title: Treatment effects in multiple cognitive domains in Alzheimer's disease: a two-year cohort study.
abstract: BACKGROUND
  Despite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer's disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort.
  
  
  METHODS
  A cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE).
  
  
  RESULTS
  At one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function.
  
  
  CONCLUSIONS
  The present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system.
authors.affiliation: L.C.Campbell Cognitive Neurology Research Unit, Toronto, Canada ; University of Toronto, Toronto, Ontario, Canada.
authors.forename: Pearl
authors.initials: P
authors.lastname: Behl
authors.affiliation: L.C.Campbell Cognitive Neurology Research Unit, Toronto, Canada ; Canadian Partnership for Stroke Recovery, Toronto, Ontario, Canada.
authors.forename: Jodi D
authors.initials: JD
authors.lastname: Edwards
authors.affiliation: Brain Sciences Research Program, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiss
authors.affiliation: University of Toronto, Toronto, Ontario, Canada ; Brain Sciences Research Program, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada ; Department of Psychiatry, Toronto, Ontario, Canada.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctot
authors.affiliation: Department of Psychiatry & Behavioral Neurosciences, McMaster University, Toronto, Ontario, Canada.
authors.forename: David L
authors.initials: DL
authors.lastname: Streiner
authors.affiliation: L.C.Campbell Cognitive Neurology Research Unit, Toronto, Canada ; University of Toronto, Toronto, Ontario, Canada ; Brain Sciences Research Program, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada ; Department of Medicine (Neurology), Toronto, Ontario, Canada ; Department of Psychology, Toronto, Ontario, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.affiliation: University of Toronto, Toronto, Ontario, Canada ; Department of Medicine (Neurology), Toronto, Ontario, Canada ; Department of Psychology, Toronto, Ontario, Canada ; Ontario Brain Institute, Toronto, Ontario, Canada.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Stuss