Influence of Physical Exercise on Alzheimer's Disease: From Research to Practice

Resumen

In 2017, the World Health Organization declared dementia and Alzheimer's disease (AD) a global public health priority, necessitating action to reduce the risk of developing the disease and to improve its treatment and management. Physical activity and exercise have been shown to have beneficial effects in both the prevention and progression of AD, promoting healthy aging. However, the molecular mechanisms underlying these effects, the optimal type of exercise for maximum benefit, and the impact of exercise on overall mental and physical abilities (intrinsic capacity) remain unclear. The primary objective of this work was to investigate the impact of exercise on AD patients and analyze its effects on their clinical profile. To accomplish this, six specific aims were proposed, corresponding to the six studies that make up the main part of this thesis: i) to summarize the effects of physical activity/exercise on the pathophysiological molecular pathways underlying AD (study I); ii) to evaluate the impact of exercise interventions on AD patients cognitive function, physical function, functional independence, and neuropsychiatric symptoms (study II); iii) to summary the evidence on the relationship between PA or exercise and the risk of AD, as well as the impact of exercise interventions on the progression of AD (study III); iv) to examine the effect of moderate-intensity functional training (MIFT), with short-duration sessions, on the physical function of AD patients (study IV); v) to review the definitions and methods used for assessing intrinsic capacity in older adults and proposed a new IC score (study V); vi) to determine whether the intrinsic capacity concept can be extended from older people to patients with AD (study VI). The results of this dissertation demonstrate the significant role of physical activity in the prevention and treatment of AD. Research findings suggest that physical activity may act as a protective factor against AD development by counteracting molecular pathways involved in disease progression (Study I). In AD patients, exercise has been shown to improve cognitive function, neuropsychiatric symptoms, functional independence, and physical condition, regardless of modality (Study II). Meta-analytic evidence indicates that regular physical activity reduces the risk of AD, though further research is needed to determine the optimal levels of activity (Study III). Additionally, MIFT program seems to demonstrate long-lasting improvements in physical function in AD patients. The concept of IC is valuable in assessing healthy aging and AD progression across multiple dimensions, and the development of a comprehensive score could improve individualized therapeutic interventions (Study V and VI).