NEUROLOGY 2005;64:277-281
© 2005 American Academy of Neurology
Midlife cardiovascular risk factors and risk of dementia in late life
R. A. Whitmer, PhD,
S. Sidney, MD,
J. Selby, MD,
S. Claiborne Johnston, MD and
K. Yaffe, MD
From Kaiser Permanente Division of Research (Drs. Whitmer, Sidney, and Selby), Oakland, CA; and Departments of Neurology (Drs. Claiborne Johnston and Yaffe), Epidemiology (Drs. Claiborne Johnston and Yaffe), and Psychiatry (Dr. Yaffe), University of California San Francisco.
Address correspondence and reprint requests to Dr. Rachel Whitmer, 2000 Broadway, Kaiser Permanente Division of Research, Oakland, CA 94612; e-mail: raw{at}dor.kaiser.org
Objective: To evaluate if midlife cardiovascular risk factors are associated with risk of late-life dementia in a large, diverse cohort.
Method: The authors conducted a retrospective cohort study of 8,845 participants of a health maintenance organization who underwent health evaluations from 1964 to 1973 when they were between the ages of 40 and 44. Midlife cardiovascular risk factors included total cholesterol, diabetes, hypertension, and smoking. Diagnoses of dementia were ascertained by medical records from January 1994 to April 2003.
Results: The authors identified 721 participants (8.2%) with dementia. Smoking, hypertension, high cholesterol, and diabetes at midlife were each associated with a 20 to 40% increase in risk of dementia (fully adjusted Cox proportional hazards model: HR 1.24, 95% CI 1.04 to 1.48 for hypertension, HR 1.26, 95% CI 1.08 to 1.47 for smoking, HR 1.42, 95% CI 1.22 to 1.66 for high cholesterol, and HR 1.46, 95% CI 1.19 to 1.79 for diabetes). A composite cardiovascular risk score was created using all four risk factors and was associated with dementia in a dose-dependent fashion. Compared with participants having no risk factors, the risk for dementia increased from 1.27 for having one risk factor to 2.37 for having all four risk factors (fully adjusted model: HR 2.37, 95% CI 1.10 to 5.10).
Conclusion: The presence of multiple cardiovascular risk factors at midlife substantially increases risk of late-life dementia in a dose dependent manner.
Supported by grant 1K12AR47659 from the National Institutes of Health.
Received October 19, 2003. Accepted in final form September 8, 2004.
This article has been cited by other articles:
|
|
|
|
 
N. L. Pedersen
Reaching the Limits of Genome-wide Significance in Alzheimer Disease: Back to the Environment
JAMA,
May 12, 2010;
303(18):
1864 - 1865.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Etgen, D. Sander, H. Bickel, K. Sander, and H. Forstl
Cognitive decline: the relevance of diabetes, hyperlipidaemia and hypertension
The British Journal of Diabetes & Vascular Disease,
May 1, 2010;
10(3):
115 - 122.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. E. O'Bryant, S. C. Waring, V. Hobson, J. R. Hall, C. B. Moore, T. Bottiglieri, P. Massman, and R. Diaz-Arrastia
Decreased C-Reactive Protein Levels in Alzheimer Disease
J Geriatr Psychiatry Neurol,
March 1, 2010;
23(1):
49 - 53.
[Abstract]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
S. Debette and S. Seshadri
Vascular risk factors and dementia revisited
J. Neurol. Neurosurg. Psychiatry,
November 1, 2009;
80(11):
1183 - 1184.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Alonso, T H Mosley Jr, R F Gottesman, D Catellier, A R Sharrett, and J Coresh
Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) study
J. Neurol. Neurosurg. Psychiatry,
November 1, 2009;
80(11):
1194 - 1201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Knopman
Mediterranean Diet and Late-Life Cognitive Impairment: A Taste of Benefit
JAMA,
August 12, 2009;
302(6):
686 - 687.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Fillit, G. Hess, J. Hill, P. Bonnet, and C. Toso
IV immunoglobulin is associated with a reduced risk of Alzheimer disease and related disorders
Neurology,
July 21, 2009;
73(3):
180 - 185.
[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]
|
|
|
|
|
|
|
S. P. Kennelly, B. A. Lawlor, and R. A. Kenny
Review: Blood pressure and dementia -- a comprehensive review
Therapeutic Advances in Neurological Disorders,
July 1, 2009;
2(4):
241 - 260.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. A. Ronald, Y. Chen, L. Bernas, H. H. Kitzler, K. A. Rogers, R. A. Hegele, and B. K. Rutt
Clinical field-strength MRI of amyloid plaques induced by low-level cholesterol feeding in rabbits
Brain,
May 1, 2009;
132(5):
1346 - 1354.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Whitmer, A. J. Karter, K. Yaffe, C. P. Quesenberry Jr, and J. V. Selby
Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus
JAMA,
April 15, 2009;
301(15):
1565 - 1572.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Craft
The Role of Metabolic Disorders in Alzheimer Disease and Vascular Dementia: Two Roads Converged
Arch Neurol,
March 1, 2009;
66(3):
300 - 305.
[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]
|
|
|
|
|
|
|
R. A. Whitmer, D. R. Gustafson, E. Barrett-Connor, M. N. Haan, E. P. Gunderson, and K. Yaffe
Central obesity and increased risk of dementia more than three decades later
Neurology,
September 30, 2008;
71(14):
1057 - 1064.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Beeri, J. Schmeidler, J. M. Silverman, S. Gandy, M. Wysocki, C. M. Hannigan, D. P. Purohit, G. Lesser, H. T. Grossman, and V. Haroutunian
Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology
Neurology,
September 2, 2008;
71(10):
750 - 757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Scazufca, P. R Menezes, R. Araya, V. D Di Rienzo, O. P Almeida, D. Gunnell, and D. A Lawlor
Risk factors across the life course and dementia in a Brazilian population: results from the Sao Paulo Ageing & Health Study (SPAH)
Int. J. Epidemiol.,
August 1, 2008;
37(4):
879 - 890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Mielke, Q.-L. Xue, J. Zhou, P. H. M. Chaves, L. P. Fried, and M. C. Carlson
Baseline Serum Cholesterol Is Selectively Associated With Motor Speed and Not Rates of Cognitive Decline: The Women's Health and Aging Study II
J Gerontol A Biol Sci Med Sci,
June 1, 2008;
63(6):
619 - 624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. M. Hajjar, M. Keown, P. Lewis, and A. Almor
Angiotensin Converting Enzyme Inhibitors and Cognitive and Functional Decline in Patients with Alzheimer's Disease: An Observational Study
American Journal of Alzheimer's Disease and Other Dementias,
March 1, 2008;
23(1):
77 - 83.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Knecht, H. Wersching, H. Lohmann, M. Bruchmann, T. Duning, R. Dziewas, K. Berger, and E. B. Ringelstein
High-Normal Blood Pressure Is Associated With Poor Cognitive Performance
Hypertension,
March 1, 2008;
51(3):
663 - 668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Rolandsson, A. Backestrom, S. Eriksson, G. Hallmans, and L.-G. Nilsson
Increased Glucose Levels Are Associated With Episodic Memory in Nondiabetic Women
Diabetes,
February 1, 2008;
57(2):
440 - 443.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. Simon, H. Chen, M. Schwarzschild, and A. Ascherio
Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease
Neurology,
October 23, 2007;
69(17):
1688 - 1695.
[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]
|
|
|
|
|
|
|
Y. Miyasaka, M. E. Barnes, R. C. Petersen, S. S. Cha, K. R. Bailey, B. J. Gersh, G. Casaclang-Verzosa, W. P. Abhayaratna, J. B. Seward, T. Iwasaka, et al.
Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data from a community-based cohort
Eur. Heart J.,
August 2, 2007;
28(16):
1962 - 1967.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Scarmeas
Invited Commentary: Lipoproteins and Dementia--Is It the Apolipoprotein A-I?
Am. J. Epidemiol.,
May 1, 2007;
165(9):
993 - 997.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Solomon, I. Kareholt, T. Ngandu, B. Winblad, A. Nissinen, J. Tuomilehto, H. Soininen, and M. Kivipelto
Serum cholesterol changes after midlife and late-life cognition: Twenty-one-year follow-up study
Neurology,
March 6, 2007;
68(10):
751 - 756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Staessen, T. Richart, and W. H. Birkenhager
Less Atherosclerosis and Lower Blood Pressure for a Meaningful Life Perspective With More Brain
Hypertension,
March 1, 2007;
49(3):
389 - 400.
[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. Burns and J. O'Brien
Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology
J Psychopharmacol,
November 1, 2006;
20(6):
732 - 755.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. Regan, C. Katona, Z. Walker, J. Hooper, J. Donovan, and G. Livingston
Relationship of vascular risk to the progression of Alzheimer disease
Neurology,
October 24, 2006;
67(8):
1357 - 1362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Friedlander, D. C. Norman, M. E. Mahler, K. M. Norman, and J. A. Yagiela
Alzheimer's disease: Psychopathology, medical management and dental implications.
J Am Dent Assoc,
September 1, 2006;
137(9):
1240 - 1251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Llorente and V. Urrutia
Diabetes, Psychiatric Disorders, and the Metabolic Effects of Antipsychotic Medications
Clin. Diabetes,
January 1, 2006;
24(1):
18 - 24.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Li, J. B. Shofer, W. A. Kukull, E. R. Peskind, D. W. Tsuang, J.C.S. Breitner, W. McCormick, J. D. Bowen, L. Teri, G. D. Schellenberg, et al.
Serum cholesterol and risk of Alzheimer disease: A community-based cohort study
Neurology,
October 11, 2005;
65(7):
1045 - 1050.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J Goble
Obesity in middle age and future risk of dementia: Problem is probably greater for women
BMJ,
August 20, 2005;
331(7514):
454 - 454.
[Full Text]
|
|
|
|
|
|
|
R. Whitmer, C. P Quesenberry Jr, and K. Yaffe
Obesity in middle age and future risk of dementia: Authors' reply
BMJ,
August 20, 2005;
331(7514):
455 - 455.
[Full Text]
|
|
|
|
|
|
|
R. A Whitmer, E. P Gunderson, E. Barrett-Connor, C. P Quesenberry Jr, and K. Yaffe
Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study
BMJ,
June 11, 2005;
330(7504):
1360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
