1:Distinct patterns of cognitive traits in extreme old age and Alzheimer's disease
Science of the Month - May 2025
Alzheimers Dement.
Yoshinori Nishimoto, Takashi Sasaki, Yukiko Abe, Norikazu Hara, Akinori Miyashita, Mika Konishi, Yoko Eguchi, Daisuke Ito, Nobuyoshi Hirose, Masaru Mimura, Japanese Alzheimer's Disease Neuroimaging Initiative, Takeshi Ikeuchi, Hideyuki Okano, Yasumichi Arai
Investigating the Science of Age-Related Cognitive Decline
—Molecular Mechanisms Revealed by Whole-Genome Analysis of a Large-Scale Supercentenarian Study—
A research team from the Juku, including Yoshinori Nishimoto (Lecturer, Department of Internal Medicine (Neurology)), Yasumichi Arai (Professor, Center for Supercentenarian Medical Research), and Hideyuki Okano (Professor, Keio University Regenerative Medicine Research Center (KRM)), compared the cognitive characteristics of 391 patients with Alzheimer's disease (AD) with those of 638 individuals (24 of whom were over 110 years old) selected from a group of 1,017 people aged 100 or older (supercentenarians) who participated in detailed cognitive assessments and whole-genome genetic analysis. The results revealed that the ability to follow a three-step verbal command on the Mini-Mental State Examination (MMSE), a task that AD patients typically find difficult, was preserved in the supercentenarians. Furthermore, a genome-wide association study revealed that the PTPRT gene, which is important for synapse maintenance, is associated with this cognitive characteristic in supercentenarians.
Japan, a country known for longevity, has over 95,000 supercentenarians, who offer us clues to healthy aging. The findings of this study may be utilized as a new method in clinical settings for dementia to distinguish between age-related cognitive decline and AD. Additionally, by elucidating the molecular mechanisms of age-related cognitive decline, this research is expected to contribute to extending healthy life expectancy in our super-aging society.
(Yasumichi Arai, Center for Supercentenarian Medical Research)