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Trough Melatonin Levels Differ between Early and Late Phases of Alzheimer Disease

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Objective: Melatonin has been considered to have an essential role in the pathophysiology of Alzheimer’s disease (AD) for its regulatory function on circadian rhythm and interaction with glutamate for the modulation of learning and memory. Previous studies revealed that melatonin levels decreased in patients with AD. However, melatonin supplement didn’t show promising efficacy for AD. This study compared trough melatonin levels among elderly people with different severities of cognitive deficits. Methods: We enrolled 270 elder individuals (consisting four groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild AD, and moderate-severe AD) in the learning cohort. Trough melatonin levels in plasma were measured using ELISA. Cognitive function was evaluated by Clinical Dementia Rating Scale (CDR) and Mini-Mental State Examination (MMSE). An independent testing cohort, also consisting of four groups, was enrolled for ascertainment. Results: In the learning cohort, trough melatonin levels decreased in the MCI group but elevated in the mild and moderate to severe AD groups. Trough melatonin levels were associated with CDR and MMSE in MCI or AD patients significantly. In the testing cohort, the results were similar to those in the learning cohort. Conclusion: This study demonstrated that trough melatonin levels in the peripheral blood were decreased in MCI but increased with the severity of AD. The finding supports the trials indicating that melatonin showed efficacy only in MCI but not in AD. Whether trough melatonin level has potential to be a treatment response biomarker for AD, especially its early phase needs further studies.

Abstract

Objective: Melatonin has been considered to have an essential role in the pathophysiology of Alzheimer’s disease (AD) for its regulatory function on circadian rhythm and interaction with glutamate for the modulation of learning and memory. Previous studies revealed that melatonin levels decreased in patients with AD. However, melatonin supplement didn’t show promising efficacy for AD. This study compared trough melatonin levels among elderly people with different severities of cognitive deficits. Methods: We enrolled 270 elder individuals (consisting four groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild AD, and moderate-severe AD) in the learning cohort. Trough melatonin levels in plasma were measured using ELISA. Cognitive function was evaluated by Clinical Dementia Rating Scale (CDR) and Mini-Mental State Examination (MMSE). An independent testing cohort, also consisting of four groups, was enrolled for ascertainment. Results: In the learning cohort, trough melatonin levels decreased in the MCI group but elevated in the mild and moderate to severe AD groups. Trough melatonin levels were associated with CDR and MMSE in MCI or AD patients significantly. In the testing cohort, the results were similar to those in the learning cohort. Conclusion: This study demonstrated that trough melatonin levels in the peripheral blood were decreased in MCI but increased with the severity of AD. The finding supports the trials indicating that melatonin showed efficacy only in MCI but not in AD. Whether trough melatonin level has potential to be a treatment response biomarker for AD, especially its early phase needs further studies.

참고문헌 (54)

  1. Holtzman DM, "Alzheimer’s disease : the challenge of the second century", Sci Transl Med, 3, pp.77~ (2011)
  2. Levey A, "Mild cognitive impairment : an opportunity to identify patients at high risk for progression to Alzheimer’s disease", Clin Ther, 28, pp.991~1001 (2006)
  3. Sullivan PF, "Evaluating the comparability of gene expression in blood and brain", Am J Med Genet B Neuropsychiatr Genet, 141B, pp.261~268 (2006)
  4. Cardinali DP, "The use of melatonin in Alzheimer’s disease", Neuro Endocrinol Lett, 23(Suppl 1), pp.20~23 (2002)
  5. Altun A, "Melatonin : therapeutic and clinical utilization", Int J Clin Pract, 61, pp.835~845 (2007)
  6. Hardeland R, "Antioxidative protection by melatonin : multiplicity of mechanisms from radical detoxification to radical avoidance", Endocrine, 27, pp.119~130 (2005)
  7. Ishio S, "HydroxyindoleO-methyltransferase is another target for L-glutamate-evoked inhibition of melatonin synthesis in rat pinealocytes", Brain Res, 850, pp.73~78 (1999)
  8. Yamada H, "Metabotropic glutamate receptors negatively regulate melatonin synthesis in rat pinealocytes", J Neurosci, 18, pp.2056~2062 (1998)
  9. Villela D, "Modulation of pineal melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through NF-B activation", Biomed Res Int, 2013, pp.618432~ (2013)
  10. Bavithra S, "Effect of melatonin on glutamate : BDNF signaling in the cerebral cortex of polychlorinated biphenyls(PCBs)-exposed adult male rats", Neurochem Res, 40, pp.1858~1869 (2015)
  11. Juan WS, "Melatonin improves neuroplasticity by upregulating the growth-associated protein-43(GAP-43)and NMDAR postsynaptic density-95(PSD-95)proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period", J Pineal Res, 56, pp.213~223 (2014)
  12. Zhou JN, "Early neuropathological Alzheimer’s changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels", J Pineal Res, 35, pp.125~130 (2003)
  13. Srinivasan V, "Melatonin in Alzheimer’s disease and other neurodegenerative disorders", Behav Brain Funct, 2, pp.15~ (2006)
  14. Liu RY, "Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-epsilon4", 4 genotype, 1999, pp.84, 323~327
  15. Uchida K, "Daily rhythm of serum melatonin in patients with dementia of the degenerate type", Brain Res, 717, pp.154~159 (1996)
  16. Cardinali DP, "Clinical aspects of melatonin intervention in Alzheimer’s disease progression", Curr Neuropharmacol, 8, pp.218~227 (2010)
  17. Cardinali DP, "The use of chronobiotics in the resynchronization of the sleep", wake cycle. Therapeutical application in the early phases of Alzheimer’s disease, 2011, pp.5, 80~90
  18. McCleery J, "Pharmacotherapies for sleep disturbances in dementia", Cochrane Database Syst Rev, 11, pp.CD009178~ (2016)
  19. Fourtillan JB, "Melatonin secretion occurs at a constant rate in both young and older men and women", Am J Physiol Endocrinol Metab, 280, pp.E11~ (2001)
  20. Lu PH, "Donepezil delays progression to AD in MCI subjects with depressive symptoms", Neurology, 72, pp.2115~2121 (2009)
  21. McKhann G, "Clinical diagnosis of Alzheimer’s disease : report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services task force on Alzheimer’s disease", Neurology, 34, pp.939~944 (1984)
  22. Morris JC, "The Clinical Dementia Rating(CDR) : current version and scoring rules", Neurology, 43, pp.2412~2414 (1993)
  23. Folstein MF, "“Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician", J Psychiatr Res, 12, pp.189~198 (1975)
  24. Crum RM, "Populationbased norms for the Mini-Mental State Examination by age and educational level", JAMA, 269, pp.2386~2391 (1993)
  25. Tombaugh TN, "The mini-mental state examination : a comprehensive review", J Am Geriatr Soc, 40, pp.922~935 (1992)
  26. Lim WS, "Utility of the clinical dementia rating in Asian populations", Clin Med Res, 5, pp.61~70 (2007)
  27. Rockwood K, "Interrater reliability of the Clinical Dementia Rating in a multicenter trial", J Am Geriatr Soc, 48, pp.558~559 (2000)
  28. Hughes CP, "A new clinical scale for the staging of dementia", Br J Psychiatry, 140, pp.566~572 (1982)
  29. Sack RL, "Human melatonin production decreases with age", J Pineal Res, 3, pp.379~388 (1986)
  30. Grad BR, "The role of melatonin and serotonin in aging : update", Psychoneuroendocrinology, 18, pp.283~295 (1993)
  31. Srinivasan V, "Melatonin and its agonist ramelteon in Alzheimer’s disease : possible therapeutic value", Int J Alzheimers Dis, 2011, pp.741974~ (2010)
  32. Wu YH, "The human pineal gland and melatonin in aging and Alzheimer’s disease", J Pineal Res, 38, pp.145~152 (2005)
  33. Hardeland R, "Melatonin", Int J Biochem Cell Biol, 38, pp.313~316 (2006)
  34. Cagnacci A, "Melatonin in relation to physiology in adult humans", J Pineal Res, 21, pp.200~213 (1996)
  35. Ohashi Y, "Differential pattern of the circadian rhythm of serum melatonin in young and elderly healthy subjects", Biol Signals, 6, pp.301~306 (1997)
  36. Scholtens RM, "Physiological melatonin levels in healthy older people : a systematic review", J Psychosom Res, 86, pp.20~27 (2016)
  37. Terzieva DD, "Melatonin reference limits at 3 : 00 AM and 8 : 00 AM in healthy adults", Clin Lab, 55, pp.359~361 (2009)
  38. Ji LD, "Association of disease-predisposition polymorphisms of the melatonin receptors and sunshine duration in the global human populations", J Pineal Res, 48, pp.133~141 (2010)
  39. Obayashi K, "Positive effect of daylight exposure on nocturnal urinary melatonin excretion in the elderly : a cross-sectional analysis of the HEIJO-KYO study", J Clin Endocrinol Metab, 97, pp.4166~4173 (2012)
  40. Kasper S, "Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder : a randomized, double-blind comparison with sertraline", J Clin Psychiatry, 71, pp.109~120 (2010)
  41. Owen RT. Ramelteon, "profile of a new sleep-promoting medication", Drugs Today(Barc), 42, pp.255~263 (2006)
  42. Romero A, "Synergistic neuroprotective effect of combined low concentrations of galantamine and melatonin against oxidative stress in SH-SY5Y neuroblastoma cells", J Pineal Res, 49, pp.141~148 (2010)
  43. Feng Z, "Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695transgenic mouse model of Alzheimer’s disease", J Pineal Res, 37, pp.129~136 (2004)
  44. Ramos E, "Melatonin as a versatile molecule to design novel multitarget hybrids against neurodegeneration", Future Med Chem, 9, pp.765~780 (2017)
  45. Torres-Lista V, "Neophobia, NQO1 and SIRT1 as premorbid and prodromal indicators of AD in 3xTg-AD mice", Behav Brain Res, 271, pp.140~146 (2014)
  46. Reiter RJ, "Melatonin as an antioxidant : under promises but over delivers", J Pineal Res, 61, pp.253~278 (2016)
  47. Rizzo V, "Determination of free and total(free plus protein-bound)melatonin in plasma and cerebrospinal fluid by high-performance liquid chromatography with fluorescence detection", J Chromatogr B Analyt Technol Biomed Life Sci, 774, pp.17~24 (2002)
  48. Olakowska E, "The role of melatonin in the neurodegenerative diseases", Bratisl Lek Listy, 106, pp.171~174 (2005)
  49. Srinivasan V, "Role of melatonin in neurodegenerative diseases", Neurotox Res, 7, pp.293~318 (2005)
  50. Lahiri DK, "Amyloid, cholinesterase, melatonin, and metals and their roles in aging and neurodegenerative diseases", Ann N Y Acad Sci, 1056, pp.430~449 (2005)
  51. Wongprayoon P, "Melatonin as a mitochondrial protector in neurodegenerative diseases", Cell Mol Life Sci, 74, pp.3999~4014 (2017)
  52. Song J, "The role of melatonin in the onset and progression of type 3 diabetes", Mol Brain, 10, pp.35~ (2017)
  53. Wu YH, "The human pineal gland and melatonin in aging and Alzheimer’s disease", J Pineal Res, 38, pp.145~152 (2005)
  54. Lin CH, "Benzoate, a D-amino acid oxidase inhibitor, for the treatment of early-phase Alzheimer disease : a randomized, doubleblind, placebo-controlled trial", Biol Psychiatry, 75, pp.678~685 (2014)

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