The Role of N-Methyl-D-Aspartate Receptor Neurotransmission and Precision Medicine in Behavioral and Psychological Symptoms of Dementia.
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ABSTRACT:
SUBMITTER: Lin CH
PROVIDER: S-EPMC6539199 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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The Role of N-Methyl-D-Aspartate Receptor Neurotransmission and Precision Medicine in Behavioral and Psychological Symptoms of Dementia.
Lin Chieh-Hsin CH Lane Hsien-Yuan HY
Frontiers in pharmacology 20190522
While the world's population is aging, the prevalence of dementia and the associated behavioral and psychological symptoms of dementia (BPSD) rises rapidly. BPSD are associated with worsening of cognitive function and poorer prognosis. No pharmacological treatment has been approved to be beneficial for BPSD to date. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR)-related neurotransmission leads to cognitive impairment and behavioral changes, both of which are core symptoms of BPSD. Mema ...[more]
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Project description:Objective:Behavioral and psychological symptoms of dementia (BPSD) are associated with poorer prognosis of dementia. A 24-week study demonstrated that sodium benzoate, a D-amino acid oxidase (DAAO) inhibitor, surpassed placebo in improving cognitive function in early-phase Alzheimer's disease; however, benzoate did not excel placebo in another 6-week study on BPSD. The current study examined whether the precision medicine approach was able to identify specific individuals with BPSD who could benefit from benzoate treatment. Methods:In the randomized, double-blind, placebo-controlled, 6-week trial, 97 patients with BPSD were allocated to receive 250-1500 mg/day of sodium benzoate or placebo. Cognitive function was measured by the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and behavioral and psychological symptoms were mainly measured by Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). DAAO level, amino acids (L-serine, D-serine, L-alanine, and D-alanine, glycine), and two antioxidants (catalase, superoxide dismutase) were assayed in peripheral blood. Results:After benzoate treatment, DAAO inhibition was correlated with ADAS-cog decrease (p = 0.034), while baseline DAAO level was correlated with baseline BEHAVE-AD score. Multiple linear regression analyses showed that cognitive improvement after benzoate treatment was correlated with DAAO decrease, female gender, younger age, BMI, baseline BPSD severity, and antipsychotic use. Conclusion:The finding suggests that sodium benzoate may have potential to benefit cognitive function in a fraction of BPSD patients after 6 weeks of treatment. Of note, the precision medicine approach may be helpful for identifying individuals who could respond to benzoate. More studies are warranted to confirm the preliminary findings. Trial Registration:The trial was registered online (https://clinicaltrials.gov/ct2/show/NCT02103673).
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Project description:BackgroundDementia is becoming a major public health problem worldwide with the aging of the world's population. Behavioral and psychological symptoms of dementia (BPSD), associated symptoms of dementia, not only predicts the poor prognosis of patients with dementia, but is also a major factor causing the care burden on caregivers, especially informal caregivers. For BPSD management, an alternative to existing psychotropic drugs is needed, given the benefit-harm ratio. Therefore, in this systematic review, we will evaluate the effectiveness and safety of herbal medicine for BPSD.Methods and analysisThirteen electronic databases will be comprehensively searched. Clinical studies reporting the efficacy (or effectiveness) and safety of herbal medicines in BSPD management published from their inception to December 2020 will be included. The primary outcome will be BPSD symptoms assessed by the validated tool. Moreover, total effective rate, daily living activities and quality of life of patients, burden and quality of life of caregiver, placement in a long-term care facility from home, and safety data will be regarded as the secondary outcome. Two independent researchers will perform the study selection, data extraction, and quality assessment process. To assess the methodological quality of the included studies, validated tools according to its design, such as the Cochrane Collaboration's risk of bias tool will be used. To perform meta-analysis, RevMan version 5.3 will be used, with mean differences for continuous outcomes and risk ratio for binary outcomes, and 95% confidence intervals. According to the heterogeneity and number of included studies, a fixed- or random-effects model will be used.Registration numberOSF (URL: https://osf.io/3u8ch), PROSPERO (CRD42020211000) (URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211000).
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Project description:BackgroundBehavioral and psychological symptoms of dementia (BPSD) are present in a majority of patients with dementia contributing to increased morbidity, health care costs, and caregiver burden. While there are no United States Food and Drug Administration (FDA)-approved medications for these symptoms, off-label use of medications such as antipsychotics have been shown to have significant adverse effects including increased mortality. The goal of this review is to examine the efficacy and safety of anticonvulsants in the treatment of BPSD.MethodsWe will systematically search for randomized trials of anticonvulsants compared to placebo or other treatments such as antidepressants and antipsychotics from the following sources: The Cochrane Library, MEDLINE (OVID SP) in Process and Other Non-Indexed Citations (latest version), EMBASE, clinicalTrials.gov , and the WHO Clinical Trials Registry. The studies will be limited to those published in English but the study location can be worldwide. We will include studies pertaining to individuals with dementia and symptoms of BPSD. The primary outcomes will be behavioral change as measured by validated scales and secondary outcomes will include caregiver burden, quality of life, placement in long term care facility, serious adverse effects, and treatment discontinuation due to adverse effects. Two sets of reviewers will independently screen select and extract data. We will narratively describe the major findings and conclusions from individual studies. Patients who are prescribed antiepileptic drugs (AEDs) for other indications, including seizures, will be excluded. Outcomes of interest will include a change in a validated scale that measures BPSD, serious adverse events, and caregiver quality of life outcomes. If the data are found to be appropriate for a meta-analysis, we will use a random effects model to compute summary estimates of treatment effects.DiscussionThis is a protocol for a systematic review addressing the anticonvulsant group of medications as a whole, and as such, our results will inform current clinical practice in the use of anticonvulsants for BPSD. It will also help clinicians and policy makers compare the efficacy of anticonvulsants compared to antidepressants and antipsychotics as well as identify areas which will need further study.Systematic review registrationPROSPERO CRD42017079826.
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Project description:BackgroundDementia is a major mental health problem worldwide, and an optimal anti-dementia drug that could modify its core symptoms has not been developed yet. Behavioral and psychological symptoms of dementia (BPSD), an important clinical manifestation of dementia, is closely related to disease burden, caregiver burden, and consequent social burden. In general, many experts and international guidelines prefer non-pharmacological interventions, including psychosocial intervention, and complementary and integrative medicine in the management of BPSD. However, in clinical settings, psychotropic drugs are frequently used; therefore, the need to establish and actively use effective non-pharmacological interventions is emphasized. Therefore, in this systematic review, we will evaluate the effectiveness and safety of acupuncture, a promising non-pharmacological complementary and integrative medicine, for BPSD.Methods and analysisA comprehensive search will be conducted in 13 electronic medical databases. Regardless of its design, original clinical studies, such as randomized controlled clinical trials, nonrandomized controlled clinical trials, and before-after studies, will be included to assess the beneficial effects and safety of acupuncture on BPSD. The severity of BPSD symptoms assessed by the validated tool will be considered as a primary outcome. The secondary outcome included the total effective rate, daily living activities and quality of life of patients, burden and quality of life of caregiver, placement in a long-term care facility from home, and safety data. The study selection, data extraction, and quality assessment process were performed by 2 independent researchers. The methodological quality of the included studies will be assessed using validated tools according to its design, such as the Cochrane Collaboration's risk of bias tool. RevMan version 5.3 will be used to perform the meta-analysis, with mean differences for continuous outcomes and risk ratio for binary outcomes, and 95% confidence intervals. A fixed- or random-effects model will be used according to the heterogeneity and number of included studies.Ethics and disseminationAs this protocol is for a systematic review, ethical approval is not required. The results of the systematic review will be disseminated by the publication of a manuscript in a peer-reviewed journal or presentation at a relevant conference.Registration numberOSF (URL: https://osf.io/hu5ac), PROSPERO (CRD42020211005) (URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211005).
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