Exercise and Alzheimer’s Disease

Improving Cognition Through Exercise - Part 2

Julia Basso , PhD

Affiliation: New York University, Center for Neural Science

As we age, many of us experience problems with memory.  In some cases, these issues may progress to Mild Cognitive Impairment or dementia.  Dementia is a disorder characterized by significant cognitive impairment. This impairment occurs most frequently in the areas of learning, memory, and language. These are the areas that interfere with everyday living and independence.  The most common cause of dementia (60-70% of cases) is Alzheimer’s disease (AD).  AD is a degenerative disorder of the brain typified by memory loss, problems in planning or problem solving, confusion with time or place, and changes in mood including depression. Unfortunately, these symptoms worsen over time and in later stages. Individuals who suffer from AD often need full-time care.  And, in the United States, 11% of individuals who are 65 or older have AD, with the majority (i.e., 82%) being older than 75. 

How Alzheimer’s Disease Works

Alzheimer’s disease is caused by a series of changes in the brain that ultimately lead to cell death.  In and around the cells of the brain (neurons), irregular protein formations occur. These formation create what are known as plaques (accumulation of beta-amyloid outside of neurons) and tangles (accumulation of tau inside of neurons), which are characteristic markers of AD. These irregular protein formations cause neurons to malfunction and die. As a result, this leads to significant loss of brain volume, especially in areas involved in learning and memory such as the hippocampus and cortex.

Why a person develops Alzheimer’s disease is not completely known. However, certain factors increase your risk of developing this disease. These include old age, a genetic predisposition (e.g., having the APOE-ε4 allele), a history of traumatic brain injury, a current diagnosis of Mild Cognitive Impairment (MCI), past or present cardiovascular disease, or limited education (i.e., the cognitive reserve hypothesis).  Additionally, lifestyle factors are starting to be acknowledged as contributing to this disease.  Specifically, people who engage in limited social interactions, cognitive stimulation, or physical activity have an increased risk for developing AD.

How We Can Help Our Brains

AD is certainly not an inevitable result of aging. One thing we can do to help our brains age in a healthy way is to exercise.  Scientists use rodent models to assess the effects of exercise on Alzheimer’s disease. These studies suggest that physical activity has beneficial effects on both the symptoms and underlying pathology of the disease.  For example, five months of voluntary running in AD rodents improved the ability to learn as well as decreased the beta-amyloid plaques in both the hippocampus and cortex (Adlard et al., 2005). 

Of course, five months is a long time in a rodent whose lifespan may only be two years.  Fortunately, shorter exercise interventions have also proved helpful!  Specifically, three weeks of running in AD rodents resulted in cognitive improvements as well as a decreased immune response in the brain, suggesting that exercise helps the AD brain to heal (Parachikova et al., 2008).

Exercise and Alzheimer's DiseaseExercise vs. Pharmacological Treatment

In humans, exercise has been shown to be an effective non-pharmacological treatment for Alzheimer’s disease in terms of both prevention and the slowing down of disease progression (Radak et al., 2010; Farina et al., 2014).  Unfortunately, no drugs are currently available to cure the disease and current pharmacological treatments merely help with symptom improvement. As a result, it is necessary to find non-pharmacological treatments that can help decrease the rate at which the disease advances.  Cross-sectional studies have shown that high levels of habitual physical activity enhance cognitive functioning in aging (Colcombe & Kramer, 2003), reduce the risk of dementia (Buchman et al., 2012), and decrease levels of proteins, such as beta-amyloid, that contribute to AD pathology (Brown et al., 2013). 

Additionally, several randomized-controlled trials have been conducted to examine whether long-term exercise can slow down cognitive decline after a clinical diagnosis of dementia has been made.  A recent meta-analysis examined 18 studies that included a total of 802 patients with dementia (Groot et al., 2016).  Even after disease onset, physical activity proved beneficial for cognitive functioning, with these improvements corresponding to improvements in activities of daily living.  Furthermore, the interventions that were most effective were those that were aerobic, rather than non-aerobic in nature. 

Takeaways

This collection of research indicates that exercise is helpful to improve brain functioning as we age and is even beneficial in instances of cognitive impairment or dementia. Excitingly, physical activity has the power to help stave off cognitive decline as well as improve symptoms of Alzheimer’s disease and other dementias.  At this point, aerobic exercise appears to be more useful than other non-aerobic forms of exercise to improve cognitive functioning; however, more research is warranted to examine what the best exercise prescription may be. Of course, when dealing with a diagnosis of AD, finding the energy, motivation, or resources to exercise may prove difficult.  Therefore, families and friends of individuals who suffer from this neurodegenerative disorder should encourage their loved ones to exercise.  This simple intervention will help to support positive mood and enhance cognitive functioning in this patient population.

References:

Adlard, P. A., Perreau, V. M., Pop, V., & Cotman, C. W. (2005). Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. The Journal of neuroscience, 25(17), 4217-4221.

Brown, B. M., Peiffer, J. J., Taddei, K., Lui, J. K., Laws, S. M., Gupta, V. B., … & Rainey-Smith, S. R. (2013). Physical activity and amyloid-β plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing. Molecular psychiatry18(8), 875-881.

Buchman, A. S., Boyle, P. A., Yu, L., Shah, R. C., Wilson, R. S., & Bennett, D. A. (2012). Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology78(17), 1323-1329.

Colcombe, S., & Kramer, A. F. (2003). Fitness effects on the cognitive function of older adults a meta-analytic study. Psychological science14(2), 125-130.

Farina, N., Rusted, J., & Tabet, N. (2014). The effect of exercise interventions on cognitive outcome in Alzheimer’s disease: a systematic review. International Psychogeriatrics26(01), 9-18.

Groot, C., Hooghiemstra, A. M., Raijmakers, P. G. H. M., van Berckel, B. N. M., Scheltens, P., Scherder, E. J. A., … & Ossenkoppele, R. (2016). The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageing research reviews25, 13-23.

Parachikova, A., Nichol, K. E., & Cotman, C. W. (2008). Short-term exercise in aged Tg2576 mice alters neuroinflammation and improves cognition. Neurobiology of disease, 30(1), 121-129.

Radak, Z., Hart, N., Sarga, L., Koltai, E., Atalay, M., Ohno, H., & Boldogh, I. (2010). Exercise plays a preventive role against Alzheimer’s disease. Journal of Alzheimer’s Disease20(3), 777-783.

   

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