Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI

Kathryn M Broadhouse, Maria Fiatarone Singh, Chao Suo, Nicola Gates, Wei Wen, Henry Brodaty, Nidhi Jain, Guy C Wilson, Jacinda Meiklejohn, Nalin Singh, Bernhard T Baune, Michael Baker, Nasim Foroughi, Yi Wang, Nicole Kochan, Kevin Ashton, Matt Brown, Zhixiu Li, Yorgi Mavros, Perminder S Sachdev & 1 others Michael J Valenzuela

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Abstract

Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

Original languageEnglish
Article number102182
JournalNeuroImage: Clinical
Volume25
Early online date14 Jan 2020
DOIs
Publication statusPublished - 2020

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Atrophy
Alzheimer Disease
Gyrus Cinguli
Cognition
Dementia
Hippocampus
Disease Resistance
Resistance Training
Executive Function
Dentate Gyrus
Neuroprotective Agents
Life Style
Magnetic Resonance Imaging
Cognitive Dysfunction
Therapeutics
salicylhydroxamic acid

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Broadhouse, K. M., Singh, M. F., Suo, C., Gates, N., Wen, W., Brodaty, H., ... Valenzuela, M. J. (2020). Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI. NeuroImage: Clinical, 25, [102182]. https://doi.org/10.1016/j.nicl.2020.102182
Broadhouse, Kathryn M ; Singh, Maria Fiatarone ; Suo, Chao ; Gates, Nicola ; Wen, Wei ; Brodaty, Henry ; Jain, Nidhi ; Wilson, Guy C ; Meiklejohn, Jacinda ; Singh, Nalin ; Baune, Bernhard T ; Baker, Michael ; Foroughi, Nasim ; Wang, Yi ; Kochan, Nicole ; Ashton, Kevin ; Brown, Matt ; Li, Zhixiu ; Mavros, Yorgi ; Sachdev, Perminder S ; Valenzuela, Michael J. / Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI. In: NeuroImage: Clinical. 2020 ; Vol. 25.
@article{9d56f2fe03604ff09276230e6bef064b,
title = "Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI",
abstract = "Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.",
author = "Broadhouse, {Kathryn M} and Singh, {Maria Fiatarone} and Chao Suo and Nicola Gates and Wei Wen and Henry Brodaty and Nidhi Jain and Wilson, {Guy C} and Jacinda Meiklejohn and Nalin Singh and Baune, {Bernhard T} and Michael Baker and Nasim Foroughi and Yi Wang and Nicole Kochan and Kevin Ashton and Matt Brown and Zhixiu Li and Yorgi Mavros and Sachdev, {Perminder S} and Valenzuela, {Michael J}",
note = "Copyright {\circledC} 2020 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2020",
doi = "10.1016/j.nicl.2020.102182",
language = "English",
volume = "25",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",

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Broadhouse, KM, Singh, MF, Suo, C, Gates, N, Wen, W, Brodaty, H, Jain, N, Wilson, GC, Meiklejohn, J, Singh, N, Baune, BT, Baker, M, Foroughi, N, Wang, Y, Kochan, N, Ashton, K, Brown, M, Li, Z, Mavros, Y, Sachdev, PS & Valenzuela, MJ 2020, 'Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI', NeuroImage: Clinical, vol. 25, 102182. https://doi.org/10.1016/j.nicl.2020.102182

Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI. / Broadhouse, Kathryn M; Singh, Maria Fiatarone; Suo, Chao; Gates, Nicola; Wen, Wei; Brodaty, Henry; Jain, Nidhi; Wilson, Guy C; Meiklejohn, Jacinda; Singh, Nalin; Baune, Bernhard T; Baker, Michael; Foroughi, Nasim; Wang, Yi; Kochan, Nicole; Ashton, Kevin; Brown, Matt; Li, Zhixiu; Mavros, Yorgi; Sachdev, Perminder S; Valenzuela, Michael J.

In: NeuroImage: Clinical, Vol. 25, 102182, 2020.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI

AU - Broadhouse, Kathryn M

AU - Singh, Maria Fiatarone

AU - Suo, Chao

AU - Gates, Nicola

AU - Wen, Wei

AU - Brodaty, Henry

AU - Jain, Nidhi

AU - Wilson, Guy C

AU - Meiklejohn, Jacinda

AU - Singh, Nalin

AU - Baune, Bernhard T

AU - Baker, Michael

AU - Foroughi, Nasim

AU - Wang, Yi

AU - Kochan, Nicole

AU - Ashton, Kevin

AU - Brown, Matt

AU - Li, Zhixiu

AU - Mavros, Yorgi

AU - Sachdev, Perminder S

AU - Valenzuela, Michael J

N1 - Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2020

Y1 - 2020

N2 - Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

AB - Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

U2 - 10.1016/j.nicl.2020.102182

DO - 10.1016/j.nicl.2020.102182

M3 - Article

VL - 25

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

SN - 2213-1582

M1 - 102182

ER -