NEUROPATHOLOGICAL CRITERIA FOR THE DIAGNOSIS OF ALZHEIMERS-DISEASE - ARE WE REALLY READY YET

The specific diagnosis of AD as a particular dementia from which a pat ient suffered assumes, debatably, a reasonably pure clinicopathologica l entity in which the same concatenation of lesions will not be encoun tered in others dying with a similar clinical disorder. Statistically complex computations such as multivariate analyses of morphometric dat a from our laboratory and similar attempts in Swedish and British seri es may not prove pragmatic for pathological confirmation. The Braaks' schema posits six stages in the evolution of AD. Unfortunately, applic ation of this model to 50 British autopsies cannot reliably identify t hose cases clinically diagnosed as demented. Furthermore, lack of univ ersal definition for each of the probable lesional subtypes augments t he difficulty devising a quantitative consensus. Disease stage refers to a progressive increase in anatomical (geographic) extent of involve ment, whereas, grade refers to a progressive increase in severity of a ffliction within any one site. There is only a tendency for stage and grade to prepress in parallel. Nor is it obligatory that either always does progress. More energies should be concentrated upon determining which histopathological abnormality is most injurious to neuronal inte grity. Dutch workers opine that in both normal aging and AD, claims of massive, neocortical nerve cell loss may have been based on inadequat e morphometry and/or a loss of markers. Requiring urgent resolution is whether cellular changes seen in brains of aging normals represent me rely the earliest phase of typical AD (and therefore a good model fur Alzheimer pathogenesis), or rather reflect a totally different aging s yndrome distinct from AD. We have proposed that abnormalities in the h ippocampal formation (with or without neocortical neuronal lesions) ma y underlie a decline of all higher cognitive functions in senile demen tia Alzheimer type. West and colleagues optical disector approach like wise shows that neurodegeneration associated within aging individuals' hippocampi is quantitatively and qualitatively distinct from the neur onal loss in AD. Clinical confreres' imprecision whether or when to te rm subtle cognitive loss ''incipient AD'' is understandably mirrored b y residual neuropathological struggles to dichotomize such brains as ' 'normative aging'' distinct from ''putative AD''. (C) 1997 Elsevier Sc ience Inc.