These findings suggest that dementia and its two major subtypes, Alzheimer’s disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein-E and atherosclerosis in the etiology of Alzheimer’s disease. Lancet January 18, 199; 349: 151-54

1-2 ATHEROSCLEROSIS, APOLIPOPROTEIN E, AND THE PREVALENCE OF ALZHEIMER’S DISEASE IN THE ROTTERDAM STUDY

Important progress has been made in discovering that genetic factors play a part in the etiology of Alzheimer’s disease—the apolipoprotein-E genotype. Vascular disorders have been implicated in dementia to a much lesser extent. Is atherosclerosis related to Alzheimers Disease? This study investigated the frequency of dementia in relation to atherosclerosis and apolipoprotein-E.
Conclusion: There may be an interaction between apolipoprotein-E and atherosclerosis in the etiology of Alzheimer’s disease.

STUDY

1. A population-based cross sectional study of atherosclerosis, the apolipoprotein-E genotype, and the prevalence of dementia identified 284 patients with dementia (207 with Alzheimer’s Disease, 50 with vascular dementia) and 1,698 individuals who were not demented.
2. Indicators of atherosclerosis included: 1) carotid artery wall thickness and plaques by ultrasound and 2) the ratio of ankle-to-brachial systolic blood pressure as a measure of generalized atherosclerosis. (Peripheral arterial disease was judged to be present when the ankle-brachial index was < 0.9).
3. Assessed apolipoprotein-E polymorphisms in 246 demented patients and over 90 controls without dementia.

RESULTS

1. Peripheral arterial disease and carotid artery thickness and plaques were significantly associated with Alzheimer’s disease (odds ratio 1.3 to 1.9) and with vascular dementia (odds ratio 1.9 - 3.2).
2. The apolipoprotein-E e-4 allele was associated with both Alzheimer’s disease (odds ratio 1.8) and vascular dementia (odds ratio 2.3).
3. In participants with the apolipoprotein-E e4 genotype and a high atherosclerotic score, the odds ratio for all dementia was 5; for Alzheimer’s disease—4; and for vascular dementia—20.
4. The observed associations of atherosclerosis and dementia were almost unaltered after adjustments for BP, cholesterol, and body-mass index.

DISCUSSION

1. The main findings of this study are that indicators of atherosclerosis are associated with Alzheimer’s disease as well as vascular dementia, and that the association between atherosclerosis and dementia is particularly strong in those with apolipoprotein-E e4 genotype.
2. "Our findings suggest that atherosclerosis is associated not only with a small group of vascular, or multi-infarct dementia, but also with the major subtype of dementia, Alzheimer’s disease."

CONCLUSION

These findings suggest that dementia and its two major subtypes, Alzheimer’s disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein-E and atherosclerosis in the etiology of Alzheimer’s disease.
Lancet January 18, 199; 349: 151-54 Original investigation first author from Erasmus University Medical School, Rotterdam, Netherlands

Comment:

1. Atherosclerotic disease is associated with vascular dementia, the likelihood of which increases as the severity of the atherosclerosis increases.
2. Vascular dementia is largely preventable.
3. Apolipoprotein-E may be a risk factor for atherosclerosis.
4. Apolipoprotein-E, especially homozygous e4, is a strong risk factor for Alzheimer’s.
5. Thus, both vascular dementia and Alzheimer’s may be related, in part to apolipoprotein-E levels.
6. Could controlling apolipoprotein-E reduce both vascular dementia and Alzheimer’s? RTJ

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