Neuropathology of centenarians and supercentenarians: An autopsy study

Studies of centenarians and supercentenarians provide insight into aging and substrates of cognitive impairment at the extreme limits of age. In this study, we examined pathologic findings in 15 centenarians (99-109 years) and 7 supercentenarians (111-115 years) who underwent autopsy at our institution during a 25-year period between 2000 and 2025 and compared them with a cohort of 24 older adults (70-90 years) who underwent autopsy during 2024-2025. Of the 22 centenarians and supercentenarians, 15 underwent full autopsies and 7 had brain only examinations. The average age at death of the centenarians/supercentenarians was 105 ± 5.8 years (5 males and 17 females). Of those who underwent a complete autopsy, the most common cause of death was pneumonia in 10 individuals followed by cardiac amyloidosis in 5. There was a wide spectrum of Alzheimer disease (AD) neuropathologic change with some individuals showing modest AD changes despite their advanced age. Amyloid plaque burden did not differ between older adults, centenarians and supercentenarians, but centenarians/supercentenarians had a higher burden of neurofibrillary tangles. Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) was seen in 59% of centenarian/supercentenarian participants compared with 29% of older adults while hippocampal sclerosis (HS) was seen in nearly half of centenarians and supercentenarians but not in older adults. Centenarians and supercentenarians had a higher frequency of aging-related tau astrogliopathy (ARTAG) in the frontal lobe compared with older adults (36% vs 4%). Furthermore, a higher proportion of centenarian and supercentenarian individuals demonstrated more severe cerebrovascular disease, including atherosclerosis of the basal vasculature, moderate to severe arteriolosclerosis and lacunar infarcts and microinfarcts. Thus, although our findings are based on a convenience sample and may not be generalizable to all centenarians and supercentenarians, individuals at the extreme limits of age had a high frequency of ARTAG, LATE-NC, HS, and cerebrovascular disease.