Association between cerebrospinal fluid pressure and cognition in patients with Alzheimer's disease and Lewy body dementia.

BACKGROUND: The relationship between cerebrospinal fluid pressure (CSFP) and cognition has received little research attention. The purpose of this study was to explore the relationship between CSFP and cognition in patients with Alzheimer's disease (AD) and patients with Lewy body dementia (LBD). METHOD: We included 178 participants, including 137 patients with AD and 41 patients with LBD (including dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD)). CSFP was measured by lumbar puncture, and a patient-reported history and laboratory test data were collected. Logistic and linear regression analyses were used to evaluate the associations between CSFP and cognition, the cerebrospinal fluid (CSF) / serum albumin ratio (Qalb), and CSF biomarkers of AD. RESULTS: The mean age of the included patients was 63.58 ± 8.77 years old, and the mean CSFP was 121 ± 33.72 mmH2O. A total of 76.9% of the patients had a CSFP distribution of [90-170) mmH2O, 46 patients (25.8%) had severe dementia, 83 patients (46.6%) had moderate dementia, 28 patients (15.7%) had mild dementia, and 21 patients (11.8%) had mild cognitive impairment (MCI) (including 16 patients with MCI due to AD and 5 patients with MCI due to LBD). In all patients (p value < 0.001) and in patients with AD (p value = 0.01), the mean cerebrospinal fluid pressure (CSFP) was higher in patients with MCI than in patients with dementia. In multivariate analysis, in all patients (OR: 6.37, 95% confidential interval (CI): 1.76-23.04, p = 0.005) and patients with AD (odds ratio (OR): 5.43, 95% CI: 1.41-20.87, p = 0.005), a CSFP in the lowest quartile ([50-90) mmH2O) was associated with a higher level of severe dementia than a CSFP in the highest quartile ([170-210) mmH2O). In addition, there was a significant linear correlation between CSFP and the Mini-Mental State Examination (MMSE) score in all patients with dementia (r = 0.43, p = 0.04, Durbin-Watson test (D-W test) = 0.75). CONCLUSION: In patients with AD, the mean cerebrospinal fluid pressure was higher in patients with MCI than in patients with dementia, and the decrease in CSFP was related to a more serious dementia level. However, no such relationship was found in patients with LBD.

White matter hyperintensities in cognitive impairment with Lewy body disease: a multicentre study.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are associated with cognitive deficits and worse clinical outcomes in dementia, but rare studies have been carried out of cognitive impairment in Lewy body disease (CI-LB) patients. The objective was to investigate the associations between WMHs and clinical manifestations in patients with CI-LB. METHODS: In this retrospective multicentre cohort study, 929 patients (486 with dementia with Lewy bodies [DLB], 262 with Parkinson's disease dementia [PDD], 74 with mild cognitive impairment [MCI] with Lewy bodies [MCI-LB] and 107 with Parkinson's disease with MCI [PD-MCI]) were analysed from 22 memory clinics between January 2018 and June 2022. Demographic and clinical data were collected by reviewing medical records. WMHs were semi-quantified according to the Fazekas method. Associations between WMHs and clinical manifestations were investigated by multivariate linear or logistic regression models. RESULTS: Dementia with Lewy bodies patients had the highest Fazekas scores compared with PDD, MCI-LB and PD-MCI. Multivariable regressions showed the Fazekas score was positively associated with the scores of Unified Parkinson's Disease Rating Scale Part III (p = 0.001), Hoehn-Yahn stage (p = 0.004) and total Neuropsychiatric Inventory (p = 0.001) in MCI-LB and PD-MCI patients. In patients with DLB and PDD, Fazekas scores were associated with the absence of rapid eye movement sleep behaviour disorder (p = 0.041) and scores of Unified Parkinson's Disease Rating Scale Part III (p < 0.001), Hoehn-Yahn stage (p < 0.001) and the Montreal Cognitive Assessment (p = 0.014). CONCLUSION: White matter hyperintensity burden of DLB was higher than for PDD, MCI-LB and PD-MCI. The greater WMH burden was significantly associated with poorer cognitive performance, worse motor function and more severe neuropsychiatric symptoms in CI-LB.

Costs of dementia with lewy bodies: A Chinese multicenter cross-sectional study.

INTRODUCTION: Dementia with Lewy bodies (DLB) significantly increases the economic burden on caregivers and society, but few studies have focused on the costs. This study aims to evaluate the current economic costs of DLB and its related factors. METHODS: A total of 193 patients diagnosed with probable DLB were consecutively enrolled from 6 memory clinics between August 2017 to July 2021. Data were collected from August to December of 2021, patients' per capita annual economic costs related to DLB in the year preceding the interview were evaluated, and factors related to the costs were assessed using regression analysis. RESULTS: Patients with DLB led to per capita annual total costs of US $21,378.3 in 2021, with direct medical costs, direct non-medical costs and indirect costs of US $3471.4, US $3946.4 and US $13,960.5, respectively, accounting for 16.2%, 18.5% and 65.3%, of total costs. Factors related to the costs of DLB showed that impairments in activities of daily living (ADL) and caregivers' subjective burden had a greater impact on the total, direct medical and indirect costs. CONCLUSION: The economic burden of DLB in China is huge, and indirect costs account for the largest proportion, serious impairment of the ADL and the subjective burden of caregivers, which possibly has a greater effect on costs. The substantial contributions made by family members and other unpaid caregivers of DLB should be fully recognized in strategic policy discussions and in case-level planning and assessments.

The presence and co-incidence of geriatric syndromes in older patients with mild-moderate Lewy body dementia.

INTRODUCTION: Geriatric symptoms are common in dementia cases, while few studies have focused on these symptoms in Lewy body dementia (LBD). The purpose of this study is to investigate the distributions of Apolipoprotein E (APOE) ε4 and geriatric symptoms, and explore their associaitons in Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). METHODS: A retrospective study with 185 mild-moderate probable DLB (n = 93) and PDD (n = 92) patients was assigned. Demographic and clinical characteristics, neuropsychological assessments, and APOE genotypes were recorded. Description, correlation and logistic regression models were used to analyze the presence of geriatric symptom complaints and their associations with APOE ε4. RESULTS: DLB patients displayed more frequency of fluctuating cognition, visual hallucination, rapid eye movement sleep behavior disorder, delusion, depression, anxiety, apathy, and loss of appetite, whereas the PDD cases had constipation, fear of falling, and insomnia more frequently. The APOE ε4 allele was more common in DLB than PDD (29.9% vs. 7.0%, p < 0.001), and the patients with DLB + APOE ε4 (+) were presented more delusions (p = 0.005) and apathy (p = 0.007) than patients with PDD + APOE ε4 (+). We also found that the APOE ε4 allele was significantly associated with hyperhidrosis (OR = 3.472, 95%CI: 1.082-11.144, p = 0.036) and depression (OR = 3.002, 95%CI: 1.079-8.353, p = 0.035) in DLB patients, while there were no significant associations between APOE ε4 allele and the age at visit, the age at onset, scores of MDS-UPDRS III, H&Y stage, ADL, MMSE, MOCA and NPI, as well as the presences of fluctuating cognition, VH, parkinsonism and RBD in both groups. CONCLUSION: The presence and co-incidence of geriatric symptoms are common in patients with mild-moderate LBD. The presence of APOE ε4 allele is associated with hyperhidrosis and depression, but not global cognition, activitives of daily life, motor function and other neuropsychitric symptoms in DLB. These findings improve the awareness of geriatric symptoms, and contribute to the healthcare management of mild-moderate DLB and PDD.

The vascular risk factors and vascular neuropathology in subjects with autopsy-confirmed dementia with Lewy bodies.

BACKGROUND: The frequency of vascular risk factors (VRFs) and the relationship between vascular pathology and cognitive function in neurodegenerative disease remains incompletely understood. OBJECTIVE: The purpose of this study was to describe the frequency of VRFs and vascular pathology and explore the relationship between vascular pathology and cognitive function in dementia with Lewy bodies (DLB). METHODS: This study included 363 autopsy-confirmed DLB and 753 Alzheimer's disease (AD) patients from the National Alzheimer's Coordinating Center (NACC) database. We used chi-squared test and analysis of variance to compare the VRFs and related factors in DLB and AD. Multinomial logistic regression and Spearman's correlation test were used to examine the relationship between vascular pathology and cognitive function. RESULTS: No significant differences of VRFs were identified between DLB and AD. Alzheimer's disease patients had higher rates of microinfarcts (23.5% vs. 16.3%, p = 0.005) and moderate to severe amyloid angiopathy (45.9% vs. 36.1%, p = 0.002). In DLB patients, only cerebral amyloid angiopathy (CAA) pathology was negatively correlated with memory domain (r = -0.263, p < 0.001) and language (r = -0.112,p = 0.034). The rates of APOE ε4 allele carriers (60.0% vs. 44.9%, p = 0.004) and CAA pathology (45.9% vs.23.4%, p < 0.001) were much higher in the group with an intermediate likelihood of DLB than in the group with a high likelihood. There was a negative correlation between CAA pathology and memory (logical memory) in the group with an intermediate likelihood of DLB. CONCLUSION: No difference of VRFs was identified between autopsy-confirmed DLB and AD. Cerebral amyloid angiopathy was shown to be an important pathology in DLB, which specifically correlated with memory and language. The groups with high and intermediate likelihood of DLB differed in terms of CAA pathology, and CAA pathology may play an important role in the development of DLB.

Survival and causes of death among people with clinically diagnosed dementia with Lewy bodies: A multicenter cohort study.

OBJECTIVE: A comprehensive study of the survival and causes of death of people with clinically diagnosed Dementia with Lewy bodies (DLB) were few. The aim of our study was to investigate the survival and causes of death of DLB. METHODS: The patients diagnosed with probable DLB were consecutively enrolled from five memory clinics in China across a 5-year period (2017-2021) with mortality data updated to December 2021. The endpoint was all-cause death. Survival analysis including Cox regression by groups (time both from disease onset and the first visit to death) and causes of death were evaluated. RESULTS: Of the 108 patients with DLB, 54 (50%) were men and the time from onset of disease to the first visit to the memory clinic (lag time) was 24 (12-48) months. During follow-up, 28.7% (n = 31) of the patients died. The median survival time both from disease onset and the first visit were 81 (95% cognitive impairment (CI) 69.09-92.91) and 45 (95% CI 34.78-55.22) months, respectively. The use of antipsychotic drugs (HR 0.15, 95% CI: 0.03-0.75), moderate to severe dementia (Clinical Dementia Rating [CDR]) at the first visit (HR 0.22, 95% CI 0.78 to 0.62) and the longer lag time (HR 0.943, 95% CI 0.92-0.97) predicted a shorter survival. Failure to thrive (stopped eating, drinking) or multiple organ dysfunction syndrome (MODS) maybe the most common cause of death (41.7%), followed by pneumonia or aspiration (29.2%). CONCLUSIONS: The factors associated with survival time were disease severity level, antipsychotic drug use and lag time to seek medical advice. Failure to thrive or MODS and pneumonia were probably the most common cause of death. The long-term outcomes of DLB patients may be helpful to guide clinicians counseling patients and caregivers.

Association between hemoglobin level and cognitive profile in old adults: A cross-sectional survey.

OBJECTIVE: In the present study, the association between Hemoglobin (HGB) level and cognitive profile was investigated and whether it affected the dementia risk in older adults. METHODS: A cross-sectional population-based survey that included 3519 individuals ≥65 years of age was conducted in 2019. Basic demographic characteristics were collected. The neuropsychological assessments and blood tests were administered to evaluate cognition and HGB level. Generalized additive models were used to analyze the non-linear association between HGB levels and cognitive function. Logistics regression models were utilized to analyze the associations between HGB level and dementia risk. RESULTS: Overall, 459 (12.7%) participants were diagnosed with dementia and there were more females (54.7%) than males (45.3%). The number of subjects with anemia (3%) or hyperhemoglobinemia (5.2%) was higher than participants with normal HGB level. A visual representation of the relationship between HGB level and Mini-Mental State Examination (MMSE) score showed an inverted U-curve, which is more evident in female. Logistics regression models showed that anemia (odds ratio, OR = 1.826, 95% confidence interval, CI: 1.166-2.860, p < 0.01), but not hyperhemoglobinemia, significantly increased the risk of dementia. These trends were not the same for males and females. An abnormal HGB level had greater effects in females, resulting in higher risk of dementia for females with anemia or hyperhemoglobinemia than subjects with normal HGB level including males. CONCLUSION: Both low and high HGB levels can lead to cognitive decline in the incidence of dementia, indicating an inverted U-shaped curve association may exist between HGB level and global cognitive profile.

Prevalence and risk factors of stroke in a rural area of northern China: a 10-year comparative study.

BACKGROUND AND AIMS: Stroke is currently the leading cause of death in China; however, the past decade has produced no new epidemiological studies of stroke. Therefore, the current study aimed to compare the prevalence and risk factors of stroke between 2010 and 2019. METHODS: A comparative study was used to analyze the prevalence of risk factors for stroke in a population aged 65 years or older between 2010 and 2019. Demographic characteristics, risk factors, medical history, and other clinical characteristics were collected for all participants via door-to-door interviews and inpatient hospital records. RESULTS: The standardized prevalence of stroke was 7.9% in 2010 and 14.2% in 2019 (p < 0.001). The prevalence of stroke was significantly higher in men than in women (p < 0.05) for all age groups. The risk factors of stroke were being male, hypertension, and diabetes mellitus in both 2010 and 2019. When comparing the risk factors between 2010 and 2019, these risk factors were statistically significantly more strongly associated with stroke in 2019 than in 2010. CONCLUSION: The current study suggests that the prevalence of stroke increased nearly by twofold in a population aged 65 years or older within the past 10 years. Hypertension, diabetes mellitus, and being male were the primary risk factors. In addition, these factors were more significantly associated with stroke in 2019 compared to 2010.

Clinical characteristics of Lewy body dementia in Chinese memory clinics.

BACKGROUND: Lewy body dementia (LBD), consisting of dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is the second most common type of neurodegenerative dementia in older people. The current study aimed to investigate the clinical characteristics of LBD in Chinese memory clinics. METHODS: A total of 8405 dementia medical records were reviewed, revealing 455 patients with LBD. Demographic data, neuropsychological scores, and the scale for Medial Temporal lobe Atrophy (MTA) were then analyzed from nine memory clinics in the China Lewy Body Disease Collaborative Alliance. RESULTS: The clinical proportion of LBD among the subjects and among all dementia types was 5.4% (4.9-5.9%) and 7.3% (6.7-8.0%), respectively, with a mean onset age of 68.6 ± 8.4 years. Patients with DLB comprised 5.6% (n = 348, age of onset 69.1 ± 8.3), while PDD comprised 1.7% (n = 107, age of onset 66.7 ± 8.8) of all dementia cases. There were slightly more males than females with DLB (n = 177, 50.9%) and PDD (n = 62, 57.9%). Patients with DLB had a poorer performance compared to those with PDD on the MMSE (16.8 ± 7.1 vs. 19.5 ± 5.7, p = 0.001), the MoCA (11.4 ± 6.6 vs. 14.0 ± 5.8, p<0.001), the CDR (1.8 ± 0.7 vs. 1.6 ± 0.7, p = 0.002), and the MTA (1.8 ± 0.7 vs. 1.2 ± 0.6, p = 0.002). Diagnostic differences for LBD exist among the centers; their reported proportions of those with DLB ranged from 0.7 to 11.4 and those with PDD ranged from 0.0 to 2.9%. CONCLUSIONS: Variations of diagnoses exists in different regions and the clinical proportion of LBD is likely to be underestimated in China and other regions.

Cerebrospinal fluid/serum albumin ratio in patients with Lewy body disease: a systematic review and meta-analysis.

Background: Abnormal cerebrospinal fluid (CSF)/serum albumin ratio (Qalb) levels have been observed in patients with cognitive impairment. Few studies have specifically focused on Lewy Body Disease (LBD), and the results were controversial. Thus, we conducted this systematic review and meta-analysis to investigate Qalb levels in patients with LBD by including data from different studies. Method: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for a collection of studies containing studies comparing Qalb levels in patients with LBD and healthy controls (including healthy controls and other dementia subtypes). In the initial search, 86 relevant papers were retrieved. Standardized mean differences (SMD) in Qalb levels were calculated using a random effects model. Results: A total of 13 eligible studies were included. Mean Qalb levels were significantly higher in patients with LBD compared to healthy older adults [standardized mean difference (SMD): 2.95, 95% confidence interval (CI): 0.89-5.00, Z = 2.81, p = 0.005]; and were significantly higher in patients with LBD than in patients with Alzheimer's disease (AD) (SMD: 1.13, 95% CI: 0.42-1.83, Z = 3.15, p = 0.002);whereas mean Qalb levels were significantly higher in patients with frontotemporal lobar degeneration (FTLD) compared to those with AD (SMD: 1.13, 95% CI,0.14-2.13, Z = 2.24, p = 0.03). Conclusion: Qalb levels were significantly elevated in LBD patients compared with normal older adults and were higher than those in AD patients and FTLD patients, which helped in the differential diagnosis of LBD from other neurodegenerative diseases. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024496616.

Associations Between Plasma Orexin-A Level and Constipation in Cognitive Impairment.

BACKGROUND: Constipation is a common symptom in dementia, and the cause is controversial. Rare clinical studies focused on plasma orexin-A levels and constipation in dementia. OBJECTIVE: To evaluate the associations between orexin-A and constipation in patients with cognitive impairment. METHODS: A total of 21 patients with mild cognitive impairment (MCI), 142 with Alzheimer's disease (AD), and 57 with Lewy body dementia (LBD) were conducted. Besides informant-based history, neurological examinations or neuropsychological assessments, plasma levels of orexin-A, and constipation were assessed. The associations between orexin-A and constipation were evaluated by logistic regression models. RESULTS: There were 47/220 (21.36%) cognitive impairment patients having constipation, and the proportion of constipation in LBD (61.40%) was significantly higher than AD (5.63%) and MCI (19.05%). No significant age or sex differences in the prevalence of constipation were found in the MCI, AD, and LBD groups. We found the cognitive impairment patients with constipation had lower levels of plasma orexin-A [1.00 (0.86, 1.28) versus 1.29 (1.01, 1.50) ng/ml, p < 0.001] than those without. And the plasma levels of orexin-A were significantly associated with the occurrence of constipation after adjusting for all variables in all patients with cognitive impairment (OR = 0.151, 95% CI: 0.042-0.537, p = 0.003). And the same finding was more prominent in the LBD group (p = 0.048). CONCLUSIONS: The decrease of plasma level of orexin-A is closely associated with the occurrence of constipation. Orexin-A has an intestinal protective effect and is involved in the gastrointestinal symptoms of patients with cognitive impairment.

Characterization of de novo Dementia with Lewy Body with different duration of rapid eye movement sleep behavior disorder.

BACKGROUND: Cognitive disorder, parkinsonism, autonomic dysfunction (AuD) and rapid eye movement sleep behavior disorder (RBD) can occur prior to or simultaneously with Dementia with Lewy Body (DLB) onset. RBD is generally linked with progressive neurodegenerative traits. However, associations between RBD with DLB, RBD without DLB, and RBD duration effects on DLB symptoms remain unclear. OBJECTIVES: To examine DLB symptom frequency and subtypes in RBD, and explore the effects of different RBD onset times on symptoms in de novo DLB patients. METHODS: In this multicenter investigation, we consecutively recruited 271 de novo DLB patients. All had standardized clinical and comprehensive neuropsychological evaluations. Subgroup analyses, performed based on the duration of RBD confirmed by polysomnography before the DLB diagnosis, we compared the proportion of patients with cognitive impairment, parkinsonism, and AuD features between groups. RESULTS: Parkinsonism and AuD incidences were significantly elevated in DLB patients with RBD when compared with patients without RBD. Subgroup analyses indicated no significant differences in parkinsonism between DLB patients who developed RBD ≥10 years prior to the DLB diagnosis and DLB patients without RBD. The incidence of non-tremor-predominant parkinsonism and AuD was significantly higher in DLB patients whose RBD duration before the DLB diagnosis was <10 years when compared with DLB patients without RBD. CONCLUSIONS: We identified significant symptom and phenotypic variability between DLB patients with and without RBD. Also, different RBD duration effects before the DLB diagnosis had a significant impact on symptomatic phenotypes, suggesting the existence of a slowly progressive DLB neurodegenerative subtype.

Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Analysis of clinical characteristics of mirror and TV signs in Alzheimer's disease and dementia with Lewy bodies.

OBJECTIVE: This study explored the clinical features of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) and analyzed the differences in neurologic syndromes, including mirror and TV signs, between different groups. METHODS: Patients with AD and DLB (325 and 115, respectively) hospitalized in our institution were enrolled. We compared psychiatric symptoms and neurologic syndromes between the DLB and AD groups and within each subgroup, including the mild-moderate and severe subgroups. RESULTS: The prevalence rates of visual hallucination, parkinsonism, rapid eye movement sleep behavior disorder, depression, delusion, and the Pisa sign were significantly higher in the DLB group than in the AD group. Furthermore, within the mild-moderate subgroup, the mirror sign and Pisa sign prevalence rates were significantly higher in the DLB group than in the AD group. In the severe subgroup, no significant difference was found in any neurologic sign between the DLB and AD groups. CONCLUSION: Mirror and TV signs are rare and often disregarded because they are not usually invoked during routine inpatient or outpatient interviews. According to our findings, the mirror sign is uncommon in early AD patients but common in early DLB patients and should receive increased attention.

Alzheimer's disease pathology: pathways between chronic vascular risk factors and blood-brain barrier dysfunction in a cohort of patients with different types of dementia.

Background: Blood brain barrier (BBB) breakdown is considered a potential mechanism of dementia. The Alzheimer's disease (AD) biomarkers and vascular factors are also associated with BBB permeability. Objective: In the present study, the combination effects of neuropathological biomarkers of AD and chronic vascular risk factors for BBB were investigated. Methods: The cerebrospinal fluid (CSF)/serum albumin ratio (Qalb), an indicator of BBB permeability, was measured in a total of 95 hospitalized dementia patients. The demographics, clinical information, and laboratory tests were collected from the inpatient records. The CSF neuropathological biomarkers of AD and apolipoprotein E (APOE) genotype were also collected. The mediation analysis model was used to calculate the associations among neuropathological biomarkers of AD (mediator), the Qalb, and chronic vascular risk factors. Results: Three types of dementia, AD (n = 52), Lewy body dementia (LBD, n = 19), and frontotemporal lobar degeneration (n = 24), were included with a mean Qalb of 7.18 (± 4.36). The Qalb was significantly higher in dementia patients with type 2 diabetes mellitus (T2DM, p = 0.004) but did not differ based on the presence of APOE ε4 allele, CMBs, or amyloid/tau/neurodegeneration (ATN) framework. The Qalb was negatively associated with the levels of Aß1-42 (B = -20.775, p = 0.009) and Aß1-40 (B = -305.417, p = 0.005) and positively associated with the presence of T2DM (B = 3.382, p < 0.001) and the levels of glycosylated hemoglobin (GHb, B = 1.163, p < 0.001) and fasting blood glucose (FBG, B = 1.443, p < 0.001). GHb is a direct chronic vascular risk factor for higher Qalb (total effect B = 1.135, 95% CI: 0.611-1.659, p < 0.001). Ratios of Aß1-42/Aß1-40 or t-tau/Aß1-42 were mediators of the association between the Qalb and GHb; the direct effect of GHb on the Qalb was 1.178 (95% CI: 0.662-1.694, p < 0.001). Conclusion: Glucose exposure can directly or indirectly affect BBB integrity through Aß and tau, indicating glucose affects BBB breakdown and glucose stability plays an important role in dementia protection and management.

Analysis of positron emission tomography hypometabolic patterns and neuropsychiatric symptoms in patients with dementia syndromes.

AIMS: To estimate the proportions of specific hypometabolic patterns and their association with neuropsychiatric symptoms (NPS) in patients with cognitive impairment (CI). METHODS: This multicenter study with 1037 consecutive patients was conducted from December 2012 to December 2019. 18 F-FDG PET and clinical/demographic information, NPS assessments were recorded and analyzed to explore the associations between hypometabolic patterns and clinical features by correlation analysis and multivariable logistic regression models. RESULTS: Patients with clinical Alzheimer's disease (AD, 81.6%, 605/741) and dementia with Lewy bodies (67.9%, 19/28) mostly had AD-pattern hypometabolism, and 76/137 (55.5%) of patients with frontotemporal lobar degeneration showed frontal and anterior temporal pattern (FT-P) hypometabolism. Besides corticobasal degeneration, patients with behavioral variant frontotemporal dementia (36/58), semantic dementia (7/10), progressive non-fluent aphasia (6/9), frontotemporal lobar degeneration and amyotrophic lateral sclerosis (3/5), and progressive supranuclear palsy (21/37) also mostly showed FT-P hypometabolism. The proportion of FT-P hypometabolism was associated with the presence of hallucinations (R = 0.171, p = 0.04), anxiety (R = 0.182, p = 0.03), and appetite and eating abnormalities (R = 0.200, p = 0.01) in AD. CONCLUSION: Specific hypometabolic patterns in FDG-PET are associated with NPS and beneficial for the early identification and management of NPS in patients with CI.

The characteristic of nonmotor symptoms with different phenotypes and onsets in multiple system atrophy patients.

OBJECTIVES: The characteristic of nonmotor symptoms in patients with multiple system atrophy (MSA) has varied among previous studies. The objective was to investigatethe nonmotor characteristics in MSA patients with different phenotypes, sex and different onset patterns. METHODS: We performed a retrospective review of 1492 MSA patients. All cases were evaluatedby neurologists and assessed with motormanifestations, nonmotor symptoms, auxiliary examinationand brain MRI scans. RESULTS: Multiple system atrophy-cerebellar ataxia (MSA-C) was the predominant phenotype in 998 patients. Average age of onset (56.8 ± 9.2 years) was earlier, the disease duration (2.4 ± 2.2 year) was shorter and brain MRI abnormalities (49.2 %) were more frequently in MSA-C (P < 0.001). Multiple system atrophy-parkinsonism (MSA-P) patients were more likely to have nonmotor symptoms. After adjusted significant parameters, urinary dysfunction (OR 1.441, 95 %CI = 1.067-1.946, P = 0.017), constipation (OR 1.482, 95 %CI = 1.113-1.973, P = 0.007), cognitive impairment (OR 1.509, 95 %CI = 1.074-2.121, P = 0.018) and drooling (OR 2.095, 95 %CI = 1.248-3.518, P = 0.005) were associated with the MSA-P phenotype. Males were more likely to have orthostatic hypotension, urinary dysfunction, sexual dysfunction, drooling and females in constipation and probable RBD. In different onset patterns, constipation (59.2 %) and probable RBD (28.4 %) were more frequently in autonomiconset pattern. CONCLUSIONS: MSA-C is the predominant phenotype in Chinese patients, while many nonmotor symptoms are more common in MSA-P phenotype. Patients with different sex and onset patterns have different nonmotor characteristics. The different clinical features identified could help the physician counseling of MSA patients more easily and more accurately.

Characteristics of initial symptoms in patients with dementia with Lewy body disease.

Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. Although DLB is characterized by fluctuating cognitive impairment, some symptoms may appear before cognitive impairment, including rapid eye movement, sleep behavior disorder (RBD), psychiatric symptoms, autonomic symptoms, Parkinson's symptoms, etc. Therefore, DLB may be misdiagnosed as other diseases in its early stage. Objective: This study aimed to investigate the characteristics of initial symptoms of DLB, which could potentially offer essential clues for the earliest diagnosis of this disorder. Methods: A total of 239 patients with probable DLB who visited the cognitive impairment outpatient department of Tianjin Huanhu Hospital from September 2015 to March 2021 were consecutively enrolled. We retrospectively evaluated the initial symptoms of all included participants. The time of onset of initial symptoms was also assessed. Results: The most frequent initial symptom was memory loss (53.9%), followed by psychiatric symptoms (34.7%), RBD (20.9%), parkinsonism (15.1%), and autonomic symptoms (10.1%). Significant gender and age differences existed in the initial symptoms of patients with DLB. Conclusions: Our study elucidated the initial symptoms in patients with probable DLB. RBD was significantly more reported by men than by women, whereas women showed a higher incidence of visual and auditory hallucinations. A better understanding of the initial symptoms of DLB could lead to a more accurate diagnosis.

Autonomic symptoms are predictive of dementia with Lewy bodies.

INTRODUCTION: Autonomic symptoms are common in patients with dementia with Lewy bodies (DLB). Although autonomic dysfunction is considered as one of the primary early markers in patients with DLB, there are few studies that examine the timing of the onset of autonomic symptoms in these patients. The purpose of the current study was to evaluate the time of onset of autonomic symptoms in patients with DLB using a questionnaire. METHODS: Autonomic symptoms were evaluated in patients with DLB using the Scales for Outcomes in Parkinson's disease - autonomic (SCOPA-Aut) questionnaire. Time of the onset of autonomic symptoms of patients with DLB was also assessed relative to that of memory loss. RESULTS: A total of 106 patients with DLB were included. The most frequent symptom of dysautonomia in patients with DLB was constipation (60.4%), followed by orthostatic dizziness (33%), urinary frequency (30.2%), and daytime hyperhidrosis (22.6%). The gastrointestinal system was the most prominent system of autonomic dysfunction in patients with DLB. Orthostatic dizziness, daytime hyperhidrosis, and constipation all preceded the onset of memory loss by 0.2 ± 4.9, 3.3 ± 8.6, and 3.7 ± 9.2 years, respectively, while urinary incontinence occurred 1.7 ± 1.5 years following the onset of memory loss. CONCLUSION: Many autonomic symptoms precede the onset of memory loss in patients with DLB, especially constipation and daytime hyperhidrosis. These symptoms can facilitate an early diagnosis of patients with DLB.

Pisa syndrome in dementia with Lewy bodies: A Chinese multicenter study.

BACKGROUND: Pisa syndrome (PS) is rarely reported in Dementia with Lewy bodies (DLB). The aim of this article is to investigate the prevalence rate of PS and the correlation with clinical features evaluated in patients with DLB. METHODS: A total of 209 DLB patients were consecutively recruited and underwent standardized clinical evaluation in our multicenter study. The associations between PS and clinical factors were evaluated. RESULTS: The prevalence rate of PS in patients with DLB was 15.3%, which was higher in the moderate and severe stages than mild cognitive impairment and mild stages (81.2% vs. 18.8%). Patients with PS had a longer duration of disease (P = 0.020) and parkinsonism (P = 0.003), higher scores of NPI (P = 0.028), ADL (P = 0.002) and UPDRS part III (P < 0.001), lower scores of clock drawing test (P = 0.009), visuospatial/executive abilities (P = 0.018), attention (P = 0.020), language and praxis (P = 0.020), registration (P = 0.012), greater H&Y stage (P < 0.001), and higher proportion of cholinesterase inhibitors used (P = 0.044) than those without PS. Longer disease duration (OR = 1.166, P = 0.023), presence of parkinsonism (OR = 7.971, P = 0.007), moderate and severe dementia (OR = 3.215, P = 0.021) were associated with the presence of PS. Patients had a longer duration of PS (P = 0.014) and lower mean age of onset (P = 0.040) in the group with severe lateral trunk flexion. CONCLUSION: The development of PS may be associated with longer disease duration, the presence of parkinsonism and severe stages of dementia in DLB. Cholinesterase inhibitors may have a correlation with PS. The severity of lateral flexion is related to the duration of PS and mean age of onset.