Alzheimer's risk reduced 45% by physical activity - several studies

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Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence - (45%) June 2008

The RR of dementia in the highest physical activity category compared with the lowest was 0.72 [95% confidence interval (CI) 0.60–0.86, p<0.001],
for Alzheimer's, 0.55 (95% CI 0.36–0.84, p=0.006), and
for Parkinson's 0.82 (95% CI 0.57–1.18, p=0.28).

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Neuroprotective mechanisms of exercise and the importance of fitness for healthy brain ageing - Lancet March 2025

Lancet Volume 405, Issue 10484p1093-1118 March 29, 2025 PDF is behind paywall
Atefe R Tari, PhDa,c,* ∙ Tara L Walker, PhDd,* ∙ Aleksi M Huuha, MSca,c ∙ Sigrid B Sando, PhDb,c ∙ Prof Ulrik Wisloff, PhDa ulrik.wisloff at ntnu.no

Ageing is a scientifically fascinating and complex biological occurrence characterised by morphological and functional changes due to accumulated molecular and cellular damage impairing tissue and organ function. Ageing is often accompanied by cognitive decline but is also the biggest known risk factor for Alzheimer's disease, the most common form of dementia. Emerging evidence suggests that sedentary and unhealthy lifestyles accelerate brain ageing, while regular physical activity, high cardiorespiratory fitness (CRF), or a combination of both, can mitigate cognitive impairment and reduce dementia risk. The purpose of this Review is to explore the neuroprotective mechanisms of endurance exercise and highlight the importance of CRF in promoting healthy brain ageing.
Key findings show how CRF mediates the neuroprotective effects of exercise via mechanisms such as improved cerebral blood flow, reduced inflammation, and enhanced neuroplasticity.
We summarise evidence supporting the integration of endurance exercise that enhances CRF into public health initiatives as a preventive measure against age-related cognitive decline. Additionally, we address important challenges such as lack of long-term studies with harmonised study designs across preclinical and clinical settings, employing carefully controlled and repeatable exercise protocols, and outline directions for future research.

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Chronic physical activity and the prevention of Alzheimer's disease - Sept 2025

Psychology of Sport and Exercise Volume 80, September 2025, https://doi.org/10.1016/j.psychsport.2025.102875

The growing population of older adults and the lack of cure for Alzheimer's disease (AD) has resulted in researchers identifying modifiable lifestyle factors that might prevent or slow the progression of the disease. Prospective studies exploring the relationship between baseline physical activity (PA) and the subsequent risk of a diagnoses of AD and randomized controlled trials (RCTs) testing the effects of aerobic exercise (AE) and resistance exercise (RE) on cognitive performance, blood-based biomarkers of AD, and neuroimaging measures of brain health provide some intriguing results. Exemplars of these studies and results from meta-analytic reviews (when available) are presented to provide an overview of the state of the science. In general, results from prospective studies show that PA is protective, and results from RCTs show that AE improves cognitive performance by older adults who are cognitively normal and by those with mild cognitive impairment. Promising results have been observed for AE on measures of brain health, and studies exploring the effects on biomarkers have yielded some intriguing results but are less consistent to date. Studies testing the effects of RE also find benefits for cognitive performance by older adults and consistently show improvements in brain health. In conclusion, results from prospective studies and RCTs demonstrate the potential of exercise to improve cognition, brain health, and, to a lesser extent, blood-based biomarkers. Future research linking the magnitude of the findings from RCTs with evidence from prospective studies will advance our understanding of the potential of exercise to reduce the risk of AD.
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Exercise Delays Brain Ageing Through Muscle-Brain Crosstalk - March 2025

Cell Proliferation 24 March 2025 https://doi.org/10.1111/cpr.70026
Shirin Pourteymour, Rakesh Kumar Majhi, Frode A. Norheim, Christian A. Drevon

Ageing is often accompanied by cognitive decline and an increased risk of dementia. Exercise is a powerful tool for slowing brain ageing and enhancing cognitive function, as well as alleviating depression, improving sleep, and promoting overall well-being. The connection between exercise and healthy brain ageing is particularly intriguing, with exercise-induced pathways playing key roles. This review explores the link between exercise and brain health, focusing on how skeletal muscle influences the brain through muscle–brain crosstalk. We examine the interaction between the brain with well-known myokines, including brain-derived neurotrophic factor, macrophage colony-stimulating factor, vascular endothelial growth factor and cathepsin B. Neuroinflammation accumulates in the ageing brain and leads to cognitive decline, impaired motor skills and increased susceptibility to neurodegenerative diseases. Finally, we examine the evidence on the effects of exercise on neuronal myelination in the central nervous system, a crucial factor in maintaining brain health throughout the lifespan.
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Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer’s disease - Feb 2024

Journal of Neuroinflammation Volume 21, article number 40, (2024)

Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD), characterized by the stimulation of resident immune cells of the brain and the penetration of peripheral immune cells. These inflammatory processes facilitate the deposition of amyloid-beta (Aβ) plaques and the abnormal hyperphosphorylation of tau protein. Managing neuroinflammation to restore immune homeostasis and decrease neuronal damage is a therapeutic approach for AD.
One way to achieve this is through exercise, which can improve brain function and protect against neuroinflammation, oxidative stress, and synaptic dysfunction in AD models. The neuroprotective impact of exercise is regulated by various molecular factors that can be activated in the same way as exercise by the administration of their mimetics.
Recent evidence has proven some exercise mimetics effective in alleviating neuroinflammation and AD, and, additionally, they are a helpful alternative option for patients who are unable to perform regular physical exercise to manage neurodegenerative disorders. This review focuses on the current state of knowledge on exercise mimetics, including their efficacy, regulatory mechanisms, progress, challenges, limitations, and future guidance for their application in AD therapy.
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Effectiveness of exercise for improving cognition, memory and executive function: a systematic umbrella review and meta-meta-analysis - 2024

British Journals of Sports Medicine https://doi.org/10.1136/bjsports-2024-108589
Ben Singh1, Hunter Bennett1, Aaron Miatke1,Dorothea Dumuid1, Rachel Curtis1, Ty Ferguson1, Jacinta Brinsley1, Kimberley Szeto1, Jasmine M Petersen1, Claire Gough2, Emily Eglitis1, Catherine EM Simpson1,9Christina L Ekegren3, Ashleigh E Smith1, Kirk I Erickson4,5, Carol Maher1

Objective To evaluate systematic reviews of randomised controlled trials (RCTs) on the effects of exercise on general cognition, memory and executive function across all populations and ages.

Methods Systematic reviews and meta-analyses of RCTs evaluating the effects of exercise on general cognition, memory and executive function were eligible. Data extraction and risk of bias scoring were conducted in duplicate. The A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) was used to assess the risk of bias. Effect sizes were pooled using random effects models and reported as standardised mean differences (SMD). Subgroup analyses were conducted for participant and intervention characteristics.

General cognition, memory and executive function.

Data sources CINAHL, The Cochrane Library, Embase, MEDLINE via OVID, Emcare, ProQuest Central, ProQuest Nursing and Allied Health Source, PsycINFO, Scopus, Sport Discus and Web of Science.

Results 133 systematic reviews (2,724 RCTs and 258 279 participants) were included.
Exercise significantly improved

• general cognition (SMD=0.42),
• memory (SMD=0.26) and
• executive function (SMD=0.24).

Memory and executive function improvements from exercise were greater for children and adolescents than for adults and older adults. Those with attention-deficit/hyperactivity disorder exhibited greater improvement in executive function than other populations. Effects were generally larger for low- and moderate-intensity interventions. Shorter interventions (1–3 months) and exergames (video games that require physical movement) had the largest effects on general cognition and memory. Findings remained statistically significant after excluding reviews rated as low and critically low quality.

Conclusions These findings provide strong evidence that exercise, even light intensity, benefits general cognition, memory and executive function across all populations, reinforcing exercise as an essential, inclusive recommendation for optimising cognitive
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Understanding the mechanisms of disease modifying effects of aerobic exercise in people with Alzheimer’s disease - Feb 2024

Ageing Research Reviews Volume 94, February 2024, https://doi.org/10.1016/j.arr.2024.102202 partial PDF with 164 references is online

Alzheimer’s disease (AD) is a very disabling disease. Pathologically, it is characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain that results in neurodegeneration. Its clinical manifestations include progressive memory impairment, language decline and difficulty in carrying out activities of daily living (ADL).
The disease is managed using interventions such as pharmacological interventions and aerobic exercise.
Use of aerobic exercise has shown some promises in reducing the risk of developing AD, and improving cognitive function and the ability to carry out both basic and instrumental ADL.
Although, the mechanisms through which aerobic exercise improves AD are poorly understood,
improvement in

• vascular function,
• brain glucose metabolism and cardiorespiratory fitness,
• increase in antioxidant capacity and haemoglobin level,
• amelioration of immune-related and inflammatory responses,
• modulation of concentration of circulating Neurotrophins and peptides and
• decrease in concentration of tau protein and cortisol level

among others seem to be the possible mechanisms. Therefore, understanding these mechanisms is important to help characterize the dose and the nature of the aerobic exercise to be given. In addition, they may also help in finding ways to optimize other interventions such as the pharmacological interventions. However, more quality studies are needed to verify the mechanisms.

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Physical exercise in the prevention and treatment of Alzheimer's disease - Feb 2020

J Sport Health Sci. 2020 Feb 4;9(5):394–404. doi: 10.1016/j.jshs.2020.01.004
Adrian De la Rosa a,†, Gloria Olaso-Gonzalez a,†, Coralie Arc-Chagnaud a,b, Fernando Millan a, Andrea Salvador-Pascual a, Consolacion García-Lucerga c, Cristina Blasco-Lafarga d, Esther Garcia-Dominguez a, Aitor Carretero a, Angela G Correas a, Jose Viña a,⁎, Mari Carmen Gomez-Cabrera a,⁎

Highlights
•Low levels of physical activity are a risk factor associated with Alzheimer's disease.
•Older adults who exercise are more likely to maintain cognition.
•Exercise modulates amyloid β turnover, inflammation, synthesis, and release of neurotrophins, and cerebral blood flow.

Dementia is one of the greatest global challenges for health and social care in the 21st century. Alzheimer's disease (AD), the most common type of dementia, is by no means an inevitable consequence of growing old. Several lifestyle factors may increase, or reduce, an individual's risk of developing AD. Much has been written over the ages about the benefits of exercise and physical activity. Among the risk factors associated with AD is a low level of physical activity.
The relationship between physical and mental health was established several years ago.
In this review, we discuss the role of exercise (aerobic and resistance) training as a therapeutic strategy for the treatment and prevention of AD.
Older adults who exercise are more likely to maintain cognition. We address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal studies. We will pay especial attention to the potential role of exercise in the modulation of amyloid β turnover, inflammation, synthesis and release of neurotrophins, and improvements in cerebral blood flow. Promoting changes in lifestyle in presymptomatic and predementia disease stages may have the potential for delaying one-third of dementias worldwide. Multimodal interventions that include the adoption of an active lifestyle should be recommended for older populations.
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