1138 HYPOTHALAMIC DYSFUNCTION IS RELATED TO SLEEP IMPAIRMENT AND CEREBROSPINAL-FLUID BIOMARKERS IN ALZHEIMER’S DISEASE

Abstract

Hypothalamus is a key brain region controlling several essential functions, such as the determination of the sleep-wake cycle. In fact, nuclei regulating the alteration of sleep and wake states sited in the hypothalamus are: suprachiasmatic nucleus (SCN), orexinergic nucleus, tuberomamillary nucleus (TBM). It has been described in post-mortem studies that hypothalamus is affected by the Alzheimer’s Disease (AD) pathology. Moreover, orexinergic and SCN dysfunctions have been related to sleep-wake cycle impairment. On these basis, in order to evaluate the possible in vivo alteration of the hypothalamus and its correlation with sleep impairment and cerebrospinal-fluid (CSF) biomarkers changes in AD patient, we investigated the polysomnographic sleep, the CSF AD biomarkers and orexin levels, and the hypothalamic [18F]FDG PET uptake in a population of AD patients compared to non-demented controls. We performed lumbar puncture for CSF AD biomarkers and orexin quantification, polysomnography and [18F]FDG PET in a population of AD patients. We compared the AD group to two control groups matched for age and sex with the AD population. The first group underwent PSG and CSF biomarkers and orexin analysis (Control 1), and the second group underwent [18F]FDG PET assessment (Control 2). We documented the significant reduction of hypothalamic [18F]FDG PET uptake in the AD group (n=18) compared to the Control 2 group (n=18) (p<0.0.1). Moreover, we found the increase of CSF orexin levels coupled with the marked alteration of the night-time sleep in the AD group compared to the Control 1 group (n=15) (p<0.05). Finally, we observed the significant association between the reduction of sleep efficiency and REM sleep and the reduction of hypothalamic [18F]FDG PET uptake in the AD group. Moreover, [18F]FDG PET hypothalamic uptake correlated with the higher ratio of total-tau/beta-amyloid42 CSF levels (index of marked neurodegeneration). We did not document the correlation between hypothalamic [18F]FDG PET uptake and CSF orexin levels. We documented the alteration of the hypothalamus and its correlation with both the dysregulation of night-time sleep and the CSF index of marked neurodegeneration in AD patients. none