Reduced hypocretin (orexin) levels in dementia with Lewy bodies

Lessig, Stephanie; Ubhi, Kiren; Galasko, Douglas; Adame, Anthony; Pham, Emiley; Remidios, Kelly; Chang, Michael; Hansen, Lawrence A.; Masliah, Eliezer

doi:10.1097/wnr.0b013e32833bfb7c

Cited by 37 publications

(35 citation statements)

References 24 publications

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“…Unlike some of the other atypical parkinsonian disorders, DLB is not associated with decreased CSF hypocretin levels . This is in contrast to the decreased hypocretin immunoreactivity observed in neuropathological studies of autopsied brains from DLB and AD patients . This is similar to what is observed in MSA, and this discrepancy may reflect the need for significant neuronal loss before noticeable changes in CSF hypocretin levels can be detected .…”

Section: Dlbsupporting

confidence: 45%

Sleep Disorders in Atypical Parkinsonism

Abbott

Videnović

2014

Movement Disord Clin Pract

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Sleep disorders are commonly seen in atypical parkinsonism, with particular disorders occurring more frequently in specific parkinsonian disorders. Multiple systems atrophy (MSA) is a synucleinopathy often associated with nocturnal stridor which is a serious, but treatable condition highly specific to MSA. In addition, this disorder is strongly associated with rapid eye movement (REM) sleep behavior disorder (RBD), which is also seen in dementia with Lewy bodies (DLB). RBD is far less prevalent in progressive supranuclear palsy (PSP), which is a tauopathy. Insomnia and impaired sleep architecture are the most common sleep abnormalities seen in PSP. Corticobasilar degeneration (CBD) is also a tauopathy, but has far fewer sleep complaints associated with it than PSP. In this manuscript we review the spectrum of sleep dysfunction across the atypical parkinsonian disorders, emphasize the importance of evaluating for sleep disorders in patients with parkinsonian symptoms, and point to sleep characteristics that can provide diagnostic clues to the underlying parkinsonian disorder.

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Section: Dlbsupporting

confidence: 45%

Sleep Disorders in Atypical Parkinsonism

Abbott

Videnović

2014

Movement Disord Clin Pract

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“…3 In another study, reduced neocortical orexin immunoreactivity has been shown in patients with DLB correlating with hypersomnolence and a-synuclein levels. 44 Similarly, low CSF orexin-A levels associated with short MSL or increased SOREMPs were also reported in patients with PD. 12,17 In a study by Friedman et al, lower CSF orexin-A levels in 15 patients with AD were significantly correlated with increased fragmentation of sleep.…”

Section: Discussionmentioning

confidence: 89%

“…These inconsistencies may be related to disease severity and methodological issues regarding different kits or methods of measurement. 44 To our knowledge, neurodegeneration of orexinproducing neurons in FTD has not been reported. However, since our patients with FTD had long disease durations and mostly moderate to severe dementia, reduced orexin levels might plausibly be the result of widespread loss of neurons including those located in hypothalamus.…”

Section: Discussionmentioning

confidence: 97%

Reduced Orexin-A Levels in Frontotemporal Dementia

Çoban

Bılgıç

Lohmann

et al. 2013

Am J Alzheimers Dis Other Demen

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Sleep disturbances including excessive daytime sleepiness (EDS) are encountered in frontotemporal dementia (FTD). To investigate the relationship between the plasma orexin-A levels and sleep disturbance patterns, we measured the plasma orexin-A levels and performed sleep studies in patients with FTD. The orexin-A levels were measured in 10 consecutive patients with FTD and controls by enzyme-linked immunosorbent assay. Nocturnal polysomnography (PSG) and Multiple Sleep Latency Test (MSLT) were performed in 2 patients with FTD. The orexin-A levels were significantly lower in patients with FTD compared to controls. The PSG revealed increased rapid eye movement (REM) latency in patients, whether or not they reported EDS. Mean sleep latency in MSLT was less than 10 minutes in both the patients, being shorter in patient without EDS, but none of them had REM sleep onset. Some patients with FTD may develop narcolepsy-like involuntary sleep attacks, even without complaining of EDS. Involvement of hypothalamus and a subsequent alteration in the orexin levels might be one of the determining factors in this sleep disturbance.

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“…While to date no data on MCH levels in AD exist, literature concerning HCRT-1 is heterogenous: whereas immunoreactive neurons in postmortem hypothalami and ventricular cerebrospinal fluid (CSF)-HCRT-1 levels in AD patients were found to be reduced [25], lumbar CSF levels in vivo were unaltered [26], [27], [28]. A regulation of amyloid-beta (Aβ42) by HCRT has been concluded since the infusion of HCRT-1 in animals lead to increased levels of Aβ42 in the brain interstitial fluid.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

et al. 2013

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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.

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Reduced hypocretin (orexin) levels in dementia with Lewy bodies

Cited by 37 publications

References 24 publications

Sleep Disorders in Atypical Parkinsonism

Sleep Disorders in Atypical Parkinsonism

Reduced Orexin-A Levels in Frontotemporal Dementia

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

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