NEUROLOGY 2005;65:545-551
© 2005 American Academy of Neurology
Aggregation of vascular risk factors and risk of incident Alzheimer disease
J. A. Luchsinger, MD, MPH,
C. Reitz, MD,
L. S. Honig, MD, PhD,
M. X. Tang, PhD,
Steven Shea, MD, MS and
R. Mayeux, MD, MSe
From the Taub Institute for Research of Alzheimer's Disease and the Aging Brain (Drs. Luchsinger, Reitz, Honig, Tang, and Mayeux), Gertrude H. Sergievsky Center (Drs. Luchsinger, Honig, Tang, and Mayeux), Department of Biostatistics (Drs. Tang, and Mayeux), Joseph P. Mailman School of Public Health, Department of Epidemiology (Drs. Shea, and Mayeux), Joseph P. Mailman School of Public Health, Columbia University, and Division of General Medicine (Drs. Luchsinger, Shea, Mayeux), Department of Medicine, Department of Neurology (Drs. Honig and Mayeux), and Department of Psychiatry (Drs. Mayeux), Columbia University College of Physicians and Surgeons, New York, NY.
Address correspondence and reprint requests to Dr Luchsinger, PH9E-105, 630 W. 168 St., New York, NY 10032; e-mail: jal94{at}columbia.edu
Background: The prevalence of Alzheimer disease (AD) is increasing in the elderly, and vascular risk factors may increase its risk.
Objective: To explore the association of the aggregation of vascular risk factors with AD.
Methods: The authors followed 1,138 individuals without dementia at baseline (mean age 76.2) for a mean of 5.5 years. The presence of vascular risk factors was related to incident possible and probable AD.
Results: Four risk factors (diabetes, hypertension, heart disease, and current smoking) were associated with a higher risk of AD (p < 0.10) when analyzed individually. The risk of AD increased with the number of risk factors (diabetes + hypertension + heart disease + current smoking). The adjusted hazards ratio of probable AD for the presence of three or more risk factors was 3.4 (95% CI: 1.8, 6.3; p for trend < 0.0001) compared with no risk factors. Diabetes and current smoking were the strongest risk factors in isolation or in clusters, but hypertension and heart disease were also related to a higher risk of AD when clustered with diabetes, smoking, or each other.
Conclusions: The risk of Alzheimer disease (AD) increased with the number of vascular risk factors. Diabetes and current smoking were the strongest risk factors, but clusters including hypertension and heart disease also increased the risk of AD. These associations are unlikely to be explained by misclassification of the outcome, given strong associations when only probable AD is considered.
Supported by grants from the National Institute of Aging (AG07232, AG07702, 1K08AG20856-01), from the Charles S. Robertson Memorial Gift for Research on Alzheimer's Disease, from the Blanchette Hooker Rockefeller Foundation, and from the New York City Council Speaker's Fund for Public Health Research.
Disclosure: The authors report no conflicts of interest.
Received December 8, 2004. Accepted in final form May 5, 2005.
Related Article
-
August 23 Highlights
Neurology 2005 65: 504-505.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
D. S. Knopman
Invited Commentary: Albuminuria and Microvascular Disease of the Brain--A Shared Pathophysiology
Am. J. Epidemiol.,
February 1, 2010;
171(3):
287 - 289.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N.-C. Li, A. Lee, R. A Whitmer, M. Kivipelto, E. Lawler, L. E Kazis, and B. Wolozin
Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis
BMJ,
January 12, 2010;
340(jan12_1):
b5465 - b5465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Noble, J. J. Manly, N. Schupf, M. X. Tang, R. Mayeux, and J. A. Luchsinger
Association of C-Reactive Protein With Cognitive Impairment
Arch Neurol,
January 1, 2010;
67(1):
87 - 92.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wiederkehr, D. Laurin, M. Simard, R. Verreault, and J. Lindsay
Vascular Risk Factors and Cognitive Functions in Nondemented Elderly Individuals
J Geriatr Psychiatry Neurol,
September 1, 2009;
22(3):
196 - 206.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Y. Deschaintre, F. Richard, D. Leys, and F. Pasquier
Treatment of vascular risk factors is associated with slower decline in Alzheimer disease
Neurology,
September 1, 2009;
73(9):
674 - 680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Luchsinger, A. M. Brickman, C. Reitz, S. J. Cho, N. Schupf, J. J. Manly, M. X. Tang, S. A. Small, R. Mayeux, C. DeCarli, et al.
Subclinical cerebrovascular disease in mild cognitive impairment
Neurology,
August 11, 2009;
73(6):
450 - 456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. E. Barnes, K. E. Covinsky, R. A. Whitmer, L. H. Kuller, O. L. Lopez, and K. Yaffe
Predicting risk of dementia in older adults: The late-life dementia risk index
Neurology,
July 21, 2009;
73(3):
173 - 179.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Hoffman, J. Schmeidler, G. T. Lesser, M. S. Beeri, D. P. Purohit, H. T. Grossman, and V. Haroutunian
Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons
Neurology,
May 19, 2009;
72(20):
1720 - 1726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Fitzpatrick, L. H. Kuller, O. L. Lopez, P. Diehr, E. S. O'Meara, W. T. Longstreth Jr, and J. A. Luchsinger
Midlife and Late-Life Obesity and the Risk of Dementia: Cardiovascular Health Study
Arch Neurol,
March 1, 2009;
66(3):
336 - 342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Viswanathan, W. A. Rocca, and C. Tzourio
Vascular risk factors and dementia: How to move forward?
Neurology,
January 27, 2009;
72(4):
368 - 374.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Xu, C. Qiu, M. Gatz, N. L. Pedersen, B. Johansson, and L. Fratiglioni
Mid- and Late-Life Diabetes in Relation to the Risk of Dementia: A Population-Based Twin Study
Diabetes,
January 1, 2009;
58(1):
71 - 77.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Coley, S. Andrieu, V. Gardette, S. Gillette-Guyonnet, C. Sanz, B. Vellas, and A. Grand
Dementia Prevention: Methodological Explanations for Inconsistent Results
Epidemiol. Rev.,
November 1, 2008;
30(1):
35 - 66.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Sundelof, J. Arnlov, E. Ingelsson, J. Sundstrom, S. Basu, B. Zethelius, A. Larsson, M. C. Irizarry, V. Giedraitis, E. Ronnemaa, et al.
Serum cystatin C and the risk of Alzheimer disease in elderly men
Neurology,
September 30, 2008;
71(14):
1072 - 1079.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Brickman, N. Schupf, J. J. Manly, J. A. Luchsinger, H. Andrews, M. X. Tang, C. Reitz, S. A. Small, R. Mayeux, C. DeCarli, et al.
Brain Morphology in Older African Americans, Caribbean Hispanics, and Whites From Northern Manhattan
Arch Neurol,
August 1, 2008;
65(8):
1053 - 1061.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. S. Tan, A. Beiser, R. S. Vasan, R. Au, S. Auerbach, D. P. Kiel, P. A. Wolf, and S. Seshadri
Thyroid Function and the Risk of Alzheimer Disease: The Framingham Study
Arch Intern Med,
July 28, 2008;
168(14):
1514 - 1520.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wiederkehr, M. Simard, C. Fortin, and R. van Reekum
Comparability of the Clinical Diagnostic Criteria for Vascular Dementia: A Critical Review. Part I
J Neuropsychiatry Clin Neurosci,
May 1, 2008;
20(2):
150 - 161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Akerblom, R. Costa, J. A. Luchsinger, J. J. Manly, M.-X. Tang, J. H Lee, R. Mayeux, and N. Schupf
Relation of plasma lipids to all-cause mortality in Caucasian, African-American and Hispanic elders
Age Ageing,
March 1, 2008;
37(2):
207 - 213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. E. Smith, S. Egorova, D. Blacker, R. J. Killiany, A. Muzikansky, B. C. Dickerson, R. E. Tanzi, M. S. Albert, S. M. Greenberg, and C. R. G. Guttmann
Magnetic Resonance Imaging White Matter Hyperintensities and Brain Volume in the Prediction of Mild Cognitive Impairment and Dementia
Arch Neurol,
January 1, 2008;
65(1):
94 - 100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Planel, Y. Tatebayashi, T. Miyasaka, L. Liu, L. Wang, M. Herman, W. H. Yu, J. A. Luchsinger, B. Wadzinski, K. E. Duff, et al.
Insulin Dysfunction Induces In Vivo Tau Hyperphosphorylation through Distinct Mechanisms
J. Neurosci.,
December 12, 2007;
27(50):
13635 - 13648.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Wu, B. L. Plassman, J. Liang, and L. Wei
Cognitive Function and Dental Care Utilization Among Community-Dwelling Older Adults
Am J Public Health,
December 1, 2007;
97(12):
2216 - 2221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Reitz, M.-X. Tang, J. Manly, R. Mayeux, and J. A. Luchsinger
Hypertension and the Risk of Mild Cognitive Impairment
Arch Neurol,
December 1, 2007;
64(12):
1734 - 1740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Barberger-Gateau, C. Raffaitin, L. Letenneur, C. Berr, C. Tzourio, J. F. Dartigues, and A. Alperovitch
Dietary patterns and risk of dementia: The Three-City cohort study
Neurology,
November 13, 2007;
69(20):
1921 - 1930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. van den Berg, G. J. Biessels, A. J.M de Craen, J. Gussekloo, and R.G.J. Westendorp
The metabolic syndrome is associated with decelerated cognitive decline in the oldest old
Neurology,
September 4, 2007;
69(10):
979 - 985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Anstey, C. von Sanden, A. Salim, and R. O'Kearney
Smoking as a Risk Factor for Dementia and Cognitive Decline: A Meta-Analysis of Prospective Studies
Am. J. Epidemiol.,
August 15, 2007;
166(4):
367 - 378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. V. Glinskii, T. W. Abraha, J. R. Turk, L. J. Rubin, V. H. Huxley, and V. V. Glinsky
Microvascular network remodeling in dura mater of ovariectomized pigs: role for angiopoietin-1 in estrogen-dependent control of vascular stability
Am J Physiol Heart Circ Physiol,
August 1, 2007;
293(2):
H1131 - H1137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Holsinger, J. Deveau, M. Boustani, and J. W. Williams Jr
Does This Patient Have Dementia?
JAMA,
June 6, 2007;
297(21):
2391 - 2404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Luchsinger, C. Reitz, B. Patel, M.-X. Tang, J. J. Manly, and R. Mayeux
Relation of Diabetes to Mild Cognitive Impairment
Arch Neurol,
April 1, 2007;
64(4):
570 - 575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Luchsinger, B. Patel, M.-X. Tang, N. Schupf, and R. Mayeux
Measures of Adiposity and Dementia Risk in Elderly Persons
Arch Neurol,
March 1, 2007;
64(3):
392 - 398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Xu, C. Qiu, B. Winblad, and L. Fratiglioni
The Effect of Borderline Diabetes on the Risk of Dementia and Alzheimer's Disease
Diabetes,
January 1, 2007;
56(1):
211 - 216.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Akomolafe, A. Beiser, J. B. Meigs, R. Au, R. C. Green, L. A. Farrer, P. A. Wolf, and S. Seshadri
Diabetes Mellitus and Risk of Developing Alzheimer Disease: Results From the Framingham Study
Arch Neurol,
November 1, 2006;
63(11):
1551 - 1555.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Drachman
Aging of the brain, entropy, and Alzheimer disease
Neurology,
October 24, 2006;
67(8):
1340 - 1352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Vanhanen, K. Koivisto, L. Moilanen, E. L. Helkala, T. Hanninen, H. Soininen, K. Kervinen, Y. A. Kesaniemi, M. Laakso, and J. Kuusisto
Association of metabolic syndrome with Alzheimer disease: a population-based study.
Neurology,
September 12, 2006;
67(5):
843 - 847.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sato, N. Shimogaito, X. Wu, S. Kikuchi, S.-i. Yamagishi, and M. Takeuchi
Toxic Advanced Glycation End Products (TAGE) Theory in Alzheimer's Disease
American Journal of Alzheimer's Disease and Other Dementias,
May 1, 2006;
21(3):
197 - 208.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. M. Manschot, A. M.A. Brands, J. van der Grond, R. P.C. Kessels, A. Algra, L. J. Kappelle, G. J. Biessels, and on behalf of the Utrecht Diabetic Encephalopathy S
Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes.
Diabetes,
April 1, 2006;
55(4):
1106 - 1113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Knopman
Dementia and Cerebrovascular Disease
Mayo Clin. Proc.,
February 1, 2006;
81(2):
223 - 230.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-K. Tong, N. Nicolakakis, A. Kocharyan, and E. Hamel
Vascular Remodeling versus Amyloid {beta}-Induced Oxidative Stress in the Cerebrovascular Dysfunctions Associated with Alzheimer's Disease
J. Neurosci.,
November 30, 2005;
25(48):
11165 - 11174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
