1.Lobo, A, Launer, LJ, Fratiglioni, L, et al.Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology. 2000;54:S4–S9.
2.Brookmeyer, R, Gray, S, Kawas, C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998;88:1337–1342.
3.Selkoe, DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001;81:741–766.
4.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–2497.
5.Razay, G, Vreugdenhil, A, Wilcock, G. The metabolic syndrome and Alzheimer disease. Arch Neurol. 2007;64:93–96.
6.Vanhanen, M, Koivisto, K, Moilanen, L, et al.Association of metabolic syndrome with Alzheimer disease: a population-based study. Neurology. 2006;67:843–847.
7.Casserly, I, Topol, E. Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. Lancet. 2004;363:1139–1146.
8.Roman, GC. Vascular dementia prevention: a risk factor analysis. Cerebrovasc Dis. 2005;20(suppl 2):91–100.
9.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.
10.Ott, A, Stolk, RP, van Harskamp, F, Pols, HA, Hofman, A, Breteler, MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999;53:1937–1942.
11.Ott, A, Slooter, AJ, Hofman, A, et al.Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study. Lancet. 1998;351:1840–1843.
12.Gustafson, D, Rothenberg, E, Blennow, K, Steen, B, Skoog, I. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med. 2003;163:1524–1528.
13.Grundy, SM, Cleeman, JI, Daniels, SR, et al.Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–2752.
14.Ott, A, Stolk, RP, Hofman, A, van Harskamp, F, Grobbee, DE, Breteler, MM. Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia. 1996;39:1392–1397.
15.Riekse, RG, Leverenz, JB, McCormick, W, et al.Effect of vascular lesions on cognition in Alzheimer's disease: a community-based study. J Am Geriatr Soc. 2004;52:1442–1448.
16.Vermeer, SE, Prins, ND, den Heijer, T, Hofman, A, Koudstaal, PJ, Breteler, MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348:1215–1222.
17.Pantoni, L, Leys, D, Fazekas, F, et al.Role of white matter lesions in cognitive impairment of vascular origin. Alzheimer Dis Assoc Disord. 1999;13(suppl 3):S49–S54.
18.de la Torre, JC. Alzheimer disease as a vascular disorder: nosological evidence. Stroke. 2002;33:1152–1162.
19.Ritchie, K, Lovestone, S. The dementias. Lancet. 2002;360:1759–1766.
20.Roman, GC, Royall, DR. A diagnostic dilemma: is “Alzheimer's dementia” Alzheimer's disease, vascular dementia, or both? Lancet Neurol. 2004;3:141.
21.Kovari, E, Gold, G, Herrmann, FR, et al.Cortical microinfarcts and demyelination significantly affect cognition in brain aging. Stroke. 2004;35:410–414.
22.Kalmijn, S, Foley, D, White, L, et al.Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia aging study. Arterioscler Thromb Vasc Biol. 2000;20:2255–2260.
23.Reaven, GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–1607.
24.Grundy, SM. Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab. 2007;92:399–404.
25.Gami, AS, Witt, BJ, Howard, DE, et al.Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and metaanalysis of longitudinal studies. J Am Coll Cardiol. 2007;49:403–414.
26.Elias, MF, Elias, PK, Sullivan, LM, Wolf, PA, D'Agostino, RB. Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study. Int J Obes Relat Metab Disord. 2003;27:260–268.
27.Waldstein, SR, Katzel, LI. Interactive relations of central versus total obesity and blood pressure to cognitive function. Int J Obes (Lond). 2006;30:201–207.
28.Elias, MF, Wolf, PA, D'Agostino, RB, Cobb, J, White, LR. Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. Am J Epidemiol. 1993;138:353–364.
29.Whitmer, RA, Sidney, S, Selby, J, Johnston, SC, Yaffe, K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology. 2005;64:277–281.
30.Lithell, H, Hansson, L, Skoog, I, et al.The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003;21:875–886.
31.Reitz, C, Tang, MX, Luchsinger, J, Mayeux, R. Relation of plasma lipids to Alzheimer disease and vascular dementia. Arch Neurol. 2004;61:705–714.
32.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.
33.Michikawa, M. Cholesterol paradox: is high total or low HDL cholesterol level a risk for Alzheimer's disease? J Neurosci Res. 2003;72:141–146.
34.Yaffe, K, Blackwell, T, Kanaya, AM, et al.Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology. 2004;63:658–663.
35.Arvanitakis, Z, Wilson, RS, Bienias, JL, Evans, DA, Bennett, DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004;61:661–666.
36.Luchsinger, JA, Tang, MX, Shea, S, Mayeux, R. Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004;63:1187–1192.
37.Watson, GS, Craft, S. The role of insulin resistance in the pathogenesis of Alzheimer's disease: implications for treatment. CNS Drugs. 2003;17:27–45.
38.Kanaya, AM, Barrett-Connor, E, Gildengorin, G, Yaffe, K. Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med. 2004;164:1327–1333.
39.Alberti, KG, Zimmet, P, Shaw, J: IDF Epidemiology Task Force Consensus Group. The metabolic syndrome—a new worldwide definition. Lancet. 2005;366:1059–1062.
40.Bjorntorp, P, Rosmond, R. Neuroendocrine abnormalities in visceral obesity. Int J Obes Relat Metab Disord. 2000;24(suppl 2):S80–S85.
41.Sapolsky, RM. Glucocorticoids, stress, and their adverse neurological effects: relevance to aging. Exp Gerontol. 1999;34:721–732.
42.Li, XL, Aou, S, Oomura, Y, Hori, N, Fukunaga, K, Hori, T. Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents. Neuroscience. 2002;113:607–615.
43.Waldstein, SR, Siegel, EL, Lefkowitz, D, et al.Stress-induced blood pressure reactivity and silent cerebrovascular disease. Stroke. 2004;35:1294–1298.
44.Yaffe, K, Lindquist, K, Penninx, BW, et al.Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology. 2003;61:76–80.
45.Craft, S. Insulin resistance syndrome and Alzheimer disease: pathophysiologic mechanisms and therapeutic implications. Alzheimer Dis Assoc Disord. 2006;20:298–301.
46.Mooradian, AD. Central nervous system complications of diabetes mellitus—a perspective from the blood-brain barrier. Brain Res Brain Res Rev. 1997;23:210–218.
47.Mankovsky, BN, Metzger, BE, Molitch, ME, Biller, J. Cerebrovascular disorders in patients with diabetes mellitus. J Diabetes Complications. 1996;10:228–242.
48.Small, SA. The longitudinal axis of the hippocampal formation: its anatomy, circuitry, and role in cognitive function. Rev Neurosci. 2002;13:183–194.
49.Gasparini, L, Gouras, GK, Wang, R, et al.Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogenactivated protein kinase signaling. J Neurosci. 2001;21:2561–2570.
50.Janson, J, Laedtke, T, Parisi, JE, et al.Increased risk of type 2 diabetes in Alzheimer disease. Diabetes. 2004;53:474–481.
51.de la Monte, SM, Wands, JR. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease. J Alzheimers Dis. 2005;7:45–61.
52.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.
53.Hoyer, S. Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. J Neural Transm. 1998;105:415–422.
54.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.
55.Savaskan, E, Hock, C, Olivieri, G, et al.Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer's dementia. Neurobiol Aging. 2001;22:541–546.
56.Petrovitch, H, White, LR, Izmirilian, G, et al.Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu-Asia Aging Study. Neurobiol Aging. 2000;21:57–62.
57.Abraham, KM. Animal models of obesity and metabolic syndrome: potential tools for Alzheimer's disease research. Curr Alzheimer Res. 2007;4:145–146.
58.Kwon, HM, Kim, BJ, Lee, SH, et al.Metabolic syndrome as an independent risk factor of silent brain infarction in healthy people. Stroke. 2006;37:466–470.
59.Kobayashi, S, Okada, K, Koide, H, et al.Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke. 1997;28:1932–1939.
60.Yaffe, K, Kanaya, A, Lindquist, K, et al.The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004;292:2237–2242.
61.de la Torre, JC. Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol. 2004;3:184–190.
62.Vilalta-Franch, J, Lopez-Pousa, S, Garre-Olmo, J, et al.Metabolic syndrome in Alzheimer's disease: clinical and developmental influences [Spanish]. Rev Neurol. 2008;46:13–17.