A White Matter Connection of Schizophrenia and Alzheimer’s Disease

Schizophrenia (SZ) is a severe psychiatric illness associated with an elevated risk for developing Alzheimer’s disease (AD). Both SZ and AD have white matter abnormalities and cognitive deficits as core disease features. We hypothesized that aging in SZ patients may be associated with the development of cerebral white matter deficit patterns similar to those observed in AD. We identified and replicated aging-related increases in the similarity between white matter deficit patterns in patients with SZ and AD. The white matter “regional vulnerability index” (RVI) for AD was significantly higher in SZ patients compared with healthy controls in both the independent discovery (Cohen’s d = 0.44, P = 1·10^–5, N = 173 patients/230 control) and replication (Cohen’s d = 0.78, P = 9·10^–7, N = 122 patients/64 controls) samples. The degree of overlap with the AD deficit pattern was significantly correlated with age in patients (r = .21 and .29, P < .01 in discovery and replication cohorts, respectively) but not in controls. Elevated RVI-AD was significantly associated with cognitive measures in both SZ and AD. Disease and cognitive specificities were also tested in patients with mild cognitive impairment and showed intermediate overlap. SZ and AD have diverse etiologies and clinical courses; our findings suggest that white matter deficits may represent a key intersecting point for these 2 otherwise distinct diseases. Identifying mechanisms underlying this white matter deficit pattern may yield preventative and treatment targets for cognitive deficits in both SZ and AD patients.     

A Multinational,Multicenter, Randomized,Double-Blind,Active Comparator,Phase III Clinical Trial to Evaluate the Efficacy and Safety of Donepezil Transdermal Patch in Patients With Alzheimer’s Disease

Background and PurposeOral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD).MethodsThis prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio.ResultsThe difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (p=0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups.ConclusionsIPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.     

Acetylcholinesterase inhibitors in cognitive impairment in Huntington’s disease: A brief review

Huntington’s disease (HD) is a neurodegenerative disease associated with cognitive deficits. Cognitive dysfunction may be present in the early stages of the disease, even before the onset of motor symptoms. The cognitive dysfunction includes executive dysfunction, psychomotor symptoms, visuospatial deficits, perceptual deficits, memory loss and difficulty learning new skills. Acetylcholinesterase inhibitors have shown good effect in the treatment of other types of dementia and it is postulated that it might delay cognitive decline in HD. We reviewed the evidence for Acetylcholinesterase inhibitors in the treatment of cognitive decline and dementia associated with Huntington’s disease. We identified 6 articles that investigated the role of Acetylcholinesterase inhibitors for treatment of cognitive deficits in Huntington’s disease. Following the review, the authors concluded that there is limited evidence for the use of Acetylcholinesterase inhibitors for cognitive impairment in HD.     

Promising Blood Biomarkers for Clinical Use in Alzheimer’s Disease: A Focused Update

Alzheimer’s disease (AD) is the most-common cause of neurodegenerative dementia, and it is characterized by abnormal amyloid and tau accumulation, which indicates neurodegeneration. AD has mostly been diagnosed clinically. However, ligand-specific positron emission tomography (PET) imaging, such as amyloid PET, and cerebrospinal fluid (CSF) biomarkers are needed to accurately diagnose AD, since they supplement the shortcomings of clinical diagnoses. Using biomarkers that represent the pathology of AD is essential (particularly when disease-modifying treatment is available) to identify the corresponding pathology of targeted therapy and for monitoring the treatment response. Although imaging and CSF biomarkers are useful, their widespread use is restricted by their high cost and the discomfort during the lumbar puncture, respectively. Recent advances in AD blood biomarkers shed light on their future use for clinical purposes. The amyloid β (Aβ)42/Aβ40 ratio and the concentrations of phosphorylated tau at threonine 181 and at threonine 217, and of neurofilament light in the blood were found to represent the pathology of Aβ, tau, and neurodegeneration in the brain when using automatic electrochemiluminescence technologies, single-molecule arrays, immunoprecipitation coupled with mass spectrometry, etc. These blood biomarkers are imminently expected to be incorporated into clinical practice to predict, diagnose, and determine the stage of AD. In this review we focus on advancements in the measurement technologies for blood biomarkers and the promising biomarkers that are approaching clinical application. We also discuss the current limitations, the needed further investigations, and the perspectives on their use.     

The Impact of the COVID-19 Pandemic and Social Distancing on Cognition of Alzheimer’s Disease Patients

Objective The risk of rapid cognitive decline in Alzheimer’s disease (AD) during the coronavirus disease 2019 (COVID-19) pandemic has been recognized. The purpose of this study was to investigate the cognitive decline in such patients during the COVID-19 pandemic by evaluating changes in their cognitive measure parameters before and after the pandemic. Methods This was a retrospective cohort study conducted in AD patients during their first visit and one-year regular follow-up for testing cognitive function at the Geriatric Psychiatry Clinic of Seoul St. Mary’s Hospital. Changes in the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Sum of Box for CDR (CDR-SB) scores were investigated. A time series analysis was performed to determine whether there was a significant difference in the MMSE, CDR, and CDR-SB scores of AD patients in pre- and post–COVID-19 periods. Results Overall, 130 AD patients aged 60 to 93 years were assessed. Their baseline mean MMSE score was 22.30 which had decreased to 21.08 at the one-year follow-up. Before November 2019, the average CDR differences for one year was 0.06, but after November 2019, it increased to 0.36 (p<0.001). Before November 2019, the average of the CDR-SB change value for one year was 1.69, but after November 2019, it increased to 3.00 (p<0.001). The difference in MMSE values for one year was not statistically significant. The time series analysis revealed a significant increase in the CDR and CDR-SB scores by approximately 0.47 (p=0.005) and 2.39 (p=0.002), before and after November 1, 2019, respectively. Conclusion This study revealed that the COVID-19 pandemic and social distancing worsen cognitive function in AD patients rapidly. Exposure to the COVID-19 pandemic and social distancing for at least seven months worsen cognitive decline significantly. Therefore, in order to minimize the adverse effects of the cognitive decline in these patients, the period of social distancing should be minimized.     

Biofluid Biomarkers of Alzheimer’s Disease: Progress,Problems, and Perspectives

Since the establishment of the biomarker-based A-T-N (Amyloid/Tau/Neurodegeneration) framework in Alzheimer’s disease (AD), the diagnosis of AD has become more precise, and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted. However, the A-T-N framework does not encompass the whole spectrum of AD pathologies, and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system. Therefore, we suggest the addition of an “X” to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD. In this review, we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework, analyze the problems, and present our perspectives on the diagnosis of AD.     

Incidence and Cognitive Decline of Alzheimer’s Disease and Other Dementia by Apolipoprotein ε4 Allele Presence: A Community-Based Cohort Study in Korean Elderly

Objective This study aimed to investigate the role of apolipoprotein E (APOE) ε4 allele to the incidence of dementia and cognitive decline in a cohort of a Korean community. Methods From a community-based dementia-free cohort, 357 participants were genotyped. Participants underwent 2 cognitive assessments separated by a hiatus between 6 to 7 years and were diagnosed as healthy control (n=297), Alzheimer’s disease (AD) (n=44), and other dementia (n=16) at the second assessment. Incidence risk and onset age of disease according to APOE ε4 presence were analyzed in AD and other dementia. Differences in cognitive decline rate depending on APOE ε4 were also examined across all groups. Results The relative risks and onset age of dementia were not different by the presence of the APOE ε4 allele. Cognitive decline was more prominent in the presence of APOE ε4 allele (score change=7.4) than non-presence (score change=3.1), and this interaction was significant only in the AD group (F=10.51, p=0.003). Conclusion The APOE ε4 alleles can be a critical factor in predicting cognitive change for AD in the Korean community population but not in predicting AD incidence. This finding suggest that clinicians consider the presence of APOE ε4 allele examining patients with rapid declining dementia.     

The neuroprotective effects of oxygen therapy in Alzheimer’s disease: a narrative review

Alzheimer’s disease (AD) is a degenerative neurological disease that primarily affects the elderly. Drug therapy is the main strategy for AD treatment, but current treatments suffer from poor efficacy and a number of side effects. Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD. Hypoxia is one of the important factors that contribute to the pathogenesis of AD. Multiple cellular processes synergistically promote hypoxia, including aging, hypertension, diabetes, hypoxia/obstructive sleep apnea, obesity, and traumatic brain injury. Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD, such as amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial and synaptic dysfunction. Treatments targeting hypoxia may delay or mitigate the progression of AD. Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD. Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism, tau phosphorylation, neuroinflammation, neuronal apoptosis, oxidative stress, neurotrophic factors, mitochondrial function, cerebral blood volume, and protein synthesis. In this review, we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations. We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.     

Baseline Clinical and Biomarker Characteristics of Biobank Innovations for Chronic Cerebrovascular Disease With Alzheimer’s Disease Study: BICWALZS

ObjectiveWe aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer’s disease study (BICWALZS) participants. MethodsA total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. ResultsThe mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer’s dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer’s disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. ConclusionThe BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.     

The stability of neuropsychiatric subsyndromes in Alzheimer's disease

Introduction

Neuropsychiatric symptoms are common in Alzheimer's disease. Previous research has attempted to identify subsyndromes—sets of symptoms related to one another—to clarify underlying mechanisms and treatment targets. We examined the stability of these subsyndromes over time.

Protective effects of edaravone on white matter pathology in a novel mouse model of Alzheimer’s disease with chronic cerebral hypoperfusion

White matter lesions (WMLs) caused by cerebral chronic hypoperfusion (CCH) may contribute to the pathophysiology of Alzheimer’s disease (AD). However, the underlying mechanisms and therapeutic approaches have yet to be totally identified. In the present study, we investigated a potential therapeutic effect of the free radical scavenger edaravone (EDA) on WMLs in our previously reported novel mouse model of AD (APP23) plus CCH with motor and cognitive deficits. Relative to AD with CCH mice at 12 months (M) of age, EDA strongly improved CCH-induced WMLs in the corpus callosum of APP23 mice at 12 M by improving the disruption of white matter integrity, enhancing the proliferation of oligodendrocyte progenitor cells, attenuating endothelium/astrocyte unit dysfunction, and reducing neuroinflammation and oxidative stress. The present study demonstrates that the long-term administration of EDA may provide a promising therapeutic approach for WMLs in AD plus CCH disease with cognitive deficits.     

Lamotrigine protects against cognitive deficits,synapse and nerve cell damage,and hallmark neuropathologies in a mouse model of Alzheimer’s disease

Lamotrigine (LTG) is a widely used drug for the treatment of epilepsy. Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease. However, the underlying molecular mechanisms remain unclear. In this study, amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice were used as a model of Alzheimer’s disease. Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months. The cognitive functions of animals were assessed using Morris water maze. Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay. The cell damage in the brain was investigated using hematoxylin and eosin staining. The levels of amyloid-β and the concentrations of interleukin-1β, interleukin-6 and tumor necrosis factor-α in the brain were measured using enzyme-linked immunosorbent assay. Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction. We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice; alleviated damage to synapses and nerve cells in the brain; and reduced amyloid-β levels, tau protein hyperphosphorylation, and inflammatory responses. High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds, Cd74, Map3k1, Fosb, and Spp1 expression in the brain. These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease. Furthermore, these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.     

Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study

[¹¹C]UCB-J PET for synaptic vesicle glycoprotein 2 A (SV2A) has been proposed as a suitable marker for synaptic density in Alzheimer’s disease (AD). We compared [¹¹C]UCB-J binding for synaptic density and [¹⁸F]FDG uptake for metabolism (correlated with neuronal activity) in 14 AD and 11 cognitively normal (CN) participants. We assessed both absolute and relative outcome measures in brain regions of interest, i.e., K₁ or R₁ for [¹¹C]UCB-J perfusion, V_T (volume of distribution) or DVR to cerebellum for [¹¹C]UCB-J binding to SV2A; and K_i or K_iR to cerebellum for [¹⁸F]FDG metabolism. [¹¹C]UCB-J binding and [¹⁸F]FDG metabolism showed a similar magnitude of reduction in the medial temporal lobe of AD –compared to CN participants. However, the magnitude of reduction of [¹¹C]UCB-J binding in neocortical regions was less than that observed with [¹⁸F]FDG metabolism. Inter-tracer correlations were also higher in the medial temporal regions between synaptic density and metabolism, with lower correlations in neocortical regions. [¹¹C]UCB-J perfusion showed a similar pattern to [¹⁸F]FDG metabolism, with high inter-tracer regional correlations. In summary, we conducted the first in vivo PET imaging of synaptic density and metabolism in the same AD participants and reported a concordant reduction in medial temporal regions but a discordant reduction in neocortical regions.     

The Association of Blood-Based Inflammatory Factors IL-1β, TGF-β and CRP with Cognitive Function in Alzheimer’s Disease and Mild Cognitive Impairment

Objective Many patients suffer from dementia in its most common form, Alzheimer’s disease (AD). In this study, the levels of IL-1β, TGF-β and CRP, which are involved in the inflammatory response in Alzheimer’s disease and its mild cognitive impairment (MCI), were measured and analyzed. Methods Seventy nine subjects participated in this study (mean age: 75.56 years, female: 54.3%, AD: 26, MCI: 28, normal: 25). The overall cognitive function of the subjects and the severity of the disease stage were assessed using the Mini-Mental State Examination (MMSE-K), the Clinical Dementia Rating (CDR), the Global Deterioration Scale (GDS) and the Geriatric Depression Scale-Korean (GDS-K). Results It was observed that patients with AD had significantly higher levels of IL-1β and TGF-β than the patients with MCI and normal controls. In addition, the MCI group showed a statistically significantly higher TGF-β concentration than the normal group. Conclusion These results suggest that IL-1β and TGF-β may be useful biological markers for patients with Alzheimer’s disease.     

Repeatability of parametric methods for [18F]florbetapir imaging in Alzheimer’s disease and healthy controls: A test–retest study

Accumulation of amyloid beta (Aβ) is one of the pathological hallmarks of Alzheimer’s disease (AD), which can be visualized using [¹⁸F]florbetapir positron emission tomography (PET). The aim of this study was to evaluate various parametric methods and to assess their test-retest (TRT) reliability. Two 90 min dynamic [¹⁸F]florbetapir PET scans, including arterial sampling, were acquired (n = 8 AD patient, n = 8 controls). The following parametric methods were used; (reference:cerebellum); Logan and spectral analysis (SA), receptor parametric mapping (RPM), simplified reference tissue model2 (SRTM2), reference Logan (rLogan) and standardized uptake value ratios (SUV_r(50–70)). BP_ND+1, DVR, V_T and SUVr were compared with corresponding estimates (V_T or DVR) from the plasma input reversible two tissue compartmental (2T4k_V_B) model with corresponding TRT values for 90-scan duration. RPM (r² = 0.92; slope = 0.91), Logan (r² = 0.95; slope = 0.84) and rLogan (r² = 0.94; slope = 0.88), and SRTM2 (r² = 0.91; slope = 0.83), SA (r² = 0.91; slope = 0.88), SUVr (r² = 0.84; slope = 1.16) correlated well with their 2T4k_V_B counterparts. RPM (controls: 1%, AD: 3%), rLogan (controls: 1%, AD: 3%) and SUV_r(50–70) (controls: 3%, AD: 8%) showed an excellent TRT reliability. In conclusion, most parametric methods showed excellent performance for [¹⁸F]florbetapir, but RPM and rLogan seem the methods of choice, combining the highest accuracy and best TRT reliability.     

Adjunctive treatment with high frequency repetitive transcranial magnetic stimulation for the behavioral and psychological symptoms of patients with Alzheimer's disease: a randomized,double-blind,sham-controlled study

Background

Behavioral and psychological symptoms of dementia (BPSD) occur in 70-90% of patients at different stages of Alzheimer’s Disease (AD), but the available methods for managing these problems are of limited effectiveness.

Aim

Assess the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS), applied over the left dorsolateral prefrontal cortex (DLPFC), on BPSD and cognitive function in persons with AD.

Methods

Fifty-four patients with AD and accompanying BPSD were randomly divided into an intervention group (n=27) and a control group (n=27). In addition to standard antipsychotic treatment, the intervention group was treated with 20Hz rTMS five days a week for four weeks, while the control group was treated with sham rTMS.The Behavioral Pathology in Alzheimer''s Disease Rating Scale (BEHAVE-AD), the Alzheimer''s Disease Assessment Scale-Cognitive (ADAS-Cog), and the Treatment Emergent Symptom Scale (TESS) were administered by raters who were blind to the group assignment of patients before and after four weeks of treatment.

Results

Twenty-six subjects from each group completed the study. After four weeks of antipsychotic treatment with adjunctive real or sham rTMS treatment, the mean (sd) total BEHAVE-AD scores and mean total ADAS-Cog scores of both groups significantly decreased from baseline. After adjusting for baseline values, the intervention group had significantly lower scores (i.e., greater improvement) than the control group on the BEHAVE-AD total score, on five of the seven BEHAVE-AD factor scores (activity disturbances, diurnal rhythm, aggressiveness, affective disturbances, anxieties and phobias), on the ADAS-Cog total score, and on all four ADAS-Cog factor scores (memory, language, constructional praxis, and attention). The proportion of individuals whose behavioral symptoms met a predetermined level of improvement (i.e., a drop in BEHAVE-AD total score of > 30% from baseline) in the intervention group was greater than that in the control group (73.1% vs.42.3%, X²=5.04, p=0.025).

Conclusion

Compared to treatment of AD with low-dose antipsychotic medications alone, the combination of low-dose antipsychotic medication with adjunctive treatment with high frequency rTMS can significantly improve both cognitive functioning and the behavioral and psychological symptoms that often accompany AD.     

The efficacy of mirtazapine in agitated patients with Alzheimer’s disease: A 12-week open-label pilot study

Agitation is one of the most devastating behavioral symptoms in demented patients but there is little evidence about effective and safe pharmacotherapy. We aimed to determine the effectiveness and safety of mirtazapine in treatment of agitated patients with Alzheimer’s disease (AD). The consecutive patients with AD who have significant agitation were assigned to a 12-week open-label, prospective study. Patients received mirtazapine 15–30 mg/day. The changes in Cohen-Mansfield Agitation Inventory-Short form (CMAI-SF) scores were primary outcome measurement. The change in Clinical Global Impression-Severity scale (CGI-S) scores and tolerability-safety profile were the secondary efficacy variables. Thirteen of 16 (81.25%) patients completed the study. There was a significant reduction in CMAI-SF and CGI-S between the pre- and post-treatment with mirtzapaine (p < 0.001). The mean baseline score was 26.54 ( ± 5.4) and mean reduction was 10.6 ( ± 7.5) in CMAI-SF. There was no significant side effect and cognitive deterioration. The results of this open-label pilot study suggest that mirtazapine may be an effective choice for treatment of agitated patients with AD.     

Comprehensive Management of Daily Living Activities,behavioral and Psychological Symptoms,and Cognitive Function in Patients with Alzheimer's Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer's Disease

Alzheimer''s disease (AD) is the most common cognitive disorder in the elderly. Its main clinical manifestations are cognitive decline (C), behavioral and psychological symptoms (B), and a decline in the activities of daily living (A), also known as ABC symptoms. Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis, comprehensive treatment, and prognosis of AD. To guide Chinese clinical practice for optimization of the comprehensive management of AD, in 2018, The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD. Based on a review of the evidence, the consensus summarizes the pathogenesis, pathological changes, clinical manifestations, evaluation, diagnosis, drug and non-drug treatment, and patient care for AD. Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients. The new consensus provides a feasible AD management process for clinicians.     

Effects of Yokukansan on behavioral and psychological symptoms of dementia in regular treatment for Alzheimer's disease

Yokukansan (YKS) is used frequently against behavioral and psychological symptoms of dementia (BPSD) together with donepezil in patients with Alzheimer's disease (AD). Here, we investigated the efficacy and safety of YKS in patients with AD in a non-blinded, randomized, parallel-group comparison study. Patients who had at least one symptom score of four or more on the Neuropsychiatric Inventory (NPI) subscales were enrolled in the study. The subjects were randomly assigned to the YKS-treated group (YKS/donepezil combination therapy group) and the non-YKS-treated group (donepezil monotherapy group). TSUMURA Yokukansan (TJ-54, 7.5 g, t.i.d.) was administered in a four-week study treatment period. The subjects were evaluated twice at the start (Week 0) and completion (Week 4) of the study treatment in terms of NPI, Mini-Mental Status Examination (MMSE), Disability Assessment for Dementia (DAD), Zarit Burden Interview, and Self-rating Depression Scale (SDS). The efficacy analysis was performed in 29 patients (YKS-treated group) and 32 patients (non-YKS-treated group). The NPI total score improved significantly more in the YKS-treated group than in the non-YKS-treated group. In the NPI subscales of agitation/aggression and irritability/lability, the YKS-treated group showed significantly greater improvement than the non-YKS-treated group, but no statistically significant improvement was seen with YKS in the other subscales. There were no significant differences between the YKS-treated group and the non-YKS-treated group in MMSE, DAD, Zarit Burden Interview and SDS. No adverse reactions were noted in either group. The results of this study showed that YKS is safe and effective in the treatment of BPSD in AD patients.     

Successful treatment with Yokukansan for behavioral and psychological symptoms of Parkinsonian dementia

Objective

To evaluate the efficacy and safety of Yokukansan, a traditional Chinese herbal medicine, for treating behavioral and psychological symptoms of dementia (BPSD) in patients with Parkinson disease (PD; n = 7) and those with PD with dementia (PDD; n = 7).

Background

BPSD are often seen in patients with senile dementia and have serious deleterious effects on the lives of patients and caregivers. Recent studies indicate that the traditional Chinese herbal medicine Yokukansan may be safe and beneficial for the treatment of BPSD patients.

Methods

We treated 7 PD and 7 PDD patients for 4 weeks with Yokukansan and observed them without Yokukansan for 4 weeks. Changes in behavioral and psychological symptoms were evaluated every 4 weeks according to the Neuropsychiatric Inventory (NPI) scale.

Results

Significant improvements in behavioral and psychological symptoms, particularly in the incidence and duration of hallucinations, were observed in most PD and PDD patients after 4 weeks of Yokukansan treatment. No significant changes were observed in the laboratory tests, cognitive function, activities of daily living, or parkinsonism.

Conclusion

Our results suggest that Yokukansan improves BPSD in both PD and PDD patients without worsening their cognitive function, ability to perform activities of daily living, or parkinsonism.