Physical Exercise, a Potential Non-Pharmacological Intervention for Attenuating Neuroinflammation and Cognitive Decline in Alzheimer’s Disease Patients

Abstract

This narrative review summarises the evidence for considering physical exercise (PE) as a non-pharmacological intervention for delaying cognitive decline in patients with Alzheimer’s disease (AD) not only by improving cardiovascular fitness but also by attenuating neuroinflammation. Ageing is the most important risk factor for AD. A hallmark of the ageing process is a systemic low-grade chronic inflammation that also contributes to neuroinflammation. Neuroinflammation is associated with AD, Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders. Pharmacological treatment of AD is currently limited to mitigating the symptoms and attenuating progression of the disease. AD animal model studies and human studies on patients with a clinical diagnosis of different stages of AD have concluded that PE attenuates cognitive decline not only by improving cardiovascular fitness but possibly also by attenuating neuroinflammation. Therefore, low-grade chronic inflammation and neuroinflammation should be considered potential modifiable risk factors for AD that can be attenuated by PE. This opens the possibility for personalised attenuation of neuroinflammation that could also have important health benefits for patients with other inflammation associated brain disorders (i.e., Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders). In summary, life-long, regular, structured PE should be considered as a supplemental intervention for attenuating the progression of AD in human. Further studies in human are necessary to develop optimal, personalised protocols, adapted to the progression of AD and the individual’s mental and physical limitations, to take full advantage of the beneficial effects of PE that include improved cardiovascular fitness, attenuated systemic inflammation and neuroinflammation, stimulated brain Aβ peptides brain catabolism and brain clearance.

Research trends and hotspots of exercise for Alzheimer’s disease: A bibliometric analysis

“…This finding suggests that the exercise-based rehabilitation and prevention of AD are typically multidisciplinary collaborative effort. The etiology of AD is closely related to neuroscience and aging ( Atri, 2019 ; Ribaric, 2022 ). Meanwhile exercise intervention and prevention belong to the category of sports science and rehabilitation, and their mechanism research involves behavior, cognition, physiology, and biochemistry.…”

“…By analyzing the journals about exercise and AD, we determined that researchers concentrated in the fields of neuroscience and geriatrics. Among them, the Journal of Alzheimer's disease ( 73 (Atri, 2019;Ribaric, 2022). Meanwhile exercise intervention and prevention belong to the category of sports science and rehabilitation, and their mechanism research involves behavior, cognition, physiology, and biochemistry.…”

“…Exercise is considered an important lifestyle modification that can help delay the beginning of cognitive deterioration and improve the quality of life of patients with AD ( Lautenschlager et al, 2008 ; Petersen et al, 2018 ). Numerous studies have found that aerobic exercise, resistance exercise, and cognitive–physical exercise can help patients with AD in many aspects, such as improving cardiovascular fitness, attenuating neuroinflammation, and supporting the brain clearance of Aß peptides ( Karssemeijer et al, 2017 ; Morris et al, 2017 ; Sun et al, 2018 ; Ribaric, 2022 ). Given the increase in the number of publications about the use of exercise in treating AD, identifying research trends and hotspots is highly significant.…”

“…The software tool, CiteSpace, is used to show a visual map of bibliometric results, such as journals, authors, institutes, keywords, citations, popular topics, and frontiers. Some reviews on the use of exercise to treat AD with different emphases have been published; however, a comprehensive and visualized analysis remains lacking ( Karssemeijer et al, 2017 ; Ribaric, 2022 ). Therefore, we conduct a bibliometric analysis of exercise and AD research to reveal the dynamic development in this field.…”

Treadmill Exercise Modulates Intestinal Microbes and Suppresses LPS Displacement to Alleviate Neuroinflammation in the Brains of APP/PS1 Mice

“…Numerous studies have shown that exercise has promising preventive and ameliorative effects as an intervention strategy in systemic-onset AD [ 18 , 19 ]. However, it is not clear what role gut microbes play in the process of improving AD through exercise, and most studies have only been conducted on individual tissues or organs; thus, there is little definitive evidence to confirm whether there are interactions between the different systems.…”