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The Role of Cardiovascular Risk Factors in Alzheimer's Disease

Published online by Cambridge University Press:  07 November 2014

Ramit Ravona-Springer ,
Michael Davidson  and
Shlomo Noy
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Abstract

The distinction between Alzheimer's disease and vascular dementia, the two most common types of dementia, has been undermined by recent advances in epidemiologic, clinical, imaging, and neuropathological studies. Cardiovascular risk factors, traditionally regarded as distinguishing criteria between the two entities, have been shown to be associated with both AD and vascular dementia. In this article, we propose mechanisms of action of cardiovascular risk factors in AD, suggest possible explanations for the overlap with vascular dementia and discuss the implications this might have on future differential diagnosis, research, and treatment strategies.

Type
Review
Information
CNS Spectrums , Volume 8 , Issue 11: Alzheimer's Disease in the 21st Century , November 2003 , pp. 824 - 831
Copyright
Copyright © Cambridge University Press 2003

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References

REFERENCES

1.Hachinski, VC, Iliff, LD, Zilhka, E, et al. Cerebral blood flow in dementia. Arch Neurol. 1975;32:632–637.CrossRefGoogle ScholarPubMed
2.Mirra, SS, Heyman, A, McKeel, D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41:479–486.CrossRefGoogle Scholar
3.Meyer, JS, Xu, G, Thornby, J, et al. Is mild cognitive impairment prodromal for vascular dementia like Alzheimer's disease? Stroke. 2002;33:1981–1985.CrossRefGoogle ScholarPubMed
4.Kalaria, RN, Ballard, C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord. 1999;13(suppl 3):S115–S123.CrossRefGoogle ScholarPubMed
5.Kalaria, RN. The role of cerebral ischemia in Alzheimer's disease. Neurobiol Aging. 2000;21:321–330.CrossRefGoogle ScholarPubMed
6.Ott, A, Stolk, RP, Hofman, A, et al. Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia. 1996;39:1392–1397.CrossRefGoogle ScholarPubMed
7.Breteler, MM. Vascular risk factors for Alzheimer's disease: an epidemiologic perspective. Neurobiol Aging. 2000;21:153–160.CrossRefGoogle ScholarPubMed
8.Bots, ML, Breteler, MM, van Kooten, F, et al. Coagulation and fibrinolysis markers and risk of dementia. The Dutch Vascular Factors in Dementia Study. Haemostasis. 1998;28:216–222.Google ScholarPubMed
9.Kalmijn, S, Launer, LJ, Lindemans, J, et al. Total homocysteine and cognitive decline in a community-based sample of elderly subjects: the Rotterdam Study. Am J Epidemiol. 1999;150:283–289.CrossRefGoogle Scholar
10.Ott, A, Breteler, MM, de Bruyne, MC, et al. Atrial fibrillation and dementia in a population-based study. The Rotterdam Study. Stroke. 1997;28:316–321.CrossRefGoogle Scholar
11.Graves, AB, van Duijn, CM, Chandra, V, et al. Alcohol and tobacco consumption as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol. 1991;(suppl 2):S48–S57.CrossRefGoogle ScholarPubMed
12.Ott, A, Breteler, MM, van Harskamp, F, et al. Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study. BMJ. 1995;310:970–973.CrossRefGoogle ScholarPubMed
13.Hofman, A, Ott, A, Breteler, MM, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet. 1997;349:151–154.CrossRefGoogle ScholarPubMed
14.Breteler, MM, Bots, ML, Ott, A, Hofman, A. Risk factors for vascular disease and dementia. Haemostasis. 1998;28:167–173.Google ScholarPubMed
15.Kivipelto, M, Helkala, EL, Laakso, MP, et al. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ. 2001;322:1447–1451.CrossRefGoogle ScholarPubMed
16.Tyas, SL, Manfreda, J, Strain, LA, Montgomery, PR. Risk factors for Alzheimer's disease: a population-based, longitudinal study in Manitoba, Canada. Int J Epidemiol. 2001;30:590–597.CrossRefGoogle ScholarPubMed
17.Kalmijn, S, Launer, LJ, Ott, A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol. 1997;42:776–782.CrossRefGoogle ScholarPubMed
18.Notkola, IL, Sulkava, R, Pekkanen, J, et al. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology. 1998;17:14–20.CrossRefGoogle ScholarPubMed
19.Diaz-Arrastia, R. Hyperhomocysteinemia: a new risk factor for Alzheimer disease? Arch Neurol. 1998;55:1407–1408.CrossRefGoogle ScholarPubMed
20.Erkinjuntti, T, Kurz, A, Gauthier, S, et al. Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet. 2002;359:1283–1290.CrossRefGoogle ScholarPubMed
21.Pratt, RD, Perdomo, CA. Donepezil-treated patients with probable vascular dementia demonstrate cognitive benefits. Ann N Y Acad Sci. 2002;977:513–522.CrossRefGoogle ScholarPubMed
22.Swan, GE, LaRue, A, Carmelli, D, et al. Decline in cognitive performance in aging twins. Heritability and biobehavioral predictors from the National Heart, Lung, and Blood Institute Twin Study. Arch Neurol. 1992;49:476–481.CrossRefGoogle ScholarPubMed
23.Launer, LJ, White, LR, Petrovitch, H, et al. Cholesterol and neuropathologic markers of AD: a population-based autopsy study. Neurology. 2001;57:1447–1452.CrossRefGoogle Scholar
24.Bonarek, M, Barberger-Gateau, P, Letenneur, L, et al. Relationships between cholesterol, apolipoprotein E polymorphism and dementia: a cross-sectional analysis from the PAQUID study. Neuroepidemiology. 2000;19:141–148.CrossRefGoogle ScholarPubMed
25.Jick, H, Zornberg, GL, Jick, SS, et al. Statins and the risk of dementia. Lancet. 2000;356:1627–1631.CrossRefGoogle ScholarPubMed
26.Wolozin, B, Kellman, W, Ruosseau, P, et al. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol. 2000;57:1439–1443.CrossRefGoogle ScholarPubMed
27.Crisby, M, Carlson, LA, Winblad, B. Statins in the prevention and treatment of Alzheimer disease. Alzheimer Dis Assoc Disord. 2002;16:131–136.CrossRefGoogle ScholarPubMed
28.Mahley, RW, Rall, SC JrApolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet. 2000;1:507–537.CrossRefGoogle ScholarPubMed
29.Eichner, JE, Dunn, ST, Perveen, G, Thompson, DM, Stewart, KE, Stroehla, BC. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol. 2002;155:487–495.CrossRefGoogle ScholarPubMed
30.Slooter, AJ, Tang, MX, van Duijn, CM, et al. Apolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation. JAMA. 1997;277:818–821.CrossRefGoogle ScholarPubMed
31.Terry, JG, Howard, G, Mercuri, M, et al. Apolipoprotein E polymorphism is associated with segment-specific extracranial carotid artery intima-media thickening. Stroke. 1996;27:1755–1759.CrossRefGoogle ScholarPubMed
32.Zannad, F, Visvikis, S, Gueguen, R, et al. Genetics strongly determines the wall thickness of the left and right carotid arteries. Hum Genet. 1998;103:183–188.CrossRefGoogle ScholarPubMed
33.Vauhkonen, I, Niskanen, L, Ryynanen, M, et al. Divergent association of apolipoprotein E polymorphism with vascular disease in patients with NIDDM and control subjects. Diabet Med. 1997;14:748–756.3.0.CO;2-N>CrossRefGoogle ScholarPubMed
34.Olmer, M, Renucci, JE, Planells, R, et al. Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk. Nephrol Dial Transplant. 1997;12:691–693.CrossRefGoogle ScholarPubMed
35.Ilveskoski, E, Loimaala, A, Mercuri, MF, et al. Apolipoprotein E polymorphism and carotid artery intima-media thickness in a random sample of middle-aged men. Atherosclerosis. 2000;153:147–153.CrossRefGoogle Scholar
36.Kogawa, K, Nishizawa, Y, Hosoi, M, et al. Effect of polymorphism of apolipoprotein E and angiotensin-converting enzyme genes on arterial wall thickness. Diabetes. 1997;46:682–687.CrossRefGoogle ScholarPubMed
37.Sass, C, Zannad, F, Herbeth, B, et al. Apolipoprotein E4, lipoprotein lipase C447 and angiotensin-I converting enzyme deletion alleles were not associated with increased wall thickness of carotid and femoral arteries in healthy subjects from the Stanislas cohort. Atherosclerosis. 1998;140:89–95.CrossRefGoogle Scholar
38.Guz, G, Nurhan Ozdemir, F, Sezer, S, et al. Effect of apolipoprotein E polymorphism on serum lipid, lipoproteins, and atherosclerosis in hemodialysis patients. Am J Kidney Dis. 2000;36:826–836.CrossRefGoogle ScholarPubMed
39.van Bockxmeer, FM, Mamotte, CD. Apolipoprotein epsilon 4 homozygosity in young men with coronary heart disease. Lancet. 1992;340:879–880.CrossRefGoogle ScholarPubMed
40.Eichner, JE, Kuller, LH, Orchard, TJ, et al. Relation of apolipoprotein E phenotype to myocardial infarction and mortality from coronary artery disease. Am J Cardiol. 1993;71:160–165.CrossRefGoogle ScholarPubMed
41.Wang, XL, McCredie, RM, Wilcken, DE. Polymorphisms of the apolipoprotein E gene and severity of coronary artery disease defined by angiography. Arterioscler Thromb Vasc Biol. 1995;15:1030–1034.CrossRefGoogle ScholarPubMed
42.Tiret, L, de Knijff, P, Menzel, HJ, et al. ApoE polymorphism and predisposition to coronary heart disease in youths of different European populations. The EARS Study. European Atherosclerosis Research Study. Arterioscler Thromb. 1994;14:1617–1624.CrossRefGoogle ScholarPubMed
43.Wilson, PW, Schaefer, EJ, Larson, MG, Ordovas, JM. Apolipoprotein E alleles and risk of coronary disease. A meta-analysis. Arterioscler Thromb Vasc Biol. 1996;16:1250–1255.CrossRefGoogle ScholarPubMed
44.Premkumar, DR, Cohen, DL, Hedera, P, et al. Apolipoprotein E-epsilon 4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. Am J Pathol. 1996;148:2083–2095.Google Scholar
45.Farrer, LA, Cupples, LA, Haines, JL, et al. 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. 1997;278:1349–1356.CrossRefGoogle ScholarPubMed
46.Tang, MX, Stern, Y, Marder, K, et al. The APOE-epsilon 4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA. 1998;279:751–755.CrossRefGoogle Scholar
47.Evans, DA, Beckett, LA, Field, TS, et al. Apolipoprotein E epsilon 4 and incidence of Alzheimer disease in a community population of older persons. JAMA. 1997;277:822–824.CrossRefGoogle Scholar
48.Breitner, JC, Jarvik, GP, Plassman, BL, et al. Risk of Alzheimer disease with the epsilon 4 allele for apolipoprotein E in a population-based study of men aged 62-73 years. Alzheimer Dis Assoc Disord. 1998;12:40–44.CrossRefGoogle Scholar
49.Myers, RH, Schaefer, EJ, Wilson, PW, et al. Apolipoprotein E epsilon 4 association with dementia in a population-based study: The Framingham study. Neurology. 1996;46:673–677.CrossRefGoogle Scholar
50.Sparks, DL, Scheff, SW, Liu, H, et al. Increased density of senile plaques (SP), but not neurofibrillary tangles (NFT), in non-demented individuals with the apolipoprotein E4 allele: comparison to confirmed Alzheimer's disease patients. J Neurol Sci. 1996;138:97–104.CrossRefGoogle Scholar
51.Ghebremedhin, E, Schultz, C, Thal, DR, et al. Gender and age modify the association between APOE and AD-related neuropathology. Neurology. 2001;56:1696–1701.CrossRefGoogle ScholarPubMed
52.Bennett, DA, Wilson, RS, Schneider, JA, et al. Apolipoprotein E epsilon 4 allele, AD pathology, and the clinical expression of Alzheimer's disease. Neurology. 2003;60:246–252.CrossRefGoogle ScholarPubMed
53.Jarrett, RJ. Epidemiology and public health aspects of non-insulindependent diabetes mellitus. Epidemiol Rev. 1989;11:151–171.CrossRefGoogle Scholar
54.Stegmayr, B, Asplund, K. Diabetes as a risk factor for stroke. A population perspective. Diabetologia. 1995;38:1061–1068.CrossRefGoogle ScholarPubMed
55.Skoog, I. Risk factors for vascular dementia: a review. Dementia. 1994;5:137–144.Google ScholarPubMed
56.Tatemichi, TK, Desmond, DW, Paik, M, et al. Clinical determinants of dementia related to stroke. Ann Neurol. 1993;33:568–575.CrossRefGoogle ScholarPubMed
57.Landin, K, Blennow, K, Wallin, A, Gottfries, CG. Low blood pressure and blood glucose levels in Alzheimer's disease. Evidence for a hypometabolic disorder? J Intern Med. 1993;233:357–363.CrossRefGoogle ScholarPubMed
58.Nielson, KA, Nolan, JH, Berchtold, NC, et al. Apolipoprotein-E genotyping of diabetic dementia patients: is diabetes rare in Alzheimer's disease? J Am Geriatr Soc. 1996;44:897–904.CrossRefGoogle ScholarPubMed
59.Vanhanen, M, Kuusisto, J, Koivisto, K, et al. Type-2 diabetes and cognitive function in a non-demented population. Acta Neurol Scand. 1999;100:97–101.CrossRefGoogle Scholar
60.Curb, JD, Rodriguez, BL, Abbott, RD, et al. Longitudinal association of vascular and Alzheimer's dementias, diabetes, and glucose tolerance. Neurology. 1999;52:971–975.CrossRefGoogle ScholarPubMed
61.Luchsinger, JA, Tang, MX, Stern, Y, et al. Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol. 2001;154:635–641.CrossRefGoogle Scholar
62.Peila, R, Rodriguez, BL, Launer, LJ. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes. 2002;51:1256–1262.CrossRefGoogle ScholarPubMed
63.Launer, LJ, Ross, GW, Petrovitch, H, et al. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000;21:49–55.CrossRefGoogle ScholarPubMed
64.Skoog, I, Lernfelt, B, Landahl, S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996;347:1141–1145.CrossRefGoogle ScholarPubMed
65.Li, H, Forstermann, U. Nitric oxide in the pathogenesis of vascular disease. J Pathol. 2000;190:244–254.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
66.Faraci, FM, Heistad, DD. Regulation of large cerebral arteries and cerebral microvascular pressure. Circ Res. 1990;66:8–17.CrossRefGoogle ScholarPubMed
67.Swain, RA, St Clair, L. The role of folic acid in deficiency states and prevention of disease. J Fam Pract. 1997;44:138–144.Google ScholarPubMed
68.Elkind, MS, Sacco, RL. Stroke risk factors and stroke prevention. Semin Neurol. 1998;18:429–440.CrossRefGoogle ScholarPubMed
69.Duthie, SJ. Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull. 1999;55:578–592.CrossRefGoogle ScholarPubMed
70.Leblhuber, F, Walli, J, Artner-Dworzak, E, et al. Hyperhomocysteinemia in dementia. J Neural Transm. 2000;107:1469–1474.CrossRefGoogle ScholarPubMed
71.Seshadri, S, Beiser, A, Selhub, J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346:476–483.CrossRefGoogle ScholarPubMed
72.Vermeer, SE, van Dijk, EJ, Koudstaal, PJ, et al. Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann Neurol. 2002;51:285–289.CrossRefGoogle ScholarPubMed
73.De Groot, JC, De Leeuw, FE, Oudkerk, M, et al. Periventricular cerebral white matter lesions predict rate of cognitive decline. Ann Neurol. 2002;52:335–341.CrossRefGoogle ScholarPubMed
74.Cheng, A, Braunstein, JB, Dennison, C, et al. Reducing global risk for cardiovascular disease: using lifestyle changes and pharmacotherapy. Clin Cardiol. 2002;25:205–212.CrossRefGoogle ScholarPubMed
75.Korczyn, AD. Mixed dementia—the most common cause of dementia. Ann N Y Acad Sci. 2002;977:129–134.CrossRefGoogle ScholarPubMed
76.Shi, J, Perry, G, Smith, MA, Friedland, RP. Vascular abnormalities: the insidious pathogenesis of Alzheimer's disease. Neurobiol Aging. 2000;21:357–61.CrossRefGoogle ScholarPubMed
77.Korczyn, AD. The complex nosological concept of vascular dementia. J Neurol Sci. 2002;203–204.Google ScholarPubMed
78.Snowdon, DA, Greiner, LH, Mortimer, JA, et al. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA. 1997;277:813–817.CrossRefGoogle ScholarPubMed
79. in t'Veld, BA, Ruitenberg, A, Hofman, A, et al. Nonsteroidal antiin-flammatory drugs and the risk of Alzheimer's disease. N Engl J Med. 2001;345:1515–1521.CrossRefGoogle Scholar
80.Breitner, JC, Welsh, KA, Helms, MJ, et al. Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging. 1995;16:523–530.CrossRefGoogle ScholarPubMed
81.Forette, F, Seux, ML, Staessen, JA, et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998;352:1347–1351.CrossRefGoogle ScholarPubMed
82.Breitner, JC, Gau, BA, Welsh, KA, et al. Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study. Neurology. 1994;44:227–232.CrossRefGoogle ScholarPubMed
83.McGeer, PL, Schulzer, M, McGeer, EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology. 1996;47:425–432.CrossRefGoogle ScholarPubMed
84.Stewart, WF, Kawas, C, Corrada, M, Metter, EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997;48:626–632.CrossRefGoogle ScholarPubMed
85.Vagnucci, AH Jr, Li, WW. Alzheimer's disease and angiogenesis. Lancet. 2003;361:605–608.CrossRefGoogle ScholarPubMed
86.Buee, L, Hof, PR, Delacourte, A. Brain microvascular changes in Alzheimer's disease and other dementias. Ann N Y Acad Sci. 1997;826:7–24.CrossRefGoogle ScholarPubMed
87.Perlmutter, LS, Chui, HC, Saperia, D, Athanikar, J. Microangiopathy and the colocalization of heparan sulfate proteoglycan with amyloid in senile plaques of Alzheimer's disease. Brain Res. 1990;508:13–19.CrossRefGoogle ScholarPubMed
88.Sundberg, C, Nagy, JA, Brown, LF, et al. Glomeruloid microvascular proliferation follows adenoviral vascular permeability factor/vascular endothelial growth factor-164 gene delivery. Am J Pathol. 2001;158:1145–1160.CrossRefGoogle ScholarPubMed
89.Ciallella, JR, Figueiredo, H, Smith-Swintosky, V, McGillis, JP. Thrombin induces surface and intracellular secretion of amyloid precursor protein from human endothelial cells. Thromb Haemost. 1999;81:630–637.Google ScholarPubMed
90.Tsopanoglou, NE, Maragoudakis, ME. On the mechanism of thrombin-induced angiogenesis. Potentiation of vascular endothelial growth factor activity on endothelial cells by up-regulation of its receptors. J Biol Chem. 1999;274:23969–23976.CrossRefGoogle ScholarPubMed
91.Liu, F, Lau, BH, Peng, Q, Shah, V. Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury. Biol Pharm Bull. 2000;23:735–737.CrossRefGoogle ScholarPubMed
92.Roheim, PS, Carey, M, Forte, T, Vega, GL. Apolipoproteins in human cerebrospinal fluid. Proc Natl Acad Sci U S A. 1979;76:4646–4649.CrossRefGoogle ScholarPubMed
93.Dietschy, JM, Turley, SD. Cholesterol metabolism in the brain. Curr Opin Lipidol. 2001;12:105–112.CrossRefGoogle ScholarPubMed
94.Kabara, JJ. A critical review of brain cholesterol metabolism. Prog Brain Res. 1973;40:363–382.CrossRefGoogle ScholarPubMed
95.Morell, P, Jurevics, H. Origin of cholesterol in myelin. Neurochem Res. 1996;21:463–470.CrossRefGoogle ScholarPubMed
96.Mahley, RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988;240:622–630.CrossRefGoogle ScholarPubMed
97.Simons, M, Keller, P, Dichgans, J, Schulz, JB. Cholesterol and Alzheimer's disease: is there a link? Neurology. 2001;57:1089–1093.CrossRefGoogle ScholarPubMed
98.Frears, ER, Stephens, DJ, Walters, CE, et al. The role of cholesterol in the biosynthesis of beta-amyloid. Neuroreport. 1999;10:1699–705.CrossRefGoogle ScholarPubMed
99.Kojro, E, Gimpl, G, Lammich, S, et al. Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha -secretase ADAM 10. Proc Nad Acad Sci U S A. 2001;98:5815–5820.CrossRefGoogle ScholarPubMed
100.Chapman, J, Korczyn, AD, Karussis, DM, Michaelson, DM. The effects of APOE genotype on age at onset and progression of neurodegenerative diseases. Neurology. 2001;57:1482–1485.CrossRefGoogle ScholarPubMed
101.Poirier, J. Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease. Trends Neurosci. 1994;17:525–530.CrossRefGoogle ScholarPubMed
102.Prince, M, Lovestone, S, Cervilla, J, et al. The association between APOE and dementia does not seem to be mediated by vascular factors. Neurology. 2000;54:397–402.CrossRefGoogle Scholar
103.Haraki, T, Takegoshi, T, Kitoh, C, et al. Carotid artery intima-media thickness and brachial artery flow-mediated vasodilation in asymptomatic Japanese male subjects amongst apolipoprotein E phenotypes. J Intern Med. 2002;252:114–120.CrossRefGoogle ScholarPubMed
104.Djousse, L, Myers, RH, Province, MA, et al. Influence of apolipoprotein E, smoking, and alcohol intake on carotid atherosclerosis: National Heart, Lung, and Blood Institute Family Heart Study. Stroke. 2002;33:1357–1361.CrossRefGoogle ScholarPubMed
105.Humphries, SE, Talmud, PJ, Hawe, E, et al. Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study. Lancet. 2001;358:115–119.CrossRefGoogle ScholarPubMed
106.Lambert, JC, Brousseau, T, Defosse, V, et al. Independent association of an APOE gene promoter polymorphism with increased risk of myocardial infarction and decreased APOE plasma concentrations-the ECTIM study. Hum Mol Genet. 2000;9:57–61.CrossRefGoogle ScholarPubMed
107.Lahoz, C, Schaefer, EJ, Cupples, LA, et al. Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study. Atherosclerosis. 2001;154:529–537.CrossRefGoogle ScholarPubMed
108.Scuteri, A, Bos, AJ, Zonderman, AB, et al. Is the apoE4 allele an independent predictor of coronary events? Am J Med. 2001;110:28–32.CrossRefGoogle ScholarPubMed
109.Vlassara, H, Palace, MR. Diabetes and advanced glycation endproducts. J Intern Med. 2002;251:87–101.CrossRefGoogle ScholarPubMed
110.Dickson, DW, Sinicropi, S, Yen, SH, et al. Glycation and microglial reaction in lesions of Alzheimer's disease. Neurobiol Aging. 1996;17:733–743.CrossRefGoogle ScholarPubMed
111.Ledesma, MD, Bonay, P, Colaco, C, Avila, J. Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem. 1994;269:21614–21619.CrossRefGoogle ScholarPubMed
112.Yan, SD, Chen, X, Fu, J, et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature. 1996;382:685–691.CrossRefGoogle ScholarPubMed
113.Frolich, L, Blum-Degen, D, Bernstein, HG, et al. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm. 1998;105:423–438.CrossRefGoogle ScholarPubMed
114.Qiu, WQ, Walsh, DM, Ye, Z, et al. Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J Biol Chem. 1998;273:32730–32738.CrossRefGoogle ScholarPubMed
115.Mukherjee, A, Song, E, Kihiko-Ehmann, M, et al. Insulysin hydrolyzes amyloid beta peptides to products that are neither neurotoxic nor deposit on amyloid plaques. J Neurosci. 2000;20:8745–8749.CrossRefGoogle ScholarPubMed
116.Launer, LJ. Demonstrating the case that AD is a vascular disease: epidemiologic evidence. Aging Res Rev. 2002;1:61–77.CrossRefGoogle ScholarPubMed
117.Arregui, A, Perry, EK, Rossor, M, Tomlinson, BE. Angiotensin converting enzyme in Alzheimer's disease increased activity in caudate nucleus and cortical areas. J Neurochem. 1982;38:1490–1492.CrossRefGoogle ScholarPubMed
118.Wayner, MJ, Polan-Curtain, J, Armstrong, DL. Dose and time dependency of angiotensin II inhibition of hippocampal long-term potentiation. Peptides. 1995;16:1079–1082.CrossRefGoogle ScholarPubMed
119.Hirawa, N, Uehara, Y, Kawabata, Y, et al. Long-term inhibition of renin-angiotensin system sustains memory function in aged Dahl rats. Hypertension. 1999;34:496–502.CrossRefGoogle ScholarPubMed
120.Okunishi, H, Song, K, Oka, Y, et al. In vitro pharmacology of a novel non-peptide angiotensin II-receptor antagonist, E4177. Jpn J Pharmacol. 1993;62:239–244.CrossRefGoogle ScholarPubMed
121.Braszko, JJ, Wisniewski, K. Effect of angiotensin II and saralasin on motor activity and the passive avoidance behavior of rats. Peptides. 1988;9:475–479.CrossRefGoogle ScholarPubMed
122.Lipton, SA, Kim, WK, Choi, YB, et al. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci U S A. 1997;94:5923–5928.CrossRefGoogle ScholarPubMed
123.Kruman, II, Culmsee, C, Chan, SL, et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci. 2000;20:6920–6926.CrossRefGoogle ScholarPubMed
124.Kruman, II, Kumaravel, TS, Lohani, A, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci. 2002;22:1752–1762.CrossRefGoogle ScholarPubMed
125.Lindsay, J, Laurin, D, Verreault, R, et al. Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002;156:445–453.CrossRefGoogle ScholarPubMed
126.Laurin, D, Verreault, R, Lindsay, J, et al. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol. 2001;58:498–504.CrossRefGoogle ScholarPubMed
127.Friedland, RP, Fritsch, T, Smyth, KA, et al. Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members. Proc Natl Acad Sci U S A. 2001;98:3440–3445.CrossRefGoogle ScholarPubMed
128.Ruitenberg, A, van Swieten, JC, Witteman, JC, et al. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet. 2002;359:281–286.CrossRefGoogle ScholarPubMed
129.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Press; 1994.Google Scholar
130.International Classification of Disease. 10th ed. Geneva, Switzerland: World Health Organization; 1992.Google Scholar
131.Roman, GC, Tatemichi, TK, Erkinjuntti, T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993;43:250–260.CrossRefGoogle ScholarPubMed