Feasibility Study of Neurofeedback Therapy for Alzheimer’s Disease

Objective: This study aims to evaluate the feasibility and effectiveness of neurofeedback therapy based on brain-computer interface (BCI) games in enhancing cognitive functions and reducing disruptive behaviors in patients with Alzheimer’s disease (AD). Methods: Forty-six AD patients aged 49 - 76 years were recruited for the study. Neurofeedback regulation was conducted using a BCI game designed to modulate EEG rhythms. Cognitive function was assessed using MMSE, MoCA, and ADAS-cog scales before and after a 10-day training period. EEG measurements were taken to evaluate changes in brain activity complexity. Statistical analyses were performed using SPSS25.0 software to compare pre- and post-training scores. Results: Post-intervention results showed significant improvement in the cognitive function of AD patients. The total scores of MMSE, MoCA, and ADAS-cog scales increased significantly (P < 0.01). Notable improvements were observed in memory, language, and attention domains. EEG complexity in the left frontal area also showed a significant increase (P < 0.05). Additionally, the disruptive behaviors of patients were significantly reduced, improving their overall quality of life. Conclusions: Neurofeedback therapy based on BCI games is a promising intervention for enhancing cognitive functions and reducing disruptive behaviors in AD patients. This innovative approach demonstrates significant potential for clinical application, providing a non-invasive method to improve patient outcomes. Further studies with larger sample sizes and long-term follow-ups are recommended to validate these findings and explore the specific effects of NFB training on different cognitive impairment levels.

The Efficacy and Safety of Yokukansankachimpihange for Treating Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: An Open-Label Pilot Study

Previous clinical trials have demonstrated the efficacy of yokukansan, a traditional Japanese medicine, for the treatment of behavioral and psychological symptoms of dementia (BPSD). However, less evidence is available for the treatment of BPSD with yokukansankachimpihange (YKSCH), which consists of yokukansan and two additional herbal ingredients. The present study was conducted to investigate the efficacy and safety of YKSCH for treating BPSD in patients with Alzheimer’s disease (AD). We enrolled outpatients with mild-to-moderate AD who exhibited BPSD and obtained a Neuropsychiatric Inventory (NPI) score of >3 including subscale scores for “agitation”, “anxiety”, “irritability”, and “sleep and night-time behavior change”. A daily YKSCH dose of 7.5 g was administered for 12 weeks with concomitant administration of anti-dementia medication. BPSD was evaluated using the NPI at baseline and every 4 weeks during the intervention. We also examined apathy using the Japanese translation of the Apathy Scale, the short version of the Japanese version of the Zarit Caregiver Burden Interview, and the Modified Crichton Rating Scale for Predicting Activities of Daily Living. Cognitive dysfunction was evaluated using the Mini Mental State Examination and the AD Assessment Scale-Cognitive (Japanese version). Five participants were enrolled. The NPI total score tended to decrease between the baseline and 8-week evaluations during the YKSCH intervention (Wilcoxon signed rank test, P = 0.063). In terms of the NPI subscale scores, “apathy”, “agitation”, “delusions”, and “sleep and night-time behavior change” decreased after the intervention in those who exhibited each symptom at baseline. There were no significant differences in the other scores examined. No serious adverse events were observed. YKSCH could ameliorate BPSD in patients with mild-to-moderate AD with agitation, anxiety, irritability, and sleep and night-time behavior change, and it was well-tolerated.

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.

Development and validation of a nutrition-related genetic-clinical-radiological nomogram associated with behavioral and psychological symptoms in Alzheimer’s disease

Background:Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia(BPSD)in Alzheimer’s disease(AD).This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods:This retrospective study included 165 patients with AD from the Chinese Imaging,Biomarkers,and Lifestyle(CIBL)cohort between June 1,2021,and March 31,2022.Data on demographics,neuropsychological assessments,single-nucleotide polymorphisms of AD risk genes,and regional brain volumes were collected.A multivariate logistic regression model identified BPSD-associated factors,for subsequently constructing a diagnostic nomogram.This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1,2022,and February 1,2023.Area under receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA)were used to assess the discrimination,calibration,and clinical applicability of the nomogram.Results:Factors independently associated with BPSD were:CETP rs1800775(odds ratio[OR]=4.137,95%confidence interval[CI]:1.276-13.415,P=0.018),decreased Mini Nutritional Assessment score(OR=0.187,95%CI:0.086-0.405,P<0.001),increased caregiver burden inventory score(OR=8.993,95%CI:3.830-21.119,P<0.001),and decreased brain stem volume(OR=0.006,95%CI:0.001-0.191,P=0.004).These variables were incorporated into the nomogram.The area under the ROC curve was 0.925(95%CI:0.884-0.967,P<0.001)in the internal validation and 0.791(95%CI:0.686-0.895,P<0.001)in the external validation.The calibration plots showed favorable consistency between the prediction of nomogram and actual observations,and the DCA showed that the model was clinically useful in both validations.Conclusion:A novel nomogram was established and validated based on lipid metabolism-related genes,nutritional status,and brain stem volumes,which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration:Chictr.org.cn,ChiCTR2100049131.

Amelioration of Alzheimer's disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer's disease

The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.

Application of modern neuroimaging technology in the diagnosis and study of Alzheimer’s disease

Neurological abnormalities identified via neuroimaging are common in patients with Alzheimer’s disease.However,it is not yet possible to easily detect these abnormalities using head computed tomography in the early stages of the disease.In this review,we evaluated the ways in which modern imaging techniques such as positron emission computed tomography,single photon emission tomography,magnetic resonance spectrum imaging,structural magnetic resonance imaging,magnetic resonance diffusion tensor imaging,magnetic resonance perfusion weighted imaging,magnetic resonance sensitive weighted imaging,and functional magnetic resonance imaging have revealed specific changes not only in brain structure,but also in brain function in Alzheimer’s disease patients.The reviewed literature indicated that decreased fluorodeoxyglucose metabolism in the temporal and parietal lobes of Alzheimer’s disease patients is frequently observed via positron emission computed tomography.Furthermore,patients with Alzheimer’s disease often show a decreased N-acetylaspartic acid/creatine ratio and an increased myoinositol/creatine ratio revealed via magnetic resonance imaging.Atrophy of the entorhinal cortex,hippocampus,and posterior cingulate gyrus can be detected early using structural magnetic resonance imaging.Magnetic resonance sensitive weighted imaging can show small bleeds and abnormal iron metabolism.Task-related functional magnetic resonance imaging can display brain function activity through cerebral blood oxygenation.Resting functional magnetic resonance imaging can display the functional connection between brain neural networks.These are helpful for the differential diagnosis and experimental study of Alzheimer’s disease,and are valuable for exploring the pathogenesis of Alzheimer’s disease.

Diagnostic value of amygdala volume on structural magnetic resonance imaging in Alzheimer’s disease

BACKGROUND The main clinical manifestation of Alzheimer’s disease(AD)is memory loss,which can be accompanied by neuropsychiatric symptoms at different stages of the disease.Amygdala is closely related to emotion and memory.AIM To evaluate the diagnostic value of amygdala on structural magnetic resonance imaging(sMRI)for AD.METHODS In this study,22 patients with AD and 26 controls were enrolled.Their amygdala volumes were measured by sMRI and analyzed using an automatic analysis software.RESULTS The bilateral amygdala volumes of AD patients were significantly lower than those of the controls and were positively correlated with the hippocampal volumes.Receiver operating characteristic curve analyses showed that the sensitivity of the left and right amygdala volumes in diagnosing AD was 80.8%and 88.5%,respectively.Subgroup analyses showed that amygdala atrophy was more serious in AD patients with neuropsychiatric symptoms,which mainly included irritability(22.73%),sleep difficulties(22.73%),apathy(18.18%),and hallucination(13.64%).CONCLUSION Amygdala volumes measured by sMRI can be used to diagnose AD,and amygdala atrophy is more serious in patients with neuropsychiatric symptoms.

Early onset versus late onset in Alzheimer’s disease: What is the reliable cut-off?

Objective: As the literature on conventional criteria for discriminating early-onset (EO) from late-onset (LO) Alzheimer’s disease (AD) is sparse and controversial, the aim of this study was to establish a precise age at onset (AAO) criterion, by using a specific statistical procedure, and to describe the clinical characteristics of the two sub-groups. Methods: Admixture analysis was performed to establish the AAO cut-off in a multi-center study including 2000 AD patients consecutively recruited in eight Italian Memory Clinics. None of the patients were taking acetylcholinesterase inhibitors, antipsychoticor anti-depressant drugs. At the first diagnosticvisit, they were administered the Mini Mental StateExamination, the Basic and Instrumental Activities of Daily Living and the Neuropsychiatric Inventorytoassess clinical phenomenology. Results: Using a specific statistical procedure, we established that AAO that discriminated EO-from LO-AD was 66. Compared with the LO-AD group, the EO-AD group showed longer duration of illness and a higher educational level as well as less severe functional impairment and delusions. Conclusions: Differences in sociodemographic and clinical characteristics, such as duration of illness, education and delusion severity, suggested the involvement of different pathogenic processes. Additional studies are needed to further investigate the mechanisms underlying the disorder in the two sub-groups of AD patients.

Myricetin protects hippocampal CA3 pyramidal neurons and improves learning and memory impairments in rats with Alzheimer's disease

There is currently no treatment for effectively slowing the progression of Alzheimer＇s disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The present study investigated the effects of myricetin, a member of the flavonoids, on intracerebroventricular streptozotocin induced neuronal loss and memory impairment in rat models of Alzheimer＇s disease. Myricetin at 5 or 10 mg/kg was intraperitoneally injected into rats over 21 days. Control rats were treated with 10 m L/kg saline. Behavioral test（the shuttle box test） was performed on day 22 to examine learning and memory in rats. Immediately after that, hematoxylin-eosin staining was performed to observe the morphological change in hippocampal CA3 pyramidal neurons. Myricetin greatly increased the number of hippocampal CA3 pyramidal neurons and improved learning and memory impairments in rats with Alzheimer＇s disease. These findings suggest that myricetin is beneficial for treatment of Alzheimer＇s disease.

MicroRNA biomarkers in frontotemporal dementia and to distinguish from Alzheimer's disease and amyotrophic lateral sclerosis

Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal lobes.Frontotemporal lobar degeneration is considered to be equivalent to frontotemporal dementia.Frontotemporal dementia is characterized by progressive impairments in behavior,executive function,and language.There are two main clinical subtypes:behavioral-variant frontotemporal dementia and primary progressive aphasia.The early diagnosis of frontotemporal dementia is critical for developing management strategies and interventions for these patients.Without validated biomarkers,the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features,but misdiagnosis often occurs due to overlap with a range of neurologic and psychiatric disorders.In the studies reviewed a very large number of microRNAs were found to be dysregulated but with limited overlap between individual studies.Measurement of specific miRNAs singly or in combination,or as miRNA pairs(as a ratio)in blood plasma,serum,or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls,Alzheimer’s disease,and amyotrophic lateral sclerosis.Furthermore,upregulation of miR-223-3p and downregulation of miR-15a-5p,which occurred both in blood serum and cerebrospinal fluid,distinguished behavioral-variant frontotemporal dementia from healthy controls.Downregulation of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia,respectively,from healthy controls.Possible strong miRNA biofluid biomarker contenders for behavioral-variant frontotemporal dementia are miR-223-3p,miR-15a-5p,miR-22-3p in blood serum and cerebrospinal fluid,and miR-124 in cerebrospinal fluid.No miRNAs were identified able to distinguish between behavioral-variant frontotemporal dementia and primary progressive aphasia subtypes.Further studies are warranted on investigating miRNA expression in biofluids and frontal/temporal cortical tissue to validate and extend these findings.

The Use of Anti-Diabetic Drugs in Alzheimer’s Disease, New Therapeutic Options and Future Perspective

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of memory, confusion, inability of speech and decline in the cognitive behavior. It is considered one of the most common forms of dementia. Clinical studies and preclinical data in the last decade proved that AD and Diabetes mellitus share a pathophysiological pathway, indicating that insulin resistance, oxidative stress and inflammatory response would increase the risks of developing AD in diabetic patients. This review presents briefly the etiology of AD and Diabetes, discusses the possible theories about the interplaying risk factors and the mechanism of action of anti-diabetic medications recommended for the treatment of AD. It is concluded that antidiabetics have good potential to improve dementia, especially in earlier AD stages. However, many of the underlying intricate molecular pathways are still unclear and thus thorough future research is required.

A Meta-analysis of Mood Stabilizers for Alzheimer's Disease

The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer’s disease (AD).We searched 5 databases from their inception to January 2010.Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included.These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation.Methodological quality was assessed using the Jadad score.The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (CIs) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% CIs 0.15 to 7.26, P=0.04).There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total), NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo.Only one of these studies was free of methodological limittions (Jadad score=5).In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.

Risperidone Versus Yokukansan in the Treatment of Severe Alzheimer’s Disease

PURPOSE: Patients with AD commonly exhibit behavioral and psychological symptoms of dementia (BPSD). This study is aimed to compare the efficacy of yokukansan (YKS) and risperidone (RIS) on BPSD in patients with severe Alzheimer’s disease (AD). METHODS: Thirty eight inpatients with AD were investigated. Patients were randomly as-signed to the YKS group (N = 18) or the RIS group (N = 20) and treated for 4 weeks. The primary outcomes were changes in the scores on the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination (MMSE), the Bar-thel Index, and the Cohen-Mansfield Agitation Inventory (CMAI). The frequency of extrapyramidal symptoms (EPS) and other adverse events were recorded at every visit. RESULTS: All participants in both groups completed the trial. The Barthel Index did not significantly change either in the RIS group or the YKS group. The MMSE scores did not change either in the RIS group or the YKS group. Significant improvements in mean total NPI and CMAI scores showed in both groups. Between the YKS and the RIS groups, there were no significant differences in the NPI or the CMAI scores. EPS and other serious adverse effects were not observed in either group. CONCLUSIONS: In this 4-week trial, YKS treatment significantly improved BPSD in the patients with severe AD. The present study suggests that YKS is as effective as RIS on BPSD with severe AD.

Erratum to “Is Alzheimer’s Disease an Adaptability Disorder? What Role Does Happiness Have in Treatment, Management and Prevention” [World Journal of Neuroscience 5 (2015) 180-188]

A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. A General Systems approach, which recognises functional interaction as optimal and withdrawal or inadequate and/or inappropriate response as not, provides further understanding of the relationship between emotional factors, memory and neurodegenerative (Alzheimer’s) disease.

Is Alzheimer’s Disease an Adaptability Disorder? What Role Does Happiness Have in Treatment, Management and Prevention

A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. Maladaptive responses, to control the change in external environment that are sensed or perceived, and which lead to disorder or to susceptibility to disease, exemplify a General Systems Theory approach, in which appropriate and adequate responses to environmental change, in behavioural terms, by a person, whether independently, or as the recipient or giver, or both, leads to functional interaction and happiness.

Progress on early diagnosing Alzheimer’s disease

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions.The disease follows a continuum,starting with preclinical stages,progressing to mild cognitive and behavioral impairment,ultimately leading to dementia.Early detection of AD is crucial for better diagnosis and more effective treatment.However,the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive,and mostly are still not able to detect early disease state.Consequently,there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD.Various non-cognitive manifestations,including behavioral abnormalities,sleep disturbances,sensory dysfunctions,and physical changes,have been observed in the preclinical AD stage before occurrence of notable cognitive decline.Recent research advances have identified several biofluid biomarkers as early indicators of AD.This review focuses on these non-cognitive changes and newly discovered biomarkers in AD,specifically addressing the preclinical stages of the disease.Furthermore,it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.

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

An association between the location of white matter changes and the behavioral and psychological symptoms of dementia in Alzheimer's disease patients

Objective:The frontal lobe may be involved in circuits associated with depression,apathy,aggression,and other psychiatric symptoms.Although white matter changes(WMC)are related to the severity of behavioral and psychological symptoms of dementia(BPSD)in patients with Alzheimer’s disease(AD),it is unclear which part of the WMC may play the most important role in BPSD.This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients.Methods:Among patients diagnosed with Alzheimer’s disease between 2009 and2014,387 patients were retrospectively reviewed after those with pre‐existing organic brain syndrome,psychiatric diseases,or toxic‐metabolic encephalopathy were excluded.Patients’demographic and laboratory data,WMC measured with brain computed tomography and scored using the age‐related white matter changes(ARWMC)scale,and neuropsychological tests,including the cognitive abilities screening instrument(CASI),the Mini‐Mental State Examination(MMSE),the clinical dementia rating scale with sum‐box(CDR‐SB),and the neuropsychiatric inventory(NPI)were analyzed.Results:There was no significant difference in the NPI between patients with and without a history of stroke,hypertension,and diabetes.No significant difference in the NPI was identified between different sexes or different Apolipoprotein E(APOE)alleles.The NPI score was significantly correlated with the duration of education(r=–0.4515,P=0.0172),CASI(r=–0.2915,P<0.0001),MMSE(r=–0.8476,P<0.0001),and CDR‐SB(r=2.2839,P<0.0001).WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC(P=0.0255).After adjusting for age,duration of education,and CASI,WMC in the right frontal lobe remained significantly associated with the NPI score(β=3.8934,P=0.042).Conclusions:WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis.Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.

Grifola frondosa polysaccharides alleviate Alzheimer's disease in rats

Objective:To evaluate the effect of Grifola frondosa polysaccharides(GFP)in a rat model of Alzheimer’s disease(AD).Methods:Seventy-five rats were divided into five groups:the normal control group and the AD group treated with or without GFP(100,200,and 400 mg/kg).Behavioral responses in the open field test and elevated plus maze test were assessed.Additionally,the levels of malondialdehyde and ferric-reducing ability of plasma,and the mRNA expressions of TNF-α,IL-6,and IL-1βin the hippocampus were measured.Results:Treatment with GFP significantly improved AD-induced behavioral changes in the open field test and elevated plus maze test(P<0.05).In addition,the level of malondialdehyde and the mRNA expressions of TNF-α,IL-6,and IL-1βwere decreased by GFP treatment in a dose-dependent manner in AD rats(P<0.05),while the level of ferric-reducing ability of plasma was significantly increased(P<0.05).Conclusions:Oral administration of GFP can reduce inflammation and oxidative stress,as well as improve behavioral responses associated with AD,suggesting its potential use in AD treatment.However,additional studies are needed to elucidate its underlying mechanisms and efficacy.