November 05, 2012

The Interaction Between Alzheimer's and Vascular Disease

Vascular Dementia 

The concept of vascular dementia is said to have ".. a rich history, a confusing present, and an uncertain future" (Whitehouse et al. In: Clinical Neuropsychiatry, Ed. Heilman and Valenstein, 1993).  In the early 20th Century arteriosclerotic (vascular) dementia was considered more common than Alzheimer's Disease.  Now it is generally considered the second commonest cause of dementia, accounting for only 10-20% of cases.

Vascular dementia combines the concepts of dementia with cerebral vascular disease.  It can result from a number of causes, including arteriosclerosis, infarcts, haemorrhage, infection and inflammation.  It increases with age and is more common in men.  High blood pressure, raised cholesterol, smoking, and diabetes are some of the risk factors associated with vascular dementia.

Vascular Dementia Compared With Alzheimer's Disease:

Unlike Alzheimer's Disease the onset of vascular dementia is usually abrupt and may accompany a stroke.  It progresses in a stepwise manner, with marked exacerbations followed by periods during which symptoms remain static and may even improve.  Conversely Alzheimer's Disease is slowly progressive, and characterised by degeneration of specific nerve cells and the accumulation of amyloid deposits in the brain; it is not considered to be of vascular origin.  Indeed, stroke and severe cardiovascular diseases are generally exclusion criteria for its clinical diagnosis.

However, during recent years, many studies suggested an association between Alzheimer's Disease and several vascular risk factors, such as high blood pressure, ischaemic heart disease, atrial fibrillation, and diabetes mellitus.

The Nun Study:

To add to this confusion, many individuals with pathological lesions of Alzheimer's Disease at post mortem do not become demented during life, although the reason for this is unknown.  This prompted Snowdon and coworkers to suspect that the clinical expression of Alzheimer's might be partly determined by the presence of other conditions such as brain infarcts.  They identified infarcts and quantitated plaques and tangles in the brain to confirm the diagnosis of Alzheimers Disease in 61 Nuns in the famous "Nun Study" (Snowdon et al. JAMA 1997; 277:813-7).  They found that those with infarcts had poorer cognitive function, and suggested that cerebrovascular disease may play a role in determining the presence and severity of the clinical symptoms of Alzheimers Disease.  As we saw in the previous Blog update, it is therefore of interest that arteriosclerosis was one of the features noted in Alzheimer’s first case report.

Is Homocysteine a "missing link?"

The actual mechanism behind the association between Alzheimer's Disease and vascular disorders remains unclear.  Possible reasons include over-diagnosis of Alzheimer's in cases of Vascular Dementia, that cerebrovascular disease affects the clinical expression of Alzheimer's or stimulates the disease process, that Alzheimer's may increase the risk of vascular disease, or that similar mechanisms may be involved in the pathogenesis of both disorders.

One such mechanism, common to both Alzheimer's Disease and Vascular Dementia, is of course high blood levels of homocysteine. However, before we look further into this, we need to understand the fascinating story behind the link between homocysteine and arteriosclerosis.

Check back again for our next Blog update about the work of Kilmer McCully.


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