Association between cardiovascular disease and dementia

Suemoto, Claudia Kimie; Ferretti, Renata Eloah; Grinberg, Lea Tenenholz; Oliveira, Kátia Cristina de; Farfel, José Marcelo; Leite, Renata Elaine Paraizo; Nitrini, Ricardo; Jacob Filho, Wilson; Pasqualucci, Carlos Augusto; ,

doi:10.1590/S1980-57642009DN30400008

Abstract

Longitudinal studies have shown association between cardiovascular risk factors and dementia. However, these studies are not capable of detecting asymptomatic cardiovascular alterations and thus may provide erroneous estimates of association. Autopsy studies could be more useful in elucidating these questions. The present clinicopathological study sought to examine the relationship between dementia, cardiovascular risk factors and disease.

Methods: 603 subjects, who underwent autopsy, were classified regarding the presence of dementia, according to post mortem cognitive classification. Demographics, cardiovascular risk factors, and anatomically-proven cardiovascular disease (myocardial hypertrophy, cerebral and carotid atherosclerosis) were compared among cognitively normal persons and individuals with dementia.

Results: Cognitive deficit was associated with advanced age, stroke, physical inactivity and low body mass index (p<0.05). Circle of Willis atherosclerosis was greater in patients with dementia than in controls on univariate analysis (p=0.01). However, this association lost significance when adjusted by age and gender (p=0.61). Heart failure and anatomopathological cardiac parameters were more severe in the control group than in demented individuals (p<0.05). Carotid artery atherosclerosis and intima-media thickness were similar in both groups.

Conclusion: Advanced age, stroke, physical inactivity and low body mass index were linked to dementia. Circle of Willis atherosclerosis was associated with dementia only when age was not considered. Our results suggest that cerebral artery atherosclerosis was not directly associated with clinical expression of dementia.

Key words: atherosclerosis; circle of Willis; carotid artery disease; cardiomyopathy; dementia.

Resumo

Estudos longitudinais tem mostrado associação entre fatores de risco cardiovascular e demência. Entretanto, estes estudos não são capazes de detectar alterações cardiovasculares assintomáticas e podem, assim, fornecer estimativas de associação errôneas. Estudos de autópsia podem ser mais úteis em elucidar estas questões. O presente estudo clinicopatológico busca examinar a relação entre demência, fatores e doença cardiovascular.

Métodos: 603 sujeitos submetidos à autópsia foram classificados quanto à presença de demência, usando uma classificação cognitiva post-mortem. Dados demográficos, fatores de risco cardiovascular e doença cardiovascular comprovada anatomicamente (hipertrofia miocárdica, aterosclerose cerebral e carotídea) foram comparados entre indivíduos cognitivamente normais e com demência.

Resultados: Déficit cognitivo esteve associado à idade avançada, acidente vascular cerebral, sedentarismo e baixo índice de massa corpórea (p<0,05). Aterosclerose do polígono de Willis foi maior em pacientes com demência do que em controles na análise univariada (p=0,01). Insuficiência cardíaca e parâmetros anatomopatológicos cardíacos foram mais graves entre o grupo controle que entre os indivíduos dementados (p<0,05). Aterosclerose de artérias carótidas e espessura íntima-média foram similares entre os grupos.

Conclusão: Idade avançada, acidente vascular cerebral, sedentarismo e baixo índice de massa corpórea estiveram relacionados à demência. Aterosclerose de polígono de Willis esteve associada à demência, somente quando a idade não foi considerada. Nossos resultados sugerem que a aterosclerose de artérias cerebrais não está diretamente relacionada com a expressão clínica de demência.

Palavras-chave: aterosclerose; polígono de Willis; doença arterial carotídea; cardiomiopatia; demência.

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References

¹ Breteler MM. Vascular risk factors for Alzheimer's disease: an epidemiologic perspective. Neurobiol Aging 2000;21:153-160.
² Aguero-Torres H, Kivipelto M, von Strauss E. Rethinking the dementia diagnoses in a population-based study: what is Alzheimer's disease and what is vascular dementia? A study from the Kungsholmen project. Dement Geriatr Cogn Disord 2006;22:244-249.
³ Ruitenberg A, de Heiker T, Bakker SL. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam study. Ann Neurol 2005;57:789-794.
⁴ Elias MF, Wolf PA, D'Agostinho 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.
⁵ Fillit H, Nash DT, Rundek T, Zuckerman A. Cardiovascular risk factors and dementia. Am J Geriatr Pharmacother. 2008;6:100-118.
⁶ De La Torre. How do heart disease and stroke become risk factors for Alzheimer's disease? Neurol Res 2006;28:637-644.
⁷ Roher AE, Esh C, Rahman A, et al. Circle of Willis atherosclerosis is a risk factor for sporadic Alzheimer's disease. Arterioscler Thromb Vasc Biol 2003;23:2055-2062.
⁸ Honig LS, Kukull W, Mayeux R. Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center. Neurology 2005;64:494-500.
⁹ Kalback W, Esh C, Castaño EM, et al. Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease. Neurol Res 2004;26:525-539.
¹⁰ Grinberg LT, Ferretti REL, Farfel JM, et al. Brain bank of the Brazilian Aging Study Group - a milestone reached and more than 1,600 collected brains. Cell Tissue Banking 2007;8: 151-162.
¹¹ Morris JC. Clinical Dementia Rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psycogeriatr 1997;9:173-176.
¹² Jorm AF. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): a review. 2. Int Psycogeriatr 2004; 16:275-293.
¹³ Rasband, W.S., ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, USA, http://rsb.info.nih.gov/ij/, 1997-2009.
» http://rsb.info.nih.gov/ij/
¹⁴ Nitrini R, Caramelli P, Herrera E Jr, et al. Incidence of dementia in a community-dwelling Brazilian population. Alzheimer Dis Assoc Disord 2004; 18:241-246.
¹⁵ Orlandi A, Bochaton-Piallat ML, Gabbiani G, Spagnoli LG. Aging, smooth muscle cells and vascular pathobiology: Implications for atherosclerosis. Atherosclerosis 2006;188:221-230.
¹⁶ Luoto TM, Haikonen S, Haapasalo H, et al. Large vessel cerebral atherosclerosis is not in direct association with neuropathological lesions of Alzheimer's disease. Eur Neurol 2009;62:93-98.
¹⁷ Newman AB. Fitzpatrick AL, Lopez O, et al. Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study. JAGS 2005;53: 1101-1107.
¹⁸ Rosano C, Newman AB. Cardiovascular disease and risk of Alzheimer's disease. Neurol Res 2006;28:612-620.
¹⁹ Johnston SC, O'Meara ES, Manolio TA, et al. Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med 2004; 140: 237-247.
²⁰ Hofman A, Ott A, Breteler M, et al. Atherosclerosis, apoliprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 1997;349: 151-154.
²¹ Van Oijen A, de Jong FJ, Witteman JCM, Hofman A, Koudstaal PJ, Breteler MMB. Atherosclerosis and risk for dementia. Ann Neurol 2007;61:403-410.
²² Manolio TA, Burke GL, O'Leary DH, et al. Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults. The Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1999;19:356-365.
²³ Schulte-Altedorneburg G, Droste DW, Kollár J, et al. Measuring carotid artery stenosis: comparison of postmortem arteriograms with planimetric gold standard. J Neurol 2005;252: 575-582.
²⁴ Beeri MS, Rapp M, Silverman JM, et al. Coronary artery disease is associated with Alzheimer's disease neuropathology in APOE4 carries. Neurology 2006;66:1399-1404.
²⁵ Kähönen-Väre M, Brunni-Hakala S, Lindroos M, Pitkala K, Strandberg T, Tilvis R. Left ventricular hypertrophy and blood pressure as predictors of cognitive decline in old age. Aging Clin Exp Res 2004;16:147-152.
²⁶ Irina A, Seppo H, Arto M, Paavo R, Hilkka S. ß-Amyloid Load Is Not Influenced by the Severity of Cardiovascular Disease in Aged and Demented Patients. Stroke 1999;30:613-618.
²⁷ Herrera E Jr, Caramelli P, Silveira AS, Nitrini R. Epidemiologic survey of dementia in a community-dwelling Brazilian population. Alzheimer Dis Assoc Disord. 2002; 16:103-108.
²⁸ Bottino CMC, Azevedo, Jr. D, Tatsch M, et al. Estimate of Dementia Prevalence in a Community Sample from São Paulo, Brazil. Dement Geriatr Cogn Disord 2008;26: 291-299.
²⁹ Ferraz-Alves TCT, Bussatto GF. Regional cerebral blood flow reductions, heart failure and Alzheimer's disease. Neurol Res 2006;28:579-587.
³⁰ 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.
³¹ Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer's disease: The Nun Study. JAMA 1997;277:813-817.
³² Sonnen JA, Larson EB, Crane PK, et al. Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann Neurol 2007;62:406-413.
³³ 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.
³⁴ Ravaglia G, Forti P, Lucicesare A, et al. Physical activity and dementia risk in the elderly: findings from a prospective Italian study. Neurology 2008;70:1786-1794.
³⁵ Isella V, Villa L, Russo A, Regazzoni R, Ferrarese C, Appolonio IM. Discriminative and predictive power of an informant report in mild cognitive impairment. J Neurol Neurosurg Psychiatry 2006;77:166-171.
³⁶ Haroutunian V, Perl DP, Purohit DP, et al. Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch Neurol 1998;55: 1185-1191.
³⁷ Haroutunian V, Purohit DP, Perl DP, et al. Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease. Arch Neurol 1999;56:713-718.
³⁸ Rockwood K, Howard K, Thomas VS, et al. Retrospective diagnosis of dementia using an informant interview based on the Brief Cognitive Rating Scale. Int Psychogeriatr 1998;10:53-60.

Publication Dates

Publication in this collection
Oct-Dec 2009

History

Received
13 Sept 2009
Accepted
03 Nov 2009

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹ Breteler MM. Vascular risk factors for Alzheimer's disease: an epidemiologic perspective. Neurobiol Aging 2000;21:153-160.

[2] ² Aguero-Torres H, Kivipelto M, von Strauss E. Rethinking the dementia diagnoses in a population-based study: what is Alzheimer's disease and what is vascular dementia? A study from the Kungsholmen project. Dement Geriatr Cogn Disord 2006;22:244-249.

[3] ³ Ruitenberg A, de Heiker T, Bakker SL. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam study. Ann Neurol 2005;57:789-794.

[4] ⁴ Elias MF, Wolf PA, D'Agostinho 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.

[5] ⁵ Fillit H, Nash DT, Rundek T, Zuckerman A. Cardiovascular risk factors and dementia. Am J Geriatr Pharmacother. 2008;6:100-118.

[6] ⁶ De La Torre. How do heart disease and stroke become risk factors for Alzheimer's disease? Neurol Res 2006;28:637-644.

[7] ⁷ Roher AE, Esh C, Rahman A, et al. Circle of Willis atherosclerosis is a risk factor for sporadic Alzheimer's disease. Arterioscler Thromb Vasc Biol 2003;23:2055-2062.

[8] ⁸ Honig LS, Kukull W, Mayeux R. Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center. Neurology 2005;64:494-500.

[9] ⁹ Kalback W, Esh C, Castaño EM, et al. Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease. Neurol Res 2004;26:525-539.

[10] ¹⁰ Grinberg LT, Ferretti REL, Farfel JM, et al. Brain bank of the Brazilian Aging Study Group - a milestone reached and more than 1,600 collected brains. Cell Tissue Banking 2007;8: 151-162.

[11] ¹¹ Morris JC. Clinical Dementia Rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psycogeriatr 1997;9:173-176.

[12] ¹² Jorm AF. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): a review. 2. Int Psycogeriatr 2004; 16:275-293.

[13] ¹³ Rasband, W.S., ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, USA, http://rsb.info.nih.gov/ij/, 1997-2009.
» http://rsb.info.nih.gov/ij/

[14] ¹⁴ Nitrini R, Caramelli P, Herrera E Jr, et al. Incidence of dementia in a community-dwelling Brazilian population. Alzheimer Dis Assoc Disord 2004; 18:241-246.

[15] ¹⁵ Orlandi A, Bochaton-Piallat ML, Gabbiani G, Spagnoli LG. Aging, smooth muscle cells and vascular pathobiology: Implications for atherosclerosis. Atherosclerosis 2006;188:221-230.

[16] ¹⁶ Luoto TM, Haikonen S, Haapasalo H, et al. Large vessel cerebral atherosclerosis is not in direct association with neuropathological lesions of Alzheimer's disease. Eur Neurol 2009;62:93-98.

[17] ¹⁷ Newman AB. Fitzpatrick AL, Lopez O, et al. Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study. JAGS 2005;53: 1101-1107.

[18] ¹⁸ Rosano C, Newman AB. Cardiovascular disease and risk of Alzheimer's disease. Neurol Res 2006;28:612-620.

[19] ¹⁹ Johnston SC, O'Meara ES, Manolio TA, et al. Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med 2004; 140: 237-247.

[20] ²⁰ Hofman A, Ott A, Breteler M, et al. Atherosclerosis, apoliprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 1997;349: 151-154.

[21] ²¹ Van Oijen A, de Jong FJ, Witteman JCM, Hofman A, Koudstaal PJ, Breteler MMB. Atherosclerosis and risk for dementia. Ann Neurol 2007;61:403-410.

[22] ²² Manolio TA, Burke GL, O'Leary DH, et al. Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults. The Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1999;19:356-365.

[23] ²³ Schulte-Altedorneburg G, Droste DW, Kollár J, et al. Measuring carotid artery stenosis: comparison of postmortem arteriograms with planimetric gold standard. J Neurol 2005;252: 575-582.

[24] ²⁴ Beeri MS, Rapp M, Silverman JM, et al. Coronary artery disease is associated with Alzheimer's disease neuropathology in APOE4 carries. Neurology 2006;66:1399-1404.

[25] ²⁵ Kähönen-Väre M, Brunni-Hakala S, Lindroos M, Pitkala K, Strandberg T, Tilvis R. Left ventricular hypertrophy and blood pressure as predictors of cognitive decline in old age. Aging Clin Exp Res 2004;16:147-152.

[26] ²⁶ Irina A, Seppo H, Arto M, Paavo R, Hilkka S. ß-Amyloid Load Is Not Influenced by the Severity of Cardiovascular Disease in Aged and Demented Patients. Stroke 1999;30:613-618.

[27] ²⁷ Herrera E Jr, Caramelli P, Silveira AS, Nitrini R. Epidemiologic survey of dementia in a community-dwelling Brazilian population. Alzheimer Dis Assoc Disord. 2002; 16:103-108.

[28] ²⁸ Bottino CMC, Azevedo, Jr. D, Tatsch M, et al. Estimate of Dementia Prevalence in a Community Sample from São Paulo, Brazil. Dement Geriatr Cogn Disord 2008;26: 291-299.

[29] ²⁹ Ferraz-Alves TCT, Bussatto GF. Regional cerebral blood flow reductions, heart failure and Alzheimer's disease. Neurol Res 2006;28:579-587.

[30] ³⁰ 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.

[31] ³¹ Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer's disease: The Nun Study. JAMA 1997;277:813-817.

[32] ³² Sonnen JA, Larson EB, Crane PK, et al. Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann Neurol 2007;62:406-413.

[33] ³³ 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.

[34] ³⁴ Ravaglia G, Forti P, Lucicesare A, et al. Physical activity and dementia risk in the elderly: findings from a prospective Italian study. Neurology 2008;70:1786-1794.

[35] ³⁵ Isella V, Villa L, Russo A, Regazzoni R, Ferrarese C, Appolonio IM. Discriminative and predictive power of an informant report in mild cognitive impairment. J Neurol Neurosurg Psychiatry 2006;77:166-171.

[36] ³⁶ Haroutunian V, Perl DP, Purohit DP, et al. Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch Neurol 1998;55: 1185-1191.

[37] ³⁷ Haroutunian V, Purohit DP, Perl DP, et al. Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease. Arch Neurol 1999;56:713-718.

[38] ³⁸ Rockwood K, Howard K, Thomas VS, et al. Retrospective diagnosis of dementia using an informant interview based on the Brief Cognitive Rating Scale. Int Psychogeriatr 1998;10:53-60.