title: Time to Treatment Initiation in People With Alzheimer Disease: A Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Alzheimer disease (AD) is a global health problem which afflicts millions of old age population worldwide. Acetylcholinesterase inhibitors and memantine are recognized drug treatments with limited clinical efficacy. It is uncertain if earlier initiation of these drugs will result in better outcomes in the longer term.
  
  
  OBJECTIVE
  To evaluate the benefit of early treatment among people with AD.
  
  
  METHODS
  Prospective randomized controlled trials were systematically searched from the OVID databases. The trials were eligible if study participants diagnosed with AD and were randomized to have early or late treatment. Any clinical assessment scales on cognitive function, physical function, behavioral problems, and the overall clinical status were the primary outcomes, and any reported adverse events were the secondary outcomes.
  
  
  RESULTS
  Ten randomized trials were identified between 2000 and 2010. A total of 3092 participants with AD with mean age 75.8 years were randomly assigned to receive early treatment or treatment delayed by placebo intervention for around 6 months. Compared with late treatment, early AD drug treatment showed no significant benefit on cognitive function [mean difference (MD) of Alzheimer's Disease Assessment Scale- Cognitive Subscale = -0.49, 95% CI = -1.67 to 0.69], physical function (MD of Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory = 0.47, 95% CI = -1.44 to 2.39), behavioral problems (MD of Neuropsychiatric Inventory = -0.26, 95% CI = -2.70 to 2.18), and clinical status (MD of Clinician's Interview-Based Impression of Change plus Caregiver Input = 0.02, 95% CI = -0.23 to 0.27). Nausea was the most common adverse events in acetylcholinesterase inhibitor users, while memantine did not result in more side effects than the placebo group. For both drugs, early treatment had comparable adverse events when compared with late treatment.
  
  
  CONCLUSIONS
  Earlier AD drug treatment by around 6 months did not result in significant difference in cognitive function, physical function, behavioral problems, and clinical status. This study included relative high proportion of early AD with the follow-up less than 2 years. Future studies can be conducted to further investigate the long-term findings.
authors.affiliation: Jockey Club, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong; Stanley Ho, Big Data Decision Analytics Research Centre, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Kelvin K F
authors.initials: KK
authors.lastname: Tsoi
authors.affiliation: Jockey Club, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong; Stanley Ho, Big Data Decision Analytics Research Centre, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Hoyee W
authors.initials: HW
authors.lastname: Hirai
authors.affiliation: Jockey Club, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Joyce Y C
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong. Electronic address: tkwok@cuhk.edu.hk.
authors.forename: Timothy C Y
authors.initials: TC
authors.lastname: Kwok
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology*; D032763:Behavior Control; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D015259:Dopamine Agents / Q000627:therapeutic use; D015577:Geriatric Assessment; D006801:Humans; D008559:Memantine / Q000627:therapeutic use; D009483:Neuropsychological Tests; D016032:Randomized Controlled Trials as Topic; D061665:Time-to-Treatment
chemical_list: D002800:Cholinesterase Inhibitors; D015259:Dopamine Agents; D008559:Memantine
keywords: AChEIs; Alzheimer disease; Dementia; early treatment; memantine