Distinct patterns of cognitive traits in extreme old age and Alzheimer's disease

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Abstract

INTRODUCTION: Clinical features of cognitive performance in extreme old age differ from those of pathological cognitive decline in Alzheimer's disease (AD). METHODS: We compared cognitive traits between 638 centenarians aged 100–115 years and 208 and 221 patients with AD from independent facilities. RESULTS: The presence of the apolipoprotein E (APOE) ε4 allele did not affect Mini-Mental State Examination (MMSE) scores in centenarians. Centenarians retained the ability to follow three consecutive commands, associated with their educational background and activities of daily living. Cognitive retention remained unchanged in semi-supercentenarians (aged ≥ 105 years) and supercentenarians (aged ≥110 years). A quantitative genome-wide association study (GWAS) identified two loci associated with maintaining the ability to follow three consecutive commands. DISCUSSION: This is the first study to compare cognitive traits between >600 centenarians and patients with AD. Centenarians attained higher MMSE scores for the phenotype of following three consecutive commands than patients with AD, being useful in clinical practice. Highlights: Cognitive phenotypes in centenarians differ from those in the AD groups Clinical trait to follow consecutive instructions is retained in centenarians but not in AD groups GWAS identified SNPs related to the maintained trait of MMSE in centenarians.

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Nishimoto, Y., Sasaki, T., Abe, Y., Hara, N., Miyashita, A., Konishi, M., … Arai, Y. (2025). Distinct patterns of cognitive traits in extreme old age and Alzheimer’s disease. Alzheimer’s and Dementia, 21(4). https://doi.org/10.1002/alz.70155

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