International Psychogeriatrics

Research Article

The relationship of excess cognitive impairment in MCI and early Alzheimer's disease to the subsequent emergence of psychosis

Elise A. Weamera1a2, James E. Emanuela1, Daniel Varona1, Sachiko Miyaharaa3, Patricia A. Wilkosza1, Oscar L. Lopeza1a2, Steven T. DeKoskya1 and Robert A. Sweeta1a2a4 c1

a1 Department of Psychiatry, University of Pittsburgh, Pittsburgh, U.S.A.

a2 Department of Neurology, University of Pittsburgh, Pittsburgh, U.S.A.

a3 Department of Epidemiology, University of Pittsburgh, Pittsburgh, U.S.A.

a4 VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA. U.S.A.


Background: Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype associated with greater cognitive impairment. Knowing when the cognitive course of AD + P subjects diverges from that of subjects without psychosis would enhance understanding of how genetic variation results in AD + P and its associated cognitive burden. This study seeks to determine whether the degree of cognitive impairment and cognitive decline in early AD predicts subsequent AD + P onset.

Methods: 361 subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis were evaluated every 6 months until psychosis onset.

Results: Severity of cognitive dysfunction was a strong predictor of AD + P up to two years prior to psychosis onset. Cognition did not decline more rapidly prior to onset of AD + P.

Conclusions: Individuals who will develop AD + P already demonstrate excess cognitive impairment during the mild stages of disease. Genetic variation and brain pathophysiology may lead to a cognitive risk phenotype which is present prior to dementia onset.

(Received February 04 2008)

(Revised April 09 2008)

(Revised May 20 2008)

(Accepted May 22 2008)

(Online publication September 25 2008)


c1 Correspondence should be addressed to: Robert A. Sweet, M.D., Associate Professor of Psychiatry and Neurology, Biomedical Science Tower, Rm W-1645, 3811 O'Hara Street, Pittsburgh, PA 15213–2593, U.S.A. Phone + 1 412 383 8548; Fax + 1 412 624 9910. Email: