Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: Probably even at early disease stages

Brain Structure and Function

Volumn 214, Issue 4, 2010, Pages 303-317

  Borghammer, Per ^a   Chakravarty, Mallar ^a,b,c   Jonsdottir, Kristjana Yr ^b   Sato, Noriko ^d   Matsuda, Hiroshi ^e   Ito, Kengo ^f   Arahata, Yutaka ^f   Kato, Takashi ^f   Gjedde, Albert ^a,b  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

^b AARHUS UNIVERSITY   (Denmark)

^c ALLEN INSTITUTE FOR BRAIN SCIENCE   (United States)

^d National Center Hospital of Neurology and Psychiatry   (Japan)

^e SAITAMA MEDICAL UNIVERSITY   (Japan)

^f NATIONAL CENTER FOR GERIATRICS AND GERONTOLOGY   (Japan)

Author keywords

CBF; Glucose; Normalization; Parkinson's disease; PET; SPECT

Indexed keywords

CYSTEINE ETHYL ESTER TC 99M; FLUORODEOXYGLUCOSE;

BRAIN BLOOD FLOW; BRAIN DISEASE; CLINICAL FEATURE; CORTICAL HYPOMETABOLISM; CORTICAL HYPOPERFUSION; DATA ANALYSIS; DISEASE COURSE; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GLUCOSE TRANSPORT; HUMAN; IMAGE ANALYSIS; IMAGE PROCESSING; META ANALYSIS; PARKINSON DISEASE; POSITRON EMISSION TOMOGRAPHY; PRINCIPAL COMPONENT ANALYSIS; PRIORITY JOURNAL; REVIEW; SIMULATION; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; SUBCORTEX; SYSTEMATIC REVIEW; AGED; BRAIN CIRCULATION; BRAIN CORTEX; BRAIN MAPPING; FEMALE; MALE; METHODOLOGY; MIDDLE AGED; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; SCINTISCANNING; THREE DIMENSIONAL IMAGING;

AGED; BRAIN MAPPING; CEREBRAL CORTEX; CEREBROVASCULAR CIRCULATION; FEMALE; HUMANS; IMAGING, THREE-DIMENSIONAL; MAGNETIC RESONANCE IMAGING; MALE; META-ANALYSIS AS TOPIC; MIDDLE AGED; PARKINSON DISEASE; POSITRON-EMISSION TOMOGRAPHY; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON;

EID: 77955474301     PISSN: 18632653     EISSN: 18632661     Source Type: Journal    
DOI: 10.1007/s00429-010-0246-0     Document Type: Review

References (82)

1. Abe Y, Kachi T, Kato T, Arahata Y, Yamada T, Washimi Y, Iwai K, Ito K, Yanagisawa N, Sobue G (2003) Occipital hypoperfusion in Parkinson's disease without dementia: correlation to impaired cortical visual processing. J Neurol Neurosurg Psychiatry 74:419-422 (Pubitemid 36379360)
2. Agniel A, Celsis P, Viallard G, Montastruc JL, Rascol O, Demonet JF, Marc-Vergnes JP, Rascol A (1991) Cognition and cerebral blood flow in lateralised parkinsonism: lack of functional lateral asymmetries. J Neurol Neurosurg Psychiatry 54:783-786
3. Ahl B, Weissenborn K, van den Hoff J, Fischer-Wasels D, Kostler H, Hecker H, Burchert W (2004) Regional differences in cerebral blood flow and cerebral ammonia metabolism in patients with cirrhosis. Hepatology 40:73-79 (Pubitemid 38868925)
4. Antonini A, De Notaris R, Benti R, De Gaspari D, Pezzoli G (2001) Perfusion ECD/SPECT in the characterization of cognitive deficits in Parkinson's disease. Neurol Sci 22:45-46 (Pubitemid 33622083)
5. Arahata Y, Hirayama M, Ieda T, Koike Y, Kato T, Tadokoro M, Ikeda M, Ito K, Sobue G (1999) Parieto-occipital glucose hypometabolism in Parkinson's disease with autonomic failure. J Neurol Sci 163:119-126 (Pubitemid 29234234)
6. Ben-Shachar D, Bonne O, Chisin R, Klein E, Lester H, Aharon-Peretz J, Yona I, Freedman N (2007) Cerebral glucose utilization and platelet mitochondrial complex I activity in schizophrenia: a FDG-PET study. Prog Neuropsychopharmacol Biol Psychiatry 31:807-813 (Pubitemid 46671478)
7. Berding G, Odin P, Brooks DJ, Nikkhah G, Matthies C, Peschel T, Shing M, Kolbe H, van Den Hoff J, Fricke H, Dengler R, Samii M, Knapp WH (2001) Resting regional cerebral glucose metabolism in advanced Parkinson's disease studied in the off and on conditions with [(18)F]FDG-PET. Mov Disord 16:1014-1022 (Pubitemid 36041213)
8. Bes A, Guell A, Fabre N, Dupui P, Victor G, Geraud G (1983) Cerebral blood flow studied by Xenon-133 inhalation technique in parkinsonism: loss of hyperfrontal pattern. J Cereb Blood Flow Metab 3:33-37 (Pubitemid 13129632)
9. Biesold D, Inanami O, Sato A, Sato Y (1989) Stimulation of the nucleus basalis of Meynert increases cerebral cortical blood flow in rats. Neurosci Lett 98:39-44 (Pubitemid 19054315)
10. Bohnen NI, Minoshima S, Giordani B, Frey KA, Kuhl DE (1999) Motor correlates of occipital glucose hypometabolism in Parkinson's disease without dementia. Neurology 52:541-546 (Pubitemid 29075600)
11. Borghammer P, Jonsdottir KY, Cumming P, Ostergaard K, Vang K, Ashkanian M, Vafaee M, Iversen P, Gjedde A (2008) Normalization in PET group comparison studies-the importance of a valid reference region. Neuroimage 40:529-540
12. Borghammer P, Aanerud J, Gjedde A (2009a) Data-driven intensity normalization of PET group comparison studies is superior to global mean normalization. Neuroimage 46(4):981-988
13. Borghammer P, Cumming P, Aanerud J, Forster S, Gjedde A (2009b) Subcortical elevation of metabolism in Parkinson's disease-a critical reappraisal in the context of global mean normalization. Neuroimage 47(4):1514-1521
14. Borghammer P, Cumming P, Aanerud J, Gjedde A (2009c) Artefactual subcortical hyperperfusion in PET studies normalized to global mean: lessons from Parkinson's disease. Neuroimage 45:249-257
15. Borghammer P, Ostergaard K, Cumming P, Gjedde A, Rodell A, Hall N, Chakravarty MM (2009d) A deformation-based morphometry study of patients with early-stage Parkinson's disease. Eur J Neurol [Epub ahead of print]
16. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24:197-211 (Pubitemid 36007810)
17. Buchsbaum MS, Buchsbaum BR, Hazlett EA, Haznedar MM, Newmark R, Tang CY, Hof PR (2007) Relative glucose metabolic rate higher in white matter in patients with schizophrenia. Am J Psychiatry 164:1072-1081 (Pubitemid 47121396)
18. Burton EJ, McKeith IG, Burn DJ, Williams ED, O'Brien JT (2004) Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls. Brain 127:791-800 (Pubitemid 38478524)
19. Cudennec A, Bonvento G, Duverger D, Lacombe P, Seylaz J, MacKenzie ET (1993) Effects of dorsal raphe nucleus stimulation on cerebral blood flow and flow-metabolism coupling in the conscious rat. Neuroscience 55:395-401 (Pubitemid 23211351)
20. Dagher A, Nagano-Saito A (2007) Functional and anatomical magnetic resonance imaging in Parkinson's disease. Mol Imaging Biol 9:234-242 (Pubitemid 47028739)
21. Duvernoy HM (1999) The human brain: surface, three-dimensional sectional anatomy with MRI, and blood supply. Springer, Vienna
22. Eberling JL, Richardson BC, Reed BR, Wolfe N, Jagust WJ (1994) Cortical glucose metabolism in Parkinson's disease without dementia. Neurobiol Aging 15:329-335 (Pubitemid 24194874)
23. Eckert T, Barnes A, Dhawan V, Frucht S, Gordon MF, Feigin AS, Eidelberg D (2005) FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 26:912-921 (Pubitemid 40825033)
24. Eckert T, Van Laere K, Tang C, Lewis DE, Edwards C, Santens P, Eidelberg D (2007) Quantification of Parkinson's disease-related network expression with ECD SPECT. Eur J Nucl Med Mol Imaging 34:496-501 (Pubitemid 46426989)
25. Eidelberg D, Moeller JR, Dhawan V, Sidtis JJ, Ginos JZ, Strother SC, Cedarbaum J, Greene P, Fahn S, Rottenberg DA (1990) The metabolic anatomy of Parkinson's disease: complementary [18F]fluorodeoxyglucose and [18F]fluorodopa positron emission tomographic studies. Mov Disord 5:203-213 (Pubitemid 20311769)
26. Eidelberg D, Moeller JR, Dhawan V, Spetsieris P, Takikawa S, Ishikawa T, Chaly T, Robeson W, Margouleff D, Przedborski S et al (1994) The metabolic topography of parkinsonism. J Cereb Blood Flow Metab 14:783-801 (Pubitemid 24266530)
27. EidelbergD,Moeller JR,Antonini A, Kazumata K, Nakamura T, Dhawan V, Spetsieris P, deLeon D, Bressman SB, Fahn S (1998) Functional brain networks in DYT1 dystonia. Ann Neurol 44:303-312 (Pubitemid 28421433)
28. Feigin A, Antonini A, Fukuda M, De Notaris R, Benti R, Pezzoli G, Mentis MJ, Moeller JR, Eidelberg D (2002) Tc-99m ethylene cysteinate dimer SPECT in the differential diagnosis of parkinsonism. Mov Disord 17:1265-1270 (Pubitemid 36041340)
29. Firbank MJ, Colloby SJ, Burn DJ, McKeith IG, O'Brien JT (2003) Regional cerebral blood flow in Parkinson's disease with and without dementia. Neuroimage 20:1309-1319 (Pubitemid 37268148)
30. Fox PT, Mintun MA, Reiman EM, Raichle ME (1988) Enhanced detection of focal brain responses using intersubject averaging and change-distribution analysis of subtracted PET images. J Cereb Blood Flow Metab 8:642-653
31. Frisina PG, Haroutunian V, Libow LS (2009) The neuropathological basis for depression in Parkinson's disease. Parkinsonism Relat Disord 15:144-148
32. Gai WP, Halliday GM, Blumbergs PC, Geffen LB, Blessing WW (1991) Substance P-containing neurons in the mesopontine tegmentum are severely affected in Parkinson's disease. Brain 114(Pt 5):2253-2267
33. German DC, Manaye KF, White CL III, Woodward DJ, McIntire DD, Smith WK, Kalaria RN, Mann DM (1992) Disease-specific patterns of locus coeruleus cell loss. Ann Neurol 32:667-676
34. Ghaemi M, Raethjen J, Hilker R, Rudolf J, Sobesky J, Deuschl G, Heiss WD (2002) Monosymptomatic resting tremor and Parkinson's disease: a multitracer positron emission tomographic study. Mov Disord 17:782-788 (Pubitemid 41295025)
35. Globus M, Mildworf B, Melamed E (1985) Cerebral blood flow and cognitive impairment in Parkinson's disease. Neurology 35:1135-1139 (Pubitemid 15003446)
36. Habeck C, Foster NL, Perneczky R, Kurz A, Alexopoulos P, Koeppe RA, Drzezga A, Stern Y (2008) Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease. Neuroimage 40:1503-1515
37. Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nature clinical practice 4:600-609
38. Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F (1987) Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci USA 84:5976-5980 (Pubitemid 17135731)
39. Hosey LA, Thompson JL, Metman LV, van den Munckhof P, Braun AR (2005) Temporal dynamics of cortical and subcortical responses to apomorphine in Parkinson disease: an H2(15)O PET study. Clin Neuropharmacol 28:18-27 (Pubitemid 40269714)
40. Hu MT, Taylor-Robinson SD, Chaudhuri KR, Bell JD, Labbe C, Cunningham VJ, Koepp MJ, Hammers A, Morris RG, Turjanski N, Brooks DJ (2000) Cortical dysfunction in non-demented Parkinson's disease patients: a combined (31)P-MRS and (18)FDG-PET study. Brain 123(Pt 2):340-352 (Pubitemid 30055157)
41. Huang C, Tang C, Feigin A, Lesser M, Ma Y, Pourfar M, Dhawan V, Eidelberg D (2007) Changes in network activity with the progression of Parkinson's disease. Brain 130:1834-1846 (Pubitemid 47343798)
42. Imon Y, Matsuda H, Ogawa M, Kogure D, Sunohara N (1999) SPECT image analysis using statistical parametric mapping in patients with Parkinson's disease. J Nucl Med 40:1583-1589 (Pubitemid 29471145)
43. Jellinger K (1988) The pedunculopontine nucleus in Parkinson's disease, progressive supranuclear palsy and Alzheimer's disease. J Neurol Neurosurg Psychiatry 51:540-543
44. Kalpouzos G, Chetelat G, Baron JC, Landeau B, Mevel K, Godeau C, Barre L, Constans JM, Viader F, Eustache F, Desgranges B (2009) Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging. Neurobiol Aging 30(1):112-124
45. Karbe H, Holthoff V, Huber M, Herholz K, Wienhard K, Wagner R, Heiss WD (1992) Positron emission tomography in degenerative disorders of the dopaminergic system. J Neural Transm Park Dis Dement Sect 4:121-130
46. Kikuchi A, Takeda A, Kimpara T, Nakagawa M, Kawashima R, Sugiura M, Kinomura S, Fukuda H, Chida K, Okita N, Takase S, Itoyama Y (2001) Hypoperfusion in the supplementary motor area, dorsolateral prefrontal cortex and insular cortex in Parkinson's disease. J Neurol Sci 193:29-36 (Pubitemid 33062392)
47. Kimbrell TA, Ketter TA, George MS, Little JT, Benson BE, Willis MW, Herscovitch P, Post RM (2002) Regional cerebral glucose utilization in patients with a range of severities of unipolar depression. Biol Psychiatry 51:237-252 (Pubitemid 34142636)
48. Kitamura S, Ujike T, Kuroki S, Sakamoto S, Soeda T, Iio M, Terashi A (1988) Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease. No To Shinkei 40:979-985
49. Kondo S, Tanaka M, Sun X, Okamoto K, Hirai S (1994) Cerebral blood flow and oxygen metabolism in patients with pure akinesia and progressive supranuclear palsy. Rinsho Shinkeigaku 34:531-537 (Pubitemid 24296016)
50. Kuhl DE, Metter EJ, Riege WH (1984) Patterns of local cerebral glucose utilization determined in Parkinson's disease by the [18F]fluorodeoxyglucose method. Ann Neurol 15:419-424 (Pubitemid 14145566)
51. Lacombe P, Sercombe R, Verrecchia C, Philipson V, MacKenzie ET, Seylaz J (1989) Cortical blood flow increases induced by stimulation of the substantia innominata in the unanesthetized rat. Brain Res 491:1-14 (Pubitemid 19159072)
52. Leenders KL, Wolfson L, Gibbs JM, Wise RJ, Causon R, Jones T, Legg NJ (1985) The effects of L-DOPA on regional cerebral blood flow and oxygen metabolism in patients with Parkinson's disease. Brain 108(Pt 1):171-191 (Pubitemid 15133833)
53. Ma Y, Tang C, Spetsieris PG, Dhawan V, Eidelberg D (2007) Abnormal metabolic network activity in Parkinson's disease: test-retest reproducibility. J Cereb Blood Flow Metab 27:597-605
54. Ma Y, Tang C, Moeller JR, Eidelberg D (2009) Abnormal regional brain function in Parkinson's disease: truth or fiction? Neuroimage 45:260-266
55. Minoshima S, Frey KA, Foster NL, Kuhl DE (1995) Preserved pontine glucose metabolism in Alzheimer disease: a reference region for functional brain image (PET) analysis. J Comput Assist Tomogr 19:541-547
56. Mito Y, Yoshida K, Yabe I, Makino K, Hirotani M, Tashiro K, Kikuchi S, Sasaki H (2005) Brain 3D-SSP SPECT analysis in dementia with Lewy bodies, Parkinson's disease with and without dementia, and Alzheimer's disease. Clin Neurol Neurosurg 107:396-403 (Pubitemid 40980384)
57. Moeller JR, Strother SC, Sidtis JJ, Rottenberg DA (1987) Scaled subprofile model: a statistical approach to the analysis of functional patterns in positron emission tomographic data. J Cereb Blood Flow Metab 7:649-658
58. Moeller JR, Nakamura T, Mentis MJ, Dhawan V, Spetsieres P, Antonini A, Missimer J, Leenders KL, Eidelberg D (1999) Reproducibility of regional metabolic covariance patterns: comparison of four populations. J Nucl Med 40:1264-1269 (Pubitemid 29385633)
59. Montastruc JL, Celsis P, Agniel A, Demonet JF, Doyon B, Puel M, Marc-Vergnes JP, Rascol A (1987) Levodopa-induced regional cerebral blood flow changes in normal volunteers and patients with Parkinson's disease. Lack of correlation with clinical or neuropsychological improvements. Mov Disord 2:279-289
60. Nagano-Saito A, Washimi Y, Arahata Y, Kachi T, Lerch JP, Evans AC, Dagher A, ItoK(2005)Cerebral atrophy and its relation to cognitive impairment in Parkinson disease. Neurology 64:224-229
61. Otsuka M, Ichiya Y, Hosokawa S, Kuwabara Y, Tahara T, Fukumura T, Kato M, Masuda K, Goto I (1991) Striatal blood flow, glucose metabolism and 18F-dopa uptake: difference in Parkinson's disease and atypical parkinsonism. J Neurol Neurosurg Psychiatry 54:898-904
62. Otsuka M, Ichiya Y, Kuwabara Y, Hosokawa S, Sasaki M, Yoshida T, Fukumura T, Kato M, Masuda K (1996) Glucose metabolism in the cortical and subcortical brain structures in multiple system atrophy and Parkinson's disease: a positron emission tomographic study. J Neurol Sci 144:77-83 (Pubitemid 27019161)
63. Peppard RF, Martin WR, Carr GD, Grochowski E, Schulzer M, Guttman M, McGeer PL, Phillips AG, Tsui JK, Calne DB (1992) Cerebral glucose metabolism in Parkinson's disease with and without dementia. Arch Neurol 49:1262-1268
64. Perlmutter JS, Raichle ME (1985) Regional blood flow in hemiparkinsonism. Neurology 35:1127-1134 (Pubitemid 15003445)
65. Piert M, Koeppe RA, Giordani B, Minoshima S, Kuhl DE (1996) Determination of regional rate constants from dynamic FDGPET studies in Parkinson's disease. J Nucl Med 37:1115-1122 (Pubitemid 26329516)
66. Playford ED, Jenkins IH, Passingham RE, Nutt J, Frackowiak RS, Brooks DJ (1992) Impaired mesial frontal and putamenactivation in Parkinson's disease: a positron emission tomography study. Ann Neurol 32:151-161
67. Powers WJ, Videen TO, Markham J, Black KJ, Golchin N, Perlmutter JS (2008) Cerebral mitochondrial metabolism in early Parkinson's disease. J Cereb Blood Flow Metab 28:1754-1760
68. Rougemont D, Baron JC, Collard P, Bustany P, Comar D, Agid Y (1984) Local cerebral glucose utilisation in treated and untreated patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 47:824-830 (Pubitemid 14059374)
69. Sasaki M, Ichiya Y, Hosokawa S, Otsuka M, Kuwabara Y, Fukumura T, Kato M, Goto I, Masuda K (1992) Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia. Ann Nucl Med 6:241-246 (Pubitemid 23049369)
70. Scarmeas N, Habeck CG, Zarahn E, Anderson KE, Park A, Hilton J, Pelton GH, Tabert MH, Honig LS, Moeller JR, Devanand DP, Stern Y (2004) Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance. Neuroimage 23:35-45 (Pubitemid 39119433)
71. Shimada H, Hirano S, Shinotoh H, Aotsuka A, Sato K, Tanaka N, Ota T, Asahina M, Fukushi K, Kuwabara S, Hattori T, Suhara T, Irie T (2009) Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. Neurology 73(4):273-278
72. Spetsieris P, Ma Y, Dhawan V, Moeller JR, Eidelberg D (2006) Highly automated computer-aided diagnosis of neurological disorders using functional brain imaging. Proc SPIE: Med Imag 6144:5M1-5M12
73. Underwood MD, Bakalian MJ, Arango V, Mann JJ (1995) Effect of chemical stimulation of the dorsal raphe nucleus on cerebral blood flow in rat. Neurosci Lett 199:228-230
74. Van Laere K, Santens P, Bosman T, De Reuck J, Mortelmans L, Dierckx R (2004) Statistical parametric mapping of (99m)Tc-ECD SPECT in idiopathic Parkinson's disease and multiple system atrophy with predominant parkinsonian features: correlation with clinical parameters. J Nucl Med 45:933-942 (Pubitemid 47611679)
75. Vander Borght T, Minoshima S, Giordani B, Foster NL, Frey KA, Berent S, Albin RL, Koeppe RA, Kuhl DE (1997) Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched for dementia severity. J Nucl Med 38:797-802
76. Videbech P, Ravnkilde B, Pedersen TH, Hartvig H, Egander A, Clemmensen K, Rasmussen NA, Andersen F, Gjedde A, Rosenberg R (2002) The Danish PET/depression project: clinical symptoms and cerebral blood flow. A regions-of-interest analysis. Acta Psychiatr Scand 106:35-44 (Pubitemid 34828146)
77. Wolfson LI, Leenders KL, Brown LL, Jones T (1985) Alterations of regional cerebral blood flow and oxygen metabolism in Parkinson's disease. Neurology 35:1399-1405 (Pubitemid 15242411)
78. Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC (1996) A unified statistical approach for determining significant signals in images of cerebral activation. Hum Brain Mapp 4:58-73 (Pubitemid 26195721)
79. Worsley KJ, Liao CH, Aston J, Petre V, Duncan GH, Morales F, Evans AC (2002) A general statistical analysis for fMRI data. Neuroimage 15:1-15 (Pubitemid 34852200)
80. Yakushev I, Hammers A, Fellgiebel A, Schmidtmann I, Scheurich A, Buchholz HG, Peters J, Bartenstein P, Lieb K, Schreckenberger M (2009) SPM-based count normalization provides excellent discrimination of mild Alzheimer's disease and amnestic mild cognitive impairment from healthy aging. Neuroimage 44:43-50
81. Yanase D, Matsunari I, Yajima K, Chen W, Fujikawa A, Nishimura S, Matsuda H, Yamada M (2005) Brain FDG PET study of normal aging in Japanese: effect of atrophy correction. Eur J Nucl Med Mol Imaging 32:794-805 (Pubitemid 41125422)
82. Zarow C, Lyness SA, Mortimer JA, Chui HC (2003) Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra inAlzheimer and Parkinson diseases.ArchNeurol 60:337-341 (Pubitemid 36314358)