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Oscar L. Lopez, MD; Stephen R. Wisniewski, PhD; James T. Becker, PhD; François Boller, MD, PhD; Steven T. DeKosky, MD

Arch Neurol. 1999;56:1266-1272.

Objective  To examine whether the use of psychiatric medication and the presence of abnormal behaviors affects the progression of Alzheimer disease.

Design  Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: (1) Mini-Mental State Examination score of 9 or lower; (2) Blessed Dementia Rating Scale score of 15 or higher for activities of daily living; (3) nursing home admission; and (4) death, evaluated using a proportional hazard model with 9 variables: psychosis, insomnia, wandering, aggression, psychomotor agitation, depression, and use of antidepressants, antipsychotic agents, or sedatives/hypnotics.

Setting  Multidisciplinary dementia research clinic.

Patients  We examined baseline and follow-up behavioral symptoms and the use of psychiatric medication in 179 mildly to moderately impaired patients with probable Alzheimer disease participating in a longitudinal study of dementia. Patients were observed from 2.4 to 172 months (mean duration±SD, 49.5±27.4 months).

Results  Nine patients (5%) were taking sedatives/hypnotics; 16 (9%), antipsychotic agents; and 22 (12%), antidepressants at study entry. Patients taking antipsychotic agents had lower Mini-Mental State Examination scores and higher Blessed Dementia Rating Scale scores for activities of daily living than patients not taking any medication. Using proportional hazard analysis with time-dependent covariates for individual psychiatric symptoms and medications, we found that the development of psychosis was associated with functional decline (time to Blessed Dementia Rating Scale score of 15), institutionalization, aggression, and agitation with functional decline after adjusting for age at study entry, education, Mini-Mental State Examination scores, and Blessed Dementia Rating Scale scores. Use of antipsychotic medication was associated with functional decline, and sedatives/hypnotics with death. Neither the presence of psychiatric symptoms nor use of medication was associated with rate of cognitive decline (time to Mini-Mental State Examination score of 9).

Conclusions  These findings indicate that the use of antipsychotic agents and sedatives can affect the natural course of Alzheimer disease. Psychosis, agitation, and aggression are important predictors of outcome, even when the effects of medication to treat them is taken into account.

From the Alzheimer's Disease Research Center (Drs Lopez, Becker, and DeKosky) and the Departments of Neurology (Drs Lopez, Becker, and DeKosky), Psychiatry (Drs Becker and DeKosky), and Epidemiology (Dr Wisniewski), University of Pittsburgh, Pittsburgh, Pa; and the Centre Paul Broca, Paris, France (Dr Boller).

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