Studies have shown that rural residents face disadvantages concerning medical access and socio-economic conditions. However, the social determinants of health among older people in rural areas are still unclear. The Neuron to Environmental Impact across Generations (NEIGE) study investigated the social determinants of health among older rural adults. A survey was conducted among the older residents of Tokamachi City, Japan. We randomly selected study participants (N = 1,346) from four stratified groups by age (65-74 and 75-84 years) and residential area (Tokamachi center downtown and Matsunoyama mountain). The survey collected data on socio-economic status, lifestyle, health, and neighborhood environment. Blood and urine sampling were also conducted, and physical activity was assessed. Magnetic resonance brain imaging (MRI) and Apo-E gene were also examined in the analysis. In total, 527 people participated in the NEIGE study (participation rate: 39.2%). The average age of the participants was 73.5 (standard deviation, 5.6) years, and 47.3% were male. No differences in demographics were found between downtown and mountain residents, except for educational attainment, which was lower among mountain residents. Lifestyles were similar, except for the higher percentage of everyday drinkers (33.3-35.3%) in the mountain area. Concerning physical health, muscle mass, grip strength, and measured physical activity were significantly higher among mountain residents. However, gait speed and balance were better among downtown residents. The findings of the NEIGE study will help elucidate the social determinants of health in older rural adults in Japan, and emphasize the different outcomes between downtown and mountain areas.