�������Different Modalities of Exercise and Their Effectiveness as a Treatment for Patients with Alzheimer’s Disease: A Proposed Study����Cesar Carrera �
Background
Alzheimer’s Disease (AD), the most common type of dementia, is a brain disorder caused by damage to nerve cells in the brain. Once the damage is done, it cannot be undone
AD is a progressive disease, developing gradually over time. It begins with mild memory loss and can lead to the inability to carry on a conversation, carry out daily activities, or respond to the environment
While changes in memory and thinking are a normal part of aging, AD is not. AD typically affects people aged 60 or older and the risk of incidence increases with age
Currently, there is no known cure for AD, but research suggests that being physically active can lower the risk of memory loss and slow the progression of the disease (Cass, 2017)
Fig. 1. Graphical abstract of main results. Abbreviations: 6MWD, 6-minute walking distance; 95%CI, 95% confidence interval; BBS, Berg balance scale; MD, mean difference; MMSE, mini-mental state examination; NPI, Neuropsychiatric Inventory. (López-Ortiz et al., 2021)
Literature Review
Research has looked at various modalities of prescribed exercise for AD treatment (Aerobic, Resistance, Flexibility, and Combined) (Yan et al., 2023)
Collectively, there are mixed results in both primary and secondary research
Some results suggest aerobic is the better modality to delay AD progression, others claim flexibility training is superior to aerobic in this context (Yu et al.,2021). Others claim resistance training shows the most potential (Huang et al., 2022)
Few analyses have found non-significant clinical benefit of exercise altogether for PwAD (Lamb et al., 2018)
Overall, research has supported exercise as a treatment for patients with Alzheimer's disease (PwAD) in slowing the progression of AD and significantly improving other aspects such as quality of life (QOL)
Fig. 2 Graphical abstract: main results of the umbrella review. *Not specifying the test used to assess global cognition and physical function. Abbreviations: ADL activities of daily living, BBS Berg Balance Scale, CI confidence interval, FRT Functional Reach Test, MD mean difference, OR odds ratio, PA physical activity, SMD standardized mean. (López-Ortiz et al., 2022)
Rationale
Results of prior research has left people affected by AD in the dark. It is still unclear which modality or modalities of exercise are most effective for delaying progression of AD and improving QOL in PwAD
Barriers to exercise for PwAD include cognitive impairments (forgetting the exercise), physical limitations (gait and balance impairments), lack of social support, and lack of safe and suitable environments
If exercise can slow the progression of AD, but barriers keep patients from exercising, it is important to study exercise as a treatment for AD, as significant clinical benefits would outweigh risks and barriers for PwAD
Further research is needed to find the most beneficial and appropriate exercise protocols for PwAD
Fig. 3 Scores on STROOP, 6-meter walking speed and leg strength for the intervention vs. control group. There were no beneficial effects of the exercise vs. control group on cognitive function.
Purpose and Hypothesis
The purpose of this study is to delve deeper into the literature, identify gaps in research, and help in the development of practical guidelines for exercise prescription in PwAD
Out of the different modalities of exercise, it is hypothesized that a combined training exercise modality (aerobic and resistance) paired with cognitive training will be the most beneficial regarding the delay of AD progression and in improving QOL
6
N=200 (100 male [24 w/ MCI; 27 w/ AD]; 100 female [24 w/ MCI; 25 w/ AD]; 60-75 years old)
Inclusion: Mild Cognitive Impairment (MCI) or AD. No comorbidities. Physically active. Currently enrolled in a exercise treatment protocol
MCI is a high-risk factor for AD
Participants randomly assorted into 3 groups : Aerobic Group, Resistance Training Group, Lag Control which will later be the Combination Training Group (Resistance and Aerobic Training)
Resistance: 8 MCI and 9 AD male; 8 MCI and 9 AD female
Aerobic: 8 MCI and 9 AD male; 8MCI and 9 AD female
Combination/Lag Control: 8 MCI and 9 AD male; 8MCI and 9 AD female
Methodology – Participants
7
Pretest/posttest lag control group design with two 12-wk iterations. Groups assessed before (pretest) and after (posttest 1) the first iteration.
Participants who serve as the lag control receive the intervention during iteration 2 and are assessed a third time at the end of this iteration (posttest 2).
This design was chosen as an ethical means of implementing a health promoting intervention without withholding treatment from research participants.
Methodology - Design
Methodology – Dependent Variables –Primary Outcomes
- CVF
VO2submax
-Muscular Strength
10 repetition maximum (10 RM) on bench and seated leg press
Handgrip strength
- Muscular Endurance
Push up and Ab Crunch tests till failure
- Body Composition
Height, weight, waist to hip ratio (WHR), skin-fold measurements
- Disease Progression
Cognitive Function: Alzheimer's Disease Assessment Scale – Cognitive (ADAS-Cog)
Functional Independence: Barthel Index (ADL)
Methodology – Dependent Variables- Secondary Outcomes
- Quality of Life
Mental Health: Neuropsychiatric Inventory (NPI)
Functional Independence: Barthel Index (ADL)
Cognitive Function: Mini-Mental State Examination (MMSE)
- Physical Function
Berg Balance Scale (BBS)
6 Minute Walk Test (6MWT)
Functional Reach Test (FRT)
Methodology – Independent Variable
75 min of planned exercise training. Progressive overload will be emphasized on a weekly basis either through more intensity or more volume, when appropriate. All groups (including control) will be receiving cognitive training in addition to treatment. Cognitive training to be conducted before treatment sessions.
Resistance
Compound lifts 2xweek upper and lower body split. Chest press variations, row variations, squat variations and ab crunches.
Aerobic
Steady state cardiovascular training 3xweek at 60% max heart rate. At least 150 min/week of Cycling or walking on inclined treadmill.
Combined (lag Control)
Compound lifts 2xweek upper and lower body split. Chest press variations, row variations, squat variations and ab crunches. Steady state cardiovascular training 2xweek at 60% max heart rate. Cycling or walking on inclined treadmill
Statistical Analysis
A series of 3 (treatment vs control) X 2 (pre vs post) mixed factorial analyses of variance (3x2 mixed factorial ANOVAs) will be used to assess the effects of the exercise interventions on body composition, cardiovascular, strength, muscular endurance, and disease progression outcomes
There will also be an analysis for the secondary outcomes: Physical function and Quality of Life
Anticipated findings
Although aerobic exercise seems to be more researched and therefore more supported to aid in the improvement of cognitive function and improvement of quality of life in PwAD, there is a lack of research on the effects resistance training has on this disease. We cannot fully exclude resistance training from being a potentially more effective modality for AD treatment.
Therefore, it is anticipated that when paired with cognitive training, combined exercise training (aerobic and resistance training) will be most effective in slowing cognitive decline and improving overall health and quality of life.
Fig. 3. Forrest plot for efficacy of combined cognitive-physical intervention compared to control group. A standardized difference in means > 0 favors intervention and < 0 favors the control arm. Box size represents study weighing. Diamond represents overall effect size and 95% confidence intervals. Notes: AD = Alzheimer’s disease; MCI = mild cognitive impairment; MMSE = Mini–Mental State Examination; ADAS-Cog = Alzheimer’s Disease Assessment Scale-Cognitive Subscale. (Karssemeijer et al., 2017)
Conclusion
About 6.9 million people in the United States age 65 and older live with AD.
There is no cure for AD and severe AD can lead to dehydration, poor nutrition or infection. These complications can result in death. (Mayo Clinic, 2024)
With such high risk of incidence, it is necessary to further research this disease and to discover how we can treat, manage, and prevent it
Exercise has been a supported treatment for improving QOL and cognitive function in PwAD
This study eagerly anticipates that a combined exercise modality when paired with cognitive training will be the better option for AD treatment. Results from the current study will support these claims
References