Behavioral Disturbances in Dementia and Beyond: Time for a New Conceptual Frame?

Ambrogio, Federico; Martella, Lucia; Odetti, Patrizio; Monacelli, Fiammetta

doi:10.3390/ijms20153647

Cited by 12 publications

(3 citation statements)

References 83 publications

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“…Therefore, the external validity of this finding is limited. In accordance with previous reports [26, 33], there was also consensus in our study regarding the need to have protocols for the use of atypical antipsychotics for BPSD in order to help physicians in clinical practice and in benefit of patients and their families, a finding that could indicate an insufficient knowledge or application of guidelines in practice [34-36].…”

Section: Discussionsupporting

confidence: 88%

Use of Antipsychotics in Patients with Behavioral and Psychological Symptoms of Dementia: Results of a Spanish Delphi Consensus

Manzano-Palomo

Agüera-Ortíz

García-Caballero

et al. 2020

Dement Geriatr Cogn Disord

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Background: Behavioral and psychological symptoms of dementia (BPSD) are difficult to manage and associated with poor outcome. Objectives: The aim of this study was to reach consensus on the use of antipsychotics in patients with BPSD in Spain. Methods: A qualitative, multicenter, two-round Delphi study was carried out, with the participation of specialists involved in the care of dementia patients throughout Spain. They completed a 76-item questionnaire related to the identification of BPSD, treatment with antipsychotics, follow-up of patients, barriers for the use of atypical antipsychotics, and effects of antipsychotics on quality of life. Results: A total of 162 specialists in neurology, psychiatry, and geriatrics (61% men) with a mean (SD) age of 45.9 (10) years participated in the study. Almost all participants (96.9%) strongly agreed that atypical antipsychotics are safer and better tolerated than typical antipsychotics. There was agreement on the importance to review the indication and dose of the antipsychotic drug at least every 3 months. There was consistent high rate of agreement on the beneficial impact of atypical antipsychotics on the quality of life of patients with dementia and their caregivers. A consensus was also reached on the need of detecting BPSD in patients with dementia as it decreases the quality of life of both patients and caregivers, and the need to routinely screen for dementia in elderly patients with no previous psychiatric history in the presence of suggestive symptoms of BPSD. Finally, the participants in the study agreed that administrative barriers for the prescription of atypical antipsychotics in Spain hinder the access to this drug group and favor the prescription of typical antipsychotics. Conclusions: The participants in the study agreed that atypical antipsychotics should be preferred to typical antipsychotics in the management of BPSD. Wide consensus was reached about the importance of early identification of BPSD in persons with cognitive impairment, the use and management of atypical antipsychotic drugs and their favorable impact on patients and caregiver’s quality of life.

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Section: Discussionsupporting

confidence: 88%

Use of Antipsychotics in Patients with Behavioral and Psychological Symptoms of Dementia: Results of a Spanish Delphi Consensus

Manzano-Palomo

Agüera-Ortíz

García-Caballero

et al. 2020

Dement Geriatr Cogn Disord

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“…Thus, the complete pharmacological profile and possible side effects (beyond cognitive) of donepezil remain poorly understood (Jelic and Darreh-Shori, 2010), necessitating further in-depth translational studies using both longterm and acute treatments. This problem is important since affective and other behavioral deficits are particularly common An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish in AD patients (Ambrogio et al, 2019;Khachaturian and Radebaugh, 2019), yet there are no established and approved pharmacotherapies to treat these deficits (Khachaturian and Radebaugh, 2019).…”

Section: Introductionmentioning

confidence: 99%

An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish

et al. 2020

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Background: A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish ( Danio rerio) is rapidly becoming a powerful novel model organism in neuroscience and central nervous system drug screening. Aim: Here, we characterize the effects of 24-h donepezil administration on anxiety-like behavioral and endocrine responses in adult zebrafish. Methods: We evaluated zebrafish anxiety-like behaviors in the novel tank, the light-dark and the shoaling tests, paralleled by assessing brain acetylcholinesterase activity and whole-body cortisol levels. Results: Overall, donepezil dose-dependently decreased zebrafish locomotor activity in the novel tank test and reduced time in light in the light-dark test, likely representing hypolocomotion and anxiety-like behaviors. Donepezil predictably decreased brain acetylcholinesterase activity, also increasing whole-body cortisol levels, thus further linking acetylcholinesterase inhibition to anxiety-like behavioral and endocrine responses. Conclusion: Collectively, these findings suggest negative modulation of zebrafish affective behavior by donepezil, support the key role of cholinergic mechanisms in behavioral regulation in zebrafish, and reinforce the growing utility of zebrafish models for studying complex behavioral processess and their neuroendocrine and neurochemical regulation.

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“…Alzheimer's disease (AD) is the most common form of age-related neurodegenerative disease. It is reported that approximately more than 42.3 million people worldwide suffer from progressive cognitive impairment caused by AD (Ambrogio et al, 2019 ), and data from epidemiological analyses suggest that the number of people with AD will be more than twice the current number in 2060 (Matthews et al, 2019 ). As the disease progresses, AD patients may experience varying degrees of cognitive and memory insult, such as language, visuospatial, motor, and executive function deficits (McKhann et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and immunological characterization of cuproptosis-related molecular clusters in Alzheimer's disease

Lai

Lin

et al. 2022

Front. Aging Neurosci.

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IntroductionAlzheimer's disease is the most common dementia with clinical and pathological heterogeneity. Cuproptosis is a recently reported form of cell death, which appears to result in the progression of various diseases. Therefore, our study aimed to explore cuproptosis-related molecular clusters in Alzheimer's disease and construct a prediction model.MethodsBased on the GSE33000 dataset, we analyzed the expression profiles of cuproptosis regulators and immune characteristics in Alzheimer's disease. Using 310 Alzheimer's disease samples, we explored the molecular clusters based on cuproptosis-related genes, along with the related immune cell infiltration. Cluster-specific differentially expressed genes were identified using the WGCNA algorithm. Subsequently, the optimal machine model was chosen by comparing the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting. Nomogram, calibration curve, decision curve analysis, and three external datasets were applied for validating the predictive efficiency.ResultsThe dysregulated cuproptosis-related genes and activated immune responses were determined between Alzheimer's disease and non-Alzheimer's disease controls. Two cuproptosis-related molecular clusters were defined in Alzheimer's disease. Analysis of immune infiltration suggested the significant heterogeneity of immunity between distinct clusters. Cluster2 was characterized by elevated immune scores and relatively higher levels of immune infiltration. Functional analysis showed that cluster-specific differentially expressed genes in Cluster2 were closely related to various immune responses. The Random forest machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.9829). A final 5-gene-based random forest model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.8529 and 0.8333). The nomogram, calibration curve, and decision curve analysis also demonstrated the accuracy to predict Alzheimer's disease subtypes. Further analysis revealed that these five model-related genes were significantly associated with the Aβ-42 levels and β-secretase activity.ConclusionOur study systematically illustrated the complicated relationship between cuproptosis and Alzheimer's disease, and developed a promising prediction model to evaluate the risk of cuproptosis subtypes and the pathological outcome of Alzheimer's disease patients.

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Behavioral Disturbances in Dementia and Beyond: Time for a New Conceptual Frame?

Cited by 12 publications

References 83 publications

Use of Antipsychotics in Patients with Behavioral and Psychological Symptoms of Dementia: Results of a Spanish Delphi Consensus

Use of Antipsychotics in Patients with Behavioral and Psychological Symptoms of Dementia: Results of a Spanish Delphi Consensus

An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish

Identification and immunological characterization of cuproptosis-related molecular clusters in Alzheimer's disease

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