Hypothalamic structure and function in Alzheimer's disease and Lewy-body dementia: a systematic review and meta-analysis

BackgroundChanges to sleep, weight, and endocrine function are common in Alzheimers disease (AD) and Lewy-body dementia (LBD). The cause of these is not known, but they may be related to hypothalamic neurodegeneration. MethodsWe performed a systematic search of MEDLINE and EMBASE of studies using structural magnetic resonance imaging to examine hypothalamic volume in people with 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 as the effect measure, and a narrative synthesis was used to examine the relationship between hypothalamic volume and sleep, eating, and endocrine function. ResultsWe identified 6542 articles which resulted in 12 included studies, most which had a low to moderate risk of bias. The meta-analysis included 454 people with mild-moderate AD (Mini-Mental State (MMSE) range: 19.2-26.1) and 715 controls. We found that people with AD had a significantly smaller hypothalamus (pooled SMD: -0.49, t=-3.47, p=0.018, 95%CI: -0.86 to - 0.13). There was significant heterogeneity of a moderate degree (Tau2=0.0665, 95%CI:0.005-0.8090; I2=67%, 95%CI:21.5%-86.1%; Q=15.16, p<0.01), but no evidence of publication bias. Only one study examined people with LBD, finding qualitative evidence of lower hypothalamic volume compared to controls. Hypothalamic volume loss in AD was more marked in men and may be associated with plasma levels of sex hormones and decreased bone mineral density. ConclusionReduced hypothalamic volume is seen early in AD and LBD and this may influence endocrine function. A better understanding of hypothalamic degeneration in dementia may help elucidate how pathology relates to symptoms in AD and LBD and reveal new targets for intervention.