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.

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.

Streptococcus mutans (S. mutans) is generally regarded as a major contributor to dental caries because of its ability to synthesize extracellular polysaccharides (EPS) that aid in the formation of plaque biofilm. The VicRKX system of S. mutans plays an important role in biofilm formation. The aim of this study was to investigate the effects of vicK gene on specific characteristics of EPS in S. mutans biofilm. We constructed single-species biofilms formed by different mutants of vicK gene. Production and distribution of EPS were detected through atomic force microscopy, scanning electron microscopy and confocal laser scanning microscopy. Microcosmic structures of EPS were analyzed by gel permeation chromatography and gas chromatography-mass spectrometry. Cariogenicity of the vicK mutant was assessed in a specific pathogen-free rat model. Transcriptional levels of cariogenicity-associated genes were confirmed by quantitative real-time polymerase chain reaction. The results showed that deletion of vicK gene suppressed biofilm formation as well as EPS production, and EPS were synthesized mostly around the cells. Molecular weight and monosaccharide components underwent evident alterations. Biofilms formed in vivo were sparse and contributed a decreased degree of caries. Moreover, expressional levels of genes related to EPS synthesis were down-regulated, except for gtfB. Our report demonstrates that vicK gene enhances biofilm formation and subsequent caries development. And this may due to its regulations on EPS metabolism, like synthesis or microcosmic features of EPS. This study suggests that vicK gene and EPS can be considered as promising targets to modulate dental caries.
Animals ; Biofilms ; Dental Caries ; Dental Plaque ; Rats ; Streptococcus mutans/genetics*