Alzheimerʹs-type pathology in schizophrenia with dementia

There is controversy regarding the role of Alzheimerʹs disease (AD)-type neuropathologic features in the cognitive impairment present in many elderly individuals with schizophrenia. Aside from the presence of a sizable number of elderly schizophrenics with severe cognitive impairment and little or no AD-type pathology, the disagreement is fueled by disparate interpretations of the less extreme degrees of AD-like changes. We therefore sought to examine the relationship between AD-type neuropathology and dementia in a manner that does not rely on categorical diagnoses of AD. We examined the clinical records and brains from 170 deceased individuals, aged 45-105, of whom 68 met DSM-III-R criteria for schizophrenia. Ratings of “definite cognitive impairment” (DCI) were assigned to 47 of the schizophrenics, including 17 of the 18 aged ≥85, and to 51 of the 102 nonschizophrenics. Among all schizophrenics, 14 measures of neocortical and allocortical neurofibrillary tangles, neuritic plaques, and total plaques were all higher in the group with definite cognitive impairment, by factors ranging from 1.6 (maximum neocortical total plaques by thioflavine S stain) to 62 (average neocortical neuritic plaques by Alz 50 immunohistochemistry); 11 of these differences were statistically significant (p=0.001-0.035). Among schizophrenics aged 45-84 (N=50, 30 with DCI), the results were similar, while ages of groups with and without DCI did not differ. ANOVA on the entire sample, covarying for age, revealed significant main effects of DCI on 13 of the measures and schizophrenia on 6, without significant interactions. We conclude that AD-type neuropathologic changes are related to the cognitive impairment of elderly schizophrenics in a manner similar to that for individuals without schizophrenia.