Increased orexin cerebrospinal fluid (CSF) levels have been described in MCI and AD dementia.47 48 Conversely, a postmortem study found 40% fewer orexinergic neurons in the hypothalamus of patients with AD compared with controls.49 Given this evidence, it has been hypothesised that orexin may be upregulated in early AD stages in response to neurodegeneration, which may in turn lead to impaired sleep–wake cycle regulation.50 However, other studies have found no differences between patients with AD and controls, and there is little information concerning CSF orexin levels in preclinical AD.50 Here, HCRT is linked to Alzheimer disease.