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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We thank M. Belshe, M. Bhatter, M. Binod, S. Bowditch, C. Dang, A. Hayenga, A. Horn, E. Hur, C. Markeley, E. Mormino, M. Nicholas, L. Zhang and A. Zhu for their assistance, A. Mander for his aid in task design, and M. Rubens and A. Gazzaley for use of their aging template brain. This work was supported by awards R01-AG031164 (M.P.W.), R01-AG034570 (W.J.), R01-AG08415 (S.A.-I.) and F32-AG039170 (B.A.M.) from the US National Institutes of Health.
The authors declare no competing financial interests.
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Mander, B., Rao, V., Lu, B. et al. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat Neurosci 16, 357–364 (2013). https://doi.org/10.1038/nn.3324
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