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Researchers Chart 25 Years of SuperAger Brain Findings to Inform Dementia Treatments

A special issue in Alzheimer’s & Dementia distills the unique brain structures that enable exceptional memory in adults over 80.

Image
Image depicts neurons from the brain of a 90-year-old female SuperAger. Neurons are from the 2nd cellular layer (layer II) of the entorhinal cortex, a brain region that is crucial for memory and among the first regions to develop Alzheimer’s disease pathologic changes. Nassif et al. (2022) found that layer II entorhinal cortex neurons are significantly larger in SuperAgers compared to same-aged peers and, surprisingly, younger individuals; these large neurons may underly the exceptional memory abilities found in SuperAgers.
Tamar Gefen holds a younger brain that is used for comparison with brain tissue of SuperAgers.
Engraving brain in retro orange color on turquoise green background

Overview

  • Since 2000, Northwestern’s SuperAging Program has enrolled 290 individuals over 80 whose memory rivals people at least 30 years younger and autopsied 77 donated brains.
  • Imaging shows these SuperAgers maintain youthful brain morphology, with minimal cortical thinning and an unusually thick anterior cingulate cortex.
  • Analysis reveals dual protective pathways: some individuals resist forming amyloid plaques and tau tangles, while others remain cognitively intact despite their presence.
  • Cellular studies identify elevated von Economo neuron counts, larger entorhinal neurons, preserved cholinergic innervation and lower inflammatory microglia levels.
  • The perspective calls for developing interventions that harness these neurobiological and cellular markers to bolster resistance and resilience against Alzheimer’s disease.