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.

Association between marital status and cognitive impairment based on a cross-sectional study in China.

BACKGROUND: Marital status may have an impact on the elderly population's health, but few studies in China discussed about the association between marital status and cognitive impairment. OBJECTIVE: To investigate the relationship between marital status and cognitive impairment. To compare the influences of marital status on dementia between men and women. METHODS: This study was based on a representative national cross-sectional epidemiological survey in China. We randomly selected 13 provinces and municipalities and included 19,276 participants aged 65 years or older in our study. Data was collected by interviewing the participants about their sociodemographic characteristics, and neuropsychological testing was administered to the participants by neurologists. To analyze the association between marital status and cognitive impairment, multiple logistic regression was based on a series of models. RESULTS: Among the 19,276 subjects, about 77.2% were married, 1.6% were single, 21.2% were divorced/separated or widowed. The odds ratios (OR) of dementia were higher in single (OR: 2.13, CI: 1.53-2.97; p < 0.001), divorced/separated/widowed when they were ≤55 years old (OR: 1.75, CI: 1.30-2.35; p < 0.001), and divorced/separated/widowed when they were >55 years old (OR: 1.16, CI: 1.03-1.31; p < 0.001) participants than in married ones. Divorced/separated/widowed ≤55 men had about 2.75 times increase in dementia risk than married men. CONCLUSION: People with long-term divorced/separated/widowed status would be associated to cognitive impairment more than those with short-term divorced/separated/widowed status. Men may be affected by marriage disruption more than women in terms of increasing the risk of dementia.

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.

Temporal Variation in Disease Onset and Clinical Features of Lewy Body Disease in China.

BACKGROUND: Lewy body dementia is the second most common neurodegenerative dementia, but data concerning the onset age and clinical features in the prodromal stage remain limited in China. OBJECTIVE: To investigate the associations between onset age and clinical manifestations of cognitive impairment with Lewy bodies in a large-sample cohort. METHODS: We included 74 patients with mild cognitive impairment with Lewy bodies (MCI-LB), 533 patients with dementia with Lewy bodies (DLB), 118 patients with Parkinson's disease with MCI (PD-MCI), and 313 patients with Parkinson's disease dementia (PDD) in this multicenter cohort from 22 memory clinics of China from 1 January 2018 to 31 March 2022. The onset age, clinical manifestations, and neuropsychological assessments were recorded and analyzed after reviewing the medical records. RESULTS: The average onset age of memory loss was 68.28 (±7.00) years, and parkinsonism happened 2.00 (±1.24) years later for patients with MCI-LB. The average onset age of parkinsonism was 60.56 (±8.96) years, and the memory loss happened 3.49 (±3.02) years later for patients with PD-MCI. Rapid eye movement sleep behavior disorder and visual hallucinations were frequently reported in MCI-LB, DLB, and PDD, while visual hallucinations were least frequently reported in PD-MCI. Lower scores of MMSE and depression, and higher scores of activities of daily living and delusions, were independently associated with older onset age in DLB. CONCLUSION: The onset of PD-MCI precedes MCI-LB, and memory loss occurs 3 years after parkinsonism. The onset age is associated with cognition and neuropsychiatric symptoms in process.

Sex differences in clinical cognitive impairment with Lewy bodies: a Chinese multicenter study.

BACKGROUND: Research on sex ratios of Lewy body dementia is controversial, established in small samples, and rarely focused on prodromal stage. The objective is to investigate the clinical sex ratios (men/women) and their associations with clinical features among individuals with mild cognitive impairment with Lewy bodies (MCI-LB), dementia with Lewy bodies (DLB), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) in China. METHODS: We conducted a multicenter cohort study, including 1038 individuals with probable MCI-LB, DLB, PD-MCI, or PDD diagnosis from 22 memory clinics in China from January 2018 to March 2022, and recorded their demographic and clinical data by reviewing medical records. Descriptive and regression analyses were used to calculate the sex ratio (men/women), and its associations with demographic and clinical data. RESULTS: In this study, men comprised 35.14% (men/women sex ratio = 0.54) for MCI-LB, 46.72% (men/women sex ratio = 0.88) for DLB, 63.56% (men/women sex ratio = 1.74) for PD-MCI, and 52.40% (men/women sex ratio = 1.10) for PDD. Sex ratios roughly increased with age. Men had more parkinsonism (p = 0.000) and less fluctuating cognition (p = 0.024) in MCI-LB, and those with PD-MCI had more RBD (p = 0.001). Women with PD-MCI had lower MMSE scores (ß ± standard error = - 1.24 ± 0.58, p = 0.04), more irritability (0.95 ± 0.46, p = 0.04) and fluctuating cognition (- 3.41 ± 1.31, p = 0.01), and less parkinsonism (- 2.10 ± 0.97, p = 0.03) than men after adjusting for demographic and cardiometabolic conditions. CONCLUSION: There were more women in DLB and MCI-LB, and more men in PD-MCI and PDD. The sex distribution, demographic, and clinical characteristics differed, which strengthened the independence and heterogeneity of the four diseases, and indicated sex-sensitive strategies for management of dementia necessary.

Blood pressure control and risk of post-stroke dementia among the elderly: A population-based screening study.

Background: Post-stroke dementia (PSD) has adverse effects on the quality of work and life in elderly stroke survivors. There are inconsistent results on the impacts of blood pressure control on the risk of PSD in people aged 65 years and above. Objective: This study was performed to explore whether poorly-controlled blood pressure was associated with an increasing risk of PSD. Methods: The study population was enrolled from cross-sectional research conducted in 106 communities of rural northern China. In Phase I, a total of 7,448 people aged ≥65 years, including 830 with stroke history, completed a questionnaire, a physical examination, and a cognitive assessment. Phase II further confirmed the diagnosis of PSD. Well-controlled blood pressure was defined as an average systolic blood pressure of <140 mmHg and average diastolic blood pressure of <90 mmHg over two readings in person. Failure to meet these criteria was considered as poorly-controlled blood pressure. Results: The crude prevalence rate of PSD among stroke survivors aged 65 years and over was 17.8% [95% confidence interval (CI) 15.2-20.4%]. Among the 830 stroke survivors, the proportions of PSD gradually increased with age and the crude prevalence rates for PSD were 10.2% (95% CI 5.6-14.9%), 14.8% (95% CI 10.1-19.5%), 18.8% (95% CI 14.1-23.5%), and 27.4% (95% CI 20.8-34.1%) in subjects aged 65-69, 70-74, 75-79 and ≥80 years, respectively. Participants in the poorly-controlled blood pressure group were more likely to suffer from PSD (28.4 vs.15.3%, P < 0.001), be older (75.81 ± 4.97 vs. 74.74 ± 5.83, P < 0.05), and have a worse cognitive level (22.26 ± 7.05 vs. 24.10 ± 6.02, P < 0.05). Compared with well-controlled blood pressure patients, poorly-controlled blood pressure in stroke survivors significantly increased risk of PSD (odds ratio = 2.20, 95% CI 1.45-3.32) after adjusting for age, gender, and education. Conclusions: The crude prevalence of PSD among stroke survivors aged ≥65 years was 17.8% at community level. In addition to lower education level and older age, poorly-controlled blood pressure was also an independent risk factor for PSD among the elderly, which is amenable to intervention. Therefore, it is essential to control blood pressure to reduce PSD incidence.

Corrigendum: Blood pressure control and risk of post-stroke dementia among the elderly: A population-based screening study.

[This corrects the article DOI: 10.3389/fneur.2022.956734.].

Association between prevalence rate of dementia with Lewy bodies and sleep characteristics in Chinese old adults.

Introduction: Few studies are available on the prevalence and sleep-related factors of dementia with Lewy bodies (DLB) in Chinese older adults, aiming to explore the associations between sleep characteristics and DLB. Methods: A cross-sectional study with 7,528 individuals aged ≥65 years in 106 communities in Northern China was conducted from April 2019 to January 2020. Questionaries (including demographic characteristics, comorbidities, lifestyles, and sleep characteristics) were administered, and neuropsychological assessments and physical examination were conducted in phase I; screening for probable DLB was done in phase II. Logistic regressions were used to assess associations. Results: A total of 919 (12.2%, 919/7,528) participants had dementia, and 101 (1.3%, 101/7,528) participants were diagnosed with DLB. The prevalence of dementia and DLB were slightly higher or equal in women, increased with age, and roughly decreased with nighttime sleep duration. Of the 101 participants, all of them (100.0%) had cognitive impairment, 46 (44.54%) displayed fluctuating cognition, 72 (71.29%) of them showed visual hallucination, 22 (21.78%) individuals reported RBD, and 27.71% showed Parkinsonism. Sleeping for <5 h (adjusted OR = 1.795, 95%CI: 1.055-3.054, p < 0.05) or having hypersomnolence (adjusted OR = 31.213, 95% CI: 17.618-55.301, p < 0.001) were significantly associated with the occurrence of DLB. Sleep duration of <5 h or >8 h had combined diagnostic value for DLB (AUC = 0.783, 95%CI: 0.734-0.831, p < 0.001). Conclusions: The current prevalence of DLB is 1.3% in Northern China. Short or long nighttime sleep duration is independently associated with the occurrence of dementia and DLB.

Prevalence of Constipation in Elderly and Its Association With Dementia and Mild Cognitive Impairment: A Cross-Sectional Study.

BACKGROUND: Constipation and dementia have similar epidemiological characteristics. Changes in intestinal flora and characteristics of the brain-gut axis play roles in the pathogeneses of the two diseases, suggesting that there may be a close connection between the two. Most of the studies on constipation in dementia patients have focused on the population with α-synucleinopathies [Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB)]. Few studies have reported the prevalence of constipation in all-cause dementia and mild cognitive impairment (MCI) populations. OBJECTIVE: To assess the prevalence of constipation in patients with all-cause dementia and MCI subtypes and to explore the association between constipation with dementia and MCI subtypes. METHODS: From May 2019 to December 2019, we conducted a population-based cross-sectional survey. A total of 11,743 participants aged 65 or older from nine cities in China were surveyed. Participants underwent a series of clinical examinations and neuropsychological measurements. Constipation, dementia, MCI and MCI subtype were diagnosed according to established criteria through standard diagnostic procedures. RESULTS: The overall age- and sex-adjusted prevalence of constipation in individuals aged 65 years and older was 14.8% (95% CI, 14.6-15.0). The prevalence rates of constipation were19.2% (95% CI, 17.3-21.0), 19.1% (95% CI, 16.8-21.5), 14.4% (95% CI, 12.8-15.9), and 13.8% (95% CI, 13.0-14.6) in the dementia, non-amnestic (na)-MCI, amnestic (a)-MCI and normal cognition populations, respectively. Multivariate logistic regression analysis showed that higher prevalence of constipation was associated with dementia (p = 0.0.032, OR = 1.18, 95% CI: 1.02-1.38) and na-MCI (p = 0.003, OR = 1.30, 95% CI: 1.09-1.54). CONCLUSION: The present study found a high prevalence of constipation in elderly individuals in China, and higher in patients with dementia and na-MCI.

[Efficacy observation on electroacupuncture in the treatment of oculomotor impairment caused by ophthalmic nerve injury].

OBJECTIVE: To observe the difference in the clinical efficacy on oculomotor impairment between electroacupuncture and acupuncture and explore the best therapeutic method in the treatment of this disease. METHODS: Sixty cases of oculomotor impairment were randomized into an electroacupuncture group and an acupuncture group, 30 cases in each one. In the electroacupuncture group, the points were selected on extraocular muscles, the internal needling technique in the eye was used in combination of electroacupuncture therapy. In the acupuncture group, the points and needling technique were same as the electroacupuncture group, but without electric stimulation applied. The treatment was given 5 times a week, 15 treatments made one session. After 3 sessions of treatment, the clinical efficacy, palpebral fissure size, pupil size, oculomotor range and the recovery in diplopia were compared before and after treatment in the two groups. RESULTS: In the electroacupuncture group, the palpebral fissure size was (9.79+/-2.65)mm and the eyeball shifting distance was (18.12+/-1. 30)mm, which were hig-her than (8.23+/-2.74)mm and (16.71+/-1. 44)mm respectively in the acupuncture group. In the electroacupuncture group, the pupil diameter was (0. 44 +/-0. 42)mm, which was less than (0. 72 +/- 0. 53)mm in the acupuncture group, indicating the significant difference (all P<0. 05). The cured rate was 63. 33% (19/30) and the total effective rate was 93.33% (28/30) in the electroacupuncture group, which was better than 36.67% (11/30) and 83. 333 (25/30) in the acupuncture group separately, indicating the significant difference (all P<0. 05). CONCLUSION: Electroacupuncture presents the obvious advantages in the treatment of oculomotor impairment, characterized as quick and high effect, short duration of treatment and remarkable improvements in clinical symptoms, there are important significance for the improvement of survival quality of patients.

Nicotinamide mononucleotide adenylyltransferase 1 gene NMNAT1 regulates neuronal dendrite and axon morphogenesis in vitro.

BACKGROUND: Wallerian degeneration is a self-destructive process of axonal degeneration that occurs after an axonal injury or during neurodegenerative disorders such as Parkinson's or Alzheimer's disease. Recent studies have found that the activity of the nicotinamide adenine dinucleotide (NAD) synthase enzyme, nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) can affect the rate of Wallerian degeneration in mice and drosophila. NMNAT1 protects neurons and axons from degeneration. However, the role of NMNAT1 in neurons of central nervous system is still not well understood. METHODS: We set up the culture of primary mouse neurons in vitro and manipulated the expression level of NMNAT1 by RNA interference and gene overexpression methods. Using electroporation transfection we can up-regulate or down-regulate NMNAT1 in cultured mouse dendrites and axons and study the neuronal morphogenesis by immunocytochemistry. In all functional assays, FK-866 (CAS 658084-64-1), a highly specific non-competitive inhibitor of nicotinamide phosphoribosyltransferase was used as a pharmacological and positive control. RESULTS: Our results showed that knocking down NMNAT1 by RNA interference led to a marked decrease in dendrite outgrowth and branching and a significant decrease in axon growth and branching in developing cortical neurons in vitro. CONCLUSIONS: These findings reveal a novel role for NMNAT1 in the morphogenesis of developing cortical neurons, which indicate that the loss of function of NMNAT1 may contribute to different neurodegenerative disorders in central nervous system.

Limited hippocampal neurogenesis in SAMP8 mouse model of Alzheimer's disease.

Increasing adult neurogenesis in the hippocampal formation (HF) has been proposed as a potential foundation for neuronal repair in Alzheimer's disease (AD), but the evidence remains controversial. We used P8 strain of senescence-accelerated mice (SAMP8) as a model of AD to investigate changes in adult neurogenesis. We examined new proliferating cells and their survival in the dentate gyrus (DG) of the HF using 5-bromodeoxyuridine (BrdU) labeling and investigated newborn cell development and differentiation with a combination of phenotype markers. In 5-month-old SAMP8, the number of BrdU(+) cells in the DG was significantly increased relative to controls, in accordance with the rising numbers of doublecortin-positive (DCX(+)) immature neurons. Some of these BrdU(+) cells migrated to cornu ammonis 1 (CA1), possibly related to the compensation of neuronal loss. However, the capacity of neurogenesis to compensate neuronal loss during neurodegeneration was limited. First, only half of the BrdU(+) cells survived 4weeks after mitosis, and even fewer developed into neuron-specific nuclear protein positive (NeuN(+)) mature neurons. Second, the number of BrdU(+) cells and DCX(+) cells was decreased in 10-month-old SAMP8, which exhibited progressive neurodegeneration. In addition, the results provided insight into astrocytes as a crucial component of the neurogenic niche. The number of newborn astrocytes and expression of glial fibrillary acidic protein (GFAP) were diminished in the DG of SAMP8 animals, possibly explaining the insufficient neurogenesis. Thus, stimulating limited neurogenesis in AD by improving the neurogenic niche may have therapeutic potential.