PLATELET PAROXETINE BINDING TO 5-HT UPTAKE SITES IN ELDERLY PATIENTS WITH ALZHEIMER's DISEASE WITH AGITATION AND AGGRESSION

Abstract

Introduction: Currently a large body of literature supports the relationship between aggression and serotoninergic dysfunction. Furthermore, patients with AD have well-established findings regarding pathology in the serotoninergic system at the Central Nervous System level (Andersson et al. 1991.) The authors' (Mintzer et al.1998) and others (Lanctot et al. 1997) challenge data supports the presence of serotoninergic dysfunction in agitated (Mintzer et al. 1998) and agitated/aggressive AD patients (Lanctot et al. 1997). It is, however, not known if this is a state phenomenon secondary to an AD-related process or a trait phenomenon that is manifested in predisposed AD patients. This study addresses this issue by assessing 5-HT uptake sites in aggressive and nonaggressive AD patients' platelets, an organ not known to be affected by the primary AD process. Objective: Explore possible differences, specifically in binding affinity (Kd) and maximum number of binding sites (Bmax), in 5-HT uptake sites in platelets between patients with AD, AD with behavioral disturbances, and age-matched normal control subjects using [3H]paroxetine platelet binding. Methods: The authors have already recruited, rated, and obtained samples from elderly AD patients without behavioral disturbances (n=6, CMAI: 1), and 8 elderly AD subjects with agitated aggressive behaviors (n=8, CMAI: 2.96). All subjects were objectively rated for cognitive function, depression, anxiety, and behavioral symptoms. Blood samples and paroxetine binding was performed accordingly to Andersson et al. (1991) procedures. Results: All the subjects were able to tolerate the procedure. Preliminary data in the AD/Agitated group (n=5) showed a Bmax of 6,000 fmol/mg and a Kd of 0.08934 nM. In the Nonagitated group (n=4) Bmax was 4,084.5 fmol/mg and Kd was 0.056745 nM. Final data are presented by group (AD with and without behavioral disturbances and controls), and correlations are examined with disease severity.