April 24, 2025
Keio University School of Medicine
A research team including Senior Lecturer Yoshihito Nishimoto from the Division of Neurology, Keio University School of Medicine, Professor Yasumichi Arai from the Center for Supercentenarian Medical Research, Professor Hideyuki Okano from the Keio University Regenerative Medicine Research Center (KRM), and Professor Takeshi Ikeuchi from the Brain Research Institute at Niigata University has, through a collaborative study of supercentenarians, clarified the clinical differences between age-related cognitive decline and Alzheimer's disease. Furthermore, while the ApoE gene associated with amyloid accumulation in Alzheimer's disease is known as a major risk factor, the team discovered that genes involved in maintaining synapses (connections between nerve cells) are associated with age-related cognitive decline.
Japan is facing a super-aged society ahead of the rest of the world. A major societal challenge is how to support patients with dementia from the perspectives of treatment and care. In Japan, a country known for its longevity, there are over 90,000 people aged 100 or older (supercentenarians), who offer us clues to healthy longevity. The Center for Supercentenarian Medical Research at the Keio University School of Medicine has been conducting research on supercentenarians for over 30 years and has garnered attention worldwide.
Research from the Center had already revealed that although supercentenarians experience memory loss, their rate of developing severe Alzheimer's disease is low, as is the prevalence of the ApoE4 gene, a risk factor for the disease. This study targeted 638 individuals from a cohort of 1,017 supercentenarians who had previously participated in home-visit surveys and cooperated with detailed cognitive assessments and whole-genome genetic analysis. The study closely examined their cognitive characteristics and compared them with those of 391 patients with Alzheimer's disease. The results showed that the "three-stage command" task in the Mini-Mental State Examination (MMSE), which patients with Alzheimer's disease find difficult, was preserved in supercentenarians. Furthermore, a genome-wide association study revealed that these cognitive characteristics in supercentenarians are associated with the PTPRT (protein tyrosine phosphatase receptor T) gene, which is important for synapse maintenance.
The findings of this study are expected to be utilized in clinical settings for dementia where the MMSE is routinely used, serving as a new method to distinguish between Alzheimer's disease and age-related cognitive decline, and contributing to healthy longevity in a super-aged society. The study is also expected to lead to a better understanding of the pathology of age-related cognitive decline. These research findings were published on April 15, 2025 (U.S. Eastern Time), in Alzheimer's & Dementia , the official journal of the U.S. National Institute on Aging (NIA).
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