Objective:To analyze the correlation between caregiver characteristics and clinical manifestations of patients with Alzheimer′s disease (AD) dementia.Methods:It was a cross-sectional study. A total of 167 patients with AD dementia and 167 matched caregivers from Chinese Imaging, Biomarkers, and Lifestyle study of Alzheimer′s Disease (CIBL) study between January 1 and December 31, 2023 were consecutively selected as the study subjects. The data such as gender, age, body max index (BMI), waist to hip ratio, educational years, combined chronic diseases, disease course and the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL), Mini-Nutritional Assessment (MNA), and Dietary Diversity Score (DDS) of the patients were collected. The data such as gender, educational years, the relationship with patients, and the Caregiver Burden Inventory (CBI) score in the caregivers were also evaluated. According to the gender of caregivers, the patients were divided into female caregiver group (108 cases) and male caregiver group (59 cases). The Spearman correlation and multiple linear regression analyses were used to assess the impact of the caregiver characteristics on the cognitive function, NPS, activities of daily living, and nutritional status of the patients with AD dementia.Results:Among the 167 patients with AD dementia, 80 cases were men, and 87 cases were women, with a mean age of (68.43±7.51) years. Among the 167 matched caregivers, 59 were spouse, 98 were offspring, and 10 were others (nanny or other relatives). The AD patients in the male caregiver group had lower BMI and MNA scores than those in female caregivers′ group [(23.35±3.70) vs (24.80±3.33) kg/m 2, 22.00 (20.00, 24.50) vs 24.00 (21.00, 26.00) points] (both P<0.05). The educational years of the caregivers was negatively related to the ADL score ( r=-0.196), and was positively related to the MNA score of the patients ( r=0.180) (both P<0.05); while the CBI score of the caregiver was positively related to the age ( r=0.180), NPI score ( r=0.568) and ADL scores ( r=0.702) in the patients, and it was negatively related to the BMI ( r=-0.163), MMSE score ( r=-0.499), MoCA score ( r=-0.491) and MNA scores ( r=-0.387) in the patients (all P<0.05). The shorter educational years and elevated CBI score were independent risk factors for the decline in the MMSE score ( β=0.310, 95% CI: 0.021-0.598; β=-0.225, 95% CI:-0.297--0.154) and MNA score ( β=0.204, 95% CI: 0.067-0.340; β=-0.082, 95% CI:-0.116--0.049), as well as the increase in the NPI score ( β=-0.628, 95% CI:-1.208--0.047; β=0.575, 95% CI: 0.431-0.718) and ADL score ( β=-0.519, 95% CI:-0.860--0.179; β=0.361, 95% CI: 0.277-0.445) in the patients with AD dementia (all P<0.001). Conclusions:A low educational level of caregivers and a heavy caregiver burden are associated with decreased cognitive function, worsening NPS, reduced ADL, and declining nutritional status in patients with AD dementia.

Objective:To analyze the correlation between caregiver characteristics and clinical manifestations of patients with Alzheimer′s disease (AD) dementia.Methods:It was a cross-sectional study. A total of 167 patients with AD dementia and 167 matched caregivers from Chinese Imaging, Biomarkers, and Lifestyle study of Alzheimer′s Disease (CIBL) study between January 1 and December 31, 2023 were consecutively selected as the study subjects. The data such as gender, age, body max index (BMI), waist to hip ratio, educational years, combined chronic diseases, disease course and the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL), Mini-Nutritional Assessment (MNA), and Dietary Diversity Score (DDS) of the patients were collected. The data such as gender, educational years, the relationship with patients, and the Caregiver Burden Inventory (CBI) score in the caregivers were also evaluated. According to the gender of caregivers, the patients were divided into female caregiver group (108 cases) and male caregiver group (59 cases). The Spearman correlation and multiple linear regression analyses were used to assess the impact of the caregiver characteristics on the cognitive function, NPS, activities of daily living, and nutritional status of the patients with AD dementia.Results:Among the 167 patients with AD dementia, 80 cases were men, and 87 cases were women, with a mean age of (68.43±7.51) years. Among the 167 matched caregivers, 59 were spouse, 98 were offspring, and 10 were others (nanny or other relatives). The AD patients in the male caregiver group had lower BMI and MNA scores than those in female caregivers′ group [(23.35±3.70) vs (24.80±3.33) kg/m 2, 22.00 (20.00, 24.50) vs 24.00 (21.00, 26.00) points] (both P<0.05). The educational years of the caregivers was negatively related to the ADL score ( r=-0.196), and was positively related to the MNA score of the patients ( r=0.180) (both P<0.05); while the CBI score of the caregiver was positively related to the age ( r=0.180), NPI score ( r=0.568) and ADL scores ( r=0.702) in the patients, and it was negatively related to the BMI ( r=-0.163), MMSE score ( r=-0.499), MoCA score ( r=-0.491) and MNA scores ( r=-0.387) in the patients (all P<0.05). The shorter educational years and elevated CBI score were independent risk factors for the decline in the MMSE score ( β=0.310, 95% CI: 0.021-0.598; β=-0.225, 95% CI:-0.297--0.154) and MNA score ( β=0.204, 95% CI: 0.067-0.340; β=-0.082, 95% CI:-0.116--0.049), as well as the increase in the NPI score ( β=-0.628, 95% CI:-1.208--0.047; β=0.575, 95% CI: 0.431-0.718) and ADL score ( β=-0.519, 95% CI:-0.860--0.179; β=0.361, 95% CI: 0.277-0.445) in the patients with AD dementia (all P<0.001). Conclusions:A low educational level of caregivers and a heavy caregiver burden are associated with decreased cognitive function, worsening NPS, reduced ADL, and declining nutritional status in patients with AD dementia.

Objective:To analyze the gender difference in behavioral and psychological symptoms of dementia (BPSD) of amnestic mild cognitive impairment (aMCI) and Alzheimer′s disease (AD).Methods:It was a cross-sectional study. The clinical data of 201 patients with aMCI and 146 patients with AD were continuously collected from the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease (CIBL) cohort between June 1, 2021 to February 1, 2023 in Beijing Tiantan Hospital, Capital Medical University. The BPSD subtypes were compared between different gender. The gender-different BPSD subtypes were divided into depression group (126 cases) and non-depression group (221 cases), anxiety group (140 cases) and non-anxiety group (207 cases), indifference group (131 cases) and non-indifference group (216 cases). The sociodemographic data (age, sex, education level, marital status), hypertension, diabetes, stroke, heart disease, hyperlipidemia, smoking history, drinking history, carrier status of apolipoprotein E epsilon4 allele (APOE ε4), and the scores of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activity of Daily Living (ADL) were compared by using hypothesis testing. Multivariate logistic regression was used to analyze the gender differences of BPSD in aMCI and AD patients.Results:The incidence rates of depression and anxiety in female were both significantly higher than those in male (44.93% vs 23.57%, 44.93% vs 33.57%), and the incidence rate of apathy was significantly lower than that in male (32.37% vs 45.71%) (all P<0.05). The proportion of female and ADL scores in depression group were both significantly higher than those in non-depression group [73.81% vs 51.58%, 22.00 (20.00, 30.00) vs 20.00 (20.00, 26.00) points], and the proportion of smoking and drinking history and MoCA scores in depression group were all significantly lower than those in non-depression group [13.49% vs 25.79%, 19.84% vs 35.75%, 16.00 (10.00, 22.00) vs 19.00 (13.00, 24.00) points] (all P<0.05). The proportion of female and ADL scores in anxiety group were both significantly higher than those in non-anxiety group [66.43% vs 55.07%, 23.00 (20.00, 30.75) vs 20.00 (20.00, 25.00) points], and the MMSE and MoCA scores in anxiety group were both significantly lower than those in non-anxiety group [23.00 (16.00, 27.00) vs 24.00 (19.00, 28.00) points, 16.00 (10.00, 21.00) vs 20.00 (13.00, 13.00) points] (all P<0.05). The proportion of female and the MMSE and MoCA scores in apathy group were all significantly lower than those in non-apathy group [51.15% vs 64.81%, 19.00 (11.00, 25.00) vs 26.00 (22.00, 28.00) points, 14.00 (7.00, 19.00) vs 21.00 (15.25, 24.00) points], and the age, proportion of APOE ε4 carriers and ADL scores in apathy group were all significantly higher [67.0 (61.0, 76.0) vs 66.0 (60.0, 71.0) years, 42.74% vs 31.31%, 27.00 (22.00, 38.00) vs 20.00 (20.00, 22.00) points] (all P<0.05). Female ( OR=2.384, 95% CI: 1.274-4.459) and decrease in MoCA score ( OR=0.955, 95% CI: 0.914-0.998) were positively correlated with risk of depression. Female ( OR=1.704, 95% CI: 1.077-2.695) was positively correlated with risk of anxiety. Male ( OR=0.558, 95% CI: 0.333-0.936), decrease in MoCA scores ( OR=0.937, 95% CI: 0.894-0.983) and increase in ADL scores ( OR=1.070, 95% CI: 1.027-1.116) were positively correlated with risk of apathy (all P<0.05). Conclusions:There are significant gender differences in BPSD in aMCI and AD patients. Female is positively correlated with risk of depression and anxiety, while male is positively correlated with the occurrence of apathy. Clinical attention should be paid to hierarchical management of BPSD patients of different gender.

Objective:To analyze the correlation between blood pressure variability (BPV) and behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD).Methods:In this retrospective cohort study, sixty-nine patients with AD from Beijing Tiantan Hospital, Capital Medical University, the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease were consecutively collected from February 1 to August 31, 2023. The patients were divided into the BPSD group (50 patients) and the control group (19 patients) according to with or without BPSD. The patients′ general information were collected, such as age at enrolment, gender, duration of education, and history of hypertension, diabetes, cerebral infarction, hyperlipoidemia, smoking, alcohol consumption, and carrier status of apolipoprotein E epsilon4 allele (APOE ε4). The 24-hour ambulatory blood pressure monitoring instruments were also used to collect the patients′ mean systolic blood pressure, mean diastolic blood pressure and 12 BPV indicators, which covered standard deviation (SD) and coefficient of variation (CV) of systolic and diastolic blood pressure throughout the day, daytime and nighttime. The Montreal Cognitive Assessment (MoCA) was used to assess their cognitive function, and the Activity of Daily Living (ADL)-14 items was used to assess their daily living abilities; hypothesis tests were used to compare the general information, MoCA scores, ADL-14 items scores, mean blood pressure and BPV indicators between the two groups; the multivariate logistic regression analysis was conducted to explore the related factors of BPSD in AD patients; Spearman correlation analysis was used to test the correlation between the total score of neuropsychiatric inventory (NPI) and BPV indicators in AD patients with BPSD.Results:In the BPSD group, the incidence rate of hypertension and MoCA scores were both significantly lower than those in the control group [44.00% vs 73.70%, (9.72±5.60) vs (14.53±5.52) points], but ADL-14 items scores and nocturnal systolic blood pressure CV were both significantly higher [23.00 (17.00, 29.25) vs 14.00 (14.00, 17.00) points, 8.89%±2.26% vs 7.52%±2.30%] (all P<0.05). Elevated ADL-14 items scores ( OR=1.379, 95% CI: 1.131-1.681) and nocturnal systolic blood pressure CV ( OR=1.387, 95% CI: 1.003-1.918) were positive correlation factors for the risk of BPSD in AD patients (all P<0.05). The daytime systolic blood pressure SD ( r=0.375) and CV ( r=0.357) were both positively correlated with total NPI scores in AD patients with BPSD (all P<0.05). Conclusion:BPV is correlated with BPSD in AD patients. Nocturnal systolic blood pressure CV is a positive correlation factor for the risk of BPSD in AD patients, and the total scores of NPI in AD patients are positively correlated with daytime systolic blood pressure SD and CV. It suggests that controlling BPV is a potential therapeutic measure to improve the BPSD of AD patients.

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.

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

Objectives:To analyze the potential biomarkers of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD) continuum.Methods:A prospective cohort study was consecutively conducted on 179 patients with AD continuum (135 presented with BPSD, 44 patients without BPSD as control) from Capital Medical University, Beijing Tiantan Hospital, the Chinese imaging biomarkers and lifestyle cohort between January 1, 2021 and December 31, 2022. Gender, age, body max index, education level, diagnosis, the apolipoprotein E epsilon4 allele (APOE ε4) carrier status, the scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), cerebrospinal fluid (CSF) AD-related pathological biomarkers (Aβ 42, Aβ 40, Aβ 42/40, tTau, pTau181), and blood biomarkers (white blood cell count, red blood cell count, hemoglobin, platelet, total bilirubin, albumin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose, erythrocyte sedimentation rate, homocysteine, vitamin B 12, folate) were compared between the two groups by using hypothesis testing and univariate logistic regression analysis. Multivariate logistic regression analysis was used to analyze the potential biomarkers associated with BPSD in patients with AD. Results:Among the 179 patients with AD continuum in the final analysis, 77 patients were men, 102 cases were women; 35 patients were identified with mild cognitive impairment (MCI) due to AD and 144 patients with AD dementia stage, the mean age was (66.54±9.75) years. Compared with those in control group, patients with BPSD had lower cerebrospinal fluid (CSF) Aβ 40 and blood hemoglobin levels [7.08 (4.42, 15.42) vs 9.62 (6.45, 12.12) pg/L, (132.70±13.37) vs (138.80±14.38) g/L] ( U=-1.856, t=2.579, P<0.05). The levels of CSF Aβ 40 ( OR=0.030, 95% CI: 0.001-0.760) and blood hemoglobin ( OR=0.051, 95% CI: 0.004-0.670) were independently negatively associated with BPSD in patients with AD continuum (both P<0.05). Conclusion:The decreased levels of CSF Aβ 40 and blood hemoglobin could be considered as potential biomarkers in detecting BPSD in patients with AD continuum.

Empathy is one of the basic qualities that modern clinicians need to possess.Although traditional Chinese medicine has no definition for empathy,it does have practical applications.TCM clinical empathy,nurtured by Chinese excellent traditional culture,can be seen in TCM classics and clinical practice of famous doctors of previous generations,and has been inherited in the spiritual thinking of modern colleges and universities of Chinese medicine.However,at present,there is a relative lack of special training courses for"empathy"in Chinese medicine higher education.This paper first briefly describes the connotation,history,and neuroscience mechanism of the concept of"empathy".Secondly,the manifestations and characteristics of"empathy"in the clinical practice of traditional Chinese medicine were sorted out.Finally,we use modern medicine and psychology for reference,and combine the characteristics of traditional Chinese medicine to make suggestions for the cultivation of the ability of"empathy"in clinical Chinese medicine.

Objective:To explore the impact factors of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD).Methods:The clinical data of 116 patients with AD admitted to the Outpatient Department of Cognitive Neurology of Beijing Tiantan Hospital, Capital Medical University from June 1, 2021 to March 1, 2022 were collected continuously. The patients were divided into BPSD group ( n=85) and control group ( n=31) according to the presence or absence of BPSD. The sociodemographic data (gender, age, body mass index, years of education), the medical history of hypertension, diabetes mellitus, hyperlipidemia, and the scores of the Mini-Mental State Examination (MMSE), the Activity of Daily Living (ADL), Mini-Nutritional Assessment scale (MNA) and Caregiver Burden Inventory (CBI) were compared between the two groups with hypothesis test and univariate logistic regression analysis. The statistically significant factors in hypothesis test and univariate logistic regression analysis were enrolled in multivariate logistic regression analysis to further identify the factors associated with BPSD in patients with AD. Results:There was no significant statistics differences in the gender, age, body max index, years of education and the medical history of hypertension, diabetes mellitus, hyperlipidemia between the two groups (all P>0.05). Compared with control group, patients with BPSD had lower scores of MMSE and MNA scales [(16.24±7.52) vs (20.81±5.09) points, (21.62±3.75) vs (24.87±2.89) points] (both P<0.001) and higher scores of ADL and CBI scales [29.00 (22.00, 38.50) vs 22.00 (20.00, 25.00) points, 25.00 (12.50, 41.00) vs 3.00 (0.00, 11.00) points](both P<0.001). The multiple logistic regression analysis demonstrated that the decreased MNA scores ( OR=0.762, 95% CI: 0.631-0.922; P=0.005) and elevated CBI scores ( OR=1.077, 95% CI: 1.029-1.128; P=0.002) were associated with BPSD in patients with AD. Conclusion:The malnutrition or the risk of malnutrition and greater caregiver burden can independently contribute to the onset of BPSD in patients with AD.

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTS^LepRb) neurons notably activated breathing. Moreover, stimulation of NTS^LepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTS^LepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTS^LepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTS^LepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca²⁺ transients in most NTS^LepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.
Leptin/pharmacology* ; Membrane Potentials ; Neurons/metabolism* ; Solitary Nucleus/metabolism*