Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study

Abstract

Objective: To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or mild cognitive impairment (MCI).

Design: : The authors examined cognitive function in a new analysis of an existing data set, the Cardiovascular Health Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data.

Setting: Community.

Participants: The authors examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 participants for the modified Mini-Mental State Examination (3MS) analysis and 350 participants for the digit symbol substitution test (DSST) analysis had sufficient follow-up data and apolipoprotein-∊ (APOE) genotyping.

Measurements: The 3MS and DSST were administered annually and analyzed using mixed-effects models including APOE4 status.

Results: : Mean 3MS and DSST scores did not differ between AD with psychosis (AD + P) and without psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis.

Conclusions: Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD + P may exert their effects by acceleration of the neurodegenerative process.

Figure 1. Flow Chart of Inclusion/Exclusion Criteria and Number of Subjects Included in Analyses

CHS, Cardiovascular Health Study; AD, Alzheimer Disease; MCI, Mild Cognitive Impairment; NPI, Neuropsychiatric Inventory; 3MS, Modified Mini-Mental Status Examination; APOE, Apolipoprotein-ε; DSST, Digit Symbol Substitution Test.

Figure 2. Means of Cognitive Test Scores by Presence of Psychosis

Panel A: Observed means with quadratic fit lines of Modified Mini-Mental State Examination (3MS) test scores. Quadratic fit lines were generated from mixed-effect model using linear and quadratic terms including age at baseline, race, gender, education, APOE4 grouping and psychotic grouping as fixed effects and intercept and time as random effects (N=362). Panel B: Observed means with linear fit lines of Digit Symbol Substitution Test (DSST) test scores. Linear fit lines were generated from mixed-effect model using linear terms including age at baseline, race, gender, education, APOE4 grouping and psychotic grouping as fixed effects and intercept and time as random effects (N=350).