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.

Role of antipsychotics for treating behavioral and psychological symptoms of dementia

Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes （NHs） for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the preva-lence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest effcacy in reducing symptoms of aggression and psychosis in dementia, there is insuffcient evidence to routinely rec-ommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.

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.

Quantitative evaluation of severity of behavioral and psychological symptoms of dementia in patients with vascular dementia

To quantitatively evaluate severity of behavioral and psychological symptoms of dementia(BPSD)for vascular dementia(VD).Changes of 51 patients with VD in BPSD between the first and 24th week were assessed using the Neuropsychiatric Inventory(NPI)and the behavioral pathology in Alzheimer’s disease(BEHAVE-AD)rating scale,in detrended fluctuation analysis(DFA)represented by diurnal activity(DA),evening activity(EA),and nocturnal activity(NA),and the relationships were analyzed.The subscores of activity disturbances,diurnal rhythm disturbances,and anxieties and phobias in the BEHAVE-AD score,and that of agitation,irritability,and sleep disorder in the NPI score were significantly increased compared with the first week,as was for the changes for EA in the DFA value.A linear correlation was observed between the changes of activity disturbances plus anxieties and phobias,and those of DA,and between the development of diurnal rhythm and those of EA,the vehement and autism scores and those of DA,and the difference in sleep disorder scores and those of EA,respectively.Analysis of DA,NA,and EA may reflect the fluctuational degrees of VD-BPSD,can provide a useful assessment of VD-BPSD accompanied by clinical scores for VD.

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.