加齢による運動による脳の活性化 (AGUEDA)

Participants will engage in supervised 24-week resistance exercise program with goal of maintaining 180 minutes of exercise per week.

This group will perform a 24-week resistance exercise program. Participants will engage in 180 minutes/week of resistance exercise (3 supervised sessions peer week, 60 min/session). The training will consist of a combination of upper and lower body exercises using elastic bands and participants' body weight as the primary resistance. Exercise load and intensity will be based on the number of repetitions (i.e.,10-12 repetitions), resistance of the elastic bands, in ascending order with seven intensities, and also on the exercises' difficulty (i.e., three levels). The prescribed targeted intensity will reach 70-80% of the participants' maximum rating perceived exertion (i.e., 7-8 RPE).The progression (horizontal) will be standardized according to the execution time and RPE, and individualized according to execution speed and band resistance. Heart rate will be monitored in all sessions. Further, intrinsic motivation before and after session and sleep quality will be registered.

Control group will be asked to maintain their usual lifestyle.

The main outcome is change in executive function from baseline to 6 months. The 3-month measure is used to assess the trajectory of the change. A comprehensive neuropsychological battery will assess several domains of executive function: working memory, cognitive flexibility and inhibitory control.

PET (positron emission tomography) scan using the tracer Neuraceq (Florbetaben F18) will measure levels of the protein amyloid beta in the brain.

MRI (magnetic resonance imaging) will measure brain morphology including volume, area, cortical thickness and shapes by a T1-weighted MPRAGE structural sequence.

MRI (magnetic resonance imaging) will measure hippocampal morphology including volume, area, cortical thickness, shapes by a high resolution hippocampus sequence.

MRI (magnetic resonance imaging) will measure white matter structure and lesions by diffusion weighted acquisition sequence.

MRI (magnetic resonance imaging) will measure brain function including both resting state and n-back working memory task-evoked patterns. Measures of brain activity and brain connectivity will be calculated.

MRI (magnetic resonance imaging) will measure cerebral blood flow by Pseudo-Continuous Arterial Spin Labeling (pCASL) sequence.

Saliva and blood samples will be used to determine peripheral amyloid beta

Saliva and blood samples will be used to determine peripheral neurology biomarkers including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and cathepsin B (CTSB).

Visuospatial memory will be assessed by the Rey-Osterreith figure (ROF) test, verbal memory by the Rey Auditory Verbal Learning Test (RAVLT) and confrontational word memory by the boston Naming Test (short version, BNT).

Intelligence will be assessed by the Wechsler Adult Intelligence Scale (WAIS-IV). 3 subtests for crystallized intelligence (Similarities, Vocabulary, information) and 3 subtests for fluid intelligence (Block Design, Matrix Reasoning, Visual Puzzles).

General cognition will be assessed by the Telephone Interview for Cognitive Status (STICS-m), the Mini mental state examination (MMSE) and the Montreal Cognitive Assessment (MOCA. vocabulary/language and subjective and objective cognitive decline will be assessed by paper-based tests.

Vocabulary/language, and subjective and objective cognitive decline will be assessed by paper-based tests.

Muscular strength will be assessed by laboratory (i.e. isokinetic test) and field- based (i.e., handgrip and functional tests) tests

Senior Fitness Test and Short Physical Performance Battery will assess overall physical functioning and z-scores will be calculated.

Gait analysis will be assessed by the OptoGait System

Cardiorespiratory fitness will be assessed by 2 field-based tests ( i.e., 6-min walking test and 2-km walking test)

A battery of questionnaire will assess psychological ill-being (i.e. depression, anxiety, stress or negative affect).

A battery of questionnaire will assess psychological well-being (i.e. self-esteem, self-concept, self-efficacy, self-image, positive affect, optimism, happiness and satisfaction with life).

This will be self-reported using the Health Survey Short Form (SF-36).

Physical activity at different intensities (average min/day), sedentary time (average min/day) and sleep (average min/day) will be measured using Actigraph GT3X + accelerometers

Type of sedentary behaviors will be self-reported by questionnaire.

This will be self-reported using the food-frequency questionnaire (FFQ) and the PREDIMED-14 questionnaire.

Body composition [i.e., lean mass (kg), fat mass (kg), and bone mineral content and density (z-score)] will be assessed using a dual-energy x-ray absorptiometer (DXA). Full- body, bilateral hips and lumbar spine scans will be acquired.

Neck adipose tissue will be assessed by MRI

Systolic and diastolic blood pressure will be assessed by a blood pressure monitor

Saliva and blood samples will be used to determine peripheral biomarkers including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), glucose, insulin, HDL and LDL cholesterol

Blood samples will be stored for genetic analyses, including APOE and BDNF genotypes

Saliva and fecal samples will be used to determine oral and gut microbiota including the most representative phyla (i.e., firmicutes, bacteroidetes, and proteobacteria.