A thorough neuropathological analysis of several hundred cases from a prospective dementia study shows degenerative disorders such as dementia of Alzheimer type (DAT) and frontal lobe dementia (FLD) of non-Alzheimer type to be the prevailing disorders.

The pattern of basic changes relatable to neuronal atrophy in DAT correlates better to functional parameters and symptomatology than do senile plaques and neurofibrillary tangle density and distribution. The etiological or pathogenetic role of amyloid and of a cholinergic deficit also remains unclear. The dominating disease pattern may be blurred by confounding additional alterations with more pronounced frontal case pathology, as found in a limited number of cases. Another and much more common factor is structural white matter attenuation associated with cerebrovascular pathology as well as frank infarctions in a smaller but still important number of DAT cases. The concurrence of degenerative and other brain changes each at subthreshold levels may cause signs and symptoms of a dementia difficult to classify.

Frontal lobe dementia of non-Alzheimer type, the next most common dementing degenerative disorder, displays only the basic changes found in DAT but derives its separate clinical profile from the frontal predominance of lesions. It may be confounded with Pick's disease and others possibly belonging to the same group, but also with frontally projected dementias due to lesions ranging from thalamic infarcts to brain stem afflictions.

The topographic pattern of lesions rather than the structural details forms a useful basis for a clinical classification of the dementing disorders.