# Exercise as it relates to Disease/Investigating effects of moderate-high intensity exercise on Alzheimer's patient's

An investigation into the effects of 'Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A Randomized Controlled Trial' and related studies.

# What is the background to this research?

There is a growing trend of people suffering from Alzheimer’s Disease due to an ageing population. Pharmacological treatment has limited benefits with little improvement over recent years creating a necessity for alternate treatments. Studies have proposed that physical activity has benefits in the prevention of cognitive decline and dementia leading into old age that retains the capacity to accomplish daily tasks in older adults. There is a clear dose-response between greater exercise levels and greater cognitive performance in healthy adults. While exercise can improve conditions for Alzheimer’s patients, there are meta-analysis’ that do not greatly support these claims. However current research does not account for community dwelling patients which make up a great number of Alzheimer’s sufferer’s.
This study is one of the first (published 2016) to be researched examining continuously supervised moderate-to-high intensity aerobic exercise and the effects they may offer on cognitive, neuropsychiatric and depressive symptoms of community-dwelling patients with mild Alzheimer’s Disease and if these effects can improve quality of life.

# Where is the research from?

The research was conducted in various tertiary and health care locations across Denmark by a large number of contributing authors, many of whom have previous research in either Dementia, Alzheimer’s Disease, or are from the discipline of Sports medicine. Such a multi-discipline and large study has merit and expertise across many institutions combined into creating the study.

# What kind of research was this?

The Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer’s Disease: The Effect of Physical Exercise (ADEX) is a multi-center, single-blind, randomized trial study.

# What did the research involve?

Participants were randomized to a control group, which received treatment as usual, or an intervention group, which performed 60 min of supervised moderate-to-high intensity aerobic exercise three times weekly for 16 weeks. Participants were included every six months over a period of 2.5 years. After screening for eligibility and obtaining informed consent, assessors completed the baseline assessments. Subsequently, participants were using a computerized random-number generator. In the case of an unequal number of participants in one center, randomization was set up to favor the intervention group. The intervention group participated in three weekly exercise sessions in small groups overseen by a physiotherapist. The first four weeks were devoted to adapting the participants to exercise, focusing on lower limb extremities, whilst also exercising aerobically once weekly. The subsequent twelve weeks were devoted to moderate-to-high intensity aerobic exercise; 3×10 minutes on training equipment with a few minutes’ rest. Heart rate was continuously monitored with an intensity of 70-80% submaximal work. Intensity was monitored as patients adapted to the physical activity. The Control group were treated with their standard interventions, provided with access to medical staff to accommodate particulars during the study period. The principle measure was the Symbol Digit Modalities Test (SDMT) assessing mental speed, and attention through decoding symbols and numbers in a time period. Secondary measures included the Alzheimer’s Disease Assessment Scale –Cognitive Subscale (ADAS-Cog) verbal memory test, the Stroop Color and Word Test (Stroop) incongruent score, verbal fluency and the MMSE The Hamilton Depression Rating Scale (HAMD-17) measured depressions symptom severity in patients. Caregivers also received questionnaires as part of the study to determine quality of life. The study had particularly good design including large quantities of patients measured by validated scales. Supervision was essential to the exercise component of the program and resulted in high adherence. This study did not factor in physical activity monitoring outside of study exercise which could have impacted the study. There may appear to be a selection bias to the applicability of patients, meaning the intervention may not be suitable for all patients. There was also little differentiation in which neuropsychiatric symptoms were affected by the exercise, or other means in a diverse study. Further studies should make the distinction between exercise, and other factors to confirm dose-dependent effects.

# What were the basic results?

Results have alluded that physical activity may hinder disease progression. Through IIT and Per Protocol Analysis it was determined that there were little important differences in pre study scales between the intervention group and the control group, nor were there significant differences between demographics between control, low and high exercise groups. SDMT results from beginning to follow up studies showed minor changes favouring the intervention group. There were major changes to the total neuropsychiatric symptoms initially assessed and re assessed post study, lessening severity in the intervention group. Secondary measures showed no real changes in either group during follow-up procedures. Quality of Life was deemed to significantly improve in high exercise patients. There were no decreases in severity of depressive symptoms, however these were already low during initial measures. The variances that the intervention group experienced could be attested to the increasing of present symptoms in the control group, which were delayed in the intervention group. The result invariances could also be due to higher scored measures which are less likely to change over the study.

# What conclusions can we take from this research?

Although the results showed a negative outcome for the principle measure, high adherence of the program confirmed other studies’ conclusions that aerobic exercise is practical for Alzheimer’s patients. Other outcomes not studied during the research will still be met, for example a decrease in cardiovascular risk factors or decreases in pro-inflammatory cytokines in patients may have improved during the study regardless. Neuropsychiatric symptoms however did improve showing positive cognition effects, even if they cannot be differentiated by the cause in the study, this is still a positive for those participating and good findings for further research. There should also be some distinction if improvement is constrained in the short term. There are few studies of exercise with patients displaying Alzheimer’s disease with results being unreliable. Other randomised studies have established that exercise has positive effects on many facets of cognition with mild impairments. A study by Baker et. al is an especially large randomised trial of aerobic exercise in Mild Cognitive Impairment using similar measures to this study showed improvements to executive function however no improvement to memory measures, indicating some areas of cognition are more susceptible to adaptation to exercise than others. Most studies researched have unsupervised methodologies which can create data collection issues. There have been previous issues with smaller sample sizes and underscores measures of exercise intensity. A 2017 review into cognitive benefits of exercise in Alzheimer’s has concluded more research is needed to confirm the actual benefits of an exercise intervention, and to establish a dose-response relationship.

# Practical advice

Physical activity as a means of an Alzheimer’s intervention has prospective merit, to be used in addition to other treatments provided, particular in community settings. Although there is no differentiation if the exercise, or the social interactions, caused benefits in patients, group exercises utilizing both of these factors could show improvements in symptom severity. Social interaction could also be a reason for higher adherence to interventions. As evidence points to exercise slowing the progression of the disease, living an active lifestyle as early as possible over the lifespan would logically be a useful prevention strategy. In Australia, there are foundations behind the research and treatment of Alzheimer’s, such as the Australian Alzheimer's research Foundation and the Brain Foundation in which general information can be obtained.

# References

* ↑ Alzheimer's Disease and Dementia. (2018). Facts and Figures. [online] Available at: [Accessed 16 Sep. 2018].
* ↑ Castellani, R. and Perry, G. (2012). Pathogenesis and Disease-modifying Therapy in Alzheimer's Disease: The Flat Line of Progress. Archives of Medical Research, 43(8), pp.694-698.
* ↑ Kulmala, J., Solomon, A., Kåreholt, I., Ngandu, T., Rantanen, T., Laatikainen, T., Soininen, H., Tuomilehto, J. and Kivipelto, M. (2014). Association between mid- to late life physical fitness and dementia: evidence from the CAIDE study. Journal of Internal Medicine, 276(3), pp.296-307.
* ↑ Sofi, F., Valecchi, D., Bacci, D., Abbate, R., Gensini, G., Casini, A. and Macchi, C. (2010). Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. Journal of Internal Medicine, 269(1), pp.107-117.
* ↑ Weuve, J. (2004). Physical Activity, Including Walking, and Cognitive Function in Older Women. JAMA, 292(12), p.1454.
* ↑ Forbes, D., Thiessen, E., Blake, C., Forbes, S. and Forbes, S. (2014). Exercise programs for people with dementia. Sao Paulo Medical Journal, 132(3), pp.195-196.
* ↑ Smith A (1982) Symbol Digit Modalities Test (SDMT) Manual (revised 1982), Western Psychological Services, Los Angeles.
* ↑ Rosen WG , Mohs RC , Davis KL (1984) A new rating scale for Alzheimer’s disease. Am J Psychiatry 141, 1356–1364.
* ↑ Golden C (1978) Stroop color and word test manual. Stoelting Co., Chicago
* ↑ Folstein MF , Folstein SE , McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12, 189–198.
* ↑ Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23, 56–62.
* ↑ Nascimento, C., Pereira, J., Andrade, L., Garuffi, M., Talib, L., Forlenza, O., Cancela, J., Cominetti, M. and Stella, F. (2014). Physical Exercise in MCI Elderly Promotes Reduction of Pro-Inflammatory Cytokines and Improvements on Cognition and BDNF Peripheral Levels. Current Alzheimer Research, 11(8), pp.799-805.
* ↑ Baker LD , Frank LL , Foster-Schubert K , Green PS , Wilkinson CW , McTiernan A , Plymate SR , Fishel MA , Watson GS , Cholerton BA , Duncan GE , Mehta PD , Craft S (2010) Effects of aerobic exercise on mild cognitive impairment: A controlled trial. Arch Neurol 67, 71–79.
* ↑ Ohman H , Savikko N , Strandberg TE , Pitkälä KH (2014) Effect of physical exercise on cognitive performance in older adults with mild cognitive impairment or dementia: A systematic review. Dement Geriatr Cogn Disord 38, 347–365
* ↑ Lamotte, G., Shah, R., Lazarov, O. and Corcos, D. (2016). Exercise Training for Persons with Alzheimer's Disease and Caregivers: A Review of Dyadic Exercise Interventions. Journal of Motor Behavior, 49(4), pp.365-377.