Article

β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation

  • Nature Neuroscience volume 18, pages 10511057 (2015)
  • doi:10.1038/nn.4035
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Abstract

Independent evidence associates β-amyloid pathology with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here we show that β-amyloid burden in medial prefrontal cortex (mPFC) correlates significantly with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation was not direct, but instead statistically depended on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly.

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Acknowledgements

We thank D. Baquirin, M. Belshe, M. Bhatter, M. Binod, S. Bowditch, C. Dang, J. Gupta, A. Hayenga, D. Holzman, A. Horn, E. Hur, J. Jeng, S. Kumar, J. Lindquist, C. Markeley, E. Mormino, M. Nicholas, S. Rashidi, M. Shonman, 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.J.) and F32-AG039170 (B.A.M.) from the US National Institutes of Health.

Author information

Affiliations

  1. Sleep and Neuroimaging Laboratory, University of California, Berkeley, California, USA.

    • Bryce A Mander
    • , Vikram Rao
    • , Jared M Saletin
    •  & Matthew P Walker
  2. Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA.

    • Shawn M Marks
    • , Jacob W Vogel
    • , William J Jagust
    •  & Matthew P Walker
  3. Division of Pulmonary and Critical Care Medicine, California Pacific Medical Center, San Francisco, California, USA.

    • Brandon Lu
  4. Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.

    • Sonia Ancoli-Israel
  5. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.

    • William J Jagust

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Contributions

B.A.M. designed the study, conducted the experiments, analyzed the data and wrote the manuscript. S.M.M. aided in data analysis and manuscript preparation. J.W.V. aided in data collection, analysis and manuscript preparation. V.R. aided in data analysis and manuscript preparation. B.L. aided in study screening procedures and manuscript preparation. J.M.S. provided data analytic tools and aided in data analysis and manuscript preparation. S.A.-I. aided in study design and manuscript preparation. W.J.J. provided the subject pool and data analytic tools and aided in study design, PET data analysis and manuscript preparation. M.P.W. designed the study, aided in data analysis and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Bryce A Mander or Matthew P Walker.

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