positive status were associated with faster decline. FAQ, easily performed in the clinic, was identified by CART as the only predictor for trajectory classes with 82.3[percnt] accuracy. Study Supported by: Lilly Disclosure: Dr. Hochstetler has received personal compensation for activities with Eli Lilly & Co. as an employee. Dr. Trzepacz has received personal compensation for activities with Eli Lilly & Co. as an employee. Dr. Wang has received personal compensation for activities with Eli Lilly & Company as an employee. Dr. Yu has received personal compensation for activities with Eli Lilly & Company as an employee. Dr. Case has received personal compensation for activities with Eli Lilly & Company as an employee. Dr. Leoutsakos has nothing to disclose. Dr. Henley has received personal compensation for activities with Eli Lilly & Co. as an employee. Dr. Henley holds stock and/or stock options in Eli Lilly & Co. Dr. Degenhardt has received personal compensation for activities with Eli Lilly & Company as an employee. Dr. Degenhardt holds stock and/or stock options in Eli Lilly & Company. Dr. Lyketsos has received personal compensation for activities with Pfizer Inc., Forest Laboratories, Eli Lilly & Company, Takeda Pharmaceutical Company, and Elan as a consultant.