This report summarizes the neuropathologic findings in the first 106 autopsies of CERAD (Consortium to Establish a Registry for Alzheimer's Disease) dementia patients diagnosed clinically as having Alzheimer's disease (AD). In 92 (87%) of the 106 cases, neuropathologists confirmed Alzheimer's disease (AD) as the primary dementing illness. Coexistent Parkinson's disease (PD) changes were present in 19 (21%) and vascular lesions of varying nature and size in 26 (28%) of these 92 AD cases. The 14 cases in which AD was not interpreted as the primary dementing illness can be divided into four major subgroups based on their neuropathology findings: PD and related pathology (n = 5), hippocampal sclerosis (n = 3), miscellaneous neurodegenerative and other disorders (n = 3), and no significant changes (n = 3). Despite the relatively high level of clinical diagnostic accuracy, further refinement of assessment batteries may facilitate distinction of non-AD dementias from AD.

The clinical-neuropathologic correlations in CERAD patients generally confirm those in prior studies, indicating that the presence of cerebral infarction in patients with AD is associated with greater overall severity of clinical dementia and poorer performance on specific tests of language and cognitive function.

In an attempt to define possible subgroups ofAlzheimer's disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimer's disease.

Compared with patients with AD alone, those with LBV had a greater frequency of extrapyramidal manifestations, somewhat better recall on a selected memory task at their final evaluation, and a significantly lower frequency of neocortical neurofibrillary tangles at autopsy. There were no differences between the two groups, however, in survival time from entry into the study.