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Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study

BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j2709 (Published 22 June 2017) Cite this as: BMJ 2017;357:j2709

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Re: Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study

To the Editor,
A decline in cognitive function is often synonymous with aging and leaves the elderly population at greater risk of developing dementia1. This is of particular significance as the elderly population is growing at a rapid rate given the advances in healthcare provision and medicine2, placing a greater strain on healthcare services. As a result, attention has shifted towards prevention with a focus on modifiable risk factors such as exercise. It has previously been reported that various forms of exercise, such as aerobic and resistance training, have the capacity to improve cognitive function3. With this in mind, it is reasonable to predict that the prevalence of dementia decreases in accordance with increased physical activity, an assumption that has been supported in the past4. However, the findings reported by Sabia and colleagues5 suggest the contrary. While this study is an impressive contribution to the growing body of literature, like many others who have responded to this article, we propose that some of the results need to be interpreted with caution for fear that the “brain-train” message becomes “lost in translation”. Interestingly, the authors conclude that reverse causation can explain the reduction in time spent exercising during the 9-years prior to dementia diagnosis. In other words, physical activity levels decrease during this time period due to patients being in a pre-clinical phase of dementia.

Sabia and colleagues5 have critiqued several other prospective cohort studies that claim a reduction in activity levels as a pre-cursor for dementia. In spite of this, we would like to highlight several physiological factors that may underlie the onset of dementia and how exercise can in fact delay the onset of this disease. The first of these concerns cerebral blood flow and underlying vasoreactivity, that decrease inexorably with age6. In support, a recent prospective cohort study has shown that an accelerated decline in cerebral blood flow is a risk-factor for developing dementia7. It has also been demonstrated that physical activity has the capacity to attenuate this decline, favourably reducing the brains “functional age” by over a decade6. Attention should also be directed to the effect exercise has on brain volume and structure. Neurodegeneration and a reduction in brain volume are hallmark features of dementia4. While this decline can prove to be fatal, exercise has been shown to induce neurogenesis within the hippocampus and increase brain volume4 8. We are not arguing that exercise has the capacity to reverse the progression of dementia once diagnosed. However, collectively, these studies strongly suggest that physical activity constitutes a potentially important neuroprotective countermeasure.

A finding from the present study that warrants further discussion relates to the effect exercise has on cognition with ageing. Sabia and colleagues5 reported that the difference in the cognitive scores between those that completed the recommended levels of physical activity and those that did not, was four times as large at the age of 80 years than at 50 years. It is interesting that this result was only considered very briefly, as we propose that it highlights the importance of physical activity with increasing age and the associated neuroprotective benefits. Even more significantly, cognitive decline has major financial and social implications, amplified if the condition develops into dementia9. As a result of the societal impact that this finding may have, it could be beneficial to explore the result further. It should also be noted that physical activity levels were obtained through self-report measures once every four years on average5. While we recognise the difficulties with obtaining data from a cohort of this size, collecting the questionnaires annually may provide a more accurate representation of physical activity levels where physiological measurements are not feasible.

On a final note, we are interested in ascertaining the interaction between the covariates and the risk of dementia. Livingston and colleagues8 recently published results that weighed the impact of various risk-factors for dementia. While a sedentary lifestyle predisposed to dementia, other factors such as hypertension, obesity and diabetes were also deemed contributory. Physical activity has the collective capacity to attenuate all of these risk-factors and therefore, the impact of exercise may be greater than first thought (the whole being more than simply the sum of the parts!). It would be interesting to know if Sabia and colleagues5 considered how exercise, or indeed the lack of, affected the covariates described in their study.

References
1. Portet F, Ousset PJ, Visser PJ, et al. Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer's Disease. J Neurol Neurosur Ps 2006;77(6):714-18. doi: 10.1136/jnnp.2005.085332
2. World Health Organization. Facts about ageing Geneva, Switzerland: World Health Organization 2014 [Available from: http://www.who.int/ageing/about/facts/en/ accessed 03/10/2017.
3. Northey JM, Cherbuin N, Pumpa KL, et al. Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med 2017:1-9. doi: 10.1136/ bjsports-2016-096587
4. Ahlskog EJ, Geda YE, Graff-Radford NR, et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clinic Proceedings 2011;86(9):876-84.
5. Sabia S, Dugravot A, Dartigues JF, et al. Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study. BMJ 2017;357:j2709. doi: 10.1136/bmj.j2709
6. Bailey DM, Marley CJ, Brugniaux JV, et al. Elevated Aerobic Fitness Sustained Throughout the Adult Lifespan Is Associated With Improved Cerebral Hemodynamics. Stroke 2013;44(11):3235-38. doi: 10.1161/Strokeaha.113.002589
7. Wolters FJ, Zonneveld HI, Hofman A, et al. Cerebral Perfusion and the Risk of Dementia: A Population-Based Study. Circulation 2017;136(8):719-28. doi: 10.1161/CIRCULATIONAHA.117.027448
8. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet 2017 doi: 10.1016/S0140-6736(17)31363-6
9. Deary IJ, Corley J, Gow AJ, et al. Age-associated cognitive decline. Br Med Bull 2009;92:135-52. doi: 10.1093/bmb/ldp033

Competing interests: No competing interests

20 October 2017
Damian M. Bailey
Professor of Physiology & Biochemistry, Royal Society Wolfson Research Fellow
Thomas A. Calverley, Christopher J. Marley, Benjamin Stacey, Thomas S. Owens, Lewis Fall, George Rose and Martin Steggall
University of South Wales
Neurovascular Research Laboratory, Alfred Russell Wallace Building, Faculty of Life Sciences and Education, University of South Wales, UK CF37 4AT