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Abstract

Background: While there is considerable epidemiologic evidence that cardiovascular risk factors increase risk of incident Alzheimer disease (AD), few studies have examined their effect on progression after an established AD diagnosis.
Objective: To examine the effect of vascular factors, and potential age modification, on rate of progression in a longitudinal study of incident dementia.
Methods: A total of 135 individuals with incident AD, identified in a population-based sample of elderly persons in Cache County, UT, were followed with in-home visits for a mean of 3.0 years (range: 0.8 to 9.5) and 2.1 follow-up visits (range: 1 to 5). The Clinical Dementia Rating (CDR) Scale and Mini-Mental State Examination (MMSE) were administered at each visit. Baseline vascular factors were determined by interview and physical examination. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) or MMSE as the outcome, and vascular index or individual vascular factors as independent variables.
Results: Atrial fibrillation, systolic hypertension, and angina were associated with more rapid decline on both the CDR-Sum and MMSE, while history of coronary artery bypass graft surgery, diabetes, and antihypertensive medications were associated with a slower rate of decline. There was an age interaction such that systolic hypertension, angina, and myocardial infarction were associated with greater decline with increasing baseline age.
Conclusion: Atrial fibrillation, hypertension, and angina were associated with a greater rate of decline and may represent modifiable risk factors for secondary prevention in Alzheimer disease. The attenuated decline for diabetes and coronary artery bypass graft surgery may be due to selective survival. Some of these effects appear to vary with age.
GLOSSARY: 3MS = revised Modified Mini-Mental State Examination for epidemiologic studies; AF = atrial fibrillation; CABG = coronary artery bypass graft surgery; CCHS = Copenhagen City Heart Study; CCSMHA = Cache County Study on Memory, Health, and Aging; CDR = Clinical Dementia Rating; CVD = cardiovascular disease; DM = diabetes mellitus; DPS = Dementia Progression Study; MI = myocardial infarction; MMSE = Mini-Mental State Examination; SBP = systolic blood pressure.

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REFERENCES

1.
Refolo LM, Malester B, LaFrancois J, et al. Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis 2000;7:321–331.
2.
Launer LJ, Ross GW, Petrovitch H, et al. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging 2000;21:49–55.
3.
Skoog I, Lernfelt B, Landahl S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet 1996;347:1141–1145.
4.
Hofman A, Ott A, Breteler MM, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet 1997;349:151–154.
5.
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.
6.
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.
7.
Honig LS, Tang MX, Albert S, et al. Stroke and the risk of Alzheimer disease. Arch Neurol 2003;60:1707–1712.
8.
Akomolafe A, Beiser A, Meigs JB, et al. Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study. Arch Neurol 2006;63:1551–1555.
9.
Bhargava D, Weiner MF, Hynan LS, Diaz-Arrastia R, Lipton AM. Vascular disease and risk factors, rate of progression, and survival in Alzheimer’s disease. J Geriatr Psychiatry Neurol 2006;19:78–82.
10.
Silvestrini M, Pasqualetti P, Baruffaldi R, et al. Cerebrovascular reactivity and cognitive decline in patients with Alzheimer disease. Stroke 2006;37:1010–1015.
11.
Regan C, Katona C, Walker Z, Hooper J, Donovan J, Livingston G. Relationship of vascular risk to the progression of Alzheimer disease. Neurology 2006;67:1357–1362.
12.
Launer LJ. The epidemiologic study of dementia: a life-long quest? Neurobiol Aging 2005;26:335–340.
13.
Mielke MM, Zandi PP, Sjogren M, et al. High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology 2005;64:1689–1695.
14.
Breitner JC, Wyse BW, Anthony JC, et al. APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study. Neurology 1999;53:321–331.
15.
Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 2000;157:708–714.
16.
Tschanz JT, Welsh-Bohmer KA, Plassman BL, Norton MC, Wyse BW, Breitner JC. An adaptation of the modified mini-mental state examination: analysis of demographic influences and normative data: the Cache County Study. Neuropsychiatry Neuropsychol Behav Neurol 2002;15:28–38.
17.
Silverman JM, Breitner JC, Mohs RC, Davis KL. Reliability of the family history method in genetic studies of Alzheimer’s disease and related dementias. Am J Psychiatry 1986;143:1279–1282.
18.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–944.
19.
Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250–260.
20.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
21.
Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140:566–572.
22.
Mohs RC, Schmeidler J, Aryan M. Longitudinal studies of cognitive, functional and behavioural change in patients with Alzheimer’s disease. Stat Med 2000;19:1401–1409.
23.
Morris JC. Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psychogeriatr 1997;9 suppl 1:173–176; discussion 177–178.
24.
Pavlik VN, Doody RS, Massman PJ, Chan W. Influence of premorbid IQ and education on progression of Alzheimer’s disease. Dement Geriatr Cogn Disord 2006;22:367–377.
25.
Dickerson BC, Salat DH, Bates JF, et al. Medial temporal lobe function and structure in mild cognitive impairment. Ann Neurol 2004;56:27–35.
26.
Truelsen T, Lindenstrom E, Boysen G. Comparison of probability of stroke between the Copenhagen City Heart Study and the Framingham Study. Stroke 1994;25:802–807.
27.
Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke 1991;22:312–318.
28.
Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC. Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology 2002;59:880–886.
29.
Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 2006;5:735–741.
30.
Khachaturian AS, Zandi PP, Lyketsos CG, et al. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch Neurol 2006;63:686–692.
31.
Lyketsos CG, Toone L, Tschanz J, et al. A population-based study of the association between coronary artery bypass graft surgery (CABG) and cognitive decline: the Cache County study. Int J Geriatr Psychiatry 2006;21:509–518.
32.
Selnes OA, McKhann GM. Neurocognitive complications after coronary artery bypass surgery. Ann Neurol 2005;57:615–621.
33.
Brayne C, Gill C, Huppert FA, et al. Vascular risks and incident dementia: results from a cohort study of the very old. Dement Geriatr Cogn Disord 1998;9:175–180.
34.
Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R. Diabetes mellitus and risk of Alzheimer’s disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol 2001;154:635–641.
35.
Hassing LB, Johansson B, Nilsson SE, et al. Diabetes mellitus is a risk factor for vascular dementia, but not for Alzheimer’s disease: a population-based study of the oldest old. Int Psychogeriatr 2002;14:239–248.
36.
Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L. Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Neurology 2004;63:1181–1186.
37.
Hayden KM, Zandi PP, Lyketsos CG, et al. Vascular risk factors for incident Alzheimer disease and vascular dementia: the Cache County study. Alzheimer Dis Assoc Disord 2006;20:93–100.
38.
Risner ME, Saunders AM, Altman JF, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J 2006;6:246–254.
39.
Kivipelto M, Helkala EL, Laakso MP, et al. 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.
40.
Notkola IL, Sulkava R, Pekkanen J, et al. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer’s disease. Neuroepidemiology 1998;17:14–20.

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Published In

Neurology®
Volume 69Number 19November 6, 2007
Pages: 1850-1858
PubMed: 17984453

Publication History

Published online: November 5, 2007
Published in print: November 6, 2007

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Authors

Affiliations & Disclosures

M. M. Mielke, PhD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
P. B. Rosenberg, MD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
J. Tschanz, PhD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
L. Cook, MStat
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
C. Corcoran, ScD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
K. M. Hayden, PhD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
M. Norton, PhD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
P. V. Rabins, MD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
R. C. Green, MD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
K. A. Welsh-Bohmer, PhD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
J.C.S. Breitner, MD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
R. Munger, PhD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.
C. G. Lyketsos, MD
From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.

Notes

Address correspondence and reprint requests to Dr. Michelle M. Mielke, Johns Hopkins University School of Medicine, Department of Psychiatry, Division of Geriatric Psychiatry and Behavioral Sciences, 550 N. Broadway, Suite 308, Baltimore, MD 21205 [email protected]

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