Crosstalk between Depression, Anxiety, and Dementia: Comorbidity in Behavioral Neurology and Neuropsychiatry

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (15 December 2020) | Viewed by 100062

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Guest Editor
Neuroscience Research Group, Hungarian Academy of Sciences, University of Szeged (MTA-SZTE), 6720 Szeged, Hungary
Interests: neurohormones; neuropeptides; tryptophan; kynurenine; psychiatry; neurology; depression; anxiety; dementia; cognition; antidepressant; translational research
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Special Issue Information

Dear Colleagues,

The symptoms of depression, anxiety, and dementia are a spectrum of the most common and frequently comorbid manifestations present in patients suffering from neurodegenerative and psychiatric diseases. These illnesses constitute one of the most complex and challenging research fields due to multifactorial causative factors, heterogeneous pathogenesis, and mental and behavioral manifestations. The diseases that present these symptoms range from Alzheimer’s disease, Parkinson’s disease, immunological multiple sclerosis, genetic Huntington’s disease and amyotrophic lateral sclerosis, infectious prion disease, sequelae to stroke and HIV infection, to psychiatric diseases, including depressive disorder, bipolar disorder, anxiety disorder, and autism spectrum disorder.

This Special Issue highlights the most recent research on depression, anxiety, and dementia with attention to the comorbidity in a range of diseases. We cordially invite authors to contribute original research articles focusing on, but not limited to the following:

  • Etiology, pathogenesis, and progression mechanism;
  • Early diagnosis including biomarker, bio-imaging, biosensors;
  • Therapeutic strategies, novel targets;
  • Novel drug discovery and development, naturally driven biomedicines, natural bioactive molecules, vaccines;
  • Antidepressants, anti-anxiolytics, cognitive enhancers;
  • Nanobiotechnology, nanosimilars, nanobiosimilars;
  • Preclinical in vitro models, animal models;
  • Bench-to-bedside translation research;
  • Bedside-to-bench translational research.

Review articles including expert opinions, systematic analysis, metanalysis, and other statistical and analytical methods are also welcome.

Dr. Masaru Tanaka
Guest Editor

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Keywords

  • depression
  • anxiety
  • dementia
  • Alzheimer’s disease
  • Parkinson’s disease
  • multiple sclerosis
  • Huntington’s disease
  • amyotrophic lateral sclerosis
  • prion disease
  • HIV dementia
  • stroke
  • antidepressants
  • anxiolytics
  • nootropic agents
  • neuroprotective

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Published Papers (12 papers)

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Editorial

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3 pages, 198 KiB  
Editorial
Editorial of Special Issue “Crosstalk between Depression, Anxiety, and Dementia: Comorbidity in Behavioral Neurology and Neuropsychiatry”
by Masaru Tanaka and László Vécsei
Biomedicines 2021, 9(5), 517; https://doi.org/10.3390/biomedicines9050517 - 6 May 2021
Cited by 66 | Viewed by 5596
Abstract
“Where there is light, there must be shadow, [...] Full article

Research

Jump to: Editorial, Review

22 pages, 4208 KiB  
Article
Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats
by Katalin Eszter Ibos, Éva Bodnár, Zsolt Bagosi, Zsolt Bozsó, Gábor Tóth, Gyula Szabó and Krisztina Csabafi
Biomedicines 2021, 9(2), 112; https://doi.org/10.3390/biomedicines9020112 - 25 Jan 2021
Cited by 17 | Viewed by 3995
Abstract
Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and [...] Read more.
Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Serum LH and corticosterone levels were determined to assess kisspeptin1 receptor (Kiss1r) activation and hypothalamic-pituitary-adrenal axis (HPA) stimulation, respectively. GABA release from the nucleus accumbens (NAc) and dopamine release from the ventral tegmental area (VTA) and NAc were measured via ex vivo superfusion. Kp-8 decreased open arm time and entries in EPM, and also raised corticosterone concentration, pointing to an anxiogenic effect. Moreover, the decrease in arm entries in EPM, the delayed increase in immobility accompanied by reduced ambulatory activity in OF, and the reduction in interactions with marbles show that Kp-8 suppressed exploratory and spontaneous locomotion. The increase in GABA release from the NAc might be in the background of hypolocomotion by inhibiting the VTA-NAc dopaminergic circuitry. As Kp-8 raised LH concentration, it could activate Kiss1r and stimulate the reproductive axis. As Kiss1r is associated with hyperlocomotion, it is more likely that neuropeptide FF receptor activation is involved in the suppression of locomotor activity. Full article
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29 pages, 5286 KiB  
Article
Sex-Dependent End-of-Life Mental and Vascular Scenarios for Compensatory Mechanisms in Mice with Normal and AD-Neurodegenerative Aging
by Aida Muntsant, Francesc Jiménez-Altayó, Lidia Puertas-Umbert, Elena Jiménez-Xarrie, Elisabet Vila and Lydia Giménez-Llort
Biomedicines 2021, 9(2), 111; https://doi.org/10.3390/biomedicines9020111 - 24 Jan 2021
Cited by 19 | Viewed by 5239
Abstract
Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative disorders strongly contributing to the total disability-adjusted life years. Interestingly, the morbidity/mortality paradox points to females having a worse healthy life expectancy. Since bidirectional interactions between cardiovascular and Alzheimer’s diseases (AD) have [...] Read more.
Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative disorders strongly contributing to the total disability-adjusted life years. Interestingly, the morbidity/mortality paradox points to females having a worse healthy life expectancy. Since bidirectional interactions between cardiovascular and Alzheimer’s diseases (AD) have been reported, the study of this emerging field is promising. In the present work, we further explored the cardiovascular–brain interactions in mice survivors of two cohorts of non-transgenic and 3xTg-AD mice, including both sexes, to investigate the frailty/survival through their life span. Survival, monitored from birth, showed exceptionally worse mortality rates in females than males, independently of the genotype. This mortality selection provided a “survivors” cohort that could unveil brain–cardiovascular interaction mechanisms relevant for normal and neurodegenerative aging processes restricted to long-lived animals. The results show sex-dependent distinct physical (worse in 3xTg-AD males), neuropsychiatric-like and cognitive phenotypes (worse in 3xTg-AD females), and hypothalamic–pituitary–adrenal (HPA) axis activation (higher in females), with higher cerebral blood flow and improved cardiovascular phenotype in 3xTg-AD female mice survivors. The present study provides an experimental scenario to study the suggested potential compensatory hemodynamic mechanisms in end-of-life dementia, which is sex-dependent and can be a target for pharmacological and non-pharmacological interventions. Full article
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16 pages, 1517 KiB  
Article
Early Depression Independently of Other Neuropsychiatric Conditions, Influences Disability and Mortality after Stroke (Research Study—Part of PROPOLIS Study)
by Katarzyna Kowalska, Łukasz Krzywoszański, Jakub Droś, Paulina Pasińska, Aleksander Wilk and Aleksandra Klimkowicz-Mrowiec
Biomedicines 2020, 8(11), 509; https://doi.org/10.3390/biomedicines8110509 - 17 Nov 2020
Cited by 16 | Viewed by 3757
Abstract
Post-stroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. The nature of the relationship between PSD and mortality still remains unknown. One hypothesis is that PSD could be more frequent in those patients who are more vulnerable to physical disability, a [...] Read more.
Post-stroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. The nature of the relationship between PSD and mortality still remains unknown. One hypothesis is that PSD could be more frequent in those patients who are more vulnerable to physical disability, a mediator variable for higher level of physical damage related to higher risk of mortality. Therefore, the authors’ objective was to explore the assumption that PSD increases disability after stroke, and secondly, that mortality is higher among patients with PSD regardless of stroke severity and other neuropsychiatric conditions. We included 524 consecutive patients with acute stroke or transient ischemic attack, who were screened for depression between 7–10 days after stroke onset. Physical impairment and death were the outcomes measures at evaluation check points three and 12 months post-stroke. PSD independently increased the level of disability three (OR = 1.94, 95% CI 1.31–2.87, p = 0.001), and 12 months post-stroke (OR = 1.61, 95% CI 1.14–2.48, p = 0.009). PSD was also an independent risk factor for death three (OR = 5.68, 95% CI 1.58–20.37, p = 0.008) and 12 months after stroke (OR = 4.53, 95% CI 2.06–9.94, p = 0.001). Our study shows the negative impact of early PSD on the level of disability and survival rates during first year after stroke and supports the assumption that depression may act as an independent mediator for disability leading to death in patients who are more vulnerable for brain injury. Full article
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15 pages, 537 KiB  
Article
Depression as a Risk Factor for Dementia and Alzheimer’s Disease
by Vanesa Cantón-Habas, Manuel Rich-Ruiz, Manuel Romero-Saldaña and Maria del Pilar Carrera-González
Biomedicines 2020, 8(11), 457; https://doi.org/10.3390/biomedicines8110457 - 28 Oct 2020
Cited by 46 | Viewed by 6900
Abstract
Preventing the onset of dementia and Alzheimer’s disease (AD), improving the diagnosis, and slowing the progression of these diseases remain a challenge. The aim of this study was to elucidate the association between depression and dementia/AD and to identify possible relationships between these [...] Read more.
Preventing the onset of dementia and Alzheimer’s disease (AD), improving the diagnosis, and slowing the progression of these diseases remain a challenge. The aim of this study was to elucidate the association between depression and dementia/AD and to identify possible relationships between these diseases and different sociodemographic and clinical features. In this regard, a case-control study was conducted in Spain in 2018–2019. The definition of a case was: A person ≥ 65 years old with dementia and/or AD and a score of 5–7 on the Global Deterioration Scale (GDS). The sample consisted of 125 controls; among the cases, 96 had dementia and 74 had AD. The predictor variables were depression, dyslipidemia, type 2 diabetes mellitus, and hypertension. The results showed that depression, diabetes mellitus, and older age were associated with an increased likelihood of developing AD, with an Odds Ratio (OR) of 12.9 (95% confidence interval (CI): 4.3–39.9), 2.8 (95% CI: 1.1–7.1) and 1.15 (95% CI: 1.1–1.2), respectively. Those subjects with treated dyslipidemia were less likely to develop AD (OR 0.47, 95% CI: 0.22–1.1). Therefore, depression and diabetes mellitus increase the risk of dementia, whereas treated dyslipidemia has been shown to reduce this risk. Full article
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21 pages, 2019 KiB  
Article
An Exploratory Pilot Study with Plasma Protein Signatures Associated with Response of Patients with Depression to Antidepressant Treatment for 10 Weeks
by Eun Young Kim, Hee-Sung Ahn, Min Young Lee, Jiyoung Yu, Jeonghun Yeom, Hwangkyo Jeong, Hophil Min, Hyun Jeong Lee, Kyunggon Kim and Yong Min Ahn
Biomedicines 2020, 8(11), 455; https://doi.org/10.3390/biomedicines8110455 - 28 Oct 2020
Cited by 10 | Viewed by 3880
Abstract
Major depressive disorder (MDD) is a leading cause of global disability with a chronic and recurrent course. Recognition of biological markers that could predict and monitor response to drug treatment could personalize clinical decision-making, minimize unnecessary drug exposure, and achieve better outcomes. Four [...] Read more.
Major depressive disorder (MDD) is a leading cause of global disability with a chronic and recurrent course. Recognition of biological markers that could predict and monitor response to drug treatment could personalize clinical decision-making, minimize unnecessary drug exposure, and achieve better outcomes. Four longitudinal plasma samples were collected from each of ten patients with MDD treated with antidepressants for 10 weeks. Plasma proteins were analyzed qualitatively and quantitatively with a nanoflow LC−MS/MS technique. Of 1153 proteins identified in the 40 longitudinal plasma samples, 37 proteins were significantly associated with response/time and clustered into six according to time and response by the linear mixed model. Among them, three early-drug response markers (PHOX2B, SH3BGRL3, and YWHAE) detectable within one week were verified by liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS) in the well-controlled 24 patients. In addition, 11 proteins correlated significantly with two or more psychiatric measurement indices. This pilot study might be useful in finding protein marker candidates that can monitor response to antidepressant treatment during follow-up visits within 10 weeks after the baseline visit. Full article
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13 pages, 882 KiB  
Article
The Role of GPR120 Receptor in Essential Fatty Acids Metabolism in Schizophrenia
by Joanna Rog, Anna Błażewicz, Dariusz Juchnowicz, Agnieszka Ludwiczuk, Ewa Stelmach, Małgorzata Kozioł, Michal Karakula, Przemysław Niziński and Hanna Karakula-Juchnowicz
Biomedicines 2020, 8(8), 243; https://doi.org/10.3390/biomedicines8080243 - 24 Jul 2020
Cited by 16 | Viewed by 4571
Abstract
A growing body of evidence confirms abnormal fatty acid (FAs) metabolism in the pathophysiology of schizophrenia. Omega-3 polyunsaturated fatty acids (PUFAs) are endogenous ligands of the G protein-coupled receptors, which have anti-inflammatory properties and are a therapeutic target in many diseases. No clinical [...] Read more.
A growing body of evidence confirms abnormal fatty acid (FAs) metabolism in the pathophysiology of schizophrenia. Omega-3 polyunsaturated fatty acids (PUFAs) are endogenous ligands of the G protein-coupled receptors, which have anti-inflammatory properties and are a therapeutic target in many diseases. No clinical studies are concerned with the role of the GPR120 signaling pathway in schizophrenia. The aim of the study was to determine the differences in PUFA nutritional status and metabolism between patients with schizophrenia (SZ group) and healthy individuals (HC group). The study included 80 participants (40 in the SZ group, 40 in the HC group). There were no differences in serum GPR120 and PUFA concentrations and PUFA intake between the examined groups. In the HC group, there was a relationship between FAs in serum and GPR120 concentration (p < 0.05): α-linolenic acid (ALA) (R = −0.46), docosahexaenoic acid (DHA) (R = −0.54), omega-3 PUFAs (R = −0.41), arachidonic acid (AA) (R = −0.44). In the SZ group, FA serum concentration was not related to GPR120 (p > 0.05). In the HC group, ALA and DHA serum concentrations were independently associated with GPR120 (p < 0.05) in the model adjusted for eicosapentaenoic acid (EPA) and accounted for 38.59% of GPR120 variability (p < 0.05). Our results indicate different metabolisms of FAs in schizophrenia. It is possible that the diminished anti-inflammatory response could be a component connecting GPR120 insensitivity with schizophrenia. Full article
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Review

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20 pages, 756 KiB  
Review
Crosstalk between Depression and Dementia with Resting-State fMRI Studies and Its Relationship with Cognitive Functioning
by Junhyung Kim and Yong-Ku Kim
Biomedicines 2021, 9(1), 82; https://doi.org/10.3390/biomedicines9010082 - 16 Jan 2021
Cited by 22 | Viewed by 5417
Abstract
Alzheimer’s disease (AD) is the most common type of dementia, and depression is a risk factor for developing AD. Epidemiological studies provide a clinical correlation between late-life depression (LLD) and AD. Depression patients generally remit with no residual symptoms, but LLD patients demonstrate [...] Read more.
Alzheimer’s disease (AD) is the most common type of dementia, and depression is a risk factor for developing AD. Epidemiological studies provide a clinical correlation between late-life depression (LLD) and AD. Depression patients generally remit with no residual symptoms, but LLD patients demonstrate residual cognitive impairment. Due to the lack of effective treatments, understanding how risk factors affect the course of AD is essential to manage AD. Advances in neuroimaging, including resting-state functional MRI (fMRI), have been used to address neural systems that contribute to clinical symptoms and functional changes across various psychiatric disorders. Resting-state fMRI studies have contributed to understanding each of the two diseases, but the link between LLD and AD has not been fully elucidated. This review focuses on three crucial and well-established networks in AD and LLD and discusses the impacts on cognitive decline, clinical symptoms, and prognosis. Three networks are the (1) default mode network, (2) executive control network, and (3) salience network. The multiple properties emphasized here, relevant for the hypothesis of the linkage between LLD and AD, will be further developed by ongoing future studies. Full article
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35 pages, 3142 KiB  
Review
Monitoring the Redox Status in Multiple Sclerosis
by Masaru Tanaka and László Vécsei
Biomedicines 2020, 8(10), 406; https://doi.org/10.3390/biomedicines8100406 - 12 Oct 2020
Cited by 63 | Viewed by 8401
Abstract
Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem [...] Read more.
Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients provide evidence on the disturbance of reduction-oxidation (redox) homeostasis, such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discusses the components of redox homeostasis, including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species cover frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive, as well as pro-oxidative stressors. The antioxidative enzyme systems cover the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring the battery of reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products helps to evaluate the redox status of MS patients to expedite the building of personalized treatment plans for the sake of a better quality of life. Full article
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15 pages, 1229 KiB  
Review
Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases—A Systematic Review and Meta-Analysis of Clinical Trials
by Ana Sofia Vargas, Ângelo Luís, Mário Barroso, Eugenia Gallardo and Luísa Pereira
Biomedicines 2020, 8(9), 331; https://doi.org/10.3390/biomedicines8090331 - 5 Sep 2020
Cited by 56 | Viewed by 28320
Abstract
Psilocybin is a naturally occurring tryptamine known for its psychedelic properties. Recent research indicates that psilocybin may constitute a valid approach to treat depression and anxiety associated to life-threatening diseases. The aim of this work was to perform a systematic review with meta-analysis [...] Read more.
Psilocybin is a naturally occurring tryptamine known for its psychedelic properties. Recent research indicates that psilocybin may constitute a valid approach to treat depression and anxiety associated to life-threatening diseases. The aim of this work was to perform a systematic review with meta-analysis of clinical trials to assess the therapeutic effects and safety of psilocybin on those medical conditions. The Beck Depression Inventory (BDI) was used to measure the effects in depression and the State-Trait Anxiety Inventory (STAI) was used to measure the effects in anxiety. For BDI, 11 effect sizes were considered (92 patients) and the intervention group was significantly favored (WMD = −4.589; 95% CI = −4.207 to −0.971; p-value = 0.002). For STAI-Trait, 11 effect sizes were considered (92 patients), being the intervention group significantly favored when compared to the control group (WMD = −5.906; 95% CI = −7.852 to −3.960; p-value ˂ 0.001). For STAI-State, 9 effect sizes were considered (41 patients) and the intervention group was significantly favored (WMD = −6.032; 95% CI = −8.900 to −3.164; p-value ˂ 0.001). The obtained results are promising and emphasize the importance of psilocybin translational research in the management of symptoms of depression and anxiety, since the compound may be effective in reducing symptoms of depression and anxiety in conditions that are either resistant to conventional pharmacotherapy or for which pharmacologic treatment is not yet approved. Moreover, it may be also relevant for first-line treatment, given its safety. Full article
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40 pages, 2798 KiB  
Review
The Biomedical Uses of Inositols: A Nutraceutical Approach to Metabolic Dysfunction in Aging and Neurodegenerative Diseases
by Antonio J. López-Gambero, Carlos Sanjuan, Pedro Jesús Serrano-Castro, Juan Suárez and Fernando Rodríguez de Fonseca
Biomedicines 2020, 8(9), 295; https://doi.org/10.3390/biomedicines8090295 - 20 Aug 2020
Cited by 51 | Viewed by 9638
Abstract
Inositols are sugar-like compounds that are widely distributed in nature and are a part of membrane molecules, participating as second messengers in several cell-signaling processes. Isolation and characterization of inositol phosphoglycans containing myo- or d-chiro-inositol have been milestones for understanding the physiological [...] Read more.
Inositols are sugar-like compounds that are widely distributed in nature and are a part of membrane molecules, participating as second messengers in several cell-signaling processes. Isolation and characterization of inositol phosphoglycans containing myo- or d-chiro-inositol have been milestones for understanding the physiological regulation of insulin signaling. Other functions of inositols have been derived from the existence of multiple stereoisomers, which may confer antioxidant properties. In the brain, fluctuation of inositols in extracellular and intracellular compartments regulates neuronal and glial activity. Myo-inositol imbalance is observed in psychiatric diseases and its use shows efficacy for treatment of depression, anxiety, and compulsive disorders. Epi- and scyllo-inositol isomers are capable of stabilizing non-toxic forms of β-amyloid proteins, which are characteristic of Alzheimer’s disease and cognitive dementia in Down’s syndrome, both associated with brain insulin resistance. However, uncertainties of the intrinsic mechanisms of inositols regarding their biology are still unsolved. This work presents a critical review of inositol actions on insulin signaling, oxidative stress, and endothelial dysfunction, and its potential for either preventing or delaying cognitive impairment in aging and neurodegenerative diseases. The biomedical uses of inositols may represent a paradigm in the industrial approach perspective, which has generated growing interest for two decades, accompanied by clinical trials for Alzheimer’s disease. Full article
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16 pages, 1445 KiB  
Review
Animal-Assisted and Pet-Robot Interventions for Ameliorating Behavioral and Psychological Symptoms of Dementia: A Systematic Review and Meta-Analysis
by Sangki Park, Ahream Bak, Sujin Kim, Yunkwon Nam, Hyeon soo Kim, Doo-Han Yoo and Minho Moon
Biomedicines 2020, 8(6), 150; https://doi.org/10.3390/biomedicines8060150 - 2 Jun 2020
Cited by 28 | Viewed by 9971
Abstract
Patients with dementia suffer from psychological symptoms such as depression, agitation, and aggression. One purpose of dementia intervention is to manage patients’ inappropriate behaviors and psychological symptoms while taking into consideration their quality of life (QOL). Animal-assisted intervention (AAI) and pet-robot intervention (PRI) [...] Read more.
Patients with dementia suffer from psychological symptoms such as depression, agitation, and aggression. One purpose of dementia intervention is to manage patients’ inappropriate behaviors and psychological symptoms while taking into consideration their quality of life (QOL). Animal-assisted intervention (AAI) and pet-robot intervention (PRI) are effective intervention strategies for older people with cognitive impairment and dementia. In addition, AAI and PRI have been shown to have positive effects on behavioral and psychological symptoms of dementia (BPSD). However, studies into the association between AAI/PRI and BPSD have elicited inconsistent results. Thus, we performed a meta-analysis to investigate this association. We analyzed nine randomized controlled trials on AAI and PRI for dementia patients published between January 2000 and August 2019 and evaluated the impact of AAI/PRI on agitation, depression, and QOL. We found that AAI and PRI significantly reduce depression in patients with dementia. Subsequent studies should investigate the impact of AAI and PRI on the physical ability and cognitive function of dementia patients and conduct a follow-up to investigate their effects on the rate of progression and reduction of symptoms of dementia. Our research will help with neuropsychological and environmental intervention to delay or improve the development and progression of BPSD. Full article
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