Alzheimer disease subjects with psychosis have increased schizotypal symptoms before dementia onset

Recent findings have demonstrated the familiality of psychotic symptoms occurring during Alzheimer disease (AD with psychosis, AD+P), particularly for subjects with multiple psychotic symptoms. We have proposed a model in which genes that confer a small risk for psychosis interact with neurodegenerative illness to yield manifest psychotic symptoms during AD. One prediction of this model would be that AD+P subjects would have evidence of increased degrees of subsyndromal psychosis before AD onset.

We used the psychosis (positive symptoms) and psychotic personality disorder sections (paranoid, schizoid, and schizotypal) of the Family Interview for Genetic Studies (FIGS) to interview the primary caregivers of AD subjects. Caregivers were specifically instructed to answer questions with regard to the subject's behavior before AD onset. Interviewers were blind to presence of psychosis during AD. Subjects were grouped by whether they had at least one or had multiple psychotic symptoms during AD.

Scores on the FIGS subscales were generally low, reflecting a low frequency of endorsement of psychotic symptoms before AD. There was a trend for the schizotypal scores to be elevated in the AD+P group, which was highly significant in the AD+P group with multiple psychotic symptoms. There was no significant association of paranoid or schizoid scores with either group.

Although limited by small sample size and retrospective design, these data are novel in that they indicate an association of subsyndromal psychotic symptoms before AD onset with psychosis in AD. Subsyndromal psychosis might be useful for classifying AD+P families for genetic mapping studies. Prospective confirmation is required.