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Hypothalamic dysfunction is related to sleep impairment and CSF biomarkers in Alzheimer’s disease

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Abstract

Hypothalamus is a key brain region regulating several essential homeostatic functions, including the sleep–wake cycle. Alzheimer’s disease (AD) pathology affects nuclei controlling sleep–wake rhythm sited in this brain area. Since only post-mortem studies documented the relationship between hypothalamic atrophy and sleep–wake cycle impairment, we investigated in AD patients the possible hypothalamic in vivo alteration using 2-deoxy-2-(18F) fluoro-d-glucose ([18F]FDG) positron emission tomography ([18F]FDG PET), and its correlations with sleep impairment and cerebrospinal-fluid (CSF) AD biomarkers (tau proteins and β-amyloid42). We measured sleep by polysomnography, CSF AD biomarkers and orexin levels, and hypothalamic [18F]FDG PET uptake in a population of AD patients compared to age- and sex-matched controls. We documented the significant reduction of hypothalamic [18F]FDG PET uptake in AD patients (n = 18) compared to controls (n = 18) (p < 0.01). Moreover, we found the increase of CSF orexin levels coupled with the marked alteration of nocturnal sleep in AD patients than controls. We observed the significant association linking the reduction of both sleep efficiency and REM sleep to the reduction of hypothalamic [18F]FDG PET uptake in the AD group, which in turn negatively correlated with the total-tau/beta-amyloid42 ratio (index of more marked neurodegeneration). Moreover, controls but not AD patients showed [18F]FDG PET interconnections between hypothalamus and limbic system. We documented the in vivo dysfunction of hypothalamus in AD patients, which lost the physiological connections with limbic system and was correlated with both nocturnal sleep disruption and CSF AD biomarkers.

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Acknowledgements

We thank Prof. Carlo Chiaramonte for helping us in the statistical analysis.

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Authors and Affiliations

  1. Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome “Tor Vergata”, Viale Oxford 81, 00133, Rome, Italy

    Claudio Liguori, Francesca Izzi, Nicola Biagio Mercuri & Placidi Fabio

  2. Department of Biomedicine and Prevention, University of Rome ‘Tor Vergata’, Rome, Italy

    Agostino Chiaravalloti, Andrea Cimini & Orazio Schillaci

  3. IRCSS Neuromed, Pozzilli, Italy

    Agostino Chiaravalloti & Orazio Schillaci

  4. Clinical Biochemistry and Molecular Biology, University of Rome “Tor Vergata”, Rome, Italy

    Marzia Nuccetelli & Sergio Bernardini

  5. Neurology Unit, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy

    Giuseppe Sancesario & Nicola Biagio Mercuri

  6. IRCCS Fondazione Santa Lucia, Rome, Italy

    Nicola Biagio Mercuri

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  1. Claudio Liguori
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  2. Agostino Chiaravalloti
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Correspondence to Claudio Liguori.

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Conflicts of interest

Claudio Liguori, Agostino Chiaravalloti, Nicola Biagio Mercuri, Marzia Nuccetelli, Giuseppe Sancesario, Francesca Izzi, Andrea Cimini, Sergio Bernardini, Orazio Schillaci, and Fabio Placidi declare no conflict of interest or financial disclosures.

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Liguori, C., Chiaravalloti, A., Nuccetelli, M. et al. Hypothalamic dysfunction is related to sleep impairment and CSF biomarkers in Alzheimer’s disease. J Neurol 264, 2215–2223 (2017). https://doi.org/10.1007/s00415-017-8613-x

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  • DOI: https://doi.org/10.1007/s00415-017-8613-x

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