Central serotonergic activity is related to the aggressive behaviors of Alzheimer's disease

The clinical correlates of reduced serotonin (5-HT) in Alzheimer's disease (AD) remain unknown. The hypothesis of this study was that altered central serotonergic activity is related to aggression in AD. Twenty-two institutionalized, nondepressed elderly (12 M/10 F, mean age +/- SD: 82.2 +/- 6.4) with probable AD, severe cognitive impairment (MMSE = 4.1 +/- 4.7) and significant behavioral disturbance (Neuropsychiatric Inventory (NPI) score > or = 8) were studied. The prolactin (PRL) response to d,l-fenfluramine (60 mg p.o.) was used as an index of central serotonergic function. The NPI aggression score, NPI irritability score, and Behavioral Pathology in AD aggression score were positively correlated to prolactin concentrations following fenfluramine challenge (r(S) =.61, p =.003; r(S) =.53, p =.012; and r(S) =.47, p =.029 respectively). In addition, aggressive patients showed a greater mean PRL increase (% baseline) (215 +/- 60, n = 11) than nonaggressive subjects (123 +/- 54, n = 11) (p =.01, 2-tailed t-test). The change in PRL concentration depended on level of cognitive impairment (p =.0004) and the gender x aggression interaction (p =.015) with the overall regression model accounting for 74% of the variance (r = 0.86, F = 11.9, p =.0001). Female aggressive subjects with less cognitive impairment had the largest response to fenfluramine challenge. These results suggest a complex link between aggression in AD and central serotonergic dysfunction having interactions with gender and cognitive impairment.