Serum MHPG strongly predicts conversion to Alzheimer's disease in behaviorally characterized subjects with down syndrome

Journal of Alzheimer's Disease

Volumn 43, Issue 3, 2015, Pages 871-891

  Dekker, Alain D ^a,b   Coppus, Antonia M W ^c,d,e   Vermeiren, Yannick ^b   Aerts, Tony ^b   Van Duijn, Cornelia M ^d   Kremer, Berry P ^a   Naudé, Pieter J W ^a   Van Dam, Debby ^b   De Deyn, Peter P ^a,b  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b UNIVERSITY OF ANTWERP   (Belgium)

^c Center for the Intellectually Disabled   (Netherlands)

^d ERASMUS MEDICAL CENTER   (Netherlands)

^e RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Alzheimer's disease; behavioral and psychological signs and symptoms of dementia (BPSD); biogenic amines; biomarkers; Down syndrome; MHPG; RP HPLC

Indexed keywords

3,4 DIHYDROXYPHENYLACETIC ACID; 4 HYDROXY 3 METHOXYPHENYLETHYLENE GLYCOL; 5 HYDROXYINDOLEACETIC ACID; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; ANTICONVULSIVE AGENT; ANTIDEPRESSANT AGENT; BIOGENIC AMINE; DOPAMINE; HOMOVANILLIC ACID; NEUROLEPTIC AGENT; NORADRENALIN; SEROTONIN; AMYLOID BETA PROTEIN; BIOLOGICAL MARKER; PEPTIDE FRAGMENT;

ADULT; AGGRESSIVENESS; ALZHEIMER DISEASE; APATHY; ARTICLE; BEHAVIORAL AND PSYCHOLOGICAL SIGNS AND SYMPTOMS OF DEMENTIA; BLOOD LEVEL; CIRCADIAN RHYTHM; CONTROLLED STUDY; DEMENTIA; DEPRESSION; DOWN SYNDROME; ELECTROCHEMICAL DETECTION; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; SYMPTOM; BLOOD; DISEASE COURSE; MIDDLE AGED;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; BIOLOGICAL MARKERS; BIOMARKERS; DISEASE PROGRESSION; DOPAMINE; DOWN SYNDROME; FEMALE; HUMANS; MALE; METHOXYHYDROXYPHENYLGLYCOL; MIDDLE AGED; NOREPINEPHRINE; PEPTIDE FRAGMENTS;

EID: 84914675690     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-140783     Document Type: Article

References (107)

1. Bittles AH, Bower C, Hussain R, Glasson EJ (2007) The four ages of Down syndrome. Eur J Public Health 17, 221-225.
2. Lott IT, Dierssen M (2010) Cognitive deficits and associated neurological complications in individuals with Down's syndrome. Lancet Neurol 9, 623-633.
3. Zigman WB, Lott IT (2007) Alzheimer's disease in Down syndrome: Neurobiology and risk. Ment Retard Dev Disabil Res Rev 13, 237-246.
4. Ness S, Rafii M, Aisen P, Krams M, Silverman W, Manji H (2012) Down's syndrome and Alzheimer's disease: Towards secondary prevention. Nat Rev Drug Discov 11, 655-656.
5. Wilcock DM (2012) Neuroinflammation in the aging down syndrome brain; lessons from Alzheimer's disease. Curr Gerontol Geriatr Re 2012, 170276.
6. Leverenz JB, Raskind MA (1998) Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: A regional quantitative analysis. Exp Neurol 150, 296-304.
7. Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol 17, 278-282.
8. Borroni B, Costanzi C, Padovani A (2010) Genetic susceptibility to behavioural and psychological symptoms in Alzheimer disease. Curr Alzheimer Res 7, 158-164.
9. Finkel SI, Costa e Silva J, Cohen G, Miller S, Sartorius N (1996) Behavioral and psychological signs and symptoms of dementia: A consensus statement on current knowledge and implications for research and treatment. Int Psychogeriatr 8(Suppl 3), 497-500.
10. Vermeiren Y, Le Bastard N, Van Hemelrijck A, Drinkenburg WH, Engelborghs S, De Deyn PP (2013) Behavioral correlates of cerebrospinal fluid amino acid and biogenic amine neurotransmitter alterations in dementia. Alzheimers Dement 9, 488-498.
11. Finkel S (2000) Introduction to behavioural and psychological symptoms of dementia (BPSD). Int J Geriatr Psychiatry 15(Suppl 1), S2-S4.
12. Weamer EA, Emanuel JE, Varon D, Miyahara S, Wilkosz PA, Lopez OL, Dekosky ST, Sweet RA (2009) The relationship of excess cognitive impairment in MCI and early Alzheimer's disease to the subsequent emergence of psychosis. Int Psychogeriatr 21, 78-85.
13. Ball SL, Holland AJ, Watson PC, Huppert FA (2010) Theoretical exploration of the neural bases of behavioural disinhibition, apathy and executive dysfunction in preclinical Alzheimer's disease in people with Down's syndrome: Potential involvement of multiple frontal-subcortical neuronal circuits. J Intellect Disabil Res 54, 320-336.
14. De Deyn PP, Engelborghs S, Saerens J, Goeman J, Marien P, Maertens K, Nagels G, Martin JJ, Pickut BA (2005) The Middelheim Frontality Score: A behavioural assessment scale that discriminates frontotemporal dementia from Alzheimer's disease. Int J Geriatr Psychiatry 20, 70-79.
15. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J (1994) The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology 44, 2308-2314.
16. Reisberg B, Borenstein J, Salob SP, Ferris SH, Franssen E, Georgotas A (1987) Behavioral symptoms in Alzheimer's disease: Phenomenology and treatment. J Clin Psychiatry 48(Suppl), 9-15.
17. Reisberg B, Auer SR, Monteiro IM (1996) Behavioral pathology in Alzheimer's disease (BEHAVE-AD) rating scale. Int Psychogeriatr 8(Suppl 3), 301-308; discussion 351-354.
18. Engelborghs S, De Deyn PP (1997) The neurochemistry of Alzheimer's disease. Acta Neurol Belg 97, 67-84.
19. Engelborghs S, Vloeberghs E, Le Bastard N, Van Buggenhout M, Marien P, Somers N, Nagels G, Pickut BA, De Deyn PP (2008) The dopaminergic neurotransmitter system is associated with aggression and agitation in frontotemporal dementia. Neurochem Int 52, 1052-1060.
20. Herrmann N, Lanctôt KL, Khan LR (2004) The role of norepinephrine in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci 16, 261-276.
21. Lanari A, Amenta F, Silvestrelli G, Tomassoni D, Parnetti L (2006) Neurotransmitter deficits in behavioural and psychological symptoms of Alzheimer's disease. Mech Ageing Dev 127, 158-165.
22. Lanctôt KL, Herrmann N, Mazzotta P (2001) Role of serotonin in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci 13, 5-21.
23. Kendler KS, Heninger GR, Roth RH (1982) Influence of dopamine agonists on plasma and brain levels of homovanillic acid. Life Sci 30, 2063-2069.
24. Meltzer HY (1989) Clinical studies on the mechanism of action of clozapine: The dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology (Berl) 99(Suppl), S18-S27.
25. Coppus AW, Fekkes D, Verhoeven WM, Tuinier S, Egger JI, van Duijn CM (2007) Plasma amino acids and neopterin in healthy persons with Down's syndrome. J Neural Transm 114, 1041-1045.
26. Kopin IJ (1985) Catecholamine metabolism: Basic aspects and clinical significance. Pharmacol Rev 37, 333-364.
27. DeMet EM, Halaris AE (1979) Origin and distribution of 3-methoxy-4-hydroxyphenylglycol in body fluids. Biochem Pharmacol 28, 3043-3050.
28. Elsworth JD, Redmond DE Jr, Roth RH (1982) Plasma and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) as indices of brain norepinephrine metabolism in primates. Brain Res 235, 115-124.
29. Coppus A, Evenhuis H, Verberne GJ, Visser F, van Gool P, Eikelenboom P, van DuijinC(2006) Dementia and mortality in persons with Down's syndrome. J Intellect Disabil Res 50, 768-777.
30. Coppus AM, Schuur M, Vergeer J, Janssens AC, Oostra BA, Verbeek MM, van Duijn CM (2012) Plasma beta amyloid and the risk of Alzheimer's disease in Down syndrome. Neurobiol Aging 33, 1988-1994.
31. Aylward EH, Burt DB, Thorpe LU, Lai F, Dalton A (1997) Diagnosis of dementia in individuals with intellectual disability. J Intellect Disabil Res 41(Pt 2), 152-164.
32. Burt DB, Aylward EH (2000) Test battery for the diagnosis of dementia in individuals with intellectual disability.Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Intellectual Disability. J Intellect Disabil Res 44(Pt 2), 175-180.
33. World Health Organization (2010) ICD-10: International Statistical Classification of diseases and related Health Problems, 10th revision, http://apps.who.int/classifications/icd10/browse/2010/en
34. Holland AJ, Hon J, Huppert FA, Stevens F,Watson P (1998) Population-based study of the prevalence and presentation of dementia in adults with Down's syndrome. Br J Psychiatry 172, 493-498.
35. Strydom A, Chan T, Fenton C, Jamieson-Craig R, Livingston G, Hassiotis A (2013) Validity of criteria for dementia in older people with intellectual disability. Am J Geriatr Psychiatry 21, 279-288.
36. Evenhuis HM,Kengen MMF, Eurlings HAL(1998) Dementie Vragenlijst voor Verstandelijk Gehandicapten (DVZ).
37. Kraijer DW, Kema GN, de Bildt AA (2004) Sociale Redzaamheidsschaal voor Verstandelijk Gehandicapten (SRZ/SRZI).
38. Van Dam D, Vermeiren Y, Aerts T, De Deyn PP (2014) Novel and sensitive reversed-phase high-pressure liquid chromatography method with electrochemical detection for the simultaneous and fast determination of eight biogenic amines and metabolites in human brain tissue. J Chromatogr A 1353, 28-39.
39. Brent PJ, Chahl LA (1991) Effects of naloxone-precipitated withdrawal after a single dose of morphine on catecholamine concentrations in guinea-pig brain. Neurochem Res 16, 525-531.
40. Widmann R, Sperk G (1986) Topographical distribution of amines and major amine metabolites in the rat striatum. Brain Res 367, 244-249.
41. Kelland MD, Freeman AS, Chiodo LA (1990) Serotonergic afferent regulation of the basic physiology and pharmacological responsiveness of nigrostriatal dopamine neurons. J Pharmacol Exp Ther 253, 803-811.
42. Jenner P, Sheehy M,Marsden CD (1983) Noradrenaline and 5-hydroxytryptamine modulation of brain dopamine function: Implications for the treatment of Parkinson's disease. Br J Clin Pharmacol 15(Suppl 2), 277S-289S.
43. Trillo L, Das D, Hsieh W, Medina B, Moghadam S, Lin B, Dang V, Sanchez MM, De Miguel Z, Ashford JW, Salehi A (2013) Ascending monoaminergic systems alterations in Alzheimer's disease. translating basic science into clinical care. Neurosci Biobehav Rev 37, 1363-1379.
44. Eisenhofer G,Kopin IJ, GoldsteinDS(2004) Catecholamine metabolism: A contemporary view with implications for physiology and medicine. Pharmacol Rev 56, 331-349.
45. Mann DM, Yates PO, Marcyniuk B, Ravindra CR (1985) Pathological evidence for neurotransmitter deficits in Down's syndrome of middle age. J Ment Defic Res 29(Pt 2), 125-135.
46. Godridge H, Reynolds GP, Czudek C, Calcutt NA, Benton M (1987) Alzheimer-like neurotransmitter deficits in adult Down's syndrome brain tissue. J Neurol Neurosurg Psychiatry 50, 775-778.
47. Reynolds GP, Godridge H (1985) Alzheimer-like brain monoamine deficits in adults withDown's syndrome. Lancet 2, 1368-1369.
48. Yates CM, Ritchie IM, Simpson J, Maloney AF, Gordon A (1981) Noradrenaline in Alzheimer-type dementia and Down syndrome. Lancet 2, 39-40.
49. Coyle JT, Oster-Granite ML, Gearhart JD (1986) The neurobiologic consequences of Down syndrome. Brain Res Bull 16, 773-787.
50. Whittle N, Sartori SB, Dierssen M, Lubec G, Singewald N (2007) Fetal Down syndrome brains exhibit aberrant levels of neurotransmitters critical for normal brain development. Pediatrics 120, e1465-e1471.
51. Kay AD, Schapiro MB, Riker AK, Haxby JV, Rapoport SI, Cutler NR (1987) Cerebrospinal fluid monoaminergic metabolites are elevated in adults with Down's syndrome. Ann Neurol 21, 408-411.
52. Schapiro MB, Kay AD, May C, Ryker AK, Haxby JV, Kaufman S, Milstien S, Rapoport SI (1987) Cerebrospinal fluid monoamines in Down's syndrome adults at different ages. J Ment Defic Res 31(Pt 3), 259-269.
53. Bondareff W, Mountjoy CQ, Roth M (1982) Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology 32, 164-168.
54. Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM (2007) Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease. Neurobiol Aging 28, 327-335.
55. Palmer AM, DeKosky ST (1993) Monoamine neurons in aging and Alzheimer's disease. J Neural Transm Gen Sect 91, 135-159.
56. Storga D, Vrecko K, Birkmayer JG, Reibnegger G (1996) Monoaminergic neurotransmitters, their precursors and metabolites in brains of Alzheimer patients. Neurosci Lett 203, 29-32.
57. Cross AJ, Crow TJ, Johnson JA, Joseph MH, Perry EK, Perry RH, Blessed G, Tomlinson BE (1983) Monoamine metabolism in senile dementia of Alzheimer type. J Neurol Sci 60, 383-392.
58. Raskind MA, Peskind ER, Halter JB, Jimerson DC (1984) Norepinephrine and MHPG levels in CSF and plasma in Alzheimer's disease. Arch Gen Psychiatry 41, 343-346.
59. Wetterberg L, Gustavson KH, Backstrom M, Ross SB, Froden O (1972) Low dopamine-beta-hydroxylase activity in Down's syndrome. Clin Genet 3, 152-153.
60. Lake CR, Ziegler MG, Coleman M, Kopin IJ (1979) Evaluation of the sympathetic nervous system in trisomy-21 (Down's syndrome). J Psychiatr Res 15, 1-6.
61. Coleman M, Campbell M, Freedman LS, Roffman M, Ebstein RP, Goldstein M (1974) Serum dopamine-betahydroxylase levels in Down's syndrome. Clin Genet 5, 312-315.
62. Benson PF, Southgate J (1971) Diminished activity of platelet monoamine oxidase in Down's syndrome. Am J Hum Genet 23, 211-214.
63. Fowler CJ, Wiberg A, Gustavson KH, Winblad B (1981) Platelet monoamine oxidase activity in Down's syndrome. Clin Genet 19, 307-311.
64. Lott IT, Chase TN, Murphy DL (1972) Down's syndrome: Transport, storage, and metabolism of serotonin in blood platelets. Pediatr Res 6, 730-735.
65. Gustavson KH,Wetterberg L, Backstrom M, Ross SB(1973) Catechol-O-methyltransferase activity in erythrocytes in Down's syndrome. Clin Genet 4, 279-280.
66. Ohtsuki S (2004) New aspects of the blood-brain barrier transporters; its physiological roles in the central nervous system. Biol Pharm Bull 27, 1489-1496.
67. Lambert GW, Kaye DM, Vaz M, Cox HS, Turner AG, Jennings GL, Esler MD (1995) Regional origins of 3-methoxy-4-hydroxyphenylglycol in plasma: Effects of chronic sympathetic nervous activation and denervation, and acute reflex sympathetic stimulation. J Auton Nerv Syst 55, 169-178.
68. Goldstein DS, Eisenhofer G, Kopin IJ (2003) Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther 305, 800-811.
69. Toneff T, Funkelstein L, Mosier C, Abagyan A, Ziegler M, Hook V (2013) Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters. Peptides 46, 126-135.
70. Liu Y, Yoo MJ, Savonenko A, Stirling W, Price DL, Borchelt DR, Mamounas L, Lyons WE, Blue ME, Lee MK (2008) Amyloid pathology is associated with progressive monoaminergic neurodegeneration in a transgenic mouse model of Alzheimer's disease. J Neurosci 28, 13805-13814.
71. Salehi A, Faizi M, Colas D, Valletta J, Laguna J, Takimoto-Kimura R, Kleschevnikov A,Wagner SL, Aisen P, Shamloo M, Mobley WC (2009) Restoration of norepinephrinemodulated contextual memory in a mouse model of Down syndrome. Sci Transl Med 1, 7ra17.
72. Davisson MT, Schmidt C, Akeson EC (1990) Segmental trisomy of murine chromosome 16: A new model system for studying Down syndrome. Prog Clin Biol Res 360, 263-280.
73. Reeves RH, Irving NG, Moran TH,Wohn A, Kitt C, Sisodia SS, Schmidt C, Bronson RT, Davisson MT (1995) A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet 11, 177-184.
74. Faizi M, Bader PL,TunC, Encarnacion A, Kleschevnikov A, Belichenko P, Saw N, Priestley M, Tsien RW, Mobley WC, ShamlooM(2011) Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down syndrome: Activation of beta1-adrenergic receptor by xamoterol as a potential cognitive enhancer. Neurobiol Dis 43, 397-413.
75. Pennington BF, Moon J, Edgin J, Stedron J, Nadel L (2003) The neuropsychology of Down syndrome: Evidence for hippocampal dysfunction. Child Dev 74, 75-93.
76. Aylward EH, Li Q, HoneycuttNA,WarrenAC, Pulsifer MB, Barta PE, Chan MD, Smith PD, Jerram M, Pearlson GD (1999) MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia. Am J Psychiatry 156, 564-568.
77. Dierssen M, Vallina IF, Baamonde C, Garcia-Calatayud S, Lumbreras MA, Florez J (1997) Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome. Brain Res 749, 238-244.
78. Lockrow J, Boger H, Gerhardt G, Aston-Jones G, Bachman D, GranholmAC (2011)Anoradrenergic lesion exacerbates neurodegeneration in a Down syndrome mouse model. J Alzheimers Dis 23, 471-489.
79. Seidl R, KaehlerST, Prast H, Singewald N, Cairns N, Gratzer M, Lubec G (1999) Serotonin (5-HT) in brains of adult patients with Down syndrome. J Neural Transm Suppl 57, 221-232.
80. Lambert GW, Kaye DM, Cox HS, Vaz M, Turner AG, Jennings GL, EslerMD(1995) Regional 5-hydroxyindoleacetic acid production in humans. Life Sci 57, 255-267.
81. Rosner F, Ong BH, Paine RS, Mahanand D (1965) Bloodserotonin activity in trisomic and translocation Down's syndrome. Lancet 1, 1191-1193.
82. Tu JB, Zellweger H (1965) Blood-serotonin deficiency in Down's syndrome. Lancet 2, 715-716.
83. Boullin DJ, O'Brien RA (1971) Abnormalities of 5-hydroxytryptamine uptake and binding by blood platelets from children with Down's syndrome. J Physiol 212, 287-297.
84. Mann DM, Yates PO (1983) Serotonin nerve cells in Alzheimer's disease. J Neurol Neurosurg Psychiatr 46, 96.
85. Bowen DM, Allen SJ, Benton JS, Goodhardt MJ, Haan EA, Palmer AM, Sims NR, Smith CC, Spillane JA, Esiri MM, Neary D, Snowdon JS, Wilcock GK, Davison AN (1983) Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease. J Neurochem 41, 266-272.
86. Volicer L, Direnfeld LK, Freedman M, Albert ML, Langlias PJ, Bird ED (1985) Serotonin and 5-hydroxyindoleacetic acid in CSF. Difference in Parkinson's disease and dementia of the Alzheimer's type. Arch Neurol 42, 127-129.
87. Blakely RD, De Felice LJ, Hartzell HC (1994) Molecular physiology of norepinephrine and serotonin transporters. J Exp Biol 196, 263-281.
88. Walker JC, Dosen A, Buitelaar JK, Janzing JG (2011) Depression in Down syndrome: A review of the literature. Res Dev Disabil 32, 1432-1440.
89. Gulesserian T, Engidawork E, Cairns N, Lubec G (2000) Increased protein levels of serotonin transporter in frontal cortex of patients with Down syndrome. Neurosci Lett 296, 53-57.
90. Nieoullon A (2002) Dopamine and the regulation of cognition and attention. Prog Neurobiol 67, 53-83.
91. Mann DM, Yates PO, Marcyniuk B (1987) Dopaminergic neurotransmitter systems in Alzheimer's disease and in Down's syndrome at middle age. J Neurol Neurosurg Psychiatry 50, 341-344.
92. Lange-Asschenfeldt C (2013) Vascular factors in the pathogenesis of Alzheimer's disease. Nervenarzt 84, 732-737.
93. Goldstein N, Goldstein R, Terterov D, Kamensky AA, Kovalev GI, Zolotarev YA, Avakyan GN, Terterov S (2012) Blood-brain barrier unlocked. Biochemistry (Mosc) 77, 419-424.
94. Eustace A, Coen R, Walsh C, Cunningham CJ, Walsh JB, Coakley D, Lawlor BA (2002) A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease. Int J Geriatr Psychiatry 17, 968-973.
95. PankowA, Knobel A,Voss M, HeinzA(2012) Neurobiological correlates of delusion: Beyond the salience attribution hypothesis. Neuropsychobiology 66, 33-43.
96. Melamed E, FriedbergG, Zoldan J (1999) Psychosis: Impact on the patient and family. Neurology 52, S14-S16.
97. Mitchell RA, Herrmann N, Lanctôt KL (2011) The role of dopamine in symptoms and treatment of apathy in Alzheimer's disease. CNS Neurosci Ther 17, 411-427.
98. Mega MS, Cummings JL, Fiorello T, Gornbein J (1996) The spectrum of behavioral changes in Alzheimer's disease. Neurology 46, 130-135.
99. Marin RS (1996) Apathy: Concept, syndrome, neural mechanisms, and treatment. Semin Clin Neuropsychiatry 1, 304-314.
100. Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9, 357-381.
101. Sublette ME, Postolache TT (2012) Neuroinflammation and depression: The role of indoleamine 2,3-dioxygenase (IDO) as a molecular pathway. Psychosom Med 74, 668-672.
102. Stuerenburg HJ, Ganzer S, Muller-Thomsen T (2004) 5-Hydroxyindoleacetic acid and homovanillic acid concentrations in cerebrospinal fluid in patients with Alzheimer' disease, depression and mild cognitive impairment. Neuro Endocrinol Lett 25, 435-437.
103. Vermeiren Y, Van Dam D, Aerts T, Engelborghs S, De Deyn PP (2014) Monoaminergic neurotransmitter alterations in postmortem brain regions of depressed and aggressive Alzheimer patients. Neurobiol Aging. doi 10.1016/j.neurobiolaging.2014.05.31
104. Moret C, BrileyM(2011) The importance of norepinephrine in depression. Neuropsychiatr Dis Treat 7, 9-13.
105. Duke AA, Begue L, Bell R, Eisenlohr-Moul T (2013) Revisiting the serotonin-aggression relation in humans: A meta-analysis. Psychol Bull 139, 1148-1172.
106. Moran M, Lynch CA, Walsh C, Coen R, Coakley D, Lawlor BA (2005) Sleep disturbance in mild to moderate Alzheimer's disease. Sleep Med 6, 347-352.
107. Vitiello MV, Borson S (2001) Sleep disturbances in patients with Alzheimer's disease: Epidemiology, pathophysiology and treatment. CNS Drugs 15, 777-796.