Hypothalamic imaging in Alzheimer's disease and Lewy body dementia: A systematic review and meta-analysis

Symptoms related to sleep, weight, and endocrine dysfunction are common in Alzheimer's disease (AD) and Lewy body dementia (LBD). The cause of these symptoms is not known, but they may be related to hypothalamic neurodegeneration. We performed a systematic search of MEDLINE and EMBASE for studies using MRI or PET imaging to examine the hypothalamus in AD or LBD. The Newcastle-Ottawa scale was used to assess the risk of bias. A random-effects meta-analysis was conducted using the standardised mean difference (SMD) in hypothalamic volume, and a narrative synthesis was used to examine associations between hypothalamic imaging and sleep, weight, and endocrine function. We screened 8891 articles which identified 22 studies for inclusion in the narrative synthesis of which 6 were suitable for meta-analysis. 86 % had a low to moderate risk of bias. People with mild-moderate AD had a smaller hypothalamus compared to controls (SMD=-0.49[-0.86,-0.13],p = 0.018;I²=67 %[21.5 %-86.1 %];n = 454(AD),715(controls)), and had differences in hypothalamic metabolism and connectivity. Two studies in LBD found lower grey matter and serotonin transporter binding in the hypothalamus compared to controls. Hypothalamic differences in AD were associated with male sex, worse sleep, lower bone mineral density and plasma levels of sex hormones. Body mass index was not associated with hypothalamic volume in AD, although further studies are needed. Lower hypothalamic volume is seen in AD and this may influence sleep and endocrine function. A better understanding of hypothalamic degeneration may help elucidate how pathology relates to symptoms in AD and LBD and reveal new targets for intervention.