Effects of a multicomponent resistance-based exercise program with protein, vitamin D and calcium supplementation on cognition in men with prostate cancer treated with ADT: secondary analysis of a 12-month randomised controlled trial.

Niamh Liana Mundell, Patrick J Owen, Jack Dalla Via, Helen Macpherson, Robin M Daly, Patricia M Livingston, Timo Rantalainen, Stephen Foulkes, Jerremy Millar, Declan G Murphy, Steve F Fraser

Journal: BMJ open 2022;12(6):e060189

PMID: 35750461

Plain Language Summary

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Androgen deprivation therapy (ADT) for local and advanced prostate cancer (PCa) is effective at reducing androgens, and thus inhibiting tumour progression. However, testosterone reduces the production of a highly neurotoxic protein (amyloid beta peptide 40), which is linked with the development of dementia and Alzheimer’s disease. The aim of this study was to investigate the effects of a multi-component resistance-based exercise programme with daily protein, vitamin D and calcium supplementation on cognitive function compared with usual care in PCa survivors treated with ADT. This study is a secondary analysis of a 12-month single-blinded, two-arm randomised controlled trial. Participants (n = 70) were randomised (1:1 ratio) to either: (a) multi-component exercise intervention including progressive resistance training, body-weight impact and balance exercises, as well as a daily nutritional supplement containing whey protein, calcium and vitamin D, or (b) usual care control receiving 1000 IU vitamin D only. Results show that a multicomponent exercise training and nutritional supplementation intervention did not improve cognitive function in men treated with ADT for PCa compared with usual care. Authors conclude that cognitive decline associated with ADT may mechanistically differ to that of general age-related cognitive declines, thus it is important that future studies also examine other intervention modalities.

Abstract

OBJECTIVES

The aim of this preplanned secondary analysis of a 12-month randomised controlled trial was to investigate the effects of a multicomponent exercise programme combined with daily whey protein, calcium and vitamin D supplementation on cognition in men with prostate cancer treated with androgen deprivation therapy (ADT).

DESIGN

12-month, two-arm, randomised controlled trial.

SETTING

University clinical exercise centre.

PARTICIPANTS

70 ADT-treated men were randomised to exercise-training plus supplementation (Ex+ Suppl, n=34) or usual care (control, n=36).

INTERVENTION

Men allocated to Ex + Suppl undertook thrice weekly resistance training with weight-bearing exercise training plus daily whey protein (25 g), calcium (1200 mg) and vitamin D (2000 IU) supplementation.

PRIMARY AND SECONDARY OUTCOME MEASURES

Cognition was assessed at baseline, 6 and 12 months via a computerised battery (CogState), Trail-making test, Rey auditory-verbal learning test and Digit span. Data were analysed with linear mixed models and an intention-to-treat and prespecified per-protocol approach (exercise-training: ≥66%, nutritional supplement: ≥80%).

RESULTS

Sixty (86%) men completed the trial (Ex + Suppl, n=31; control, n=29). Five (7.1%) men were classified as having mild cognitive impairment at baseline. Median (IQR) adherence to the exercise and supplement was 56% (37%-82%) and 91% (66%-97%), respectively. Ex + Suppl had no effect on cognition at any time.

CONCLUSIONS

A 12-month multicomponent exercise training and supplementation intervention had no significant effect on cognition in men treated with ADT for prostate cancer compared with usual care. Exercise training adherence below recommended guidelines does not support cognitive health in men treated with ADT for prostate cancer.

TRIAL REGISTRATION NUMBER

Australian and New Zealand Clinical Trial Registry (ACTRN12614000317695, registered 25/03/2014) and acknowledged under the Therapeutic Goods Administration Clinical Trial Notification Scheme (CT-2015-CTN-03372-1 v1).

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Address: Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia [email protected].; Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.; Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.; Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.; Faculty of Health, Deakin University, Geelong, Victoria, Australia.; Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.; Faculty of Sport and Health Sciences, Department of Health Sciences, Jyvaskylan Yliopisto, Jyvaskyla, Finland.; Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.; Radiation Oncology, Alfred Hospital, Melbourne, Victoria, Australia.; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
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