Parkinson's Disease Dementia and Potential Therapeutic Strategies

CNS Neuroscience and Therapeutics

Volumn 17, Issue 1, 2011, Pages 32-44

  Caviness, John N ^a   Lue, LihFen ^b   Adler, Charles H ^a   Walker, Douglas G ^b  

^a Mayo Clinic College of Medicine   (United States)

^b SUN HEALTH RESEARCH INSTITUTE   (United States)

Author keywords

Biomarker; Cortex; Dementia; Movement disorders Parkinson's disease; Parkinson's disease; Therapy

Indexed keywords

ACETYLCHOLINE; ALPHA SYNUCLEIN; AMANTADINE; CATECHOL METHYLTRANSFERASE INHIBITOR; CHOLINERGIC RECEPTOR BLOCKING AGENT; DONEPEZIL; DOPA DECARBOXYLASE INHIBITOR; DOPAMINE RECEPTOR STIMULATING AGENT; GALANTAMINE; LEVODOPA; MEMANTINE; MONOAMINE; MONOAMINE OXIDASE B INHIBITOR; RIVASTIGMINE;

AMNESIA; ATTENTION DISTURBANCE; CLINICAL FEATURE; DEMENTIA; DRUG WITHDRAWAL; ELECTROENCEPHALOGRAPHY; ELECTROPHYSIOLOGY; EVOKED CORTICAL RESPONSE; HUMAN; MYOCLONUS; NERVE DEGENERATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PARKINSON DISEASE; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW;

BIOLOGICAL MARKERS; BRAIN; DEMENTIA; HUMANS; PARKINSON DISEASE;

EID: 78751481767     PISSN: 17555930     EISSN: 17555949     Source Type: Journal    
DOI: 10.1111/j.1755-5949.2010.00216.x     Document Type: Review

References (174)

1. Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sorensen P. Risk of dementia in Parkinson's disease. Neurology 2001;56:730-736.
2. Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease. Arch Neurol. 2003;60:387-392.
3. Aarsland D, Zaccai J, Brayne C. A systematic review of prevalence studies of dementia in Parkinson's disease. Mov Disord 2005;20:1255-1263.
4. Hobson P, Meara J. Risk and incidence of dementia in a cohort of older subjects with Parkinson's disease in the United Kingdom. Mov Disord 2004;19:1043-1049.
5. Hughes TA, Ross HF, Musa S, Bhattacherjee S, Nathan RN, Mindham RHS, Spokes EGS. A 10-year study of the incidence of and factors predicting dementia in Parkinson's disease. Neurology 2000;54:1596-1602.
6. Harhangi BS, de Rijk MC, van Duijn CM, Ban Broeckhoven C, Hofman A, Breteler MMB. APOE and the risk of PD with or without dementia in a population-based study. Neurology 2000;54:1272-1276.
7. Levy G, Tang MX, Cote LJ, Louis ED, Alfaro B, Mejia H, Stern Y, Marder K. Motor impairment in PD. Neurology 2000;55:539-544.
8. Levy G, Schupf N, Tang MX, Cote LJ, Louis ED, Mejia H, Stern Y, Marder K. Combined effect of age and severity on the risk of dementia in Parkinson's disease. Ann Neurol 2002a;51:722-729.
9. Parsian A, Racette B, Goldsmith LJ, Perlmutter JS. Parkinson's disease and apolipoprotein E: Possible association with dementia but not age at onset. Genomics 2002;79:458-461.
10. Levy G, Jacobs DM, Tang MX, Cote LJ, Louis ED, Alfaro B, Mejia H, Stern Y, Marder K. Memory and executive function impairment predict dementia in Parkinson's disease. Mov Disord 2002b;17:1221-1226.
11. Emre M. What causes mental dysfunction in Parkinson's disease? Mov Disord 2003;18(Suppl 6):S63-S71.
12. Braak H, Rub U, Steur ENHJ, Del Tredici KD, de Vos RAI. Cognitive status correlates with neuropathologic stage in Parkinson's disease. Neurology 2005;64:1404-1410.
13. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC .
14. Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord 2007;22:1689-1707.
15. Pezzoli G, Zini M. Levodopa in Parkinson's disease: From the past to the future. Expert Opin Pharmacotherapy 2010;11:627-635.
16. Mena MA, Casarejos MJ, Solano RM, de Yebenes JG. Half a century of L-DOPA. Curr Topics Medicinal Chem 2009;9:880-893.
17. Weintraub D, Comella CL, Horn S. Parkinson's disease-Part 3: Neuropsychiatric symptoms. Am J Manage Care 2008;14:S59-S69.
18. Miyasaki JM, Shannon K, Voon V, et al. Practice parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2006;66:996-1002.
19. Poewe W, Gauthier S, Aarsland D, et al. Diagnosis and management of Parkinson's disease dementia. Clin Pract 2008;62:1581-1587.
20. Aarsland D, Laake K, Larsen JP, Janvin C. Donepezil for cognitive impairment in Parkinson's disease: A randomized controlled study. J Neurol Neurosurg Psychiatry 2002;72:708-712.
21. Burn D, McKeith IG. Current treatment of dementia with Lewy bodies and dementia associated with Parkinson's disease. Mov Disord 2003;18(Suppl 6):S72-S79.
22. Leroi I, Brandt J, Geich SG, Lyketsos CG, Grill S, Thompson R, Marsh L. Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease. Int J Geriatr Psychiatry 2004;19:1-8.
23. Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: A double-blind, placebo-controlled, multicentre trial. Lancet Neurol 2009;8:613-618.
24. Fabbrini G, Barbanti P, Aurillia C, Pauletti C, Lenzi GL, Meco G. Donepezil in the treatment of hallucinations and delusions in Parkinson's disease. Neurol Sci 2002;23:41-43.
25. Jesse S, Steinacker P, Lehnert S, Gillardon F, Hengerer B, Otto M. Neurochemical approaches in the laboratory diagnosis of Parkinson and Parkinson Dementia Syndromes: A review. CNS Neurosci Therap 2009;15:157-182.
26. Biomarkers Definitions Working Group. Biomarker and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Therap 2001;69:89-95.
27. Dahof M, Alvan G, Dahl SG, Kuhlmann J, Paintaud G. Mechanism-based pharmacokinetic-pharmacodynamic modeling-A new classification of biomarkers. Pharmaceut Res 2005;22:1432-1437.
28. Bothe MR, Uttner I, Otto M. Sharpening the boundaries of Parkinson-associated dementia: Recommendation for a neuropsychological diagnostic procedure. J Neural Transm 2010;117:353-367.
29. Pagonabarraga J, Kulisevsky J, Liebaria G, Garcia-Sanchez C, Pascual-Sedano B, Gironell A. Parkinson's disease-Cognitive Rating Scale: A new cognitive scale specific for Parkinson's disease. Mov Disord 2008;23:998-1005.
30. Mamikonyan E, Mober PJ, Siderowf A, et al. Mild cognitive impairment is common in Parkinson's disease patients with normal Mini-Mental State Examination (MMSE) scores. Parkinsonism Related Disord 2009;15:226-231.
31. Nazem S, Siderowf AD, Duda JE, et al. Montreal cognitive assessment performance in patients with Parkinson's disease with "Normal" global cognition according to mini-mental state examination score. J Am Geriatr Soc 2009;57:304-308.
32. Hoops S, Nazem S, Siderowf AD, Duda JE, Xie SX, Stern MB, Weintraub D. Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology 2009;73:1738-1745.
33. Kulisevsky J, Pagonabarraga J. Cognitive impairment in Parkinson's Disease: Tools for diagnosis and assessment. Mov Disord 2009;24:1103-1110.
34. Mahieux F, Fenelon G, Flahault A, Manifacier M-J, Denyse M, Boller F. Neuropsychological prediction of dementia in Parkinson's disease. J Neurol, Neurosurg, Psychiatry 1998;64:178-183.
35. Caviness JN, Driver-Dunckley ED, Connor DJ, et al. Defining mild cognitive impairment in Parkinson's disease. Mov Disord 2007;22:1272-1277.
36. Janvin C, Aarsland D, Larsen JP, Hugdahl K. Neuropsychological profile of patients with Parkinson's disease without dementia. Dementia Geriatric Cognit Disord 2003;15:126-131.
37. Petersen RC, Doody R, Kurz A, et al. Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985-1992.
38. Levy G. Dementia in Parkinson's disease challenges the "Gold Standard". Ann Neurol 2005;58:663-665.
39. Brown DE, Dababo MA, Bigio EH, Risser RC, Eagan KP, Hladik CL, White CL. Neuropathologic evidence that the Lewy body variant of Alzheimer Disease represents coexistence of Alzheimer disease and idiopathic Parkinson disease. J Neuropathol Exp Neurol 1998;57:39-46.
40. Jellinger KA, Seppi K, Wenning GK, Poewe W. Impact of coexistent Alzheimer pathology on the natural history of Parkinson's disease. J Neural Transm 2002;109:329-339.
41. Apaydin H, Ahlskog JE, Parisi JE, Boeve BF, Dickson DW. Parkinson disease neuropathology: Later-developing dementia and loss of the levodopa response. Arch Neurol 2002;59:102-112.
42. Hurtig HI, Trojanowski JQ, Galvin J, et al. Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease. Neurology 2000;54:1916-1921.
43. Colosimo C, Hughes AJ, Kilford L, Lees AJ. Lewy body cortical involvement may not always predict dementia in Parkinson's disease. J Neurol, Neurosurg Psychiatry 2003;74:852-856.
44. Glosser G. Neurobehavioral aspects of movement disorders. Neurol Clin 2001;19:535-551.
45. Lopez OL, Becker JT, Kaufer DI, et al. Research evaluation and prospective diagnosis of dementia with Lewy bodies. Arch Neurol 2002;59:43-46.
46. Dickson DW, Uchikado H, Fujishiro H, Tsuboi Y. Evidence in favor of Braak staging of Parkinson's disease. Mov Disord 2010;25(Suppl 1):S78-S82.
47. Halliday GM, McCann H. The progression of pathology in Parkinson's disease. Ann N Y Acad Sci 2010;1184:188-195.
48. Hindle JV. Ageing, neurodegeneration and Parkinson's disease. Age Ageing 2010:39:156-161.
49. Burack MA, Hartlein JA, Flores HP, Taylor-Reinwald L, Perlmutter JS, Cairns J. In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia. Neurology 2010;74:77-84.
50. McKeith IG, Dickson DW, Lowe J, et al. For the Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: Third report on the DLB consortium. Neurology 2005;65:1863-1872.
51. Kalra S, Grosset DG, Benamer HT. Differentiating vascular Parkinsonism from idiopathic Parkinson's disease: A systematic review. Mov Disord 2010;25:149-156.
52. Hamos JE, DeGennaro LJ, Drachman DA. Synaptic loss in Alzheimer's disease and other dementias. Neurology 1989;39:355-361.
53. Masliah E, Terry RD, DeTeresa RM, Hansen LA. Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease. Neurosci Lett 1989;103:234-239.
54. Scheff SW, DeKosky ST, Price DA. Quantitative assessment of cortical synaptic density in Alzheimer's disease. Neurobiol Aging 1990;11:29-37.
55. Mouton PR, Price DL, Walker LC. Empirical assessment of synapse numbers in primate neocortex. J Neurosci Methods 1997;75:119-126.
56. Hansen LA, Daniel SE, Wilcock GK, Love S. Frontal cortical synaptophysin in Lewy body diseases: Relation to Alzheimer's disease and dementia. J Neurol, Neurosurg Psychiatry 1998;64:653-656.
57. Wakabayashi K, Honer WG, Masliah E. Synapse alterations in the hippocampal-entorhinal formation in Alzheimer's disease with and without Lewy body disease. Brain Res 1994;667:24-32.
58. Zhan SS, Beyreuther K, Schmitt HP. Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia. Dementia 1993;4:66-74.
59. Lewis DA, Campbell MJ, Foote SL, Morrison JH. The monoaminergic innervation of primate neocortex. Human Neurobiol 1986;5:181-188.
60. Smiley, JF. Monoamines and acetylchonine in primate cerebral cortex: What anatomy tells us about function. Revista Brasileira de Biologia 1996;56(Suppl 1):153-164.
61. Berger B, Trottier S, Gaspar P, Verney C, Alvarez C. Major dopamine innervation of the cortical motor areas in the cynomolgus monkey. A radioautographic study with comparative assessment of serotonergic afferents. Neurosci Lett 1986;72:121-127.
62. Kucherenko RP, Otellin VA. Ultrastructure of the serotoninergic system of the motor region of the cerebral cortex. Neurosci Behav Physiol 1991;21:199-203.
63. Scatton B, Javoy-Agid F, Rouquier L, Dubois G, Agid Y. Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease. Brain Res 1983;275:321-328.
64. Whitehouse PJ, Hedreen JC, White CL, Price DL. Basal forebrain neurons in the dementia of Parkinson disease. Ann Neurol 1983;13:243-248.
65. Ibarretxe-Bilbao N, Tolosa E, Junque C, Marti M-J. MRI and cognitive impairment in Parkinson's disease. Mov Disord 2009;24(Suppl 2)S748-S753.
66. Burton EJ, McKeith IB, Burn DJ, Williams ED, O'Brien JT. Cerebral atrophy in Parkinson's disease with and without dementia: A comparison with Alzheimer's disease, dementia with Lewy bodies and controls. Brain 2004;127:791-800.
67. Burton EJ, McKeith IG, Burn DJ, O'Brien J T. Brain atrophy rates in Parkinson's disease with and without dementia using serial magnetic resonance imaging. Mov Disord 2005;20:1571-1576.
68. Camicioli R, Moore MM, Kinney A, Corbridge E, Glassberg K, Kaye JA. Parkinson's disease is associated with hippocampal atrophy. Mov Disord 2003;18:784-790.
69. Summerfield C, Junque C, Tolosa E, et al. Structural brain changes in Parkinson's disease with dementia. Arch Neurol 2005;62:281-285.
70. Hu MT, White SJ, Chaudhuri KR, Morris RG, Bydder GM, Brooks DJ. Correlating rates of cerebral atrophy in Parkinson's disease with measures of cognitive decline. J Neural Transm 2001;108:571-580.
71. Chan D, Janssen JC, Whitwell JL, et al. Change in rates of cerebral atrophy over time in early-onset alzheimer's disease: Longitudinal MRI study. Lancet 2003;362:1121-1122.
72. Beyer MK, Janvin CC, Larsen JP. A magnetic resonance imaging study of patients with Parkinson's disease with mild cognitive impairment and dementia using voxel-based morphometry. J Neurol Neurosurg Psychiatry 2007;78:254-259.
73. Wild EJ, Fox NC. Serial volumetric MRI in Parkinsonian disorders. Mov Disord 2009;24(Suppl 2):S691-S698.
74. Au WL, Adams JR, Troianno JR, Stoessl AJ. Parkinson's disease: In vivo assessment of disease progression using positron emission tomography. Brain Res Mol Brain Res 2005;134:24-33.
75. Brooks DJ. The role of structural and functional imaging in Parkinsonian states with a description of PET technology. Semin Neurol 2008;28:435-445.
76. Huang C, Mattis P, Perrine K, Brown N, Dhawan V, Eidelberg D. Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease. Neurology 2008;70:1470-1477.
77. Nobili F, Abbruzzese G, Morbelli S, Marchese R, Girtler N, Dessi B. Amnestic mild cognitive impairment in Parkinson's disease: A brain perfusion SPECT study. Mov Disord 2009;24:414-421.
78. Brooks DJ. Imaging amyloid in Parkinson's disease dementia and dementia with Lewy bodies with positron emission tomography. Mov Disord 2009;24(Suppl 2):S742-S747.
79. 18F]FDG PET study. Paper presented at Movement Disorders Society Meeting. Istanbul, Turkey, 2007.
80. Edison P, Rowe CC, Rinne J, et al. Amyloid load in Lewy body dementia (LBD), Parkinson's disease dementia (PDD) and Parkinson's disease (PD) measured with 11C-PIB PET. Neurology 2007;68(Suppl 1):A98.
81. Gomperts SN, Rentz DM, Becker JA, et al. Imaging amyloid deposition in Lewy body diseases. Neurology 2007;68(Suppl 1):A51.
82. Walter U, Skoloudik, Berg D. Transcranial sonography findings related to non-motor features of Parkinson's disease. J Neurol Sci 2010;289:123-127.
83. Johansen KK, White LR, Sando SB, Aasly JO. Biomarkers: Parkinson disease with dementia and demtnia with Lewy bodies. Parkinsonism Related Disord 2010;16:307-315.
84. Sirakov AA, Mezan IS. EEG findings in Parkinsonism. Electroencephalogr Clin Neurophysiol 1963;15:321.
85. Neufeld MY, Inzelberg R, Korczyn AD. EEG in demented and non-demented parkinsonian patients. Acta Neurol Scand 1988;78:1-5.
86. Soikkeli R, Partanen J, Soininen H, Paakkonen A, Riekkinen P. Slowing of EEG in Parkinson's disease. Electroencephalogr Clin Neurophysiol 1991;79:159-165.
87. Neufeld MY, Blumen S, Attkin I, Parmet Y, Korczyn AD. EEG frequency analysis in demented and nondemented Parkinsonian patients. Dementia 1994;5:23-28.
88. Salinsky MC, Oken BS, Morehead L. Test-retest reliability in EEG frequency analysis. Electroencephalogr Clin Neurophysiol 1991;79:382-392.
89. Gasser T, Bacher P, Steinberg H. Test-retest reliability of spectral parameters of the EEG. Electroencephalogr Clin Neurophysiol 1985;60:312-319.
90. Caviness JN, Hentz JG, Evidente VGH, et al. Both early and late cognitive dysfunction affects the electroencephalogram in Parkinson's disease. Parkinsonism Related Disord 2007;13:348-354.
91. Bonani L, Thomas A, Tiraboschi P, Perfetti B, Varanese S, Onofrj M. EEG comparisons in early Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease with demtnia patients with a 2-year follow-up. Brain 2008;131:690-705.
92. Steriade M, Gloor P, Llinas RR et al. Basic mechanisms of cerebral rhythmical activities. Electroencephalogr Clin Neurophysiol 1990;76:481-508.
93. Kozelka JW, Pedley TA. Beta and Mu rhythms. J Clin Neurophysiol 1990;7:191-207.
94. Ray WJ, Cole HW. EEG alpha activity reflects attentional demands, and beta activity reflects emotional and cognitive processes. Science 1985;228:750-752.
95. Nakamura S, Sadato N, Oohashi T, Nishina E, Fuwamoto Y, Yonekura Y. Analysis of music-brain interaction with simultaneous measurement of regional cerebral blood flow and electroencephalogram beta rhythm in human subjects. Neurosci Lett 1999;275:222-226.
96. Niedermeyer E. The normal EEG of the waking adult. In: Nidermeyer E, Da Silva FL, editors. Electroencephalography, Ch. 9. Philadelphia Lippincott Williams & Wilkins; 2005;178-180.
97. Vanderwolf CH. Neocortical and hippocampal activation in relation to behaviour: Effects of atropine, eserine, phenothiazines and amphetamine. J Comp Physiol Psychol 1975;88:300-323.
98. Stewart DJ, MacFabe DF, Vandervwolf CH. Cholinergic activation of the electrocorticogram: Role of substantia innominata and effects of atropine and quinnuclioninyl benzylate. Brain Res 1984;322:219-232.
99. Buzsaki G, Bickford RG, Ponomareff G, Thal LJ, Mandel RT, Gage FG. Nucleus basalis and thalamic control of neocortical activity in the freely moving rat. J Neurol Sci 1988;8:4007-4026.
100. Neufeld MY, Inzelberg R, Korczyn AD. EEG in demented and non-demented parkinsonian patients. Acta Neurol Scand 1988;78:1-5.
101. Kimura I, Ohnuma A, Seki H, Saso S, Kogure K. Cognitive Impairment in Parkinson's disease assessed by Visuomotor performance system and P300 potentia. Tohoku J Exp Med 1990;161:155-165.
102. Ito J. Somatosensory event-related potentials (ERPs) in patients with different types of dementia. J Neurol Sci 1994;121:139-146.
103. Starkstein S, Esteguy M, Berthier ML, Garcia H, Leiguarda R. Evoked potentials, reaction time and cognitive performance in on and off phases of Parkinson's disease. J Neurol, Neurosurg Psychiatry 1989;52:338-340.
104. Prabhakar S, Syal P, Srivastava T. P300 in newly diagnosed non-dementing Parkinson's disease: Effect of dopaminergic drugs. Neurol India 2000;48:239-242.
105. Bodis-Wollmer I, Borod JC, et al. Modality dependent changes in event-related potentials correlate with specific cognitive functions in nondemented patients with Parkinson's disease. J Neural Transm 1995;9:197-209.
106. Stanzione P, Semprini R, Pierantozzi M., et al. Age and stage dependency of P300 latency alternations in non-demented Parkinson's disease patients without therapy. Electroencephalogr Clin Neuropysiol 1998;108:80-91.
107. Hanafusa H, Motomura N, Fukai M. Event-related potentials in senile dementia of Alzheimer's type, multiinfarct dementia and Parkinson's disease. The Japanese J Psychiatry Neurol 1991;45:667-670.
108. Hayashi R, Hanyu N, Shindo M, Tamaru F, Yansagisawa N. Event-related Potentials, reactions time, and cognitive state in Patients with Parkinson's disuse. Adv Neurol 1993;60:429-433.
109. Matsui H, Nishinaka K, Oda M, Kubori T, Udaka F. Auditory event-related potentials in Parkinson's disease: Prominent correlation with attention. Parkinsonism Related Disord 2007;13:394-398.
110. Wang H, Wang Y, Wang D, Cui L, Tian CS, Zhang TY. Cognitive impairment in Parkinson's disease revealed by event-related potential N270. J Neurol Sci 2002;194:49-53.
111. Elwan OH, Baradah OH, Madkour O, et al. Parkinson's disease, cognition and aging Clinical, neuropsychological, electrophysiological and cranial computerized tomographic assessment. J Neurol Sci 1996;143:64-71.
112. Raudino F, Garavaglia P, Beretta S, Pellegrini G. Auditory event-related potentials in Parkinson's disease. Electromyogr Clin Neurophysiol 1997;37:409-413.
113. Caviness JN, Adler CH, Beach TG, Wetjen KJ, Caselli RJ. Small amplitude cortical myoclonus in Parkinson's disease: Physiology and clinical observations. Mov Disord 2002a;17:657-662.
114. Caviness JN. Myoclonus and neurodegenerative disease-what's in a name?. Parkinsonism Related Disord 2003a;9:185-192.
115. Caviness JN, Gwinn-Hardy KA, Adler CH, Muenter MD. Electrophysiological observations in hereditary Parkinsonism-dementia with Lewy body pathology. Mov Disord 2000;15:140-145.
116. Caviness JN, Adler CH, Beach T, Wetjen K, Caselli RJ. Myoclonus in Lewy body disorders. In: Fahn S et al. editors. Myoclonus and paroxysmal dyskinesias advances in neurology, Vol. 89. New York, New York Lippincott Williams & Wilkins, 2002b; 23-30.
117. Caviness JN. Clinical neurophysiology of myoclonus. Movement disorders. In Hallett M, editor, Handbook of clinical neurophysiology, Vol. 1, Ch. 32, 2003b;521-548.
118. Inzelberg R, Polyniki A. Are genetic and sporadic Parkinson's disease patients equally susceptible to develop dementia? J Neurol Sci 2010;289:23-26.
119. Leverenz JB, Quinn JF, Zabetian C, Zhang J, Montine KS, Montine TJ. Cognitive impairment and dementia in patients with Parkinson disease. Curr Top Med Chem 2009;9:903-912.
120. Huang X, Chen P, Kaufer D, Troster A, Poole C. Apolipoprotein E and Dementia in Parkinson's disease: A meta-analysis. Arch Neurol 2006;63:189-193.
121. Kurz MW, Dekomien G, Nilsen OB, Larsen JP, Aarsland D, Alves G. APOE alleles in Parkinson disease and their relationship to cognitive decline: A population-based, longitudinal study. J Geriatric Psychiatry Neurol 2009;22:166-170.
122. Williams-Gray CH, Goris A, et al. Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson's disease. J Neurol 2009;256:493-498.
123. Ezquerra M, Campdelacreu J, Gaig C, et al. Lack of association of APOE and tau polymorphisms with dementia in Parkinson's disease. Neurosci Lett 2008;448:20-23.
124. 42 ratio for increased risk of mild cognitive impairment. Neurology 2007;69:631-639.
125. 42 ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 2007;64:343-349.
126. Lippa CF, Duda JE, Grossman M, Hurtig HI, Aarsland D, Boeve BF. DLB and PDD boundary issues. Neurology 2007;68:812-819.
127. Aubert I, Araujo DM, Cecyre D, Robitaille Y, Gauthier S, Quirion R. Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer's and Parkinson's diseases. J Neurochem 1992;58:529-541.
128. 3H] nicotinic acetylcholine binding in Alzheimer's disease and Parkinson's disease: An autoradiographic study. Neurology 1988;38:720-723.
129. Newhouse PA, Potter A, Singh A. Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol 2004;4:36-46.
130. Bullock R, Lane R. Executive dyscontrol in dementia, with emphasis on subcortical pathology and the role of butyrylcholinesterase. Curr Alzheimer Res 2007;4:277-293.
131. Kim HJ, Chae SC, Lee DK, et al. Selective neuronal degeneration induced by soluble oligomeric amyloid beta protein. Fed Am Soc Exp Biol J 2003;17:118-120.
132. Wang X, Perry G, Smith MA, Zhu X. Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons. Neuro-degenerative Dis 2010;7:56-59.
133. Pitt J, Roth W, Lacor P, et al. Alzheimer's-associated Abeta oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicol Appl Pharmacol 2009;240:189-197.
134. Viola KL, Velasco PT, Klein WL. Why Alzheimer's is a disease of memory: The attack on synapses by A beta oligomers (ADDLs). J Nutr, Health Aging 2008;12:51S-57S.
135. Beyer K, Ariza A. The therapeutical potential of alpha-synuclein antiaggregatory agents for dementia with Lewy bodies. Curr Med Chem 2008;15:2748-2759.
136. Yuan B, Sierks MR. Intracellular targeting and clearance of oligomeric alpha-synuclein alleviates toxicity in mammalian cells. Neurosci Lett 2009;459:16-18.
137. Wisniewski T, Boutajangout A. Vaccination as a therapeutic approach to Alzheimer's disease. Mt. Sinai J Med 2010;77:17-31.
138. Masliah E, Rockenstein E, Adame A, et al. Effects of alpha-synuclein immunization in a mouse model of Parkinson's disease. Neuron 2005;46:857-868.
139. Ostrerova-Golts N, Petrucelli L, Hardy J, Lee JM, Farer M, Wolozin B. The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. J Neurosci 2000;20:6048-6054.
140. Polymeropoulos MH. Autosomal dominant Parkinson's disease and alpha-synuclein. Ann Neurol 1998;44:S63-S64.
141. Polymeropoulos MH, Lavedan C, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997;276:2045-2047.
142. Wakabayashi K, Matsumoto K, Takayama K, Yoshimoto M, Takahashi H. NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson's disease. Neurosci Lett 1997;239:45-48.
143. Uversky VN. Alpha-synuclein misfolding and neurodegenerative diseases. Curr Protein Peptide Sci 2008;9:507-540.
144. Kanzer KM, Haasen D, Karow AR, et al. Different species of α-synuclein oligomers induce calcium influx and seeding. J Neurosci 2007;27:9220-9232.
145. Jellinger KA. A critical evaluation of current staging of alpha-synuclein pathology in Lewy body disorders. Biochim Biophys Acta 2009;1792:730-740.
146. Beach TG, Adler CH, Lue L, et al. Unified staging system for Lewy body disorders: Correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 2009;117:613-634.
147. Chau KY, Ching HL, Schapira AH, Cooper JM. Relationship between alpha synuclein phosphorylation, proteasomal inhibition and cell death: Relevance to Parkinson's disease pathogenesis. J Neurochem 2009;110:1005-1013.
148. Sugeno N, Takeda A, Hasegawa T, et al. Serine 129 phosphorylation of alpha-synuclein induces unfolded protein response-mediated cell death. J Biol Chem 2008;283:23179-23188.
149. Kragh CL, Lund LB, Febbraro F, et al. {alpha}-synuclein aggregation and Ser-129 phosphorylation-dependent cell death in oligodendroglial cells. J Biol Chem 2009;284:10211-10222.
150. Inglis KJ, Chereau D, Brigham EF, et al. Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem 2009;284:2598-2602.
151. Waxman EA, Giasson BI. Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein. J Neuropathol Exp Neurol 2008;67:402-416.
152. Qing H, Wong W, McGeer EG, McGeer PL. Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications. Biochem Biophys Res Commun 2009;387:149-152.
153. Sulzer D. Clues to how alpha-synuclein damages neurons in Parkinson's disease. Mov Disord 2010;25(Suppl 1):S27-S31.
154. George JL, Mok S, Moses D, et al. Targeting the progression of Parkinson's disease. Curr Neuropharmacol 2009;7:9-36.
155. Lee MK, Stirling W, Xu Y, et al. Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 → Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc Natl Acad Sci USA 2002;99:8968-8973.
156. Van Der Putten H, Wiederhold KH, et al. Neuropathology in mice expressing human alpha-synuclein. J Neurosci 2000;20:6021-6029.
157. Xiromerisiou G, Dardiotis E, Tsimourtou V, et al. Genetic basis of Parkinson disease. Neurosurg Focus 2010;28:E7.
158. Ross OA, Braithwaite AT, Skipper LM, et al. Genomic investigation of alpha-synuclein multiplication and parkinsonism. Ann Neurol 2008;63:743-750.
159. Obi T, Nishioka K, Ross OA, et al. Clinicopathologic study of a SNCA gene duplication patient with Parkinson disease and dementia. Neurol 2008;70:238-241.
160. Ahn TB, Kim SY, Kim JY, et al. Alpha-Synuclein gene duplication is present in sporadic Parkinson disease. Neurology 2008;70:43-49.
161. Nichols WC, Pankratz N, Marek DK, et al. Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. Neurology 2009;72:310-316.
162. Mata IF, Samii A, Schneer SH, et al. Glucocerebrosidase gene mutations: A risk factor for Lewy body disorders. Archive Neurol 2008;65:379-382.
163. Wider C, Dickson DW, Wszolek ZK. Leucine-rich repeat Kinase 2 gene-associated disease: Redefining genotype-phenotype correlation. Neurodegenerat Dis 2010;7:175-179.
164. Dauer W, Ho CC. The biology and pathology of the familial Parkinson's disease protein LRRK2. Mov Disord 2010;25(Suppl 1):S40-S43.
165. Anand VS, Braithwaite SP. LRRK2 in Parkinson's disease: Biochemical functions. FEBS J 2009;276:6428-6435.
166. Webber PJ, West AB. LRRK2 in Parkinson's disease: Function in cells and neurodegeneration. FEBS J 2009;276:6436-6444.
167. Cuny GD. Kinase inhibitors as potential therapeutics for acute and chronic neurodegenerative conditions. Curr Pharmaceut Design 2009;15:3919-3939.
168. Stamper C, Siegel A, Liang WS, et al. Neuronal gene expression correlates of Parkinson's disease with dementia. Mov Disord 2008;23:1588-1595.
169. Sawada M, Imamura K, Nagatsu T. Role of cytokines in inflammatory process in Parkinson's disease. J Neural Transm Suppl 2006;70:373-381.
170. Loeffler DA, Camp DM, Conant SB. Complement activation in the Parkinson's disease substantia nigra: An immunocytochemical study. J Neuroinflammat 2006;3:29.
171. Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, Di NM, Onofrj M. Peripheral cytokines profile in Parkinson's disease. Brain, Behavior, Immunity 2009;23:55-63.
172. McGeer EG, McGeer PL. The role of anti-inflammatory agents in Parkinson's disease. CNS Drugs 2007;21:789-797.
173. Srivastava N, Seth K, Srivastava N, Khanna VK, Agrawal AK. Functional restoration using basic fibroblast growth factor (bFGF) infusion in Kainic acid induced cognitive dysfunction in rat: Neurobehavioural and neurochemical studies. Neurochem Res 2008;33:1169-1177.
174. Lee J, Boo JH, Ryu H. The failure of mitochondria leads to neurodegneration: Do mitochondria need a jump start? Adv Drug Delivery Rev 2009;61:1316-1323.