Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-23T11:00:17.738Z Has data issue: false hasContentIssue false
  • English
  • Français

Metabolic Syndrome and Alzheimer's Disease: A Link to a Vascular Hypothesis?

Published online by Cambridge University Press:  07 November 2014

Haralampos J. Milionis ,
Matilda Florentin  and
Sotirios Giannopoulos
Get access Rights & Permissions [Opens in a new window]

Abstract

Current evidence from epidemiological, neuroimaging, pathological, pharmacotherapeutic, and clinical studies indicate an association of Alzheimer's disease with risk factors of vascular atherosclerotic disease either in isolation or in aggregate. “Metabolic syndrome” (MetS) is the name for a clustering of risk factors for cardiovascular disease and type 2 diabetes that are of metabolic origin. These include central obesity, elevated plasma glucose, high blood pressure, atherogenic dyslipidemia, a prothrombotic state, and a proinflammatory state. In this article, we provide an overview of the relevant literature with regard to the relationship of Alzheimer's disease with MetS. Accumulating evidence suggests a “vascular hypothesis” to be related to the pathology of Alzheimer's disease. In the light of this evidence, clinician may consider lifestyle interventions toward an early and effective cardiovascular risk-factor management to reduce the cardiometabolic and the cognitive decline risk, while further research of other preventive strategies may be warranted.

Type
Review Articles
Information
CNS Spectrums , Volume 13 , Issue 7 , July 2008 , pp. 606 - 613
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

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.Google Scholar
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.Google Scholar
3.Selkoe, DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001;81:741–766.Google Scholar
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.Google Scholar
5.Razay, G, Vreugdenhil, A, Wilcock, G. The metabolic syndrome and Alzheimer disease. Arch Neurol. 2007;64:93–96.Google Scholar
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.CrossRefGoogle ScholarPubMed
7.Casserly, I, Topol, E. Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. Lancet. 2004;363:1139–1146.CrossRefGoogle ScholarPubMed
8.Roman, GC. Vascular dementia prevention: a risk factor analysis. Cerebrovasc Dis. 2005;20(suppl 2):91–100.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
18.de la Torre, JC. Alzheimer disease as a vascular disorder: nosological evidence. Stroke. 2002;33:1152–1162.CrossRefGoogle ScholarPubMed
19.Ritchie, K, Lovestone, S. The dementias. Lancet. 2002;360:1759–1766.Google Scholar
20.Roman, GC, Royall, DR. A diagnostic dilemma: is “Alzheimer's dementia” Alzheimer's disease, vascular dementia, or both? Lancet Neurol. 2004;3:141.Google Scholar
21.Kovari, E, Gold, G, Herrmann, FR, et al.Cortical microinfarcts and demyelination significantly affect cognition in brain aging. Stroke. 2004;35:410–414.Google Scholar
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.CrossRefGoogle ScholarPubMed
23.Reaven, GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–1607.Google Scholar
24.Grundy, SM. Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab. 2007;92:399–404.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
36.Luchsinger, JA, Tang, MX, Shea, S, Mayeux, R. Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004;63:1187–1192.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
40.Bjorntorp, P, Rosmond, R. Neuroendocrine abnormalities in visceral obesity. Int J Obes Relat Metab Disord. 2000;24(suppl 2):S80–S85.Google Scholar
41.Sapolsky, RM. Glucocorticoids, stress, and their adverse neurological effects: relevance to aging. Exp Gerontol. 1999;34:721–732.Google Scholar
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.CrossRefGoogle ScholarPubMed
43.Waldstein, SR, Siegel, EL, Lefkowitz, D, et al.Stress-induced blood pressure reactivity and silent cerebrovascular disease. Stroke. 2004;35:1294–1298.Google Scholar
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.Google Scholar
45.Craft, S. Insulin resistance syndrome and Alzheimer disease: pathophysiologic mechanisms and therapeutic implications. Alzheimer Dis Assoc Disord. 2006;20:298–301.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
47.Mankovsky, BN, Metzger, BE, Molitch, ME, Biller, J. Cerebrovascular disorders in patients with diabetes mellitus. J Diabetes Complications. 1996;10:228–242.Google Scholar
48.Small, SA. The longitudinal axis of the hippocampal formation: its anatomy, circuitry, and role in cognitive function. Rev Neurosci. 2002;13:183–194.Google Scholar
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.Google Scholar
50.Janson, J, Laedtke, T, Parisi, JE, et al.Increased risk of type 2 diabetes in Alzheimer disease. Diabetes. 2004;53:474–481.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
57.Abraham, KM. Animal models of obesity and metabolic syndrome: potential tools for Alzheimer's disease research. Curr Alzheimer Res. 2007;4:145–146.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
60.Yaffe, K, Kanaya, A, Lindquist, K, et al.The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004;292:2237–2242.Google Scholar
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.Google Scholar
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.Google Scholar