Exercise as it relates to Disease/The effect of physical activity on major outcomes associated with Alzheimer's dementia

This page is critiquing the article 'Effects of Physical Activity Training in Patients with Alzheimer’s Dementia: Results of a Pilot RCT Study' conducted by Holthoff V, Marschner K, Scharf M, Steding J, Meyer S, Koch R, and Donix M, published in the Public Library of Science Journal in 2015.

What is the background to this research?

 * This study investigates the effect of a home-based physical activity training program on functional ability, clinical symptoms and caregiver burden in patients diagnosed with Alzheimer's disease after 12 and 24 weeks. The primary outcome measure related to performance in activities of daily living.
 * While current research confirms the cognitive benefits of physical activity on the ageing brain, less has been confirmed regarding the effect it may have on people currently diagnosed with Alzheimer's disease.
 * With the incidence of Alzheimer's disease predicted to rise, researching ways to prevent further decline and maintain quality of life in people diagnosed or at risk of Alzheimer's will prove beneficial in the future. Considering there is currently no direct treatment for Alzheimer's, it is urgent to find a away to delay its progress.
 * Physical activity is a cost effective and sustainable way to reduce the burden of this disease.  However, current research fails to provide specific practical recommendations concerning the types, frequency, intensity and duration of physical activity that may be protective against Alzheimer's disease or further decline once diagnosed.

Where is the research from?

 * This research article is published in the Public Library of Science (PLOS one) Journal.
 * The authors of this research have multiple published studies in the area of brain health. However, this does appear to be one of the few studies conducted by these authors that involve a physical activity intervention.
 * While the paper was sponsored, there was no financial sponsoring or scientific contributions by the sponsor. There does not appear to be any conflict of interest or bias in the findings due to this sponsorship.

What kind of research was this?

 * This research was a pilot randomised control trial (RCT) study. This is considered high/moderate quality evidence.
 * In terms of level of evidence, this article is limited by the fact that it is a pilot study. It is therefore categorised as unfiltered information.
 * In the absence of a well-designed systematic review, a RCT is the best research design to investigate prevention and treatment of a condition, such as in the case of physical activity and Alzheimer’s disease.

What did the research involve?
Methodology
 * A total of 30 participants (aged 72.4 +/- 4.3 years) were randomised to either a home-based 12-week physical activity intervention or a control group which involved usual care.
 * Participants in the physical activity intervention group completed 30-minute sessions, 3 times per week with at least one day between sessions. These sessions were conducted with a floor-based ergometer, from a seated position in a chair familiar to the participant. The program changed between passive, motor-assisted, active resistance leg training and change of direction on the movement trainer in order to combine physical and cognitive stimuli.
 * The use of a RCT is appropriate for the desired outcomes of this study.
 * However, the methodology could be improved with the addition of an active control group. This could provide additional information relevant to the potential existence of a dose/intensity-response relationship between physical activity and the major outcomes being investigated.
 * By monitoring the participants response to the exercise, simply by measuring rate of perceived exertion, this would allow a more comprehensive evaluation of the intensity required to induce the changes observed in the results of this study.
 * The study is valid in assessing the effects of physical activity, in combination with cognitive stimulation on patient's with Alzheimer's disease.
 * The reliability of the study may be questioned given the limitations of the study. While the main results of this study support the available literature, a confirmatory study is required, as recognised by the authors.

Limitations
 * Major limitations of the study design include the small sample size, relatively brief intervention in relation to the chronic nature of the disease and the lack of an active control group.
 * There is no specific investigation regarding the additional cognitive stimuli that complimented the physical activity, or how this additional stimulus may be associated with independent effects on some outcome parameters. This makes it difficult to confirm where the effect of the intervention came from.

What were the basic results?

 * A significant difference was observed in the activities of daily living (ADL) total score between the intervention and control group. The control group experienced decreases in ADL performance at week 12 and 24 whereas patients in the intervention group remained stable.
 * Analysis of executive function and language ability revealed considerable improvements in the intervention group in terms of semantic word fluency, while the control group continued worsening.
 * Analysis of the specific behavioural symptoms including depression and anxiety revealed clinically relevant worsening in the controls.
 * Caregiver burden remained stable in the intervention group but worsened in the control group. The researchers attributed this to the behavioural symptoms or lack off. This may be an over-emphasis due to the potential bias as a result of the non-blinding of the caregivers to the intervention.
 * The intervention did not have an effect on the daily activity of participants beyond the study, as measured with a pedometer in the week before and after the intervention. This was interpreted by authors as support for the attractiveness of physical activity training at home to increase the habitual activity level per week.

What conclusions can we take from this research?

 * The conclusions made by the authors suggest that physical activity on a movement trainer in a home-based setting, which combines cognitive and physical demands, might be an effective way to promote physical activity training in patients with Alzheimer’s and modulate caregiver burden.
 * The authors suggest a transfer of benefit to activities of daily living as well as cognitive and physical skills that determine functional abilities in patients with Alzheimer’s Dementia.
 * The conclusions that I have drawn from the results are quite similar. The results certainly suggest a positive correlation between physical activity and the major outcomes of the study but the specific dose and type of exercise is unclear due to the lack of patient monitoring during the intervention.
 * The main findings of this study are confirmed in recent research. A recent meta-analysis assessing the effect of physical activity on cognitive function in diagnosed Alzheimer’s patients demonstrated that physical activity supports improved cognition. Subgroup analysis revealed different levels of outcomes were associated with varied ranges of physical activity although a dose-response relationship was still unable to be established.

Practical advice

 * This article provides practical advice for the general public, health practitioners and also future researchers.
 * For people diagnosed with Alzheimer's disease, incorporating some form of physical activity into a daily/weekly routine may help to prevent the worsening of major symptoms.
 * For researchers interested in confirming a dose-response relationship between physical activity and Alzheimer's, a study which resembles a large randomised control trial, free of bias, with multiple intervention groups may be useful.

Further information/resources
Support resources Related research
 * www.dementia.org.au
 * www.health.gov.au/physicalactivityguidelines
 * The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer Disease
 * Effects of physical activity and exercise on the cognitive function of patients with Alzheimer disease: a meta-analysis