Herbs’ Disease-matched Pharmacological Mechanisms of HuanglianJiedu Decoction in Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease

Along with cognitive deficit, behavioral and psychological symptoms in dementia (BPSD) is another characteration of Alzheimer's disease that hamper clinical management and exacerbate burden for caregivers. However, therapeutic management of BPSD remains challenging. HuanglianJiedu decoction (HLJDD), a traditional Chinese prescription which contains Coptidis rhizome(Huang lian), Scutellariae radix (Huang-qin), Phellodendri chinrnsis cortex (Huang-bai) and Gardeniae fructus (Zhi-zi), is applied to treat BPSD. So elucidating the herbs’ disease-matched pharmacological mechanisms underlying HLJDD, further put forward each herbs’ disease-matched combination are critical to the application of HLJDD. In this study, network pharmacology was used to determine the targets and biological processes regulated by HLJDD in the treatment of BPSD. Moreover, molecular docking was utilized to evaluate the binding activity between the herbs' main active ingredients and neurotransmitter receptors. The results showed that the KEGG signaling pathway of HLJDD in treating BPSD mainly lies in TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Scutellariae radix and Phellodendri chinrnsis cortex exhibited better anti-BPSD effects when compared to Coptidis rhizoma and Gardeniae fructus. Scutellariae radix exhibited superior anti-neuroinflammation functions, with better blood vessel regulation effects. Phellodendri chinrnsis cortex showed a higher binding affinity to the dopamine D2 receptor (DRD2) and 5-hydroxytryptamine receptor 2A (HTR2A). Coptidis rhizoma and Gardeniae fructus were better in neuronal signaling. In conclusion, for treating BPSD, Scutellariae radix and Phellodendri chinrnsis cortex are the principal herbs while Coptidis rhizoma and Gardeniae fructus are the ancillary herbs. Beta-sitosterol, stigmasterol, chelerythrine, campesterol and berberine are the potential effective ingredients in treating BPSD.

Digital Technologies in Dementia Care

Dementia is characterized by significant cognitive deterioration, behavioral and psychological symptoms, and expanding disability. The well-being of people with dementia is influenced by the support provided by caregivers and health professionals. Especially in the past two decades, advancements in digital technology have helped reshape the way care and treatment are delivered. The main goal of the chapter is to describe technological solutions aimed at supporting the independence and safe participation of people with dementia in meaningful activities, as well as promoting their involvement in engaging experiences that seek to delay cognitive decline and diminish behavioral and psychological symptoms. These technologies include distributed systems, robotics, wearable devices, application software, and virtual reality.

Physical exercise as a non-pharmacological strategy for reducing behavioral and psychological symptoms in elderly with mild cognitive impairment and dementia: a systematic review of randomized clinical trials

ABSTRACT Background: Elderly people with dementia may exhibit behavioral and psychological symptoms throughout the course of disease. Non-pharmacological therapies, such as regular physical activity, are considered strategies for managing these symptoms. Objective: The aim of this study was to investigate whether participation in physical exercise programs is effective in reducing behavioral and neuropsychiatric symptoms in elderly people with Mild Cognitive Impairment (MCI) and dementia. Methods: A literature review was carried out in MEDLINE (PubMed), SciELO, Web of Science, Scopus and SPORTDiscus databases from 2010 to 2020. The eligible studies were randomized clinical trials involving elderly people with mild cognitive impairment or dementia and assessing changes in neuropsychiatric and psychological symptoms as primary or secondary outcomes. The studies had a group with only physical exercise as an intervention compared to a control group. Results: Of 175 publications identified in the initial survey, only 7 studies met the eligibility criteria. Four out of 7 studies demonstrated positive effects in reducing behavioral symptoms, while the others did not report differences between gains according to the type of protocol. Conclusions: Moderate to intense aerobic and muscle strengthening exercises may have a potential benefit in the management of behavioral and psychological symptoms in dementia, but studies varied in their conclusions. This review indicates the need for further intervention studies to investigate, as a primary outcome, the absolute effect of physical exercise and its impact on behavioral and psychological symptoms in elderly people with MCI dementia, especially in the early stages of the disease.

Effectiveness and Safety of Aromatherapy in Managing Behavioral and Psychological Symptoms of Dementia: A Mixed-Methods Systematic Review

<b><i>Introduction:</i></b> Behavioral and psychological symptoms of dementia (BPSD) is the most prominent and distressing manifestation for older persons with dementia (PWD) and caregivers. Aromatherapy has demonstrated its effectiveness in managing BPSD in various studies. However, previous studies and systematic reviews have obtained inconsistent findings, and a review of qualitative studies is yet to be conducted. <b><i>Method:</i></b> A mixed-methods systematic review with a convergent segregated approach was performed to evaluate the effectiveness of aromatherapy in improving the BPSD and quality of life (QoL) of PWD and in relieving the distress and burden of caregivers, as well as its safety for PWD. Both published and unpublished quantitative and qualitative studies written in English and Chinese between January 1996 and December 2020 were retrieved from 28 databases, including MEDLINE, EMBASE, and Web of Science, based on the prespecified criteria. The methodological quality was assessed by using critical appraisal tools from the Joanna Briggs Institute. Quantitative synthesis, qualitative synthesis, and integration of quantitative and qualitative evidence were performed. <b><i>Results:</i></b> A total of 12 randomized controlled trials, 10 quasi-experimental studies, and 2 qualitative studies were included in the review. Some inconsistent findings regarding the effectiveness of aromatherapy in reducing the severity of BPSD were observed. Some studies reported that aromatherapy significantly improved the QoL of PWD and relieved the distress and burden of caregivers, promoted a positive experience among caregivers, and had very low adverse effects on PWD (with aromatherapy inhalation reporting no adverse effects). <b><i>Conclusion:</i></b> Aromatherapy, especially in the inhalation approach, could be a potentially safe and effective strategy for managing BPSD. However, more structuralized and comparable studies with sufficient sample size, adherence monitoring, and sound theoretical basis could be conducted to obtain conclusive findings.

Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease

<b><i>Background/Aims:</i></b> The behavioral and psychological symptoms of dementia (BPSD) detract from the quality of life of not only dementia patients but also their family members and caregivers. Donepezil is used to treat Alzheimer’s disease and is metabolized via cytochrome P450 (CYP) 2D6 and CYP3A4/5. It is controversial whether donepezil improves or exacerbates BPSD. This study investigated the relationships among BPSD, the pharmacokinetics of donepezil including its metabolite, 6-O-desmethyl donepezil, genetic polymorphisms of CYPs and P-glycoprotein, and patient backgrounds in 52 patients with Alzheimer’s disease. <b><i>Methods:</i></b> BPSD were assessed using the Neuropsychiatric Inventory (NPI), with scores ≥20 points defined as severe BPSD. Plasma donepezil and 6-O-desmethyl donepezil concentrations were measured using liquid chromatography–tandem mass spectrometry. <b><i>Results:</i></b> Although significant relationships between NPI scores and plasma donepezil concentrations were not seen, none of the 15 patients (29%) with high plasma donepezil concentrations (≥60 ng/mL) developed severe BPSD. Polymorphisms of <i>CYP2D6</i>, <i>CYP3A5</i>, and <i>ABCB1</i> did not influence NPI scores. There were no significant relationships between NPI and patient background factors such as dosing regimen, concomitant use of other drugs, or laboratory test results. Two patients who underwent multiple blood samplings over 2 years showed an inverse correlation between plasma donepezil concentrations and NPI scores. <b><i>Discussion/Conclusions:</i></b> These results indicate that higher plasma concentrations of donepezil contribute to preventing or alleviating rather than developing or deteriorating BPSD.

Temporal Patterns of Daily Behavioral and Psychological Symptoms of Dementia Throughout the Day

Behavioral and psychological symptoms of dementia (BPSD) are taxing for both the person with dementia (PWD) and their family caregivers. Yet, little is known about how BPSD fluctuates throughout the day (i.e., morning, daytime, evening, and night; e.g., sundowning) and how caregivers perceive BPSD at different times of the day. Using 8-day daily diary data from 173 family caregivers whose relatives were using Adult Day Services (ADS), this study investigated temporal patterns of BPSD and caregivers’ stress responses to BPSD throughout the day. Overall, the number of BPSD was highest in the evening, and caregivers’ stress reactivity to BPSD increased throughout the phases of the day (i.e., most stressful at night). However, caregivers showed lower reactivity to BPSD in the mornings and at night on days when the PWD used ADS. Our findings about fluctuations of (caregiver reactions to) BPSD throughout the day suggest target windows for just-in-time adaptive intervention.

Person-Centered Assessment of Behavior Changes in People With Dementia

Behavioral and psychological symptoms of dementia are increasingly being reconceptualized as expressions of distress and unmet needs. Measures that evaluate context are needed to increase our understanding of factors that influence these expressions. This review evaluated measures for two common behavioral states that are experienced as challenging for caregivers: apathy and resistance to care. A systematic literature search identified measures of apathy or resistance to care for people living with dementia. Eight measures of apathy and three measures of resistance to care were identified. Reliability and validity of these measures were evaluated using the COSMIN framework, as well as reported contextual factors within which the behavior occurs. The identified measures had fair to good reliability and validity in people living with dementia. However, available measures need to move beyond symptomatic constructs for this complex paradigm, and toward the varied interpersonal and contextual factors associated with behavioral expression.