title: Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise.
abstract: Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected<0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.
authors.affiliation: Regenerative Neuroscience Group, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neuroscience, School of Psychological Sciences, Monash University, Clayton, VIC, Australia.|Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Suo
authors.affiliation: Exercise Health and Performance Faculty Research Group, Faculty of Health Sciences and Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.|Hebrew SeniorLife and Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
authors.forename: M Fiatarone
authors.initials: MF
authors.lastname: Singh
authors.affiliation: Regenerative Neuroscience Group, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Gates
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: W
authors.initials: W
authors.lastname: Wen
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: P
authors.identifier: 0000-0002-9595-3220
authors.initials: P
authors.lastname: Sachdev
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.|Dementia Collaborative Research Centre, University of New South Wales, Sydney, NSW, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Brodaty
authors.affiliation: Exercise Health and Performance Faculty Research Group, Faculty of Health Sciences, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Saigal
authors.affiliation: Exercise Health and Performance Faculty Research Group, Faculty of Health Sciences, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: G C
authors.initials: GC
authors.lastname: Wilson
authors.affiliation: Exercise Health and Performance Faculty Research Group, Faculty of Health Sciences, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Meiklejohn
authors.affiliation: Exercise Health and Performance Faculty Research Group, Faculty of Health Sciences, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: B T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: Exercise Health and Performance Faculty Research Group, Faculty of Health Sciences and Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.|School of Exercise Science, Australian Catholic University, Strathfield, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Baker
authors.affiliation: Clinical and Rehabilitation Research Group, Faculty of Health Sciences, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Foroughi
authors.affiliation: Exercise Health and Performance Faculty Research Group, Faculty of Health Sciences, The University of Sydney, Lidcombe, NSW, Australia.|Department of Medicine and the Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Exercise Health and Performance Faculty Research Group, Faculty of Health Sciences and Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: Y
authors.identifier: 0000-0002-2588-0425
authors.initials: Y
authors.lastname: Mavros
authors.affiliation: Regenerative Neuroscience Group, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Lampit
authors.affiliation: Regenerative Neuroscience Group, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Leung
authors.affiliation: Regenerative Neuroscience Group, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.|School of Medical Sciences, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Valenzuela
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000628:therapy; D015444:Exercise / Q000502:physiology; D005260:Female; D066128:Gray Matter / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D055070:Resistance Training / Q000379:methods*; D013329:Structure-Activity Relationship