. Serotoninergic impairment and aggressive behavior in Alzheimer's disease. Acta Neurobiol Exp (Wars). 2005;65(3):277-86. PubMed.


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  1. The Serotonergic Malady in Alzheimer Disease: Implications for Patients and Caregivers
    Alzheimer disease (AD) is the leading cause of dementia in the aged population. Clinically characterized by a progressive loss of memory, language, and visual-spatial skills, this insidious disease progressively removes cognitive and functional abilities. Daily activities of living eventually become impossible such that patients require total care. Many patients also become agitated, disoriented, or even aggressive during the course of the disease as they lose their contextual self-identity and operate solely in the “perpetual present.”

    Despite the current knowledge regarding some of the etiologic events that lead to the pathology of the disease, namely neuronal loss, neurofibrillary tangles, amyloid-β, and senile plaques, the process remains elusive. In addition, disruption of basal forebrain cholinergic pathways and consequent cortical cholinergic denervation is another key feature not yet fully characterized. In this regard, in a recent issue of Acta Neurobiologiae Experimentalis, Zarro and colleagues (2005) discuss the effects of neurodegeneration on neurotransmitter systems such as the serotonergic system and highlight weak points in our understanding regarding this area of neurodegenerative diseases.

    Neurotransmitter systems, in particular serotonin, are crucial in the modulation of aggression, a behavior that not only results in decline of the individual’s quality of life, but also places an enormous emotional and physical burden on the caregiver. Through a systematic review of the literature, Zarro and colleagues (2005) not only illustrate the importance of serotonin in the modulation of aggression, but also bring to light the lack of unanimity in the study of this process. In their review, the authors argue eloquently that a carefully planned and systematic study of literature regarding the involvement of serotonergic impairment and aggressive behavior in AD merits full attention so that steps may be taken to improve the quality of patients’ lives and the lives of their caregivers.

    Traditional treatments for behavioral and psychological symptoms include antipsychotic medications, benzodiazepines or anticonvulsant medications, but these typically have a host of potentially hazardous side effects, especially in the elderly. Intervention directed toward serotonergic modulation could prove effective, but aggressive behavior may be amenable to treatment on several levels. Case studies have reported that anti-androgens such as medroxyprogesterone and leuprolide may placate symptoms in demented men (Amadeo, 1996). Our work suggests that anti-androgens such as leuprolide, in addition to attenuating psychomotor symptoms (Amadeo, 1996), may also actually effectively treat AD (Casadesus et al., 2004).

    Ultimately, a thorough understanding of the neurochemical dysregulation in AD will most likely include an altered balance between several transmission pathways such as serotonergic and noradrenergic pathways. Therapeutically targeting these pathways, either directly or indirectly, may prove useful. Zarro and colleagues (2005) have drawn much-needed attention to an important area of AD research. The behavioral and psychological sequelae of AD place a substantial burden on patients and caregivers that could potentially be lifted by consistent and vigorous inquiry into the neurochemical pathways implicated in the disease.


    . Antiandrogen treatment of aggressivity in men suffering from dementia. J Geriatr Psychiatry Neurol. 1996 Jul;9(3):142-5. PubMed.

    . Beyond estrogen: targeting gonadotropin hormones in the treatment of Alzheimer's disease. Curr Drug Targets CNS Neurol Disord. 2004 Aug;3(4):281-5. PubMed.

    . Serotoninergic impairment and aggressive behavior in Alzheimer's disease. Acta Neurobiol Exp (Wars). 2005;65(3):277-86. PubMed.

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