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12.09.2017 | Original Communication

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

verfasst von: Claudio Liguori, Agostino Chiaravalloti, Marzia Nuccetelli, Francesca Izzi, Giuseppe Sancesario, Andrea Cimini, Sergio Bernardini, Orazio Schillaci, Nicola Biagio Mercuri, Placidi Fabio

Erschienen in: Journal of Neurology | Ausgabe 11/2017

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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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Titel: Hypothalamic dysfunction is related to sleep impairment and CSF biomarkers in Alzheimer’s disease
verfasst von: Claudio Liguori
Agostino Chiaravalloti
Marzia Nuccetelli
Francesca Izzi
Giuseppe Sancesario
Andrea Cimini
Sergio Bernardini
Orazio Schillaci
Nicola Biagio Mercuri
Placidi Fabio
Publikationsdatum: 12.09.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 11/2017
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-017-8613-x

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