Computer Tomography and Study of the Anatomical Changes in Alzheimer’s Disease

Abstract

The role of anatomical changes in Alzheimer’s disease (AD) can be studied using computer tomography (CT) scanning. By comparing carefully selected and screened subjects to appropriately age- and sex-matched healthy controls, atrophy in AD can be shown to be due to excess cortical, but not subcortical, gray matter loss, accompanied by ventricular dilatation and increased total cerebrospinal fluid (CSF) volume. This gray matter loss and increase in CSF volume within the AD group is related to clinical severity at the time of scanning. Although these parameters can distinguish moderate—severe AD cases from controls, much overlap of gray matter volume and of lateral ventricular volume is seen between healthy controls and patients with mild AD (as defined by an MMS score of greater than 20). This is due to the heterogeneity of age-related atrophy seen in healthy controls and patients. Prospective serial scanning and cognitive testing permits study of the rate of change of both atrophy and cognitive functioning within each individual, reducing variability, and show that the rate of change of the third ventricle and lateral ventricular volumes is greater in patients with AD than in healthy controls, separating even mildly affected patients completely from the controls. The rate of atrophy change correlates with the change in global cognitive function, as measured in the AD group by global neuropsychological scores. Asymmetric cognitive decline is reflected in corresponding asymmetric rates of change of lateral ventricular size. Similar results are seen in subjects with Down’s syndrome (DS). Older DS subjects developing dementia have accelerated enlargement of lateral ventricular volume in serial CT scans compared to those DS subjects who dot not develop dementia. In nondemented DS subjects, age-re-lated brain atrophy is seen similar to that observed in aging, normal healthy subjects. These studies taken together show that dynamic anatomical changes in AD are an integral part of the disease process and not just end-stage events. Early in the disease, progressive atrophy can be documented and is associated with progressive decline in function. Demonstration of such early progression of atrophy may strengthen a diagnosis of AD and identify subclinical cases. It also has the potential to document changes in atrophy rate in response to therapeutic interventions.