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Pathologies Underlying Longitudinal Cognitive Decline in the Oldest Old.

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Brain pathologies significantly impact cognitive decline in the oldest old. Specific pathologies like gross infarcts and APOE ε4 allele are linked to memory and verbal fluency trajectories.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Cognitive Aging

Background:

  • Understanding brain pathologies' impact on cognition in the oldest old is vital for targeted interventions.
  • Cognitive trajectories and their neuropathological underpinnings in nonagenarians are not fully understood.

Purpose of the Study:

  • To investigate the relationship between specific brain pathologies and cognitive trajectories in cognitively intact older adults.
  • To determine how neurofibrillary tangles, neuritic plaques, infarcts, and APOE genotype influence memory, verbal fluency, and global cognitive scores over time.

Main Methods:

  • Longitudinal study of 220 cognitively intact participants (mean age 93.7 years) with annual neuropsychological testing and post-mortem autopsy.
  • Mixed-effects models and Poisson regression were used to analyze cognitive trajectories and their association with various pathologies.

Main Results:

  • Memory trajectory linked to APOE ε4 allele (P=0.006).
  • Verbal fluency trajectory associated with gross infarcts (P=0.008).
  • Global cognitive scores (MMSE) trajectory associated with Braak scores, gross infarcts, hippocampal sclerosis, neuritic plaques, and APOE ε4 allele.

Conclusions:

  • Multiple brain pathologies contribute to cognitive decline in the oldest old, emphasizing the need to consider comorbidities in therapeutic trials.
  • APOE ε4 allele's association with memory decline suggests roles beyond amyloid metabolism, warranting further investigation into APOE's function in brain aging.