Cardiovascular risk factors and future risk of Alzheimer’s disease

BMC Medicine

M Arfan Ikram¹  Renée FAG de Bruijn² 

[1] Department of Radiology, Erasmus MC University Medical Center, ’s-Gravendijkwal 230, Rotterdam, 3015, CE, the Netherlands;Department of Neurology, Erasmus MC University Medical Center, ’s-Gravendijkwal 230, Rotterdam, 3015, CE, the Netherlands

关键词: Alzheimer’s disease;    Dementia;    Risk factors;    Imaging markers;    Cardiovascular disease;   

Others  :  1118246
DOI  :  10.1186/s12916-014-0130-5

 received in 2014-04-04, accepted in 2014-07-15,  发布年份 2014

【 摘 要 】

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize findings on cardiovascular disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the association of clinical CVD (such as stroke and heart disease) and AD. Secondly, we summarize the relation between imaging makers of pre-clinical vascular disease and AD. Lastly, we discuss the association of cardiovascular risk factors and AD. We discuss both established cardiovascular risk factors and emerging putative risk factors, which exert their effect partly via CVD.

【 授权许可】

   
2014 de Bruijn and Ikram; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E: Alzheimer’s disease. Lancet 2011, 377:1019-1031.
• [2]Jagust W: Untangling vascular dementia. Lancet 2001, 358:2097-2098.
• [3]Iadecola C: The pathobiology of vascular dementia. Neuron 2013, 80:844-866.
• [4]de la Torre JC: Is Alzheimer’s disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol 2004, 3:184-190.
• [5]Hachinski V, Munoz DG: Cerebrovascular pathology in Alzheimer’s disease: cause, effect or epiphenomenon? Ann N Y Acad Sci 1997, 826:1-6.
• [6]Kelleher RJ, Soiza RL: Evidence of endothelial dysfunction in the development of Alzheimer’s disease: Is Alzheimer’s a vascular disorder? Am J Cardiovasc Dis 2013, 3:197-226.
• [7]Hachinski V: Stroke and Alzheimer disease: fellow travelers or partners in crime? Arch Neurol 2011, 68:797-798.
• [8]de la Torre JC: Vascular risk factor detection and control may prevent Alzheimer’s disease. Ageing Res Rev 2010, 9:218-225.
• [9]Middleton LE, Yaffe K: Promising strategies for the prevention of dementia. Arch Neurol 2009, 66:1210-1215.
• [10]Goldberg I, Auriel E, Russell D, Korczyn AD: Microembolism, silent brain infarcts and dementia. J Neurol Sci 2012, 322:250-253.
• [11]de la Torre JC: Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia. Cardiovasc Psychiatry Neurol 2012, 2012:367516.
• [12]Leys D, Henon H, Mackowiak-Cordoliani MA, Pasquier F: Poststroke dementia. Lancet Neurol 2005, 4:752-759.
• [13]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.
• [14]Troncoso JC, Zonderman AB, Resnick SM, Crain B, Pletnikova O, O'Brien RJ: Effect of infarcts on dementia in the Baltimore longitudinal study of aging. Ann Neurol 2008, 64:168-176.
• [15]Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR: Brain infarction and the clinical expression of Alzheimer disease, the Nun Study. JAMA 1997, 277:813-817.
• [16]Inaba M, White L, Bell C, Chen R, Petrovitch H, Launer L, Abbott RD, Ross GW, Masaki K: White matter lesions on brain magnetic resonance imaging scan and 5-year cognitive decline: the Honolulu-Asia aging study. J Am Geriatr Soc 2011, 59:1484-1489.
• [17]Prins ND, van Dijk EJ, den Heijer T, Vermeer SE, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM: Cerebral white matter lesions and the risk of dementia. Arch Neurol 2004, 61:1531-1534.
• [18]Garcia-Alloza M, Gregory J, Kuchibhotla KV, Fine S, Wei Y, Ayata C, Frosch MP, Greenberg SM, Bacskai BJ: Cerebrovascular lesions induce transient beta-amyloid deposition. Brain 2011, 134:3697-3707.
• [19]Noh Y, Seo SW, Jeon S, Lee JM, Kim JH, Kim GH, Cho H, Yoon CW, Kim HJ, Ye BS, Kim ST, Choe YS, Lee KH, Kim JS, Ewers M, Weiner MW, Lee JH, Werring DJ, Kang DR, Kim CS, Na DL: White matter hyperintensities are associated with amyloid burden in APOE4 non-carriers. J Alzheimers Dis 2014, 40:877-886.
• [20]Lee MJ, Seo SW, Na DL, Kim C, Park JH, Kim GH, Kim CH, Noh Y, Cho H, Kim HJ, Yoon CW, Ye BS, Chin J, Jeon S, Lee JM, Choe YS, Lee KH, Kim JS, Kim ST, Lee JH, Ewers M, Werring DJ, Weiner MW: Synergistic effects of ischemia and beta-amyloid burden on cognitive decline in patients with subcortical vascular mild cognitive impairment. JAMA Psychiatry 2014, 71:412-422.
• [21]Launer LJ, Petrovitch H, Ross GW, Markesbery W, White LR: AD brain pathology: vascular origins? Results from the HAAS autopsy study. Neurobiol Aging 2008, 29:1587-1590.
• [22]Ott A, Breteler MM, de Bruyne MC, van Harskamp F, Grobbee DE, Hofman A: Atrial fibrillation and dementia in a population-based study, the Rotterdam Study. Stroke 1997, 28:316-321.
• [23]Kwok CS, Loke YK, Hale R, Potter JF, Myint PK: Atrial fibrillation and incidence of dementia: a systematic review and meta-analysis. Neurology 2011, 76:914-922.
• [24]Bunch TJ, Weiss JP, Crandall BG, May HT, Bair TL, Osborn JS, Anderson JL, Muhlestein JB, Horne BD, Lappe DL, Day JD: Atrial fibrillation is independently associated with senile, vascular, and Alzheimer’s dementia. Heart Rhythm 2010, 7:433-437.
• [25]Muqtadar H, Testai FD, Gorelick PB: The dementia of cardiac disease. Curr Cardiol Rep 2012, 14:732-740.
• [26]Justin BN, Turek M, Hakim AM: Heart disease as a risk factor for dementia. Clin Epidemiol 2013, 5:135-145.
• [27]Duron E, Hanon O: Vascular risk factors, cognitive decline, and dementia. Vasc Health Risk Manag 2008, 4:363-381.
• [28]Knecht S, Oelschlager C, Duning T, Lohmann H, Albers J, Stehling C, Heindel W, Breithardt G, Berger K, Ringelstein EB, Kirchhof P, Wersching H: Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy. Eur Heart J 2008, 29:2125-2132.
• [29]Jack CR Jr, Shiung MM, Weigand SD, O'Brien PC, Gunter JL, Boeve BF, Knopman DS, Smith GE, Ivnik RJ, Tangalos EG, Petersen RC: Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology 2005, 65:1227-1231.
• [30]Dublin S, Anderson ML, Heckbert SR, Hubbard RA, Sonnen JA, Crane PK, Montine TJ, Larson EB: Neuropathologic changes associated with atrial fibrillation in a population-based autopsy cohort. J Gerontol A Biol Sci Med Sci 2013, 69:609-615.
• [31]Opie LH, Commerford PJ, Gersh BJ: Controversies in stable coronary artery disease. Lancet 2006, 367:69-78.
• [32]Newman AB, Fitzpatrick AL, Lopez O, Jackson S, Lyketsos C, Jagust W, Ives D, Dekosky ST, Kuller LH: Dementia and Alzheimer’s disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort. J Am Geriatr Soc 2005, 53:1101-1107.
• [33]Roberts RO, Knopman DS, Geda YE, Cha RH, Roger VL, Petersen RC: Coronary heart disease is associated with non-amnestic mild cognitive impairment. Neurobiol Aging 2010, 31:1894-1902.
• [34]Knopman DS, Petersen RC, Cha RH, Edland SD, Rocca WA: Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease. Neurology 2005, 65:986-990.
• [35]Petrovitch H, White L, Masaki KH, Ross GW, Abbott RD, Rodriguez BL, Lu G, Burchfiel CM, Blanchette PL, Curb JD: Influence of myocardial infarction, coronary artery bypass surgery, and stroke on cognitive impairment in late life. Am J Cardiol 1998, 81:1017-1021.
• [36]Ikram MA, van Oijen M, de Jong FJ, Kors JA, Koudstaal PJ, Hofman A, Witteman JC, Breteler MM: Unrecognized myocardial infarction in relation to risk of dementia and cerebral small vessel disease. Stroke 2008, 39:1421-1426.
• [37]Qiu C, Winblad B, Marengoni A, Klarin I, Fastbom J, Fratiglioni L: Heart failure and risk of dementia and Alzheimer disease: a population-based cohort study. Arch Intern Med 2006, 166:1003-1008.
• [38]Huijts M, van Oostenbrugge RJ, Duits A, Burkard T, Muzzarelli S, Maeder MT, Schindler R, Pfisterer ME, Brunner-La Rocca HP, Investigators T-C: Cognitive impairment in heart failure: results from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) randomized trial. Eur J Heart Fail 2013, 15:699-707.
• [39]Ganguli M, Fu B, Snitz BE, Hughes TF, Chang CC: Mild cognitive impairment: incidence and vascular risk factors in a population-based cohort. Neurology 2013, 80:2112-2120.
• [40]Jefferson AL, Himali JJ, Beiser AS, Au R, Massaro JM, Seshadri S, Gona P, Salton CJ, DeCarli C, O'Donnell CJ, Benjamin EJ, Wolf PA, Manning WJ: Cardiac index is associated with brain aging: the Framingham Heart Study. Circulation 2010, 122:690-697.
• [41]Hofman A, Ott A, Breteler MM, Bots ML, Slooter AJ, van Harskamp F, van Duijn CN, Van Broeckhoven C, Grobbee DE: Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet 1997, 349:151-154.
• [42]Silvestrini M, Gobbi B, Pasqualetti P, Bartolini M, Baruffaldi R, Lanciotti C, Cerqua R, Altamura C, Provinciali L, Vernieri F: Carotid atherosclerosis and cognitive decline in patients with Alzheimer’s disease. Neurobiol Aging 2009, 30:1177-1183.
• [43]van Oijen M, de Jong FJ, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM: Atherosclerosis and risk for dementia. Ann Neurol 2007, 61:403-410.
• [44]Wendell CR, Waldstein SR, Ferrucci L, O'Brien RJ, Strait JB, Zonderman AB: Carotid atherosclerosis and prospective risk of dementia. Stroke 2012, 43:3319-3324.
• [45]Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS: Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area, A histopathologic correlative study. Circulation 1995, 92:2157-2162.
• [46]Bos D, Vernooij MW, Elias-Smale SE, Verhaaren BF, Vrooman HA, Hofman A, Niessen WJ, Witteman JC, van der Lugt A, Ikram MA: Atherosclerotic calcification relates to cognitive function and to brain changes on magnetic resonance imaging. Alzheimers Dement 2012, 8:S104-S111.
• [47]Reis JP, Launer LJ, Terry JG, Loria CM, Zeki Al Hazzouri A, Sidney S, Yaffe K, Jacobs DR Jr, Whitlow CT, Zhu N, Carr JJ: Subclinical atherosclerotic calcification and cognitive functioning in middle-aged adults: the CARDIA study. Atherosclerosis 2013, 231:72-77.
• [48]Blum S, Luchsinger JA, Manly JJ, Schupf N, Stern Y, Brown TR, DeCarli C, Small SA, Mayeux R, Brickman AM: Memory after silent stroke: hippocampus and infarcts both matter. Neurology 2012, 78:38-46.
• [49]van Dijk EJ, Prins ND, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM: Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study. Stroke 2008, 39:2712-2719.
• [50]Jokinen H, Gouw AA, Madureira S, Ylikoski R, van Straaten EC, van der Flier WM, Barkhof F, Scheltens P, Fazekas F, Schmidt R, Verdelho A, Ferro JM, Pantoni L, Inzitari D, Erkinjuntti T, Group LS: Incident lacunes influence cognitive decline: the LADIS study. Neurology 2011, 76:1872-1878.
• [51]Cardenas VA, Reed B, Chao LL, Chui H, Sanossian N, DeCarli CC, Mack W, Kramer J, Hodis HN, Yan M, Buonocore MH, Carmichael O, Jagust WJ, Weiner MW: Associations among vascular risk factors, carotid atherosclerosis, and cortical volume and thickness in older adults. Stroke 2012, 43:2865-2870.
• [52]den Heijer T, van der Lijn F, Ikram A, Koudstaal PJ, van der Lugt A, Krestin GP, Vrooman HA, Hofman A, Niessen WJ, Breteler MM: Vascular risk factors, apolipoprotein E, and hippocampal decline on magnetic resonance imaging over a 10-year follow-up. Alzheimers Dement 2012, 8:417-425.
• [53]Goos JD, Kester MI, Barkhof F, Klein M, Blankenstein MA, Scheltens P, van der Flier WM: Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition. Stroke 2009, 40:3455-3460.
• [54]Goos JD, Henneman WJ, Sluimer JD, Vrenken H, Sluimer IC, Barkhof F, Blankenstein MA, Scheltens PH, van der Flier WM: Incidence of cerebral microbleeds: a longitudinal study in a memory clinic population. Neurology 2010, 74:1954-1960.
• [55]Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, Krestin GP, Breteler MM: Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology 2008, 70:1208-1214.
• [56]van Rooden S, Goos JD, van Opstal AM, Versluis MJ, Webb AG, Blauw GJ, van der Flier WM, Scheltens P, Barkhof F, van Buchem MA, van der Grond J: Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging. Radiology 2014, 270:205-211.
• [57]van Veluw SJ, Zwanenburg JJ, Engelen-Lee J, Spliet WG, Hendrikse J, Luijten PR, Biessels GJ: In vivo detection of cerebral cortical microinfarcts with high-resolution 7 T MRI. J Cereb Blood Flow Metab 2013, 33:322-329.
• [58]de Jong FJ, Schrijvers EM, Ikram MK, Koudstaal PJ, de Jong PT, Hofman A, Vingerling JR, Breteler MM: Retinal vascular caliber and risk of dementia: the Rotterdam study. Neurology 2011, 76:816-821.
• [59]Ikram MK, De Jong FJ, Van Dijk EJ, Prins ND, Hofman A, Breteler MM, De Jong PT: Retinal vessel diameters and cerebral small vessel disease: the Rotterdam Scan Study. Brain 2006, 129:182-188.
• [60]Ikram MK, de Jong FJ, Vernooij MW, Hofman A, Niessen WJ, van der Lugt A, Klaver CC, Ikram MA: Retinal vascular calibers associate differentially with cerebral gray matter and white matter atrophy. Alzheimer Dis Assoc Disord 2013, 27:351-355.
• [61]Cheung CY, Ong YT, Ikram MK, Ong SY, Li X, Hilal S, Catindig JA, Venketasubramanian N, Yap P, Seow D, Chen CP, Wong TY: Microvascular network alterations in the retina of patients with Alzheimer’s disease. Alzheimers Dement 2014, 10:135-142.
• [62]Sexton CE, Kalu UG, Filippini N, Mackay CE, Ebmeier KP: A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 2011, 32:2322 e2325-2318.
• [63]Wang JH, Lv PY, Wang HB, Li ZL, Li N, Sun ZY, Zhao BH, Huang Y: Diffusion tensor imaging measures of normal appearing white matter in patients who are aging, or have amnestic mild cognitive impairment, or Alzheimer’s disease. J Clin Neurosci 2013, 20:1089-1094.
• [64]Scola E, Bozzali M, Agosta F, Magnani G, Franceschi M, Sormani MP, Cercignani M, Pagani E, Falautano M, Filippi M, Falini A: A diffusion tensor MRI study of patients with MCI and AD with a 2-year clinical follow-up. J Neurol Neurosurg Psychiatry 2010, 81:798-805.
• [65]Binnewijzend MA, Schoonheim MM, Sanz-Arigita E, Wink AM, van der Flier WM, Tolboom N, Adriaanse SM, Damoiseaux JS, Scheltens P, van Berckel BN, Barkhof F: Resting-state fMRI changes in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 2012, 33:2018-2028.
• [66]Greicius MD, Srivastava G, Reiss AL, Menon V: Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A 2004, 101:4637-4642.
• [67]Rombouts SA, Barkhof F, Goekoop R, Stam CJ, Scheltens P: Altered resting state networks in mild cognitive impairment and mild Alzheimer’s disease: an fMRI study. Hum Brain Mapp 2005, 26:231-239.
• [68]Sheline YI, Raichle ME: Resting state functional connectivity in preclinical Alzheimer’s disease. Biol Psychiatry 2013, 74:340-347.
• [69]Kenny ER, O'Brien JT, Firbank MJ, Blamire AM: Subcortical connectivity in dementia with Lewy bodies and Alzheimer’s disease. Br J Psychiatry 2013, 203:209-214.
• [70]van Dijk EJ, Breteler MM, Schmidt R, Berger K, Nilsson LG, Oudkerk M, Pajak A, Sans S, de Ridder M, Dufouil C, Fuhrer R, Giampaoli S, Launer LJ, Hofman A: The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study. Hypertension 2004, 44:625-630.
• [71]den Heijer T, Launer LJ, Prins ND, van Dijk EJ, Vermeer SE, Hofman A, Koudstaal PJ, Breteler MM: Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe. Neurology 2005, 64:263-267.
• [72]Petrovitch H, White LR, Izmirilian G, Ross GW, Havlik RJ, Markesbery W, Nelson J, Davis DG, Hardman J, Foley DJ, Launer LJ: 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.
• [73]Qiu C, Winblad B, Fratiglioni L: The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 2005, 4:487-499.
• [74]Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ: Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging 2000, 21:49-55.
• [75]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.
• [76]Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Iivonen S, Mannermaa A, Tuomilehto J, Nissinen A, Soininen H: Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002, 137:149-155.
• [77]Joas E, Backman K, Gustafson D, Ostling S, Waern M, Guo X, Skoog I: Blood pressure trajectories from midlife to late life in relation to dementia in women followed for 37 years. Hypertension 2012, 59:796-801.
• [78]Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Levy D, Benjamin EJ, Vasan RS, Mitchell GF: Aortic stiffness, blood pressure progression, and incident hypertension. JAMA 2012, 308:875-881.
• [79]Gepner AD, Korcarz CE, Colangelo LA, Hom EK, Tattersall MC, Astor BC, Kaufman JD, Liu K, Stein JH: Longitudinal effects of a decade of aging on carotid artery stiffness: the multiethnic study of atherosclerosis. Stroke 2014, 45:48-53.
• [80]O'Rourke MF, Safar ME: Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 2005, 46:200-204.
• [81]Hanon O, Haulon S, Lenoir H, Seux ML, Rigaud AS, Safar M, Girerd X, Forette F: Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke 2005, 36:2193-2197.
• [82]Waldstein SR, Rice SC, Thayer JF, Najjar SS, Scuteri A, Zonderman AB: Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension 2008, 51:99-104.
• [83]Qiu C, Winblad B, Viitanen M, Fratiglioni L: Pulse pressure and risk of Alzheimer disease in persons aged 75 years and older: a community-based, longitudinal study. Stroke 2003, 34:594-599.
• [84]Poels MM, van Oijen M, Mattace-Raso FU, Hofman A, Koudstaal PJ, Witteman JC, Breteler MM: Arterial stiffness, cognitive decline, and risk of dementia: the Rotterdam study. Stroke 2007, 38:888-892.
• [85]Dhoat S, Ali K, Bulpitt CJ, Rajkumar C: Vascular compliance is reduced in vascular dementia and not in Alzheimer’s disease. Age Ageing 2008, 37:653-659.
• [86]Schmidt R, Launer LJ, Nilsson LG, Pajak A, Sans S, Berger K, Breteler MM, de Ridder M, Dufouil C, Fuhrer R, Giampaoli S, Hofman A, Consortium C: Magnetic resonance imaging of the brain in diabetes: the Cardiovascular Determinants of Dementia (CASCADE) Study. Diabetes 2004, 53:687-692.
• [87]Peila R, Rodriguez BL, Launer LJ, Honolulu-Asia Aging S: Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia Aging Study. Diabetes 2002, 51:1256-1262.
• [88]Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P: Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 2006, 5:64-74.
• [89]Xu W, Qiu C, Winblad B, Fratiglioni L: The effect of borderline diabetes on the risk of dementia and Alzheimer’s disease. Diabetes 2007, 56:211-216.
• [90]Reed B, Villeneuve S, Mack W, Decarli C, Chui HC, Jagust W: Associations between serum cholesterol levels and cerebral amyloidosis. JAMA Neurol 2014, 71:195-200.
• [91]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.
• [92]Anstey KJ, Lipnicki DM, Low LF: Cholesterol as a risk factor for dementia and cognitive decline: a systematic review of prospective studies with meta-analysis. Am J Geriatr Psychiatry 2008, 16:343-354.
• [93]Anstey KJ, von Sanden C, Salim A, O'Kearney R: Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies. Am J Epidemiol 2007, 166:367-378.
• [94]Reitz C, den Heijer T, van Duijn C, Hofman A, Breteler MM: Relation between smoking and risk of dementia and Alzheimer disease: the Rotterdam Study. Neurology 2007, 69:998-1005.
• [95]Tyas SL, White LR, Petrovitch H, Webster Ross G, Foley DJ, Heimovitz HK, Launer LJ: Mid-life smoking and late-life dementia: the Honolulu-Asia Aging Study. Neurobiol Aging 2003, 24:589-596.
• [96]Messner B, Bernhard D: Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol 2014, 34:509-515.
• [97]Treweek JB, Dickerson TJ, Janda KD: Drugs of abuse that mediate advanced glycation end product formation: a chemical link to disease pathology. Acc Chem Res 2009, 42:659-669.
• [98]Besser LM, Gill DP, Monsell SE, Brenowitz W, Meranus DH, Kukull W, Gustafson DR: Body mass index, weight change, and clinical progression in mild cognitive impairment and Alzheimer disease. Alzheimer Dis Assoc Disord 2014, 28:36-43.
• [99]Gu Y, Scarmeas N, Cosentino S, Brandt J, Albert M, Blacker D, Dubois B, Stern Y: Change in body mass index before and after Alzheimer’s disease onset.Curr Alzheimer Res. in press.
• [100]Tolppanen AM, Ngandu T, Kareholt I, Laatikainen T, Rusanen M, Soininen H, Kivipelto M: Midlife and late-life body mass index and late-life dementia: results from a prospective population-based cohort. J Alzheimers Dis 2014, 38:201-209.
• [101]Xu WL, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L: Midlife overweight and obesity increase late-life dementia risk: a population-based twin study. Neurology 2011, 76:1568-1574.
• [102]Trichopoulou A, Costacou T, Bamia C, Trichopoulos D: Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003, 348:2599-2608.
• [103]Frisardi V, Panza F, Seripa D, Imbimbo BP, Vendemiale G, Pilotto A, Solfrizzi V: Nutraceutical properties of Mediterranean diet and cognitive decline: possible underlying mechanisms. J Alzheimers Dis 2010, 22:715-740.
• [104]Psaltopoulou T, Sergentanis TN, Panagiotakos DB, Sergentanis IN, Kosti R, Scarmeas N: Mediterranean diet, stroke, cognitive impairment, and depression: a meta-analysis. Ann Neurol 2013, 74:580-591.
• [105]Singh B, Parsaik AK, Mielke MM, Erwin PJ, Knopman DS, Petersen RC, Roberts RO: Association of mediterranean diet with mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis 2014, 39:271-282.
• [106]Hamer M, Chida Y: Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol Med 2009, 39:3-11.
• [107]Berlin JA, Colditz GA: A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 1990, 132:612-628.
• [108]Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS Jr: Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991, 325:147-152.
• [109]van Praag H, Christie BR, Sejnowski TJ, Gage FH: Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A 1999, 96:13427-13431.
• [110]Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA: An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A 2007, 104:5638-5643.
• [111]Buchman AS, Boyle PA, Yu L, Shah RC, Wilson RS, Bennett DA: Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology 2012, 78:1323-1329.
• [112]Scarmeas N, Luchsinger JA, Schupf N, Brickman AM, Cosentino S, Tang MX, Stern Y: Physical activity, diet, and risk of Alzheimer disease. JAMA 2009, 302:627-637.
• [113]Barnes DE, Blackwell T, Stone KL, Goldman SE, Hillier T, Yaffe K: Cognition in older women: the importance of daytime movement. J Am Geriatr Soc 2008, 56:1658-1664.
• [114]Middleton LE, Manini TM, Simonsick EM, Harris TB, Barnes DE, Tylavsky F, Brach JS, Everhart JE, Yaffe K: Activity energy expenditure and incident cognitive impairment in older adults. Arch Intern Med 2011, 171:1251-1257.
• [115]Rovio S, Kareholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M: Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol 2005, 4:705-711.
• [116]Morgan GS, Gallacher J, Bayer A, Fish M, Ebrahim S, Ben-Shlomo Y: Physical activity in middle-age and dementia in later life: findings from a prospective cohort of men in Caerphilly, South Wales and a meta-analysis. J Alzheimers Dis 2012, 31:569-580.
• [117]de Bruijn RF, Schrijvers EM, de Groot KA, Witteman JC, Hofman A, Franco OH, Koudstaal PJ, Ikram MA: The association between physical activity and dementia in an elderly population: the Rotterdam Study. Eur J Epidemiol 2013, 28:277-283.
• [118]Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA: Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002, 346:476-483.
• [119]den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, Breteler MM: Homocysteine and brain atrophy on MRI of non-demented elderly. Brain 2003, 126:170-175.
• [120]Hooshmand B, Polvikoski T, Kivipelto M, Tanskanen M, Myllykangas L, Erkinjuntti T, Makela M, Oinas M, Paetau A, Scheltens P, van Straaten EC, Sulkava R, Solomon A: Plasma homocysteine, Alzheimer and cerebrovascular pathology: a population-based autopsy study. Brain 2013, 136:2707-2716.
• [121]Nilsson K, Gustafson L, Hultberg B: Elevated plasma homocysteine level is not primarily related to Alzheimer’s disease. Dement Geriatr Cogn Disord 2012, 34:121-127.
• [122]Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, Stijnen T, Hofman A, Witteman JC, Breteler MM: Inflammatory proteins in plasma and the risk of dementia: the Rotterdam Study. Arch Neurol 2004, 61:668-672.
• [123]van Oijen M, van der Meer IM, Hofman A, Witteman JC, Koudstaal PJ, Breteler MM: Lipoprotein-associated phospholipase A2 is associated with risk of dementia. Ann Neurol 2006, 59:139-144.
• [124]van Oijen M, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM: Fibrinogen is associated with an increased risk of Alzheimer disease and vascular dementia. Stroke 2005, 36:2637-2641.
• [125]Ferreira ST, Clarke JR, Bomfim TR, De Felice FG: Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement 2014, 10:S76-S83.
• [126]Serpente M, Bonsi R, Scarpini E, Galimberti D: Innate immune system and inflammation in Alzheimer’s disease: from pathogenesis to treatment. Neuroimmunomodulation 2014, 21:79-87.
• [127]Liu L, Chan C: The role of inflammasome in Alzheimer’s disease. Ageing Res Rev 2014, 15:6-15.
• [128]Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, DeStafano AL, Bis JC, Beecham GW, Grenier-Boley B, Russo G, Thorton-Wells TA, Jones N, Smith AV, Chouraki V, Thomas C, Ikram MA, Zelenika D, Vardarajan BN, Kamatani Y, Lin CF, Gerrish A, Schmidt H, Kunkle B, Dunstan ML, Ruiz A, Bihoreau MT, Choi SH, Reitz C, Pasquier F, et al.: Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 2013, 45:1452-1458.
• [129]Bugnicourt JM, Godefroy O, Chillon JM, Choukroun G, Massy ZA: Cognitive disorders and dementia in CKD: the neglected kidney-brain axis. J Am Soc Nephrol 2013, 24:353-363.
• [130]Miwa K, Tanaka M, Okazaki S, Furukado S, Yagita Y, Sakaguchi M, Mochizuki H, Kitagawa K: Chronic kidney disease is associated with dementia independent of cerebral small-vessel disease. Neurology 2014, 82:1051-1057.
• [131]Cheng KC, Chen YL, Lai SW, Mou CH, Tsai PY, Sung FC: Patients with chronic kidney disease are at an elevated risk of dementia: a population-based cohort study in Taiwan. BMC Nephrol 2012, 13:129. BioMed Central Full Text
• [132]Etgen T, Chonchol M, Forstl H, Sander D: Chronic kidney disease and cognitive impairment: a systematic review and meta-analysis. Am J Nephrol 2012, 35:474-482.
• [133]Sasaki Y, Marioni R, Kasai M, Ishii H, Yamaguchi S, Meguro K: Chronic kidney disease: a risk factor for dementia onset: a population-based study, the Osaki-Tajiri Project. J Am Geriatr Soc 2011, 59:1175-1181.
• [134]Helmer C, Stengel B, Metzger M, Froissart M, Massy ZA, Tzourio C, Berr C, Dartigues JF: Chronic kidney disease, cognitive decline, and incident dementia: the 3C Study. Neurology 2011, 77:2043-2051.
• [135]Tan ZS, Vasan RS: Thyroid function and Alzheimer’s disease. J Alzheimers Dis 2009, 16:503-507.
• [136]Tan ZS, Beiser A, Vasan RS, Au R, Auerbach S, Kiel DP, Wolf PA, Seshadri S: Thyroid function and the risk of Alzheimer disease: the Framingham Study. Arch Intern Med 2008, 168:1514-1520.
• [137]Forti P, Olivelli V, Rietti E, Maltoni B, Pirazzoli G, Gatti R, Gioia MG, Ravaglia G: Serum thyroid-stimulating hormone as a predictor of cognitive impairment in an elderly cohort. Gerontology 2012, 58:41-49.
• [138]de Jong FJ, Masaki K, Chen H, Remaley AT, Breteler MM, Petrovitch H, White LR, Launer LJ: Thyroid function, the risk of dementia and neuropathologic changes: the Honolulu-Asia aging study. Neurobiol Aging 2009, 30:600-606.
• [139]de Jong FJ, den Heijer T, Visser TJ, de Rijke YB, Drexhage HA, Hofman A, Breteler MM: Thyroid hormones, dementia, and atrophy of the medial temporal lobe. J Clin Endocrinol Metab 2006, 91:2569-2573.
• [140]Kalmijn S, Mehta KM, Pols HA, Hofman A, Drexhage HA, Breteler MM: Subclinical hyperthyroidism and the risk of dementia, the Rotterdam study. Clin Endocrinol (Oxf) 2000, 53:733-737.