Higher serum total cholesterol levels in late middle age are associated with glucose hypometabolism in brain regions affected by Alzheimer's disease and normal aging

NeuroImage

Volumn 49, Issue 1, 2010, Pages 169-176

  Reiman, Eric M ^a,b,e,g   Chen, Kewei ^a,d,g   Langbaum, Jessica B S ^a,g   Lee, Wendy ^a,g   Reschke, Cole ^a,g   Bandy, Daniel ^a,g   Alexander, Gene E ^c,g   Caselli, Richard J ^f,g  

^a BANNER ALZHEIMER S INSTITUTE   (United States)

^b UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF ARIZONA   (United States)

^d ARIZONA STATE UNIVERSITY   (United States)

^e TRANSLATIONAL GENOMICS RESEARCH INSTITUTE   (United States)

^f MAYO CLINIC   (United States)

^g ARIZONA ALZHEIMER S CONSORTIUM   (United States)

Author keywords

Aging; Alzheimer's disease; Cholesterol; Positron emission tomography

Indexed keywords

APOLIPOPROTEIN E; CHOLESTEROL;

ADULT; AGING; ALZHEIMER DISEASE; ARTICLE; BRAIN METABOLISM; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; FEMALE; GLUCOSE METABOLISM; HETEROZYGOTE; HOMOZYGOTE; HUMAN; IMAGE ANALYSIS; IMAGE DISPLAY; MAJOR CLINICAL STUDY; MALE; NEUROPATHOLOGY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL;

AGED; AGING; ALZHEIMER DISEASE; ANTICHOLESTEREMIC AGENTS; APOLIPOPROTEIN E4; BRAIN CHEMISTRY; BRAIN MAPPING; CHOLESTEROL; FEMALE; GLUCOSE; HETEROZYGOTE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; LIPID METABOLISM; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; POSITRON-EMISSION TOMOGRAPHY; RISK;

EID: 70349987633     PISSN: 10538119     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.neuroimage.2009.07.025     Document Type: Article

References (78)

1. Alexander G.E., Chen K., Pietrini P., Rapoport S.I., and Reiman E.M. Longitudinal PET evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer's disease treatment studies. Am. J. Psychiatry 159 (2002) 738-745
2. Arvanitakis Z., Schneider J.A., Wilson R.S., Bienias J.L., Kelly J.F., Evans D.A., and Bennett D.A. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 70 (2008) 1795-1802
3. Bonarek M., Barberger-Gateau P., Letenneur L., Deschamps V., Iron A., Dubroca B., and Dartigues J.F. Relationships between cholesterol, apolipoprotein E polymorphism and dementia: a cross-sectional analysis from the PAQUID study. Neuroepidemiology 19 (2000) 141-148
4. Brookmeyer R., Gray S., and Kawas C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am. J. Public Health 88 (1998) 1337-1342
5. Buxbaum J.D., Cullen E.I., and Friedhoff L.T. Pharmacological concentrations of the HMG-CoA reductase inhibitor lovastatin decrease the formation of the Alzheimer beta-amyloid peptide in vitro and in patients. Front Biosci. 7 (2002) a50-a59
6. Carlsson C.M., Gleason C.E., Hess T.M., Moreland K.A., Blazel H.M., Koscik R.L., Schreiber N.T., Johnson S.C., Atwood C.S., Puglielli L., Hermann B.P., McBride P.E., Stein J.H., Sager M.A., and Asthana S. Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease. J. Alzheimers Dis. 13 (2008) 187-197
7. Chauhan N.B., Siegel G.J., and Feinstein D.L. Effects of lovastatin and pravastatin on amyloid processing and inflammatory response in TgCRND8 brain. Neurochem. Res. 29 (2004) 1897-1911
8. Corder E.H., Saunders A.M., Strittmatter W.J., Schmechel D.E., Gaskell P.C., Small G.W., Roses A.D., Haines J.L., and Pericak-Vance M.A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261 (1993) 921-923
9. Cordle A., and Landreth G. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses. J. Neurosci. 25 (2005) 299-307
10. Cramer C., Haan M.N., Galea S., Langa K.M., and Kalbfleisch J.D. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 71 (2008) 344-350
11. Crook R., Hardy J., and Duff K. Single-day apolipoprotein E genotyping. J. Neurosci. Methods. 53 (1994) 125-127
12. Dufouil C., Richard F., Fievet N., Dartigues J.F., Ritchie K., Tzourio C., Amouyel P., and Alperovitch A. APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study. Neurology 64 (2005) 1531-1538
13. Farrer L.A., Cupples L.A., Haines J.L., Hyman B., Kukull W.A., Mayeux R., Myers R.H., Pericak-Vance M.A., Risch N., and Van Duijn C.M. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278 (1997) 1349-1356
14. Fassbender K., Simons M., Bergmann C., Stroick M., Lutjohann D., Keller P., Runz H., Kuhl S., Bertsch T., Von B.K., Hennerici M., Beyreuther K., and Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo. Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 5856-5861
15. Folstein M.F., Folstein S.E., and McHugh P.R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12 (1975) 189-198
16. Frears E.R., Stephens D.J., Walters C.E., Davies H., and Austen B.M. The role of cholesterol in the biosynthesis of beta-amyloid. NeuroReport 10 (1999) 1699-1705
17. Gottesman I.I., and Gould T.D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160 (2003) 636-645
18. Green R.C., McNagny S.E., Jayakumar P., Cupples L.A., Benke K., and Farrer L.A. Statin use and the risk of Alzheimer's disease: the MIRAGE Study. Alzheimer's and Dementia 2 (2005) 96-103
19. Haag M.D.M., Hofman A., Koudstaal P.J., Stricker B.H.C., and Breteler M.M.B. Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J. Neurol. Neurosurg. Psychiatry 80 (2009) 13-17
20. Hamilton M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 56-62 (1960)
21. Haubenwallner S., Essenburg A.D., Barnett B.C., Pape M.E., DeMattos R.B., Krause B.R., Minton L.L., Auerbach B.J., Newton R.S., Leff T., and Bisgaier C.L. Hypolipidemic activity of select fibrates correlates to changes in hepatic apolipoprotein C-III expression: a potential physiologic basis for their mode of action. J. Lipid Res. 36 (1995) 2541-2551
22. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360 (2002) 7-22
23. Hebert L.E., Scherr P.A., Bienias J.L., Bennett D.A., and Evans D.A. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch. Neurol. 60 (2003) 1119-1122
24. Howland D.S., Trusko S.P., Savage M.J., Reaume A.G., Lang D.M., Hirsch J.D., Maeda N., Siman R., Greenberg B.D., Scott R.W., and Flood D.G. Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol. J Biol. Chem. 273 (1998) 16576-16582
25. Hutter-Paier B., Huttunen H.J., Puglielli L., Eckman C.B., Kim D.Y., Hofmeister A., Moir R.D., Domnitz S.B., Frosch M.P., Windisch M., and Kovacs D.M. The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Neuron 44 (2004) 227-238
26. Jick H., Zornberg G.L., Jick S.S., Seshadri S., and Drachman D.A. Statins and the risk of dementia. Lancet 356 (2000) 1627-1631
27. Jones R.W., Kivipelto M., Feldman H., Sparks L., Doody R., Waters D.D., Hey-Hadavi J., Breazna A., Schindler R.J., and Ramos H. The atorvastatin/donepezil in Alzheimer's Disease Study (LEADe): design and baseline characteristics. Alzheimers Dement. 4 (2008) 145-153
28. Kivipelto M., Helkala E.L., Laakso M.P., Hanninen T., Hallikainen M., Alhainen K., Soininen H., Tuomilehto J., and Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ 322 (2001) 1447-1451
29. Klag M.J., Ford D.E., Mead L.A., He J., Whelton P.K., Liang K.Y., and Levine D.M. Serum cholesterol in young men and subsequent cardiovascular disease. N. Engl. J. Med. 328 (1993) 313-318
30. Kuczynski B., Jagust W., Chui H.C., and Reed B. An inverse association of cardiovascular risk and frontal lobe glucose metabolism. Neurology 72 (2009) 738-743
31. Kuhl D.E., Metter E.J., Riege W.H., and 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. 2 (1982) 163-171
32. Kuo Y.M., Webster S., Emmerling M.R., De Lima N., and Roher A.E. Irreversible dimerization/tetramerization and post-translational modifications inhibit proteolytic degradation of A beta peptides of Alzheimer's disease. Biochim. Biophys. Acta 1406 (1998) 291-298
33. Langbaum J.B.S., Chen K., Lee W., Reschke C., Bandy D., Fleisher A.S., Alexander G.E., Foster N.L., Weiner M.W., Koeppe R.A., Jagust W.J., and Reiman E.M. Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer's Disease Neuroimaging Initiative (ADNI). NeuroImage 45 (2009) 1107-1116
34. Launer L.J., White L.R., Petrovitch H., Ross G.W., and Curb J.D. Cholesterol and neuropathologic markers of AD: a population-based autopsy study. Neurology 57 (2001) 1447-1452
35. Li G., Higdon R., Kukull W.A., Peskind E., Van Valen M.K., Tsuang D., van B.G., McCormick W., Bowen J.D., Teri L., Schellenberg G.D., and Larson E.B. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology 63 (2004) 1624-1628
36. Li G., Shofer J.B., Kukull W.A., Peskind E.R., Tsuang D.W., Breitner J.C., McCormick W., Bowen J.D., Teri L., Schellenberg G.D., and Larson E.B. Serum cholesterol and risk of Alzheimer disease: a community-based cohort study. Neurology 65 (2005) 1045-1050
37. Li G., Kukull W.A., Pekind E., McCormick W., Bowen J.D., Teri L., Schellenberg G.D., and Larson E.B. Differential effect of statins on risk of AD by age, sex and APOE genotype: findings from a community-based prospective cohort study. Alzheimer Dis. Assoc. Disord. 20 (2006) S103-S104
38. Li G., Larson E.B., Sonnen J.A., Shofer J.B., Petrie E.C., Schantz A., Peskind E.R., Raskind M.A., Breitner J.C., and Montine T.J. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology 69 (2007) 878-885
39. Li L., Cao D., Desmond R., Rahman A., Lah J.J., Levey A.I., and Zamrini E. Cognitive performance and plasma levels of homocysteine, vitamin B12, folate and lipids in patients with Alzheimer disease. Dement.Geriatr. Cogn. Disord. 26 (2008) 384-390
40. Loessner A., Alavi A., Lewandrowski K.U., Mozley D., Souder E., and Gur R.E. Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age. J. Nucl. Med. 36 (1995) 1141-1149
41. Mahley R.W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240 (1988) 622-630
42. Martin M.J., Hulley S.B., Browner W.S., Kuller L.H., and Wentworth D. Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men. Lancet 2 (1986) 933-936
43. Mielke M.M., Zandi P.P., Sjogren M., Gustafson D., Ostling S., Steen B., and Skoog I. High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology 64 (2005) 1689-1695
44. Ohm T.G., Kirca M., Bohl J., Scharnagl H., Gross W., and Marz W. Apolipoprotein E polymorphism influences not only cerebral senile plaque load but also Alzheimer-type neurofibrillary tangle formation. Neuroscience 66 (1995) 583-587
45. Papassotiropoulos A., Wollmer M.A., Tsolaki M., Brunner F., Molyva D., Lutjohann D., Nitsch R.M., and Hock C. A cluster of cholesterol-related genes confers susceptibility for Alzheimer's disease. J. Clin. Psychiatry 66 (2005) 940-947
46. Pappolla M.A., Bryant-Thomas T.K., Herbert D., Pacheco J., Fabra Garcia M., Manjon M., Girones X., Henry T.L., Matsubara E., Zambon D., Wolozin B., Sano M., Cruz-Sanchez F.F., Thal L.J., Petanceska S.S., and Refolo L.M. Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology 61 (2003) 199-205
47. Parvathy S., Ehrlich M., Pedrini S., Diaz N., Refolo L., Buxbaum J.D., Bogush A., Petanceska S., and Gandy S. Atorvastatin-induced activation of Alzheimer's alpha secretase is resistant to standard inhibitors of protein phosphorylation-regulated ectodomain shedding. J. Neurochem. 90 (2004) 1005-1010
48. Prasanthi J.R., Huls A., Thomasson S., Thompson A., Schommer E., and Ghribi O. Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on beta-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells. Mol. Neurodegener 4 (2009)
49. Rea T.D., Breitner J.C., Psaty B.M., Fitzpatrick A.L., Lopez O.L., Newman A.B., Hazzard W.R., Zandi P.P., Burke G.L., Lyketsos C.G., Bernick C., and Kuller L.H. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch. Neurol. 62 (2005) 1047-1051
50. Refolo L.M., Malester B., LaFrancois J., Bryant-Thomas T., Wang R., Tint G.S., Sambamurti K., Duff K., and Pappolla M.A. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol. Dis. 7 (2000) 321-331
51. Refolo L.M., Pappolla M.A., LaFrancois J., Malester B., Schmidt S.D., Thomas-Bryant T., Tint G.S., Wang R., Mercken M., Petanceska S.S., and Duff K.E. A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease. Neurobiol. Dis. 8 (2001) 890-899
52. Reiman, E.M., Langbaum, J.B.S., 2009. Brain imaging in the evaluation of putative Alzheimer's disease-slowing, risk-reducing and prevention therapies. In: Jagust, W.J., D'Esposito, M. (Eds.), Imaging the Aging Brain. Oxford University Press, New York, pp 319-350.
53. Reiman E.M., Caselli R.J., Yun L.S., Chen K., Bandy D., Minoshima S., Thibodeau S.N., and Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the e{open}4 allele for apolipoprotein E. N. Engl. J. Med. 334 (1996) 752-758
54. Reiman E.M., Caselli R.J., Chen K., Alexander G.E., Bandy D., and Frost J. Declining brain activity in cognitively normal apolipoprotein E e{open}4 heterozygotes: a foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 3334-3339
55. Reiman E.M., Chen K., Alexander G.E., Caselli R.J., Bandy D., Osborne D., Saunders A.M., and Hardy J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 284-289
56. Reiman E.M., Chen K., Alexander G.E., Caselli R.J., Bandy D., Osborne D., Saunders A.M., and Hardy J. Correlations between apolipoprotein E e{open}4 gene dose and brain-imaging measurements of regional hypometabolism. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 8299-8302
57. Reiman E.M., Chen K., Caselli R.J., Alexander G.E., Bandy D., Adamson J.L., Lee W., Cannon A., Stephan E.A., Stephan D.A., and Papassotiropoulos A. Cholesterol-related genetic risk scores are associated with hypometabolism in Alzheimer's-affected brain regions. NeuroImage 40 (2008) 1214-1221
58. Reiman E.M., Chen K., Liu X., Bandy D., Yu M., Lee W., Ayutyanont N., Keppler J., Reeder S.A., Langbaum J.B.S., Alexander G.E., Klunk W.E., Mathis C.A., Price J.C., Aizenstein H.J., DeKosky S.T., and Caselli R.J. Fibrillar amyloid-β burden in cognitively normal people at three levels of genetic risk for Alzheimer's disease. Proc .Natl. Acad. Sci. U. S. A. 106 (2009) 6820-6825
59. Rockwood K., Kirkland S., Hogan D.B., MacKnight C., Merry H., Verreault R., Wolfson C., and McDowell I. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch. Neurol. 59 (2002) 223-227
60. Salmon E., Maquet P., Sadzot B., Degueldre C., Lemaire C., and Franck G. Decrease of frontal metabolism demonstrated by positron emission tomography in a population of healthy elderly volunteers. Acta Neurol Belg. 91 (1991) 288-295
61. Sano M. Multi-center, randomized, double-blind, placebo-controlled trial of simvastatin to slow the progression of Alzheimer's disease. Alzheimer's and Dementia 4 (2008) T200
62. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam. Clin. Pharmacol. 19 (2005) 117-125
63. Shepherd J., Blauw G.J., Murphy M.B., Bollen E.L., Buckley B.M., Cobbe S.M., Ford I., Gaw A., Hyland M., Jukema J.W., Kamper A.M., Macfarlane P.W., Meinders A.E., Norrie J., Packard C.J., Perry I.J., Stott D.J., Sweeney B.J., Twomey C., and Westendorp R.G. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360 (2002) 1623-1630
64. Shobab L.A., Hsiung G.Y., and Feldman H.H. Cholesterol in Alzheimer's disease. Lancet Neurol. 4 (2005) 841-852
65. Simons M., Keller P., De S.B., Beyreuther K., Dotti C.G., and Simons K. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc. Natl. Acad. Sci U. S. A. 95 (1998) 6460-6464
66. Snowdon D.A., Greiner L.H., Mortimer J.A., Riley K.P., Greiner P.A., and Markesbery W.R. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 277 (1997) 813-817
67. Solomon A., Kareholt I., Ngandu T., Winblad B., Nissinen A., Tuomilehto J., Soininen H., and Kivipelto M. Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study. Neurology 68 (2007) 751-756
68. Sparks D.L., and Schreurs B.G. . Trace amounts of copper in water induce β-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 11065-11069
69. Sparks D.L., Scheff S.W., Hunsaker III J.C., Liu H., Landers T., and Gross D.R. Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp. Neurol. 126 (1994) 88-94
70. Sparks D.L., Connor D.J., Browne P.J., Lopez J.E., and Sabbagh M.N. HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's disease and why it would be ill-advise to use one that crosses the blood-brain barrier. J Nutr. Health Aging 6 (2002) 324-331
71. Sparks D.L., Sabbagh M.N., Connor D.J., Lopez J., Launer L.J., Browne P., Wasser D., Johnson-Traver S., Lochhead J., and Ziolwolski C. Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch. Neurol. 62 (2005) 753-757
72. Sparks D.L., Connor D.J., Sabbagh M.N., Petersen R.B., Lopez J., and Browne P. Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial. Acta Neurol. Scand. Suppl. 185 (2006) 3-7
73. Stewart R., White L.R., Xue Q.L., and Launer L.J. Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia aging study. Arch. Neurol. 64 (2007) 103-107
74. Talairach, J., Tournoux, P., 1988. Co-Planar Stereotaxic Atlas of the Human Brain. Thieme Medical Publishers, New York.
75. Wolozin B., Kellman W., Ruosseau P., Celesia G.G., and Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch. Neurol. 57 (2000) 1439-1443
76. Wolozin B., Wang S.W., Li N.C., Lee A., Lee T.A., and Kazis L.E. Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Medicine 5 (2007) 1-28
77. Zamrini E., McGwin G., and Roseman J.M. Association between statin use and Alzheimer's disease. Neuroepidemiology 23 (2004) 94-98
78. Zandi P.P., Sparks D.L., Khachaturian A.S., Tschanz J., Norton M., Steinberg M., Welsh-Bohmer K.A., and Breitner J.C. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch. Gen. Psychiatry 62 (2005) 217-224