Relationship between clinical and radiological diagnostic criteria for Alzheimer's disease and the extent of neuropathology as reflected by 'stages':A prospective study

The distribution of pathology related to Alzheimer's disease (AD) is not un iform throughout the brain. Sites which have a predilection for the develop ment of Alzheimer-type pathology are the limbic regions and neocortical ass ociation areas. The changes in these areas of the brain develop gradually, following a well-determined sequence that allows a pathological staging of the disease process. According to the staging hypothesis, the first patholo gical alterations develop in the transentorhinal and entorhinal regions. Th e neurofibrillary pathology then spreads into the hippocampus, but not unti l the final stages does it affect the neocortex. In this study we analyse t he relationship between the pathological stages of AD, according to the sta ging hypothesis, and the clinical diagnosis in a prospectively assessed pat ient group. Prediction of any given pathological stage from the clinical di agnosis was found to be poor. This may be partly due to the fact that addit ional pathologies can alter the clinical picture and severity of dementia i n patients who are only in the initial stages of AD. Nevertheless, the NINC DS-ADRDA clinical criteria had a high sensitivity for detection of AD-relat ed pathology: the 'probable AD' category included 22/38 (57.9%) of those in the late isocortical stage, while the 'possible AD' category included 19/2 3 (82.6%) of those in the limbic stage. Using proposed neuro-imaging protoc ols for improved identification of patients with AD-related pathology, we l argely identified subjects in whom the extent of pathology had spread to th e neocortex.