title: Effects of aerobic exercise on cognition and hippocampal volume in Alzheimer's disease: study protocol of a randomized controlled trial (The FIT-AD trial).
abstract: BACKGROUND
  Alzheimer's disease, a global public health issue, accounts for 60 to 80% of all dementias. Alzheimer's disease primarily causes cognitive impairment and drugs have only modest short-term effects, highlighting a pressing need to develop effective interventions. Aerobic exercise holds promise for treating cognitive impairment in Alzheimer's disease through biologically sound mechanisms. Nonetheless, aerobic exercise studies in Alzheimer's disease are limited with mixed findings.
  
  
  METHODS
  This pilot randomized controlled trial will investigate the effects of a 6-month, individualized, moderate-intensity cycling intervention (20 to 50 minutes per session, 3 times a week) on cognition and hippocampal volume in community-dwelling older adults with mild-to-moderate Alzheimer's disease. The specific aims are to: 1) determine the immediate effect of the cycling intervention on cognition in Alzheimer's disease; 2) examine if the cycling intervention slows cognitive decline in Alzheimer's disease from baseline to 12 months; and 3) assess the effect of aerobic exercise on hippocampal volume over 12 months. Ninety subjects will be randomized on a 2:1 allocation ratio to cycling or attention control (low-intensity stretching) and followed for another 6 months. Allocations will be concealed to all investigators and outcome assessors will be blinded to group assignments and previous data. Cognition will be measured by the Alzheimer's disease Assessment Scale-Cognition at baseline before randomization and at 3, 6, 9, and 12 months. Hippocampal volume will be measured by magnetic resonance imaging at baseline and 6 and 12 months. The sample size of 90 will give 80% power to detect a 2.5-point difference in within-group changes in the Alzheimer's disease Assessment Scale-Cognition at 6 months for the cycling group.
  
  
  CONCLUSIONS
  Findings from this study will address the critical gap of exercise efficacy in Alzheimer's disease and use of magnetic resonance imaging as an outcome measure in clinical trials. This study will provide a potential treatment that may increase physical function and quality of life and curb the prohibitive costs for the growing dementia population.
  
  
  BACKGROUND
  Primary registration: (NCT01954550; date of registration: 20 September 2013). Secondary registration: (NCT01954550; date of registration: 1 October 2013).
authors.affiliation: University of Minnesota School of Nursing, 5-160 WDH 1331, 308 Harvard St SE, Minneapolis, MN 55455, USA. yuxxx244@umn.edu.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Ulf G
authors.initials: UG
authors.lastname: Bronas
authors.forename: Suma
authors.initials: S
authors.lastname: Konety
authors.forename: Nathaniel W
authors.initials: NW
authors.lastname: Nelson
authors.forename: Maurice
authors.initials: M
authors.lastname: Dysken
authors.forename: Clifford
authors.initials: C
authors.lastname: Jack
authors.forename: Jean F
authors.initials: JF
authors.lastname: Wyman
authors.forename: David
authors.initials: D
authors.lastname: Vock
authors.forename: Glenn
authors.initials: G
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D001642:Bicycling; D002985:Clinical Protocols; D003071:Cognition; D018450:Disease Progression; D005081:Exercise Therapy / Q000379:methods*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008910:Minnesota; D009483:Neuropsychological Tests; D009929:Organ Size; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012107:Research Design; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome