Trajectories of cognitive decline in Alzheimer's disease.
BACKGROUND
Late-onset Alzheimer disease (LOAD) is a clinically heterogeneous complex disease defined by progressively disabling cognitive impairment. Psychotic symptoms which affect approximately one-half of LOAD subjects have been associated with more rapid cognitive decline. However, the variety of cognitive trajectories in LOAD, and their correlates, have not been well defined. We therefore used latent class modeling to characterize trajectories of cognitive and behavioral decline in a cohort of AD subjects.


METHODS
201 Caucasian subjects with possible or probable Alzheimer's disease (AD) were evaluated for cognitive and psychotic symptoms at regular intervals for up to 13.5 years. Cognitive symptoms were evaluated serially with the Mini-mental State Examination (MMSE), and psychotic symptoms were rated using the CERAD behavioral rating scale (CBRS). Analyses undertaken were latent class mixture models of quadratic trajectories including a random intercept with initial MMSE score, age, gender, education, and APOE 4 count modeled as concomitant variables. In a secondary analysis, psychosis status was also included.


RESULTS
AD subjects showed six trajectories with significantly different courses and rates of cognitive decline. The concomitant variables included in the best latent class trajectory model were initial MMSE and age. Greater burden of psychotic symptoms increased the probability of following a trajectory of more rapid cognitive decline in all age and initial MMSE groups. APOE 4 was not associated with any trajectory.


CONCLUSIONS
Trajectory modeling of longitudinal cognitive and behavioral data may provide enhanced resolution of phenotypic variation in AD.
Wilkosz
Patricia A
PA
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Seltman
Howard J
HJ
Devlin
Bernie
B
Weamer
Elise A
EA
Lopez
Oscar L
OL
DeKosky
Steven T
ST
Sweet
Robert A
RA
D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000523:psychology*; D003071:Cognition; D018450:Disease Progression; D004522:Educational Status; D005260:Female; D006801:Humans; D008297:Male; D008960:Models, Psychological; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors