Dementia is a persistent intellectual disability with complex etiology. There are more than a hundred diseases that can cause dementia, both genetic and acquired environmental influences and triggers. The most common type of dementia in the elderly is Alzheimer’s disease (AD), in which the most important pathological change in the brain is the senile plaque composed of the core of β-amyloid-β (Aβ), followed by neurogenic fiber tangles and amyloid angiopathy. In recent years, the incidence of AD has been increasing year by year and has become one of the major diseases that seriously threaten the health of life and quality of life of the elderly.
According to the annual report of Alzheimer’s Disease International (AD International), in 2010, there were 758.54 million people older than 60 years old worldwide, of which about 4.7%, or 35.56 million people, suffered from various degrees of AD. By 2030 and 2050, this number will increase significantly, reaching 65.69 million and 115.38 million respectively, with a particular focus on The most rapid increase will be in developing countries with large populations, such as China and India. Since AD patients are unable to take care of themselves and require long-term personal care, it has become a social problem that cannot be ignored because of the pain it causes to patients and the heavy economic and psychological burden it imposes on families and society. A 2005 study by the Karolinska Institute in Sweden estimated that the global cost of dementia, including non-direct costs, is upwards of $300 billion per year, with AD accounting for the vast majority.
To date, no effective cure for AD has been found. Current first-line therapeutic drugs for AD, such as acetylcholinesterase inhibitors, can only alleviate early cognitive impairment in patients and cannot stop the progression of the disease, making the search for anti-AD drugs with therapeutic effects a current hot topic in drug development. In recent years, several promising new drugs, such as Pfizer’s Latrepirdine and Eli Lilly’s Semagacestat, have failed in phase III clinical trials, leading people to re-examine AD treatment strategies, mainly focusing on the understanding of AD pathogenesis, diagnostic flaws, target selection and clinical protocol design. In addition to marketed drugs, as of 2010, there are more than 130 AD-related drugs listed in Pharmaprojects, the world’s repository of drug research and development information, and hundreds more are in preclinical studies. These drugs include small molecule compounds, vaccines, antibodies, special agents, as well as neuronal regeneration and stem cell therapy, making the search for new ways to stop the incidence of AD a serious issue.
Since drug-based treatments for AD are costly and only delay progression, not cure, researchers are again focusing their attention on other approaches such as lifestyle interventions. The recognized risk factors for the development of AD include health status, dietary habits, genetics, gender, education, and lifestyle, and interventions for these factors may provide a new direction for the treatment of AD. Among all of these influencing factors, physical activity has gradually been found to be the best implemented and potentially effective intervention.
Epidemiological studies have found that people who are more physically active have a reduced risk of developing AD, and those who already have dementia show significant improvements in cognitive function after a certain amount of physical activity. followed 5925 women, all older than 65 years, for 6 to 8 years after recording their respective exercise habits and exercise patterns. Weuve and his group followed 18,766 nurses, and the results were consistent with Yaffe’s, in that more exercise was associated with a lower risk of dementia. Last year Middleton published a report showing that people who were more active, especially in their younger years, had a lower risk of dementia in later life, and Abbott reported that his study of 2,257 men, who walked less than 0.25 miles per day, had a more than 1.8-fold risk of dementia compared with those who walked more than 2 miles per day. A recent meta-analysis by Hamer and Chida, which included 16 measures of exercise, with 163,797 controls and 3219 patients with dementia, showed that exercise was effective in preventing and treating dementia. More recently, Angevaren et al. systematically reviewed 11 aerobic exercise programs in healthy older adults, and eight of them reported that physical exercise improved cognitive function .
There are many hypotheses about the mechanism by which physical exercise can improve dementia patients, such as moderate intensity exercise can reduce various stress responses, promote the release of neurotransmitters such as pentraxin, dopamine, acetylcholine, and norepinephrine, and increase the amount of ATP in the brain, which acts as a vasodilator and increases cerebral blood flow, and some studies have also confirmed that during exercise, specific sites such as the hippocampus cerebral blood flow supply is increased when exercise is performed. The level of cerebral blood flow is also dependent on the level of NO, and exercise increases NO synthesis in the vascular endothelium, improving angiogenesis and increasing cerebral blood supply. However, apart from epidemiological data, there is no systematic basic research on whether physical exercise can treat AD and its mechanism of action.
Nerve growth factor in the brain, especially in the hippocampus, decreases significantly with increasing age in both normal elderly people and AD patients, and is positively correlated with the condition of dementia. Animal studies have demonstrated that brain derived neurotrophic factor (BDNF) is essential for maintaining hippocampal function, synaptic plasticity, learning ability, and regulation of depression, and the Rowe study found that the expression and function of BDNF in the brain are severely affected during the development of AD. Pedersen BK found that BDNF can regulate the level of beta amyloid, and in the blood, the two concentrations are inversely proportional. They found that physical exercise can increase the synthesis and release of BDNF to improve cognitive function and delay the progression of dementia.
From the above, we can see that AD treatment is facing an awkward situation. On the one hand, the efficacy of drug treatment is uncertain and expensive, and the development of new drugs frequently fails, on the other hand, the incidence of dementia is increasing year by year, which brings an extremely heavy burden to families and society, so there is an urgent need to find other ways to treat dementia. The above information shows that physical exercise is a very promising means of treating or preventing dementia, and we should think about the possibility of preventing and treating dementia by improving lifestyle and increasing physical exercise in addition to medication when treating AD patients. Because the motor function of mild to moderate AD patients is basically unaffected, they are fully capable of simple physical exercise for therapeutic purposes.