title: Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer's disease.
abstract: OBJECTIVE
  To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time.
  
  
  METHODS
  The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores ≥ 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score ≤ 10) and functional (Blessed Dementia Rating Scale score ≥ 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval.
  
  
  RESULTS
  ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points.
  
  
  CONCLUSIONS
  Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects.
authors: Department of Geriatrics & Palliative Medicine, Mount Sinai School of Medicine, New York, NY, USA. Electronic address: carolyn.zhu@mssm.edu.
authors: Carolyn W
authors: CW
authors: Zhu
authors: Elayne E
authors: EE
authors: Livote
authors: Nikolaos
authors: N
authors: Scarmeas
authors: Marilyn
authors: M
authors: Albert
authors: Jason
authors: J
authors: Brandt
authors: Deborah
authors: D
authors: Blacker
authors: Mary
authors: M
authors: Sano
authors: Yaakov
authors: Y
authors: Stern
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D015331:Cohort Studies; 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; D016016:Proportional Hazards Models
chemical_list: D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine
keywords: Alzheimer's disease; Cholinesterase inhibitors; Longitudinal studies; Memantine; Outcomes