# Exercise as it relates to Disease/Don't forget about exercise: physical activity interventions in Alzheimer's management

This is an analysis of the research article “Moderate-to-high Intensity Physical Exercise in patients with Alzheimer’s disease: A randomised control trial” by Hoffman et al. (2015).

## What is the background to this research?

Alzheimer’s disease (AD) is a form of dementia. It is a progressive degeneration disorder of the brain, resulting in deteriorations in cognitive functionality, such as memory and thinking, as well as general quality of life and ability to perform everyday tasks. The prevalence of AD is growing with increasing life expectancy. The Australian Institute of Health and Welfare estimated that in 2011:
* 1 in 11 (9%) of all Australians aged 65 and over had dementia
* 3 in 10 (30%) of all Australians aged 85 and over had dementia
Currently there is no cure and treatment is limited. There have been no new developments in medical interventions for AD in the last decade with research into pharmacological therapies described as a ‘flat line’. Current research is exploring alternative treatments such as exercise, and its benefits against cognitive decline and maintaining quality of life.

## Where is this research from?

This research was conducted in Denmark by a group of researchers, led by Gunhild Waldemar, chairman of the Danish Dementia Research Centre at Copenhagen University and Steen Hasselbalch, a consultant neurologist and an associate professor at the University of Copenhagen. This study was undertaken in the following universities and hospitals:
Universities
* The University of Copenhagen, Denmark
* University of California-Irvine, United States of America
Hospitals
* Copenhagen University Hospital
* Aalborg University Hospital
* Aarhus University Hospital
* Odense University Hospital
* Slagelse Hospital
* Svendborg Hospital
* Roskilde Hospital
* Glostrup Hospital

## What kind of research was this?

This study is a multi-centre, single-blind, randomised controlled trial conducted between January 2012 and June 2014. The intervention of moderate-to-high intensity exercise only lasts 16 weeks, but this two and a half year time frame allowed for new participants to be introduced to the study every 6 months and for small group exercise sessions (2-5 participants) to ensure maximial supervision.

## What did the research involve?

Criteria for participants in this study included:
* Age 50–90 years
* Mini Mental State Examination (MMSE) score >19
* A care-giver who was willing to assist
* No serious medical or psychiatric illness
* If on medical treatment, stable for > 3 months
* No regular (>2/weekly) participation in high intensity exercise
Of the 608 individuals screened for eligibility, 200 were selected (mean age 70.5years) and randomised into 2 groups:
* The intervention group: 107 participants undertook 60 minutes of supervised moderate-high intensity (70-80% of maximal Heart Rate) aerobic exercise three times a week for 16 weeks
* The control group: 93 participants continued with treatment as usual for 16 weeks, then were offered 1 month of exercise after follow up
Baseline measures were taken from all participants by blinded assesses to allow unbiased comparison post intervention. The primary test measure was the Symbol Digit Modalities Test (SDMT) for mental speed and attention. Secondary test measures further assessed cognitive ability and depression. In addition, caregivers were asked to complete a Neuropsychiatric Inventory and Activities of Daily Living Inventory for their patients. A limitation of these test measures is that the caregiver’s were aware of the intervention or control group their patient were allocated, making their questionnaires subjective and open to potential bias.

## What were the basic results?

In the intervention group, 66 subjects fulfilled the criteria of attending more than 80% of the exercise sessions and exercised with intensity greater than 70% of their maximal heart rate. The SDMT is a measure of cognitive processing speed, sensitive to early changes in functioning, and thus a relevant primary test for this study on AD patients. Normative scores for the SDMT decrease as age increases, with mean values for elderly as follows: Age 64-70: 33.53 Age 70-74: 27.94 Age 75-79: 26.48 Age 80-83: 20.24 There was no significant difference between the control and intervention groups’ baseline and follow-up mean scores on the SDMT test measure (control group 25.4 to 24.1; Intervention 27.1 to 26.2. There was a statistical significance in difference of neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (caregiver questionnaire) with a decrease of symptoms in the intervention group. There were no other secondary test measures that showed a difference from baseline to follow up between groups.

## How did the researchers interpret the results?

The researchers recognise the largely insignificant results of this study, especially in regard to their primary outcome test (SDMT). They are encouraged however, by the decrease in neuropsychiatric symptoms. The researchers are critical in their findings, acknowledging the difference in neuropsychiatric symptoms between groups could be a result of increasing complications in present symptoms of the control group. The researchers suggest that insufficient participation in moderate-to-high intensity could have affected the results despite high patient participation rates.

## What conclusions can we take from this research?

While this study lacked any conclusive evidence between moderate-high intensity exercise and cognitive functioning in Alzheimer’s patients, other recent studies have found positive relationships. No research has defined an optimal exercise intensity, frequency, or duration for limiting cognitive decline. However, due to the progressive nature of AD, exercise duration should be continuous. The latest research suggests a combination of aerobic exercise, motor training and cognitive training would be beneficial for maintaining cognitive functioning in Alzheimer’s patients.

## What are the implications of this research?

This study did not provide the findings that the researchers had hypothesised. Nevertheless, the study does not discredit the value of aerobic exercise in Alzheimer’s patients. Recent research has shown positive benefits of exercise on delaying cognitive decline in the elderly. The guidelines for physical activity for older Australians recommend 30 minutes of moderate intensity exercise per day.

## Further reading

For further information on Alzheimer’s Disease and the role of physical activity see below
* For general information: https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/dementia-alzheimers-disease
* For local support and community activities: https://act.fightdementia.org.au/act/support-and-services/services-and-programs
* For brain health: http://www.yourbrainmatters.org.au/a-little-help/brain-health-checklist
* For research updates: http://www.alz.org/research/

## References

* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Hoffmann, K., Sobol, N.A., Frederiksen, K.S., Beyer, N., Vogel, A., Vestergaard, K., Brændgaard, H., Gottrup, H., Lolk, A., Wermuth, L., Jacobsen, S., Laugesen, L.P., Gergelyffy, R.G., Høgh, P., Bjerregaard, E., Andersen, B.B., Siersma, V., Johannsen, P., Cotman, C.W., Waldemar, G. & Hasselbalch, S.G. 2015, "Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial",Journal of Alzheimer's disease : JAD, vol. 50, no. 2, pp. 443.
* 1 2 Fightdementia.org.au. (2016). Alzheimer's Australia | Alzheimer's disease. [online] Available at: https://www.fightdementia.org.au/about-dementia/types-of-dementia/alzheimers-disease [Accessed 24 Sep. 2016].
* 1 2 Australian Institute of Health and Welfare 2012. Dementia in Australia. Cat. no. AGE 70. Canberra: AIHW
* ↑ Castellani, R.J. & Perry, G. 2012, "Pathogenesis and disease-modifying therapy in Alzheimer's disease: the flat line of progress", Archives of medical research, vol. 43, no. 8, pp. 694-698.
* ↑ Sofi, F., Valecchi, D., Bacci, D., Abbate, R., Gensini, G.F., Casini, A. & Macchi, C. 2011, "Physical activity and risk of cognitive decline: a meta‐analysis of prospective studies",Journal of Internal Medicine, vol. 269, no. 1, pp. 107-117.
* ↑ Kulmala, J., Solomon, A., Kåreholt, I., Ngandu, T., Rantanen, T., Laatikainen, T., Soininen, H., Tuomilehto, J., Kivipelto, M., Stockholms universitet, Samhällsvetenskapliga fakulteten & Centrum för forskning om äldre och åldrande (ARC), (tills m KI) 2014, "Association between mid- to late life physical fitness and dementia: evidence from the CAIDE study", Journal of Internal Medicine, vol. 276, no. 3, pp. 296.
* ↑ Sheridan, L.K., Fitzgerald, H.E., Adams, K.M., Nigg, J.T., Martel, M.M., Puttler, L.I., Wong, M.M. & Zucker, R.A. 2006, "Normative Symbol Digit Modalities Test performance in a community-based sample", Archives of Clinical Neuropsychology, vol. 21, no. 1, pp. 23-28.
* ↑ Vreugdenhil, A, Cannell, J, Davies, A, & Razay, G 2012, 'A community-based exercise programme to improve functional ability in people with Alzheimer's disease: a randomized controlled trial', Scandinavian Journal of Caring Sciences, vol. 26, no. 1, pp. 12-19. Available from: 10.1111/j.1471-6712.2011.00895.x. [27 September 2016].
* ↑ Kemoun, G., Thibaud, M., Roumagne, N., Carette, P., Albinet, C., Toussaint, L., Paccalin, M. & Dugué, B. 2010, "Effects of a physical training programme on cognitive function and walking efficiency in elderly persons with dementia",Dementia and Geriatric Cognitive Disorders, vol. 29, no. 2, pp. 109-114.
* 1 2 3 4 Paillard, T. 2015, "Preventive effects of regular physical exercise against cognitive decline and the risk of dementia with age advancement", Sports Medicine - Open, vol. 2;1;, no. 1, pp. 1-6.
* 1 2 Cancela, J.M., Ayán, C., Varela, S. & Seijo, M. 2016, "Effects of a long-term aerobic exercise intervention on institutionalised patients with dementia", Journal of Science and Medicine in Sport, vol. 19, no. 4, pp. 293-298.
* 1 2 Cheng, S. 2016, "Cognitive Reserve and the Prevention of Dementia: the Role of Physical and Cognitive Activities", Current Psychiatry Reports, vol. 18, no. 9, pp. 1-12.
* ↑ Brown W J, Moorhead GE and Marshall AL (2005) Choose Health: Be Active: A physical activity guide for older Australians. Canberra: Commonwealth of Australia and the Repatriation Commission, pp 4-5.