Effect of Risperidone on Behavioral and Psychological Symptoms and Cognitive Function in Dementia

Rainer, Michael; Masching, Andreas; Ertl, Michael G.; Kraxberger, E.; Haushofer, Manfred

doi:10.4088/jcp.v62n1110

Cited by 41 publications

(22 citation statements)

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“…This differential impact is consistent with prior studies indicating that cognitive performance can be improved in rodents independently of aggression [57,58]. Similarly, while both cognitive impairment and aggression accompany AD, they are not necessarily temporally colocalized and may but do not necessarily respond to identical treatments [59][60][61][62]. These behavioral manifestations in mice are directly relevant since AD can be accompanied by psychosis and agitation [63], and ApoE4 can also potentiate psychotic symptoms in humans [64].…”

Section: Nutritional Deficiency Potentiates the Impact Of Deficiency supporting

confidence: 86%

Apolipoprotein E3 as a Risk Factor for Alzheimer's Disease Under Conditions of Nutritional Imbalance

Chan

Shea

2010

JAD

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Abstract. The presence of one or more copies of the E4 allele of apolipoprotein E (ApoE) is strongly associated with of Alzheimer's disease (AD). The impact of E4 on neurodegeneration is potentiated by dietary oxidative challenge. Our prior studies in transgenic mice demonstrate that, in the face of dietary oxidative challenge, E3 does not provide any further protection than E4 or lack of murine ApoE for aggression, oxidative damage, presenilin-1 expression, and γ-secretase activity, and provides only partial reduction in phospho-tau levels. Extrapolation of these findings to the human condition leads us to hypothesize that the E3 allele may not provide sufficient neuroprotection under conditions of dietary compromise and/or oxidative challenge. Epidemiological evidence is consistent with this possibility. The E3 allele is approximately half as effective compared to E2 at buffering the impact of a single E4 allele. In addition, the risk of AD increases linearly for the genotypes E2/2, E2/3, and E3/3. It has been proposed that that clinical manifestation of AD may in some cases require the convergence of 2 or more risk factors. We hypothesize that the combined impact of dietary oxidative stress and either the ApoE3 or E4 genotype represents one such condition.Keywords: Alzheimer's disease, apolipoprotein E, diet, nutritional deficiency, oxidative stresss APOE, OXIDATIVE DAMAGE, AND ALZHEIMER'S DISEASEA major risk factor for Alzheimer's disease (AD) is the presence of the E4 allele of apolipoprotein E (ApoE), which accounts for up to 50% of the cases of AD [1][2][3][4][5]. Considerable effort has been devoted to determining the nature and extent of risk imparted by ApoE4 and what might be done to lessen this risk [6]. Oxidative damage represents an early and perhaps pivotal factor contributing to age-related decline in cogni- * Correspondence to: Thomas B. Shea, Center for Cellular Neurobiology and Neurodegeneration Research, UMassLowell, Lowell, Massachusetts 01854, USA. Tel.: +1 978 934 2881; Fax: +1 978 934 3044; E-mail: Thomas Shea@uml.edu. tive performance including that associated with AD [7][8][9][10][11][12]. Oxidative damage and ApoE4 are inter-related, as the extent of brain oxidative damage in AD is correlated with the presence of E4 [13][14][15][16]. ApoE mediates transport and clearance of lipids, including those subjected to oxidative damage. In doing so, ApoE prevents a cascade of neuronal oxidative damage by quenching downstream products of lipid oxidation, preventing secondary glutamate excitotoxicity and sequestering oxidative metals such as iron [4,17,18,20]. However, ApoE4 is thought to be less effective at this latter function [21].While over 20 other genes are suspected of being related to AD [22], deficiency in ApoE function has a particularly far-reaching impact in that it not only impairs overall brain metabolism and may impair compensato-

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Section: Nutritional Deficiency Potentiates the Impact Of Deficiency supporting

confidence: 86%

Apolipoprotein E3 as a Risk Factor for Alzheimer's Disease Under Conditions of Nutritional Imbalance

Chan

Shea

2010

JAD

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“…In a recent study by Rainer et al (19), 34 patients with a DSM-IV diagnosis of dementia (Alzheimer type, vascular, mixed or with Lewy bodies) were treated with flexible doses of risperidone (0.5-2 mg/d) for 8 wk, and at the end of treatment improvements in symptoms (clinical global impression of change scale) were reported for 82% of patients and additionally cognitive function was maintained throughout the treatment period.…”

Section: Discussionmentioning

confidence: 99%

Human Kinetic Modeling of the 5HT6 PET Radioligand ¹¹C-GSK215083 and Its Utility for Determining Occupancy at Both 5HT6 and 5HT2A Receptors by SB742457 as a Potential Therapeutic Mechanism of Action in Alzheimer Disease

et al. 2015

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Antagonism of 5-hydroxytrypamine-6 (5HT6) receptors is associated with procognitive effects in preclinical species, suggesting a therapeutic potential for this mechanism in Alzheimer disease (AD) and other cognitive diseases. In a phase 2 dose study, SB742457, a novel 5HT6 antagonist, showed increasing procognitive effects in patients with AD as the dose increased, with a procognitive signal in AD patients at a dose of 35 mg/d superior to the other doses tested (5 and 15 mg/d). Methods: In this article, we describe the quantification and pharmacologic selectivity of a new 5HT6 PET ligand ( 11 C-GSK215083) in healthy volunteers and its use to measure occupancies achieved at various doses of SB742457. Results: Kinetic analysis of 11 C-GSK215083 uptake in the human brain demonstrated the multilinear model, MA2, to represent the method of choice when a blood input was available and the full tissue reference method when no input was available. Pharmacologic dissection of the in vivo 11 C-GSK215083-specific binding showed the ligand bound mostly the 5HT6 in the striatum (blocked by SB742457 but not by the selective 5-hydroxytryptamine-2A (5HT2A) antagonist ketanserin) and the 5HT2A in the frontal cortex (blocked by both ketanserin and SB742457). Repeated administration of SB742457 (3, 15, and 35 mg/d) saturated the 5HT6 receptors at all doses. In the cortex, 5HT2A receptor occupancy was 24% ± 6% (3 mg/d), 35% ± 4% (15 mg/d), and 58% ± 19% (35 mg/d; mean ± SD), suggesting a progressive engagement of 5HT2A as the dose increased. Conclusion: Collectively, these data support the use of 11 C-GSK215083 as a 5HT6 clinical imaging tool and suggest that blocking both the 5HT6 and the 5HT2A receptors may be required for the optimal therapeutic action of SB742457 in AD.

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“…Entretanto, é possível argumentar que a melhora dos déficits cognitivos e das AVD observada nos pacientes tratados com rivastigmina ocorreria até o terceiro mês de tratamento medicamentoso, havendo depois estabilização ou até uma discreta piora (Rosler et al, 1999). O uso da risperidona é indicado para alterações de comportamento em pacientes com DA e, quando há evidências na literatura que mostram que seu uso não beneficia a cognição dos pacientes, age somente sobre o comportamento (Weiser et al, 2002;Rainer et al, 2001;Laks et al, 2001).…”

Section: Discussionunclassified

Resultados da reabilitação neuropsicológica em paciente com doença de Alzheimer leve

Ávila¹

2003

Rev. psiquiatr. clín.

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RESUMOTradicionalmente sempre houve mais grupos de suporte e informação para familiares e cuidadores de pacientes com doença de Alzheimer (DA) do que para os próprios pacientes. Entretanto, com o aumento do número de diagnósticos de DA em sua fase inicial, esta realidade está se modificando. Cresce a demanda por tratamento tanto medicamentoso como comportamental para esses pacientes. O presente trabalho tem como objetivo descrever uma experiência de reabilitação neuropsicológica (RN) em grupo, e posteriormente individual, com a mesma paciente com DA leve. CGP participou primeiramente de dois grupos de RN com duração de quatro meses cada, e em seguida iniciou RN individual por um período de 22 meses. Na RN foram trabalhados principalmente déficits de memória, linguagem e treinos de atividades de vida diária. Neste período de tratamento, verificou-se alteração positiva de seu escore no MEEM, além de nenhuma função cognitiva ter apresentado deterioração. Este estudo de caso corroborou pesquisas anteriores que apontam efeitos positivos da RN com pacientes com DA leve. Traditionally, Alzheimer's support and information groups have been developed for families and caregivers rather than for the actual patient. However, this reality is changing because of the increase in early AD diagnosis. The demand for medication and behavioral treatment for patients is also increasing. The purpose of this case report is to describe the neuropsychological rehabilitation (NR) of a mild AD patient in group and in individual sessions. First, CGP took part in two NR groups each for a 4 month period, and then started individual NR sessions for a 22 month period. In the sessions, memory and language abilities were the focus of the NR as well as the activities of daily living. During this period it was possible to observe positive changes in MMSE score, as will as preservation of other cognitive function scores. This single case study is in agreement of previous studies which also showed documented positive effects of NR with AD patients.

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Effect of Risperidone on Behavioral and Psychological Symptoms and Cognitive Function in Dementia

Cited by 41 publications

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Apolipoprotein E3 as a Risk Factor for Alzheimer's Disease Under Conditions of Nutritional Imbalance

Apolipoprotein E3 as a Risk Factor for Alzheimer's Disease Under Conditions of Nutritional Imbalance

Human Kinetic Modeling of the 5HT6 PET Radioligand ¹¹C-GSK215083 and Its Utility for Determining Occupancy at Both 5HT6 and 5HT2A Receptors by SB742457 as a Potential Therapeutic Mechanism of Action in Alzheimer Disease

Resultados da reabilitação neuropsicológica em paciente com doença de Alzheimer leve

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Effect of Risperidone on Behavioral and Psychological Symptoms and Cognitive Function in Dementia

Cited by 41 publications

References 0 publications

Apolipoprotein E3 as a Risk Factor for Alzheimer's Disease Under Conditions of Nutritional Imbalance

Apolipoprotein E3 as a Risk Factor for Alzheimer's Disease Under Conditions of Nutritional Imbalance

Human Kinetic Modeling of the 5HT6 PET Radioligand 11C-GSK215083 and Its Utility for Determining Occupancy at Both 5HT6 and 5HT2A Receptors by SB742457 as a Potential Therapeutic Mechanism of Action in Alzheimer Disease

Resultados da reabilitação neuropsicológica em paciente com doença de Alzheimer leve

Contact Info

Product

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Human Kinetic Modeling of the 5HT6 PET Radioligand ¹¹C-GSK215083 and Its Utility for Determining Occupancy at Both 5HT6 and 5HT2A Receptors by SB742457 as a Potential Therapeutic Mechanism of Action in Alzheimer Disease