Pathological and non-pathological aging, physical activity, genotype and cognition – ViAGeCo

As always, Alzheimer’s disease is an irreversible, progressive brain disease. It is the most common form of dementia and the major cause of functional dependence in the elderly. Since there is currently no cure for Alzheimer’s disease, a growing number of scientists are focusing on non-pharmacological alternative therapeutic approaches in order to slow down the decline of physical and cognitive resources and improve quality of life of patients with Alzheimer's disease. Several narrative and meta-analytical reviews suggest that regular physical activity delays the occurrence of a cognitive decline and slows down Alzheimer’s disease progress when compared with sedentary people. Despite the growing interest of the scientific community for the positive effects of chronic exercise on mental health and cognitive functions, the clinical pertinence of this phenomenon remains to be clearly established, more particularly in aged people suffering from neurodegenerative diseases. The first aim of this research project is to test if chronic exercise reduces or even compensates for cognitive decline both in patients with prodromal Alzheimer's disease (i.e., no dementia) and in aging people with no pathology of central nervous system. The neurophysiological mechanisms that mediate the effects of chronic exercise on cognitive functions remain undetermined in man, particularly in patients suffering from neurodegenerative diseases. The second aim of this research project is to examine increase in cerebral blood flow at rest as a possible explanatory mechanism induced by physical activity. As the real importance of this mechanism in the explanation of the effect of interest cannot be clearly estimated without controlling several confounding factors likely to interact with physical activity, the third aim of this research program is to determine the contribution of specific covariables. Four types of confounding factors will be taken into account: 1) factors related to life style (diet, social network); 2) factors related to cognitive reserve (education achievement, lifelong hobbies and leisure activities, jobs before retirement); 3) factors related to observance of physical activity (motivation, adherence, perseverance); and 4) factors related to genetic polymorphisms (brain-derived neurotrophic factor gene, catechol-O-methyltransferase gene, and apolipoprotein E gene). A multicentre interventional study will take place in three different sites (Bordeaux, Poitiers and Liège) to maximize recruitment of participants between 65 and 80 years of age. All participants will be separated into six groups corresponding to the combination of two independent variables: population type (aged people without any neurological disease vs. prodromal Alzheimer’s disease participants) and the type of physical activity program they will follow for six months (aerobic and strength exercise program, stretching program, or maintaining sedentary life style). Cognitive performance, cardiovascular health, and cerebral functioning will be assessed at three different times: before the onset of the training program (pre-test), at the end of the training period (post-test 1) and six months after the end of the training program (post-test 2). Three main outcomes can be considered: (1) advancement of clinical knowledge concerning the capacity of physical activity programs to reduce deleterious effects of pathological brain aging at prodromal stage of Alzheimer’s disease, (2) advancement of theoretical knowledge concerning the comprehension of neurophysiological mechanisms underpinning clinical effects of chronic exercise, (3) making recommendations on lifestyle habits in order to extend the autonomy of seniors.