Brain fuel metabolism, aging, and Alzheimer's disease

Nutrition

Volumn 27, Issue 1, 2011, Pages 3-20

  Cunnane, Stephen ^a,b   Nugent, Scott ^a,b   Roy, Maggie ^a,b   Courchesne Loyer, Alexandre ^a,b   Croteau, Etienne ^b   Tremblay, Sébastien ^a,b   Castellano, Alex ^a   Pifferi, Fabien ^c   Bocti, Christian ^a,b   Paquet, Nancy ^b   Begdouri, Hadi ^b   Bentourkia, M'hamed ^b   Turcotte, Eric ^b   Allard, Michèle ^d   Barberger Gateau, Pascale ^e,f   Fulop, Tamas ^a,b   Rapoport, Stanley I ^g  

^a UNIVERSITY INSTITUTE OF GERIATRICS OF SHERBROOKE   (Canada)

^b UNIVERSITÉ DE SHERBROOKE   (Canada)

^c UMR CNRS MNHN 7179   (France)

^d PSL RESEARCH UNIVERSITY   (France)

^e INSERM   (France)

^f UNIVERSITÉ DE BORDEAUX   (France)

^g National Institute of Aging   (United States)

Author keywords

Aging; Alzheimer's disease; Brain; Cognition; Glucose; Insulin; Ketones; Mitochondria; PET

Indexed keywords

ACETOACETIC ACID; APOLIPOPROTEIN E4; DOCOSAHEXAENOIC ACID; GLUCOSE; INSULIN; KETONE; PYRUVATE DEHYDROGENASE; TAU PROTEIN;

AGING; ALZHEIMER DISEASE; BRAIN BLOOD VESSEL; BRAIN DISEASE; BRAIN HYPOMETABOLISM; BRAIN METABOLISM; BRAIN REGION; COGNITIVE DEFECT; DIABETES MELLITUS; DIETARY INTAKE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DYSLIPIDEMIA; ENERGY METABOLISM; ENZYME ACTIVITY; FAMILY HISTORY; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; GLUCOSE UTILIZATION; GLYCOLYSIS; HIGH RISK POPULATION; HUMAN; INSULIN RESISTANCE; INSULIN SENSITIVITY; KETOGENESIS; KETOGENIC DIET; MILD COGNITIVE IMPAIRMENT; NEUROPATHOLOGY; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW;

ANIMALIA;

EID: 78649962844     PISSN: 08999007     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nut.2010.07.021     Document Type: Review

References (217)

1. Blennow K., de Leon M.J., Zetterberg H. Alzheimer's disease. Lancet 2006, 368:387-403.
2. Jack C.R., Knopman D.S., Jagust W.J., Shaw L.M., Aisen P.S., Weiner M.W., et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010, 9:119-128.
3. Sims N.R., Bowen D.M., Neary D., Davison A.N. Metabolic processes in Alzheimer's disease: adenine nucleotide content and production of 14CO2 from [U-14C]glucose in vitro in human neocortex. J Neurochem 1983, 41:1329-1334.
4. Hoyer S., Oesterreich K., Wagner O. Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type?. J Neurol 1988, 235:143-148.
5. Heininger K. The cerebral glucose-fatty acid cycle: evolutionary roots, regulation, and (patho)physiological importance. Int Rev Neurobiol 2002, 51:103-158.
6. Blass J.P. A new approach to treating Alzheimer's disease. Ann NY Acad Sci 2008, 1147:122-128.
7. Holliday M.A. Metabolic rate and organ size during growth from infancy to maturity and during late gastation and early infancy. Pediatrics 1971, 47(suppl 2). 169+.
8. Sokoloff L. Energetics of functional activation in neural tissues. Neurochem Res 1999, 24:321-329.
9. Attwell D., Iadecola C. The neural basis of functional brain imaging signals. Trends Neurosci 2002, 25:621-625.
10. Shulman R.G., Rothman D.L., Behar K.L., Hyder F. Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci 2004, 27:489-495.
11. Purdon A.D., Rapoport S.I. Energy consumption by phospholipid metabolism in mammalian brain 2007, Springer, New York.
12. Oz G., Kumar A., Rao J.P., Kodl C.T., Chow L., Eberly L.E., et al. Human brain glycogen metabolism during and after hypoglycemia. Diabetes 2009, 58:1978-1985.
13. Magistretti P.J. Brain energy metabolism. An introducation to cellular and molecular neuroscience 2004, 67-90. Academic Press, Hong Kong. J.H. Bryrne, J.L. Roberts (Eds.).
14. Pellerin L., Bouzier-Sore A.K., Aubert A., Serres S., Merle M., Costalat R., et al. Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 2007, 55:1251-1262.
15. Girouard H., Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 2006, 100:328-335.
16. Duelli R., Kuschinsky W. Brain glucose transporters: relationship to local energy demand. News Physiol Sci 2001, 16:71-76.
17. Leybaert L., De Bock M., Van Moorhem M., Decrock E., De Vuyst E. Neurobarrier coupling in the brain: adjusting glucose entry with demand. J Neurosci Res 2007, 85:3213-3220.
18. Barros L.F., Porras O.H., Bittner C.X. Why glucose transport in the brain matters for PET. Trends Neurosci 2005, 28:117-119.
19. Gottstein V.U., Held K., Muller W., Berghoff W. Utilization of ketone bodies by the human brain. Research on cerebral circulation 1970, 137-145. 5th International Salzburg Conference, Thomas CC, Springfield. J.S. Meyer, M. Reivich, H. Lecher, C.C. Thomas (Eds.).
20. Hasselbalch S.G., Madsen P.L., Hageman L.P., Olsen K.S., Justesen N., Holm S., et al. Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia. Am J Physiol 1996, 270:E746-E751.
21. Lying-Tunell U., Lindblad B.S., Malmlund H.O., Persson B. Cerebral blood flow and metabolic rate of oxygen, glucose, lactate, pyruvate, ketone bodies and amino acids. Acta Neurol Scand 1981, 63:337-350.
22. Owen O.E., Morgan A.P., Kemp H.G., Sullivan J.M., Herrera M.G., Cahill G.F. Brain metabolism during fasting. J Clin Invest 1967, 46:1589-1595.
23. Pan J.W., Telang F.W., Lee J.H., de Graaf R.A., Rothman D.L., Stein D.T., et al. Measurement of beta-hydroxybutyrate in acute hyperketonemia in human brain. J Neurochem 2001, 79:539-544.
24. Phelps M.E., Huang S.C., Hoffman E.J., Selin C., Sokoloff L., Kuhl D.E. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 1979, 6:371-388.
25. Sokoloff L. Measurement of local cerebral glucose utilization and its relation to local functional activity in the brain. Adv Exp Med Biol 1991, 291:21-42.
26. O'Sullivan F., Muzi M., Spence A.M., Mankoff D.M., O'Sullivan J.N., Fitzgerald N., et al. Nonparametric residue analysis of dynamic PET data with application to cerebral fdg studies in normals. J Am Stat Assoc 2009, 104:556-571.
27. Kimura N., Yamamoto Y., Kameyama R., Hatakeyama T., Kawai N., Nishiyama Y. Diagnostic value of kinetic analysis using dynamic 18F-FDG-PET in patients with malignant primary brain tumor. Nucl Med Commun 2009, 30:602-609.
28. Gunn R.N., Gunn S.R., Turkheimer F.E., Aston J.A., Cunningham V.J. Positron emission tomography compartmental models: a basis pursuit strategy for kinetic modeling. J Cereb Blood Flow Metab 2002, 22:1425-1439.
29. Sokoloff L., Reivich M., Kennedy C., Des Rosiers M.H., Patlak C.S., Pettigrew K.D., et al. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 1977, 28:897-916.
30. Graham M.M., Muzi M., Spence A.M., O'Sullivan F., Lewellen T.K., Link J.M., et al. The FDG lumped constant in normal human brain. J Nucl Med 2002, 43:1157-1166.
31. Huang S.C. Anatomy of SUV. Standardized uptake value. Nucl Med Biol 2000, 27:643-646.
32. Krohn K.A., Muzi M., Spence A.M. What is in a number? The FDG lumped constant in the rat brain. J Nucl Med 2007, 48:5-7.
33. Lear J.L., Ackerman R.F. Comparison of regional blood-brain transport kinetics between glucose and fluorodeoxyglucose. J Nucl Med 1992, 33:1819-1824.
34. Thie J.A. Understanding the standardized uptake value, its methods, and implications for usage. J Nucl Med 2004, 45:1431-1434.
35. Canadian Study of Health and Aging: study methods and prevalence of dementia. Can Med Assoc J 1994, 150:899-913. Canadian Study of Health, and Aging Working Group.
36. Brayne C., Gao L., Dewey M., Matthews F.E. Dementia before death in ageing societies-the promise of prevention and the reality. PLoS Med 2006, 3:e397.
37. Li Y., Rinne J.O., Mosconi L., Pirraglia E., Rusinek H., DeSanti S., et al. Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer's disease. Eur J Nucl Med Molec Imag 2008, 35:2169-2181.
38. Querfurth H.W., LaFerla F.M. Alzheimer's disease. N Engl J Med 2010, 362:329-344.
39. Lehtovirta M., Soininen H., Helisalmi S., Mannermaa A., Helkala E.L., Hartikainen P., et al. Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease: relation to apolipoprotein E polymorphism. Neurology 1996, 46:413-419.
40. Erten-Lyons D., Woltjer R.L., Dodge H., Nixon R., Vorobik R., Calvert J.F., et al. Factors associated with resistance to dementia despite high Alzheimer disease pathology. Neurology 2009, 72:354-360.
41. Jack C.R., Lowe V.J., Weigand S.D., Wiste H.J., Senjem M.L., Knopman D.S., et al. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease. Brain 2009, 132:1355-1365.
42. Herholz K., Carter S.F., Jones M. Positron emission tomography imaging in dementia. Br J Radiol 2007, 80:S160-S167.
43. Nordberg A., Rinne J.O., Kadir A., Langstrom B. The use of PET in Alzheimer disease. Nat Rev Neurol 2010, 6:78-87.
44. Silverman D.H., Mosconi L., Ercoli L., Chen W., Small G.W. Positron emission tomography scans obtained for the evaluation of cognitive dysfunction. Sem Nucl Med 2008, 38:251-261.
45. Mosconi L., Brys M., Switalski R., Mistur R., Glodzik L., Pirraglia E., et al. Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism. Proc Natl Acad Sci USA 2007, 104:19067-19072.
46. Dubois B., Feldman H.H., Jacova C., Dekosky S.T., Barberger-Gateau P., Cummings J., et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007, 6:734-746.
47. Mosconi L., Sorbi S., Nacmias B., De Cristofaro M.T., Fayyaz M., Cellini E., et al. Brain metabolic differences between sporadic and familial Alzheimer's disease. Neurology 2003, 61:1138-1140.
48. Ibanez V., Pietrini P., Alexander G.E., Furey M.L., Teichberg D., Rajapakse J.C., et al. Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease. Neurology 1998, 50:1585-1593.
49. Meltzer C.C., Zubieta J.K., Brandt J., Tune L.E., Mayberg H.S., Frost J.J. Regional hypometabolism in Alzheimer's disease as measured by positron emission tomography after correction for effects of partial volume averaging. Neurology 1996, 47:454-461.
50. Mosconi L., Tsui W.H., De Santi S., Li J., Rusinek H., Convit A., et al. Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis. Neurology 2005, 64:1860-1867.
51. Crawford J.G. Alzheimer's disease risk factors as related to cerebral blood flow. Med Hypotheses 1996, 46:367-377.
52. Hock C., Villringer K., Muller-Spahn F., Wenzel R., Heekeren H., Schuh-Hofer S., et al. Decrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer's disease monitored by means of near-infrared spectroscopy (NIRS)-correlation with simultaneous rCBF-PET measurements. Brain Res 1997, 755:293-303.
53. Kalaria R.N., Harik S.I. Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer disease. J Neurochem 1989, 53:1083-1088.
54. Marcus D.L., de Leon M.J., Goldman J., Logan J., Christman D.R., Wolf A.P., et al. Altered glucose metabolism in microvessels from patients with Alzheimer's disease. Ann Neurol 1989, 26:91-94.
55. Petersen R.C. Clinical trials for early (pre-dementia) Alzheimer's disease: a case for mild cognitive impairment. J Nutr Health Aging 2010, 14:304-305.
56. Chertkow H., Massoud F., Nasreddine Z., Belleville S., Joanette Y., Bocti C., et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ 2008, 178:1273-1285.
57. Barberger-Gateau P., Commenges D., Gagnon M., Letenneur L., Sauvel C., Dartigues J.F. Instrumental activities of daily living as a screening tool for cognitive impairment and dementia in elderly community dwellers. J Am Geriatr Soc 1992, 40:1129-1134.
58. Del Sole A., Clerici F., Chiti A., Lecchi M., Mariani C., Maggiore L., et al. Individual cerebral metabolic deficits in Alzheimer's disease and amnestic mild cognitive impairment: an FDG PET study. Eur J Nucl Med Molec Imag 2008, 35:1357-1366.
59. Petersen R.C., Smith G.E., Waring S.C., Ivnik R.J., Tangalos E.G., Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999, 56:303-308.
60. Balasse E.O., Fery F. Ketone body production and disposal: effects of fasting, diabetes, and exercise. Diabetes Metab Rev 1989, 5:247-270.
61. Dubois B., Picard G., Sarazin M. Early detection of Alzheimer's disease: new diagnostic criteria. Dialogues Clin Neurosci 2009, 11:135-139.
62. Reiman E.M., Chen K., Alexander G.E., Caselli R.J., Bandy D., Osborne D., et al. Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism. Proc Natl Acad Sci USA 2005, 102:8299-8302.
63. Reiman E.M., Chen K., Liu X., Bandy D., Yu M., Lee W., et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proc Natl Acad Sci USA 2009, 106:6820-6825.
64. Mosconi L., Mistur R., Switalski R., Tsui W.H., Glodzik L., Li Y., et al. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease. Eur J Nucl Med Molec Imag 2009, 36:811-822.
65. Drzezga A., Lautenschlager N., Siebner H., Riemenschneider M., Willoch F., Minoshima S., et al. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur J Nucl Med Molec Imag 2003, 30:1104-1113.
66. Ishii H., Ishikawa H., Meguro K., Tashiro M., Yamaguchi S. Decreased cortical glucose metabolism in converters from CDR 0.5 to Alzheimer's disease in a community: the Osaki-Tajiri Project. Int Psychogeriatr 2009, 21:148-156.
67. Mosconi L., Mistur R., Switalski R., Brys M., Glodzik L., Rich K., et al. Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease. Neurology 2009, 72:513-520.
68. Ibanez V., Pietrini P., Furey M.L., Alexander G.E., Millet P., Bokde A.L., et al. Resting state brain glucose metabolism is not reduced in normotensive healthy men during aging, after correction for brain atrophy. Brain Res Bull 2004, 63:147-154.
69. Schlageter N.L., Carson R.E., Rapoport S.I. Examination of blood-brain barrier permeability in dementia of the Alzheimer type with [68Ga]EDTA and positron emission tomography. J Cereb Blood Flow Metab 1987, 7:1-8.
70. Bourre J.M., Francois M., Youyou A., Dumont O., Piciotti M., Pascal G., et al. The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr 1989, 119:1880-1892.
71. Pifferi F., Roux F., Langelier B., Alessandri J.M., Vancassel S., Jouin M., et al. (n-3) polyunsaturated fatty acid deficiency reduces the expression of both isoforms of the brain glucose transporter GLUT1 in rats. J Nutr 2005, 135:2241-2246.
72. Ximenes da Silva A., Lavialle F., Gendrot G., Guesnet P., Alessandri J.M., Lavialle M. Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids. J Neurochem 2002, 81:1328-1337.
73. Pifferi F., Jouin M., Alessandri J.M., Haedke U., Roux F., Perriere N., et al. n-3 Fatty acids modulate brain glucose transport in endothelial cells of the blood-brain barrier. Prostaglandins Leukot Essent Fatty Acids 2007, 77:279-286.
74. Pifferi F., Jouin M., Alessandri J.M., Roux F., Perrière N., Langelier B., et al. n-3 long-chain fatty acids and regulation of glucose transport in two models of rat brain endothelial cells. Neurochem Int 2010, 56:703-710.
75. Kitajka K., Sinclair A.J., Weisinger R.S., Weisinger H.S., Mathai M., Jayasooriya A.P., et al. Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression. Proc Natl Acad Sci USA 2004, 101:10931-10936.
76. Brenna J.T., Diau G.Y. The influence of dietary docosahexaenoic acid and arachidonic acid on central nervous system polyunsaturated fatty acid composition. Prostaglandins Leukot Essent Fatty Acids 2007, 77:247-250.
77. Cunnane S.C., Plourde M., Pifferi F., Begin M., Feart C., Barberger-Gateau P. Fish, docosahexaenoic acid and Alzheimer's disease. Prog Lipid Res 2009, 48:239-256.
78. Plourde M., Vohl M.C., Vandal M., Couture P., Lemieux S., Cunnane S.C. Plasma n-3 fatty acid response to an n-3 fatty acid supplement is modulated by apoE epsilon4 but not by the common PPAR-alpha L162V polymorphism in men. Br J Nutr 2009, 102:1121-1124.
79. Fortier M., Tremblay-Mercier J., Plourde M., Chouinard-Watkins R., Vandal M., Pifferi F., et al. Higher plasma n-3 fatty acid status in the moderately healthy elderly in southern Quebec: higher fish intake or aging-related change in n-3 fatty acid metabolism?. Prostaglandins Leukot Essent Fatty Acids 2010, 82:277-280.
80. de Groot R.H., van Boxtel M.P., Schiepers O.J., Hornstra G., Jolles J. Age dependence of plasma phospholipid fatty acid levels: potential role of linoleic acid in the age-associated increase in docosahexaenoic acid and eicosapentaenoic acid concentrations. Br J Nutr 2009, 102:1058-1064.
81. Watson G.S., Craft S. Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer's disease. Eur J Pharmacol 2004, 490:97-113.
82. Hoyer S. The aging brain. Changes in the neuronal insulin/insulin receptor signal transduction cascade trigger late-onset sporadic Alzheimer disease (SAD). A mini-review. J Neural Transm 2002, 109:991-1002.
83. Schubert M., Gautam D., Surjo D., Ueki K., Baudler S., Schubert D., et al. Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci USA 2004, 101:3100-3105.
84. Steen E., Terry B.M., Rivera E.J., Cannon J.L., Neely T.R., Tavares R., et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease-is this type 3 diabetes?. J Alzheimers Dis 2005, 7:63-80.
85. Cole G.M., Frautschy S.A. The role of insulin and neurotrophic factor signaling in brain aging and Alzheimer's Disease. Exp Gerontol 2007, 42:10-21.
86. Van den Berghe G., Schoonheydt K., Becx P., Bruyninckx F., Wouters P.J. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 2005, 64:1348-1353.
87. Soeters M.R., Sauerwein H.P., Faas L., Smeenge M., Duran M., Wanders R.J., et al. Effects of insulin on ketogenesis following fasting in lean and obese men. Obesity (Silver Spring) 2009, 17:1326-1331.
88. Elahi D., Muller D.C., Egan J.M., Andres R., Veldhuist J., Meneilly G.S. Glucose tolerance, glucose utilization and insulin secretion in ageing. Novartis Found Symp 2002, 242:222-242. discussion 242-6.
89. Petersen K.F., Befroy D., Dufour S., Dziura J., Ariyan C., Rothman D.L., et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2009, 300:1140-1142.
90. Bortz W.M. A conceptual framework of frailty: a review. J Gerontol A Biol Sci Med Sci 2002, 57:M283-M288.
91. Raffaitin C., Gin H., Empana J.P., Helmer C., Berr C., Tzourio C., et al. Metabolic syndrome and risk for incident Alzheimer's disease or vascular dementia: the Three-City Study. Diabetes Care 2009, 32:169-174.
92. Bruce-Keller A.J., Keller J.N., Morrison C.D. Obesity and vulnerability of the CNS. Biochim Biophys Acta 2009, 1792:395-400.
93. Floras J.S., Meneilly G. Insulin-mediated blood flow and glucose uptake. Can J Cardiol 2001, 17:7A-10A.
94. Lewis G.F., Carpentier A., Adeli K., Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 2002, 23:201-229.
95. Carpentier A.C., Frisch F., Cyr D., Genereux P., Patterson B.W., Giguere R., et al. On the suppression of plasma nonesterified fatty acids by insulin during enhanced intravascular lipolysis in humans. Am J Physiol Endocrinol Metab 2005, 289:E849-E856.
96. Fernandez-Figares I., Shannon A.E., Wray-Cahen D., Caperna T.J. The role of insulin, glucagon, dexamethasone, and leptin in the regulation of ketogenesis and glycogen storage in primary cultures of porcine hepatocytes prepared from 60 kg pigs. Domest Anim Endocrinol 2004, 27:125-140.
97. Fukao T., Lopaschuk G.D., Mitchell G.A. Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry. Prostaglandins Leukot Essent Fatty Acids 2004, 70:243-251.
98. Wolfrum C., Asilmaz E., Luca E., Friedman J.M., Stoffel M. Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. Nature 2004, 432:1027-1032.
99. Carpentier A., Mittelman S.D., Bergman R.N., Giacca A., Lewis G.F. Prolonged elevation of plasma free fatty acids impairs pancreatic beta-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes. Diabetes 2000, 49:399-408.
100. Schapira A.H. Mitochondrial disease. Lancet 2006, 368:70-82.
101. Bough K.J., Wetherington J., Hassel B., Pare J.F., Gawryluk J.W., Greene J.G., et al. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol 2006, 60:223-235.
102. Coon K.D., Valla J., Szelinger S., Schneider L.E., Niedzielko T.L., Brown K.M., et al. Quantitation of heteroplasmy of mtDNA sequence variants identified in a population of AD patients and controls by array-based resequencing. Mitochondrion 2006, 6:194-210.
103. Gibson G.E., Starkov A., Blass J.P., Ratan R.R., Beal M.F. Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases. Biochim Biophys Acta 2010, 1802:122-134.
104. Studzinski C.M., MacKay W.A., Beckett T.L., Henderson S.T., Murphy M.P., Sullivan P.G., et al. Induction of ketosis may improve mitochondrial function and decrease steady-state amyloid-beta precursor protein (APP) levels in the aged dog. Brain Res 2008, 1226:209-217.
105. Villa R.F., Gorini A., Hoyer S. Differentiated effect of ageing on the enzymes of Krebs' cycle, electron transfer complexes and glutamate metabolism of non-synaptic and intra-synaptic mitochondria from cerebral cortex. J Neural Transm 2006, 113:1659-1670.
106. Hatanpaa K., Isaacs K.R., Shirao T., Brady D.R., Rapoport S.I. Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease. J Neuropathol Exp Neurol 1999, 58:637-643.
107. Sumpter P.Q., Mann D.M., Davies C.A., Yates P.O., Snowden J.S., Neary D. A ultrastructural analysis of the effects of accumulation of neurofibrillary tangle in pyramidal neurons of the cerebral cortex in Alzheimer's disease. Neuropathol Appl Neurobiol 1986, 12:305-319.
108. Sorbi S., Bird E.D., Blass J.P. Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 1983, 13:72-78.
109. Sims N.R., Bowen D.M., Davison A.N. [14C]acetylcholine synthesis and [14C]carbon dioxide production from [U-14C]glucose by tissue prisms from human neocortex. Biochem J 1981, 196:867-876.
110. de la Monte S.M. Insulin resistance and Alzheimer's disease. BMB Rep 2009, 42:475-481.
111. Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 2006, 545:51-64.
112. Deschamps V., Barberger-Gateau P., Peuchant E., Orgogozo J.M. Nutritional factors in cerebral aging and dementia: epidemiological arguments for a role of oxidative stress. Neuroepidemiology 2001, 20:7-15.
113. Lassen N.A., Munck O., Tottey E.R. Mental function and cerebral oxygen consumption in organic dementia. AMA Arch Neurol Psychiatry 1957, 77:126-133.
114. Terry R.D., Masliah E., Salmon D.P., Butters N., DeTeresa R., Hill R., et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991, 30:572-580.
115. Mosconi L., Pupi A., De Leon M.J. Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer's disease. Ann NY Acad Sci 2008, 1147:180-195.
116. Freemantle E., Vandal M., Tremblay-Mercier J., Tremblay S., Blachere J.C., Begin M.E., et al. Omega-3 fatty acids, energy substrates, and brain function during aging. Prostaglandins Leukot Essent Fatty Acids 2006, 75:213-220.
117. Liu F., Iqbal K., Grundke-Iqbal I., Hart G.W., Gong C.X. O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease. Proc Natl Acad Sci USA 2004, 101:10804-10809.
118. Liu Y., Liu F., Iqbal K., Grundke-Iqbal I., Gong C.X. Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett 2008, 582:359-364.
119. Bowen D.M., White P., Spillane J.A., Goodhardt M.J., Curzon G., Iwangoff P., et al. Accelerated ageing or selective neuronal loss as an important cause of dementia?. Lancet 1979, 1:11-14.
120. Ramassamy C., Averill D., Beffert U., Theroux L., Lussier-Cacan S., Cohn J.S., et al. Oxidative insults are associated with apolipoprotein E genotype in Alzheimer's disease brain. Neurobiol Dis 2000, 7:23-37.
121. Aliev G., Palacios H.H., Walrafen B., Lipsitt A.E., Obrenovich M.E., Morales L. Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease. Int J Biochem Cell Biol 2009, 41:1989-2004.
122. Bailey T.L., Rivara C.B., Rocher A.B., Hof P.R. The nature and effects of cortical microvascular pathology in aging and Alzheimer's disease. Neurol Res 2004, 26:573-578.
123. Grinberg L.T., Thal D.R. Vascular pathology in the aged human brain. Acta Neuropathol 2010, 119:277-290.
124. de la Torre J.C. Vascular basis of Alzheimer's pathogenesis. Ann NY Acad Sci 2002, 977:196-215.
125. Pluta R. Is the ischemic blood-brain barrier insufficiency responsible for full-blown Alzheimer's disease?. Neurol Res 2006, 28:665-671.
126. Borowsky I.W., Collins R.C. Metabolic anatomy of brain: a comparison of regional capillary density, glucose metabolism, and enzyme activities. J Comp Neurol 1989, 288:401-413.
127. Harik S.I., LaManna J.C. Altered glucose metabolism in microvessels from patients with Alzheimer's disease. Ann Neurol 1991, 29:573.
128. Oldendorf W.H., Cornford M.E., Brown W.J. The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol 1977, 1:409-417.
129. Pasquier F., Boulogne A., Leys D., Fontaine P. Diabetes mellitus and dementia. Diabetes Metab 2006, 32:403-414.
130. Reiman E.M., Caselli R.J., Yun L.S., Chen K., Bandy D., Minoshima S., et al. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 1996, 334:752-758.
131. Reiman E.M., Chen K., Alexander G.E., Caselli R.J., Bandy D., Osborne D., et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci USA 2004, 101:284-289.
132. Reiman E.M., Uecker A., Caselli R.J., Lewis S., Bandy D., de Leon M.J., et al. Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease. Ann Neurol 1998, 44:288-291.
133. Cahill G.F. Fuel metabolism in starvation. Annu Rev Nutr 2006, 26:1-22.
134. Cunnane S.C. Origins and evolution of the Western diet: implications of iodine and seafood intakes for the human brain. Am J Clin Nutr 2005, 82:483. author reply 483-4.
135. Robinson A.M., Williamson D.H. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol Rev 1980, 60:143-187.
136. Goldstein G.W. Relation of potassium transport to oxidative metabolism in isolated brain capillaries. J Physiol 1979, 286:185-195.
137. Guzman M., Blazquez C. Is there an astrocyte-neuron ketone body shuttle?. Trends Endocrinol Metab 2001, 12:169-173.
138. Melo T.M., Nehlig A., Sonnewald U. Neuronal-glial interactions in rats fed a ketogenic diet. Neurochem Int 2006, 48:498-507.
139. Gottstein W.J., Eachus A.H., Cheney L.C. A novel acylation of amino acids with S-carboxymethyl dialkyldithiocarbamates. J Org Chem 1970, 35:1693-1694.
140. Pardridge W.M. Blood-brain barrier transport of glucose, free fatty acids, and ketone bodies. Adv Exp Med Biol 1991, 291:43-53.
141. Daniel P.M., Love E.R., Moorehouse S.R., Pratt O.E., Wilson P. Factors influencing utilisation of ketone-bodies by brain in normal rats and rats with ketoacidosis. Lancet 1971, 2:637-638.
142. Hawkins R.A., Mans A.M., Davis D.W. Regional ketone body utilization by rat brain in starvation and diabetes. Am J Physiol 1986, 250:E169-E178.
143. Bentourkia M., Tremblay S., Pifferi F., Rousseau J., Lecomte R., Cunnane S. PET study of 11C-acetoacetate kinetics in rat brain during dietary treatments affecting ketosis. Am J Physiol Endocrinol Metab 2009, 296:E796-E801.
144. Hasselbalch S.G., Knudsen G.M., Jakobsen J., Hageman L.P., Holm S., Paulson O.B. Blood-brain barrier permeability of glucose and ketone bodies during short-term starvation in humans. Am J Physiol 1995, 268:E1161-E1166.
145. Lying-Tunell U., Lindblad B.S., Malmlund H.O., Persson B. Cerebral blood flow and metabolic rate of oxygen, glucose, lactate, pyruvate, ketone bodies and amino acids. Acta Neurol Scand 1980, 62:265-275.
146. Blomqvist G., Alvarsson M., Grill V., Von Heijne G., Ingvar M., Thorell J.O., et al. Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients. Am J Physiol Endocrinol Metab 2002, 283:E20-E28.
147. Hasselbalch S.G., Knudsen G.M., Jakobsen J., Hageman L.P., Holm S., Paulson O.B. Brain metabolism during short-term starvation in humans. J Cereb Blood Flow Metab 1994, 14:125-131.
148. Morris A.A. Cerebral ketone body metabolism. J Inherit Metab Dis 2005, 28:109-121.
149. Musa-Veloso K., Likhodii S.S., Cunnane S.C. Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals. Am J Clin Nutr 2002, 76:65-70.
150. Musa-Veloso K., Likhodii S.S., Rarama E., Benoit S., Liu Y.M., Chartrand D., et al. Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet. Nutrition 2006, 22:1-8.
151. Leino R.L., Gerhart D.Z., Duelli R., Enerson B.E., Drewes L.R. Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem Int 2001, 38:519-527.
152. Kuhl D.E., Metter E.J., Riege W.H., Phelps M.E. Effects of human aging on patterns of local cerebral glucose utilization determined by the [18F]fluorodeoxyglucose method. J Cereb Blood Flow Metab 1982, 2:163-171.
153. Ruderman N.B., Ross P.S., Berger M., Goodman M.N. Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats. Biochem J 1974, 138:1-10.
154. Pierre K., Pellerin L. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. J Neurochem 2005, 94:1-14.
155. Simpson I.A., Carruthers A., Vannucci S.J. Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 2007, 27:1766-1791.
156. Wiener R., Hirsch H.J., Spitzer J.J. Cerebral extraction of ketones and their penetration into CSF in the dog. Am J Physiol 1971, 220:1542-1546.
157. Tremblay S., Ouellet R., Rodrigue S., Langlois R., Benard F., Cunnane S.C. Automated synthesis of 11C-acetoacetic acid, a key alternate brain fuel to glucose. Appl Radiat Isot 2007, 65:934-940.
158. Pifferi F., Tremblay S., Plourde M., Tremblay-Mercier J., Bentourkia M., Cunnane S.C. Ketones and brain function: possible link to polyunsaturated fatty acids and availability of a new brain PET tracer, 11C-acetoacetate. Epilepsia 2008, 49:76-79.
159. Cross H., Ferrie C., Lascelles K., Livingston J., Mewasingh L. Old versus new antiepileptic drugs: the SANAD study. Lancet 2007, 370:314. author reply 315-6.
160. Klepper J. Impaired glucose transport into the brain: the expanding spectrum of glucose transporter type 1 deficiency syndrome. Curr Opin Neurol 2004, 17:193-196.
161. Wang D., Pascual J.M., Yang H., Engelstad K., Jhung S., Sun R.P., et al. Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol 2005, 57:111-118.
162. Falk R.E., Cederbaum S.D., Blass J.P., Gibson G.E., Kark R.A., Carrel R.E. Ketonic diet in the management of pyruvate dehydrogenase deficiency. Pediatrics 1976, 58:713-721.
163. Amiel S.A., Archibald H.R., Chusney G., Williams A.J., Gale E.A. Ketone infusion lowers hormonal responses to hypoglycaemia: evidence for acute cerebral utilization of a non-glucose fuel. Clin Sci (Lond) 1991, 81:189-194.
164. Veneman T., Mitrakou A., Mokan M., Cryer P., Gerich J. Effect of hyperketonemia and hyperlacticacidemia on symptoms, cognitive dysfunction, and counterregulatory hormone responses during hypoglycemia in normal humans. Diabetes 1994, 43:1311-1317.
165. Page K.A., Williamson A., Yu N., McNay E.C., Dzuira J., McCrimmon R.J., et al. Medium-chain fatty acids improve cognitive function in intensively treated type 1 diabetic patients and support in vitro synaptic transmission during acute hypoglycemia. Diabetes 2009, 58:1237-1244.
166. Prins M.L. Cerebral metabolic adaptation and ketone metabolism after brain injury. J Cereb Blood Flow Metab 2008, 28:1-16.
167. Van der Auwera I., Wera S., Van Leuven F., Henderson S.T. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease. Nutr Metab (Lond) 2005, 2:28.
168. Veech R.L. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids 2004, 70:309-319.
169. Freemantle E., Vandal M., Tremblay Mercier J., Plourde M., Poirier J., Cunnane S.C. Metabolic response to a ketogenic breakfast in the healthy elderly. J Nutr Health Aging 2009, 13:293-298.
170. Duara R., Barker W.W., Chang J., Yoshii F., Loewenstein D.A., Pascal S. Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease. J Cereb Blood Flow Metab 1992, 12:927-934.
171. Henderson S.T., Vogel J.L., Barr L.J., Garvin F., Jones J.J., Costantini L.C. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond) 2009, 6:31.
172. Reger M.A., Henderson S.T., Hale C., Cholerton B., Baker L.D., Watson G.S., et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging 2004, 25:311-314.
173. Risner M.E., Saunders A.M., Altman J.F., Ormandy G.C., Craft S., Foley I.M., et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J 2006, 6:246-254.
174. Roses A.D., Saunders A.M., Huang Y., Strum J., Weisgraber K.H., Mahley R.W. Complex disease-associated pharmacogenetics: drug efficacy, drug safety, and confirmation of a pathogenetic hypothesis (Alzheimer's disease). Pharmacogenom J 2007, 7:10-28.
175. Freund G., Weinsier R.L. Standardized ketosis in man following medium chain triglyceride ingestion. Metabolism 1966, 15:980-991.
176. Sims N.R., Bowen D.M., Smith C.C., Flack R.H., Davison A.N., Snowden J.S., et al. Glucose metabolism and acetylcholine synthesis in relation to neuronal activity in Alzheimer's disease. Lancet 1980, 1:333-336.
177. Willis M.W., Ketter T.A., Kimbrell T.A., George M.S., Herscovitch P., Danielson A.L., et al. Age, sex and laterality effects on cerebral glucose metabolism in healthy adults. Psychiatry Res 2002, 114:23-37.
178. Kalpouzos G., Eustache F., Desgranges B. [Cognitive reserve and neural networks in normal aging and Alzheimer's disease]. Psychol Neuropsychiatr Vieil 2008, 6:97-105.
179. Engler H., Forsberg A., Almkvist O., Blomquist G., Larsson E., Savitcheva I., et al. Two-year follow-up of amyloid deposition in patients with Alzheimer's disease. Brain 2006, 129:2856-2866.
180. Cross T.A., Pahl C., Oberhansli R., Aue W.P., Keller U., Seelig J. Ketogenesis in the living rat followed by 13C NMR spectroscopy. Biochemistry 1984, 23:6398-6402.
181. Bodoky G., Yang Z.J., Meguid M.M., Laviano A., Szeverenyi N. Effects of fasting, intermittent feeding, or continuous parenteral nutrition on rat liver and brain energy metabolism as assessed by 31P-NMR. Physiol Behav 1995, 58:521-527.
182. Croteau E., Lavallee E., Labbe S.M., Hubert L., Pifferi F., Rousseau J.A., et al. Image-derived input function in dynamic human PET/CT: methodology and validation with 11Cacetate and 18F-fluorothioheptadecanoic acid in muscle and 18F-fluorodeoxyglucose in brain. Eur J Nucl Med Molec Imag 2010, (in press).
183. Patterson C., Feightner J., Garcia A., MacKnight C. General risk factors for dementia: a systematic evidence review. Alzheimers Dement 2007, 3:341-347.
184. Pike K.E., Savage G., Villemagne V.L., Ng S., Moss S.A., Maruff P., et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain 2007, 130:2837-2844.
185. Sliwinski M.J., Hofer S.M., Hall C., Buschke H., Lipton R.B. Modeling memory decline in older adults: the importance of preclinical dementia, attrition, and chronological age. Psychol Aging 2003, 18:658-671.
186. Petersen R.C. Early diagnosis of Alzheimer's disease: is MCI too late?. Curr Alzheimer Res 2009, 6:324-330.
187. den Dunnen W.F., Brouwer W.H., Bijlard E., Kamphuis J., van Linschoten K., Eggens-Meijer E., et al. No disease in the brain of a 115-year-old woman. Neurobiol Aging 2008, 29:1127-1132.
188. Kalpouzos G., Chetelat G., Baron J.C., Landeau B., Mevel K., Godeau C., et al. Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging. Neurobiol Aging 2009, 30:112-124.
189. Petit-Taboue M.C., Landeau B., Desson J.F., Desgranges B., Baron J.C. Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping. NeuroImage 1998, 7:176-184.
190. Horwitz B., Duara R., Rapoport S.I. Age differences in intercorrelations between regional cerebral metabolic rates for glucose. Ann Neurol 1986, 19:60-67.
191. Svennerholm L., Bostrom K., Jungbjer B. Changes in weight and compositions of major membrane components of human brain during the span of adult human life of Swedes. Acta Neuropathol 1997, 94:345-352.
192. Blomqvist G., Thorell J.O., Ingvar M., Grill V., Widen L., Stone-Elander S. Use of R-beta-[1-11C]hydroxybutyrate in PET studies of regional cerebral uptake of ketone bodies in humans. Am J Physiol 1995, 269:E948-E959.
193. Frackowiak R.S., Pozzilli C., Legg N.J., Du Boulay G.H., Marshall J., Lenzi G.L., et al. Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with oxygen-15 and positron tomography. Brain 1981, 104:753-778.
194. Benson D.F., Kuhl D.E., Hawkins R.A., Phelps M.E., Cummings J.L., Tsai S.Y. The fluorodeoxyglucose 18F scan in Alzheimer's disease and multi-infarct dementia. Arch Neurol 1983, 40:711-714.
195. Cutler N.R., Haxby J.V., Duara R., Grady C.L., Kay A.D., Kessler R.M., et al. Clinical history, brain metabolism, and neuropsychological function in Alzheimer's disease. Ann Neurol 1985, 18:298-309.
196. Rapoport S.I. Positron emission tomography in normal aging and Alzheimer's disease. Gerontology 1986, 32:6-13.
197. Chawluk J.B., Alavi A., Dann R., Hurtig H.I., Bais S., Kushner M.J., et al. Positron emission tomography in aging and dementia: effect of cerebral atrophy. J Nucl Med 1987, 28:431-437.
198. Alavi A., Newberg A.B., Souder E., Berlin J.A. Quantitative analysis of PET and MRI data in normal aging and Alzheimer's disease: atrophy weighted total brain metabolism and absolute whole brain metabolism as reliable discriminators. J Nucl Med 1993, 34:1681-1687.
199. Mielke R., Pietrzyk U., Jacobs A., Fink G.R., Ichimiya A., Kessler J., et al. HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison of perfusion and metabolic pattern. Eur J Nucl Med 1994, 21:1052-1060.
200. Minoshima S., Giordani B., Berent S., Frey K.A., Foster N.L., Kuhl D.E. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol 1997, 42:85-94.
201. Duara R., Margolin R.A., Robertson-Tchabo E.A., London E.D., Schwartz M., Renfrew J.W., et al. Cerebral glucose utilization, as measured with positron emission tomography in 21 resting healthy men between the ages of 21 and 83 years. Brain 1983, 106:761-775.
202. de Leon M.J., George A.E., Ferris S.H., Christman D.R., Fowler J.S., Gentes C.I., et al. Positron emission tomography and computed tomography assessments of the aging human brain. J Comp Assist Tomog 1984, 8:88-94.
203. Duara R., Grady C., Haxby J., Ingvar D., Sokoloff L., Margolin R.A., et al. Human brain glucose utilization and cognitive function in relation to age. Ann Neurol 1984, 16:703-713.
204. Yanase D., Matsunari I., Yajima K., Chen W., Fujikawa A., Nishimura S., et al. Brain FDG PET study of normal aging in Japanese: effect of atrophy correction. Eur J Nucl Med Molec Imag 2005, 32:794-805.
205. Kochunov P., Ramage A.E., Lancaster J.L., Robin D.A., Narayana S., Coyle T., et al. Loss of cerebral white matter structural integrity tracks the gray matter metabolic decline in normal aging. NeuroImage 2009, 45:17-28.
206. Kety S.S. Human cerebral blood flow and oxygen consumption as related to aging. Res Publ Assoc Res Nervous Ment Dis 1956, 35:31-45.
207. Dastur D.K., Lane M.H., Hansen D.B., Ketty S.S., Butler R.N., Perlin S., et al. Effects of aging on cerebral circulation and metabolism in man. Human aging: A biological and biochemical study 1963, 59-78. US Government Printing Office, Washington. J.E. Biren, R.N. Butler, S.W. Greenhouse, L. Sokoloff, M.R. Yarrow (Eds.).
208. De Santi S., de Leon M.J., Convit A., Tarshish C., Rusinek H., Tsui W.H., et al. Age-related changes in brain: II. Positron emission tomography of frontal and temporal lobe glucose metabolism in normal subjects. Psychiatr Q 1995, 66:357-370.
209. Loessner A., Alavi A., Lewandrowski K.U., Mozley D., Souder E., Gur R.E. Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age. J Nucl Med 1995, 36:1141-1149.
210. Moeller J.R., Ishikawa T., Dhawan V., Spetsieris P., Mandel F., Alexander G.E., et al. The metabolic topography of normal aging. J Cereb Blood Flow Metab 1996, 16:385-398.
211. Bentourkia M., Bol A., Ivanoiu A., Labar D., Sibomana M., Coppens A., et al. Comparison of regional cerebral blood flow and glucose metabolism in the normal brain: effect of aging. J Neurolog Sci 2000, 181:19-28.
212. de Leon M.J., Convit A., Wolf O.T., Tarshish C.Y., DeSanti S., Rusinek H., et al. Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET). Proc Natl Acad Sci USA 2001, 98:10966-10971.
213. Mosconi L., Perani D., Sorbi S., Herholz K., Nacmias B., Holthoff V., et al. MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology 2004, 63:2332-2340.
214. Rimajova M., Lenzo N.P., Wu J.S., Bates K.A., Campbell A., Dhaliwal S.S., et al. Fluoro-2-deoxy-D-glucose (FDG)-PET in APOEepsilon4 carriers in the Australian population. J Alzheimers Dis 2008, 13:137-146.
215. Langbaum J.B., Chen K., Lee W., Reschke C., Bandy D., Fleisher A.S., et al. Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer's Disease Neuroimaging Initiative (ADNI). NeuroImage 2009, 45:1107-1116.
216. Kennedy A.M., Frackowiak R.S., Newman S.K., Bloomfield P.M., Seaward J., Roques P., et al. Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer's disease. Neurosci Lett 1995, 186:17-20.
217. Mosconi L., Sorbi S., de Leon M.J., Li Y., Nacmias B., Myoung P.S., et al. Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer's disease. J Nucl Med 2006, 47:1778-1786.