Methodological issues

The historical distinction between the vascular dementias and Alzheimer’s disease is a major obstacle in assessing the role of vascular disease as a risk factor for Alzheimer’s disease. Defining a condition according to its presumed aetiology can preclude a critical examination of risk factors included or excluded by that definition. Research criteria such as NINCDS-ADRDA,1 emphasise Alzheimer’s disease as a diagnosis of exclusion particularly with regard to vascular disease, therefore any association between the two will be underestimated through selective classification. The increased use of imaging techniques may cause additional confusion—namely, what bearing should evidence of subclinical cerebrovascular disease (known to be common in older populations) have on the diagnosis? However, failing to assess subclinical cerebrovascular disease in this way limits the conclusions that can be drawn from any association found between vascular risk factors and clinical Alzheimer’s disease, an important issue being whether such an association is mediated by an effect on Alzheimer’s pathology or by cognitive impairment secondary to increased cerebrovascular disease in the context of “mixed dementia”. Given high rates of mixed Alzheimer’s and cerebrovascular pathology at postmortem examination,2 a diagnostic system which attempts to subdivide dementia into mutually exclusive categories is of limited usefulness in assessing the role of disease processes which may affect both.

The problem of subclinical disease complicates the assessment not only of dementia as the outcome …