title: Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial.
abstract: BACKGROUND
  Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent.
  
  
  OBJECTIVE
  To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD.
  
  
  METHODS
  In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms.
  
  
  RESULTS
  The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: -3.5, 95% confidence interval (CI) -5.8 to -1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition.
  
  
  CONCLUSIONS
  This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Kristine
authors.initials: K
authors.lastname: Hoffmann
authors.affiliation: Musculoskeletal Rehabilitation Research Unit, University of Copenhagen, Denmark.|Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, University of Copenhagen, Denmark.
authors.forename: Nanna A
authors.initials: NA
authors.lastname: Sobol
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Kristian S
authors.initials: KS
authors.lastname: Frederiksen
authors.affiliation: Musculoskeletal Rehabilitation Research Unit, University of Copenhagen, Denmark.|Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, University of Copenhagen, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Beyer
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Asmus
authors.initials: A
authors.lastname: Vogel
authors.affiliation: Memory Clinic, Aalborg University Hospital, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Vestergaard
authors.affiliation: Dementia Clinic, Aarhus University Hospital, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Brændgaard
authors.affiliation: Dementia Clinic, Aarhus University Hospital, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Gottrup
authors.affiliation: Dementia Clinic, Odense University Hospital, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Lolk
authors.affiliation: Dementia Clinic, Odense University Hospital, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Wermuth
authors.affiliation: Department of Geriatrics, Odense University Hospital, Svendborg Hospital, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.affiliation: Department of Geriatrics, Slagelse Hospital, Denmark.
authors.forename: Lars P
authors.initials: LP
authors.lastname: Laugesen
authors.affiliation: Department of Geriatrics, Slagelse Hospital, Denmark.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gergelyffy
authors.affiliation: Regional Dementia Research Center, Region Zealand, Roskilde Hospital, University of Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Høgh
authors.affiliation: Memory Clinic, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: Eva
authors.initials: E
authors.lastname: Bjerregaard
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Birgitte B
authors.initials: BB
authors.lastname: Andersen
authors.affiliation: Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Denmark.
authors.forename: Volkert
authors.initials: V
authors.lastname: Siersma
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Johannsen
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California-Irvine, CA, USA.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Cotman
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Gunhild
authors.initials: G
authors.lastname: Waldemar
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Steen G
authors.initials: SG
authors.lastname: Hasselbalch
mesh_terms: D000203:Activities of Daily Living / Q000523:psychology*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000523:psychology / Q000628:therapy*; D003071:Cognition / Q000502:physiology*; D003863:Depression / Q000523:psychology / Q000628:therapy*; D015444:Exercise / Q000523:psychology*; D005081:Exercise Therapy / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life / Q000523:psychology*; D016896:Treatment Outcome
keywords: Alzheimer’s disease; behavioral symptoms; cognition; exercise; randomized controlled trial