New Wine in Old Bottle: Late-life Psychosis

ArticleinThe Psychiatric clinics of North America 34(2):295-318, vii · June 2011with37 Reads
DOI: 10.1016/j.psc.2011.02.008 · Source: PubMed
Abstract
Psychosis is common in late-life and exacts enormous costs to society, affected individuals, and their caregivers. A multitude of etiologies for late-life psychosis exist, the two most prototypical being schizophrenia and psychosis of Alzheimer disease (AD). As such, this article focuses on the nonaffective, neuropsychiatric causes of chronic psychosis in the elderly, specifically schizophrenia, delusional disorder, and the psychosis of AD and other dementias.
    • "Nevertheless, not many studies have investigated the interaction between AD and SCZ. Most investigations of the two diseases have focused on the differential diagnosis of AD with delusion from late-onset SCZ or delusional disorder [2]. In addition, as originally termed dementia praecox by Kraepelin, some of the patients with SCZ show cognitive deterioration without the neuropathology of neurodegenerative disease [3, 4], which hampers AD diagnosis in patients with a history of SCZ. "
    [Show abstract] [Hide abstract] ABSTRACT: Although both schizophrenia (SCZ) and Alzheimer's disease (AD) are among the most common psychiatric diseases, the interaction of these two is not well-understood. We investigated three women with SCZ who developed AD in their 60s. The patients presented with cognitive dysfunction such as loss of recent memory, which was confirmed by both clinical observations and neuropsychological tests. Their magnetic resonance and functional imaging findings were consistent with AD. Their brain atrophy advanced significantly during a 6-year observation period. However, their global cognitive function did not deteriorate significantly during this period. Although the cognitive reserve model might account for this discrepancy, our results suggest some interactions between the neuropathology of SCZ and AD and warrant further research.
    Full-text · Article · Aug 2015
    • "Existing pharmacotherapy for late-life psychosis is far from ideal in light of its risky side effect profile, especially for the psychosis of dementia. Existing psychosocial therapies for psychosis of dementia are promising, but more evidence-based data on these therapies are needed to merit widespread implementation [10]. Our study acknowledges some limitations: first our data are generalizable only to an urban area of northern Italy whereas a multicentric design would have been more informative. "
    Full-text · Article · Jan 2015
    • "Par ailleurs, l'état associant hallucinations et délires, souvent appelé « état psychotique » (Gaebel et Zielasek, 2009), n'est pas pathognomonique de la schizophrénie et peut se rencontrer dans d'autres pathologies psychiatriques, comme les troubles bipolaires ou certaines dépressions mélancoliques (Tamminga et Davis, 2007). On trouve également des états psychotiques dans de nombreuses pathologies neurologiques, le plus souvent neurodégénératives (Iglewicz et al., 2011), ou bien après l'intoxication avec des drogues dites hallucinogènes ou psychotomimétiques (Paparelli et al., 2011). Il existe toutefois des subtilités cliniques entre ces différents états psychotiques (Caton et al., 2005), et les contours nosologiques du concept de psychose restent aujourd'hui encore assez nébuleux (Gaebel et Zielasek, 2009) Inférieur et la Région Parahippocampique (Jardri et al., 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: Until now, the sole effective treatments in schizophrenia act by blocking the dopaminergic receptors. The hypothesis according to which the so-called "positive" symptoms of schizophrenia (i.e. hallucinations and delusions) are the expression of a hyperdopaminergic transmission within the Ventral Striatum, has be for forty years the main neurobiological explication that has been proposed for these symptoms. However, this hypothesis is questioned as other pharmacological models have been considered about the occurrence of the positive symptoms, notably of the visual hallucinations. In addition, the key role of the Ventral Striatum has been called into question by recent neuroimaging data. Today, schizophrenia is seen as a dynamic process, which consists of both neurodevelopmental and neurodegenerative anomalies, in which oxidative stress might be involved. Therefore, the deregulation of the dopaminergic transmission and the subsequent symptoms may be considered as the final expression of a pathological mechanisms cascade whose beginning is much prior to the symptoms onset. An early pharmacological intervention that may reduce the impact of such mechanisms could have some direct or delayed consequences on the dopaminergic transmission and the related symptoms. We hypothesize that the early activation of Peroxisome-Proliferator Activated Receptors (PPARs), molecules that reduce the oxidative stress processes and may have a direct action on the dopamine transmission, have a potential pharmacological interest in schizophrenia. We want to show that the use of the PPARα agonist fenofibrate during the onset of schizophrenia, can reduce the dopaminergic dysfunction state and the positive symptoms intensity, and thus have a disease-modifier effect. Objectives : Our first goal is to study the effect of fenofibrate on behavioral dopamine-related anomalies that are triggered by a neonatal oxidative lesion. Meanwhile, anticipating a clinical study, we want to prove that the ventral Striatum and the dopamine are involved in the different types of positive symptoms.Methods: The effect of fenofibrate is studied on an experimental model of oxidative neurodevelopmental lesion which induces only at adult age a dopaminergic dysfunction with an alteration of the Prepulse Inhibition (PPI), a behavioral dopamine-related reflex. In addition, we have performed a functional Magnetic Resonance Imaging (fMRI) study that compares the functional connectivity of the Nucleus Accumbens, which belongs to the Ventral Striatum, in case of sole auditory hallucinations or of both visual and auditory hallucinations. Results: we observe that the early introduction of fenofibrate after a neonatal oxidative lesion allows to partially but significantly restore the PPI's integrity at adult age. Moreover, we show in our fMRI study on patients with schizophrenia that the dopaminergic transmission appears to be involved in the different hallucinatory modalities. Discussion: A disease modifier effect of fenofibrate is reported on neurodevelopmentally-induced dopaminergic dysfunctions. We will complete our results using other models which allow getting additional behavioural, histological and electrophysiological data. Meanwhile, we report that the Ventral Striatum is involved in different types of positive symptoms. Our work makes considering a future evaluation of the fenofibrate's effect on the positive symptoms and the Ventral Striatum functioning in patient at the onset of schizophrenia.
    Article · Oct 2012
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