Abstract
Ancillary to decline in cognitive abilities, patients with Alzheimer’s disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = −0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.
Highlights
In Alzheimer’s disease (AD) which is predominately characterized by the decline of cognitive abilities in memory, abstraction, orientation and language, cognition-related behavioral and psychological symptoms of dementia (BPSD) frequently occur
cerebrospinal fluid (CSF)-melanin-concentrating hormone (MCH) levels showed a negative correlation with Mini Mental Status Examination (MMSE) scores in AD (r = 20.362, p,0.05) but not in the healthy subjects (HS)
CSF-MCH levels differed between AD with MMSE#20 (n = 15), AD with MMSE$21 (n = 18) and HS, (F(2,62) = 6.997, p,0.01) with post-hoc analyses showing higher levels in AD with MMSE#20 compared to HS (p,0.001)
Summary
In Alzheimer’s disease (AD) which is predominately characterized by the decline of cognitive abilities in memory, abstraction, orientation and language, cognition-related behavioral and psychological symptoms of dementia (BPSD) frequently occur. These include sleep-wake disturbances with daytime sleepiness and napping, nightly awakening, reduced REM-sleep and increased REM-onset latency, cyclic agitation and deregulation of appetite and weight [1], [2]. Animal studies have shown that the activation of MCH neurons leads to improved learning and memory performance (for references see [8]), increased REM sleep [12], [13] increased food and water intake [14] and has anxiogenic effects in mice [15]. Reduction of MCH or blockage of MCH-receptors leads to improved social recognition in rats [16], hyperactivity, leanness, hypermetabolism in mice [17], and has antidepressant effects in animals (for references see [18])
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