The Interaction Between Vascular Factors and Alzheimer's Disease
I. Skoog
Göteborg University, Institute of Clinical Neuroscience, Department of Psychiatry, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
Alzheimer's disease is a primary degenerative dementia, characterised by degeneration of specific nerve cells and the accumulation of the b-amyloid peptide in the brain, and is not considered to be of vascular origin. Indeed, stroke and severe cardiovascular diseases are generally exclusionary for the clinical diagnosis. However, during recent years both epidemiological and neuropathological studies have suggested an association between Alzheimer's disease and several vascular risk factors, such as hypertension, non-dipping blood pressure pattern, coronary heart disease, atrial fibrillation, diabetes mellitus, ischaemic white matter lesions and generalised atherosclerosis.
Although these findings may reflect an overdiagnosis of Alzheimer's disease in individuals with silent cerebrovascular disease, there are also alternative explanations. Lesions in the cerebral microcirculation with an increased vascular permeability are often reported in Alzheimer's disease. A blood-brain barrier dysfunction may therefore be involved in the aetiology and pathogenesis of Alzheimer's disease. This may increase the possibility that substances from serum reach the brain, where they may interact with neurons. Alzheimer's disease may also lead to lesions in the cerebral microvasculature, as b-amyloid interacting with endothelial cells produces superoxide radicals, which causes endothelial damage. Other factors that may be involved in the pathogenesis both of vascular disorders and Alzheimer's disease are disturbances in the renin-angiotensin system, inheritance of the apolipoprotein E e4 allele, oxidative stress with the formation of free radicals, apoptosis, and psychological stress.
In summary, the mechanism behind the association between Alzheimer's disease and vascular disorders is not clear. Possible reasons include overdiagnosis of Alzheimer's disease in cases of vascular dementia, that cerebrovascular disease may affects the clinical expression of Alzheimer's disease or stimulate the Alzheimer's disease process, that similar mechanisms may be involved in the pathogenesis of both disorders, and that Alzheimer's disease may increase the risk of vascular disease.
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