title: CDR state transition probabilities in Alzheimer's disease with and without cholinesterase inhibitor intervention in an observational cohort.
abstract: Cholinesterase inhibitors and memantine are medications used in the treatment of Alzheimer's disease (AD). These agents have been shown to reduce the rate of AD progression in randomized trials. The objective of this study is to evaluate the association between treatment with cholinesterase inhibitors or memantine and the probability of transitioning to a more severe Clinical Dementia Rating (CDR) state. Analysis was limited to possible or probable AD patients from NACC-UDS with three or more observations, baseline CDR score of 0.5 or 1, and without reported use AD drugs at enrollment. Use of an AD drug at any observation after baseline was classified as treatment. Odds of CDR stage were calculated by multinomial logistic regression controlling for baseline age, baseline MMSE score, education, marital status, race, gender, place of residence, and time since last measure. The resulting coefficients from logistic regression were used to calculate transitional probabilities. A total of 1,114 patients were included. No differences were observed in the probability of transitioning to more severe CDR states based on treatment, but treated patients had lower odds of death, OR 0.49 (95% CI 0.31 to 0.79) compared to untreated. Ultimately, this study failed to detect a difference in the probability of progressing to a more severe AD state as a result of treatment in an observational cohort of AD patients, but is limited by non-randomized treatment selection and small dataset. The NACC-UDS dataset is ongoing and this analysis may be improved if repeated when more data is available.
authors.affiliation: Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, WA 98195-7630, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bloudek
authors.forename: D Eldon
authors.initials: DE
authors.lastname: Spackman
authors.forename: David L
authors.initials: DL
authors.lastname: Veenstra
authors.forename: Sean D
authors.initials: SD
authors.lastname: Sullivan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D015331:Cohort Studies; D018450:Disease Progression; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use; D008609:Mental Status Schedule; D008875:Middle Aged; D019370:Observation; D016017:Odds Ratio; D011336:Probability; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine