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Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging.

  • Author(s): Mander, Bryce A
  • Rao, Vikram
  • Lu, Brandon
  • Saletin, Jared M
  • Lindquist, John R
  • Ancoli-Israel, Sonia
  • Jagust, William
  • Walker, Matthew P
  • et al.

Published Web Location

https://doi.org/10.1038/nn.3324Creative Commons 'BY' version 4.0 license
Abstract

Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life.

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