DOI: 10.1002/alz.079461 ISSN: 1552-5260

Association of individual and multiple comorbid neuropathologies with cognitive decline in the oldest‐old: Results from The 90+ Study

Roshni Biswas, Luohua Jiang, Claudia H. Kawas, S. Ahmad Sajjadi, Thomas J. Montine, Syed A. Bukhari, María M. M. Corrada
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Age‐related neuropathologies are common in the oldest‐old and associated with cognitive decline. In this study, we examined the associations of individual and multiple comorbid neuropathologies with cognitive decline in participants who had normal cognition in at least one in‐person visit during their time in The 90+ Study.


Our study included 251 individuals from The 90+ Study‐ a longitudinal study on aging, who had at least 2 in‐person visits, had normal cognition in at least one of them and had autopsy data. We used longitudinal Mini Mental State Examination (MMSE) scores to assess cognitive trajectories. For the first part of our analysis, we examined individual neuropathologies that were evaluated as: Alzheimer’s Disease neuropathologic change (ADNC) (intermediate/high), presence of Cerebral amyloid angiopathy (CAA), Microinfarcts (2+), atherosclerosis, arteriolosclerosis, Lewy body disease (LBD), Hippocampal sclerosis (HS), Limbic‐predominant age‐related TDP‐43 encephalopathy neuropathological change (LATE‐NC), and Age‐related tau astrogliopathy (ARTAG). For the second part of our analysis, we examined multiple comorbid neuropathologies. For this analysis we recoded each neuropathology as: 0 for absent/negligible levels, 0.4 for intermediate, or 1 for severe. These recoded scores were added to create four summary indices: all pathology index (total of all individual neuropathologies), vascular index (CAA, Microinfarcts, atherosclerosis, and arteriolosclerosis), neurodegenerative index (ADNC, LB, HS, and LATE‐NC) and non‐AD neurodegenerative index (LB, HS, and LATE‐NC). We used linear mixed effects models to examine the associations of individual neuropathologies and the pathology indices with cognitive decline.


At baseline, participants had a mean age of 93 years and a mean MMSE score of 27.6. Mean follow up time was 5.1 years (Table1). Presence of LBD (ß = ‐0.20; p = 0.07), and HS (ß = ‐0.24; p = 0.06) trends toward to an association with faster cognitive decline (Table2). All pathology index (ß = ‐0.10; p = 0.01), neurodegenerative index (ß = ‐0.17; p = 0.003) and non‐AD neurodegenerative index (ß = ‐0.16; p = 0.02) were significantly associated with faster cognitive decline (Table3).


In individuals who maintain normal cognition until age 90+ and then start declining, the rate of cognitive decline is related to the burden of neuropathologies, particularly neurodegenerative neuropathologies. Therefore, multiple comorbid neuropathologies need to be targeted for preventing cognitive decline in the oldest‐old.

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