title: Response to cholinesterase inhibitors affects lifespan in Alzheimer's disease.
abstract: BACKGROUND
  A varying response to cholinesterase inhibitor (ChEI) treatment has been reported among patients with Alzheimer's disease (AD). Whether the individual-specific response, specific ChEI agent or dose affects mortality is unclear. We aimed to examine the relationship between the 6-month response to ChEI and lifespan.
  
  
  METHODS
  Six hundred and eighty-one deceased patients with a clinical AD diagnosis and a Mini-Mental State Examination (MMSE) score of 10-26 at the start of ChEI therapy (baseline) were included in a prospective, observational, multicentre study in clinical practice. At baseline and after 6 months of treatment, the participants were assessed using the MMSE, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), the Clinician's Interview-Based Impression of Change (CIBIC), the Instrumental Activities of Daily Living (IADL) scale, and the Physical Self-Maintenance Scale (PSMS). The individuals' socio-demographic characteristics, ChEI dose, and date of death were recorded. Responses to ChEI and the association of possible risk factors with survival were analysed using general linear models.
  
  
  RESULTS
  A longer lifespan (mean of 0.5 years) was observed among the improved/unchanged patients, as measured by MMSE or CIBIC score, but not by ADAS-cog score, after 6 months of ChEI therapy. In the multivariate models, increased survival time was independently related to a better 6-month response in MMSE, CIBIC, IADL, and PSMS scores, female sex, no antihypertensive/cardiac or antidiabetic therapy, younger age, lower education, milder disease stage at baseline, and higher ChEI dose. Apolipoprotein E genotype did not affect mortality significantly. The patients who received a higher ChEI dose during the first 6 months had a mean lifespan after baseline that was 15 months longer than that of those who received a lower dose.
  
  
  CONCLUSIONS
  A better short-term response to ChEI might prolong survival in naturalistic AD patients. In individuals who received and tolerated higher ChEI doses, a longer lifespan can be expected.
authors.forename: Carina
authors.initials: C
authors.lastname: Wattmo
authors.forename: Elisabet
authors.initials: E
authors.lastname: Londos
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
mesh_terms: D000203:Activities of Daily Living / Q000523:psychology; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008017:Life Expectancy; D008297:Male; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies
chemical_list: D002800:Cholinesterase Inhibitors