Fangyu Li

White Matter Abnormalities in Two Different Subtypes of Amnestic Mild Cognitive Impairment

White matter (WM) degeneration has been found during the course of cognitive decline in both Alzheimers disease (AD) and amnestic mild cognitive impairment (aMCI), however, it is unclear whether there are different WM microstructural abnormalities between two subtypes of aMCI, including single domain aMCI (aMCI-s) and multiple domain aMCI (aMCI-m). Thirty-two patients of aMCI single-domain (aMCI-s), twenty-three patients of aMCI multiple-domain (aMCI-m) and twenty-three healthy normal controls (NC) participated in this study. Neuropsychological measures and diffusion tensor imaging (DTI) data were acquired from each subject and tract-based spatial statistics (TBSS) was implemented. It was found that both aMCI groups showed significantly reduced fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF) than NC. It was also identified that, as compared to aMCI-m, aMCI-s showed significantly decreased FA in the left SLF, left uncinate fasciculus (UF) and left inferior longitudinal fasciculus (ILF), while significantly increased FA in the left anterior thalamic radiation (ATR). The correlation analysis showed that FA values in the regions with group difference were significantly correlated with cognitive functions as measured by Boston naming test and trail making test. These results suggested that the variations of aMCI may be differentiated by FA indexes and DTI may help to understand why specific signs and symptoms occur in patients.

Efficacy and Safety of Donepezil in Chinese Patients with Severe Alzheimer’s Disease: A Randomized Controlled Trial

BACKGROUND Donepezil has been used worldwide for the treatment of severe Alzheimers disease (AD). Whether it is also appropriate for severe AD in Chinese patients remains unknown. OBJECTIVE To determine whether donepezil is effective and tolerable for Chinese patients with severe AD. METHODS The present study was a 24-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study conducted at 38 investigational hospitals in China. Patients with severe AD were enrolled in this trial. Patients were randomly assigned in a 1:1 ratio to receive either donepezil or placebo (5 mg for 6 weeks and10 mg for the remaining 18 weeks). The efficacy for donepezil were evaluated by the SIB, the Clinicians Interview-Based Impression of Change-Plus caregiver input (CIBIC-plus) and the MMSE. Safety parameters were monitored throughout. RESULTS A total of 313 patients included the donepezil (n = 157) and the placebo groups (n = 156). Donepezil group improved more in SIB scores (least squares [LS] mean difference: 4.8, 95% CI 1.56 to 8.08, p = 0.004) and CIBIC-plus scores (drug-placebo difference: -0.4, 95% CI -0.66 to 0.03, p = 0.04) than placebo groups at Week 24. The MMSE scores between drug and placebo groups did not differ significantly. Twenty-nine patients with serious adverse events (SAEs) were reported in donepezil (n = 11) and placebo groups (n = 18) (p = 0.08). Most SAEs were not considered drug-related. CONCLUSION Donepezil for 24 weeks was more effective than placebo and showed good safety and tolerability in Chinese patients with severe AD. This study supports utility of the drug in severe stages of AD in the Chinese population.

The cost of Alzheimer's disease in China and re-estimation of costs worldwide

The socioeconomic costs of Alzheimers disease (AD) in China and its impact on global economic burden remain uncertain.

Trajectories of Multidimensional Caregiver Burden in Chinese Informal Caregivers for Dementia: Evidence from Exploratory and Confirmatory Factor Analysis of the Zarit Burden Interview

BACKGROUND Despite its popularity, the latent structure of 22-item Zarit Burden Interview (ZBI) remains unclear. There has been no study exploring how caregiver multidimensional burden changed. OBJECTIVE The aim of the work was to validate the latent structure of ZBI and to investigate how multidimensional burden evolves with increasing global burden. METHODS We studied 1,132 dyads of dementia patients and their informal caregivers. The caregivers completed the ZBI and a questionnaire regarding caregiving. The total sample was randomly split into two equal subsamples. Exploratory factor analysis (EFA) was performed in the first subsample. In the second subsample, confirmatory factor analysis (CFA) was conducted to validate models generated from EFA. The mean of weighted factor score was calculated to assess the change of dimension burden against the increasing ZBI total score. RESULTS The result of EFA and CFA supported that a five-factor structure, including role strain, personal strain, incompetency, dependency, and guilt, had the best goodness-of-fit. The trajectories of multidimensional burden suggested that three different dimensions (guilt, role strain and personal strain) became the main subtype of burden in sequence as the ZBI total score increased from mild to moderate. Factor dependency contributed prominently to the total burden in severe stage. CONCLUSION The five-factor ZBI is a psychometrically robust measure for assessing multidimensional burden in Chinese caregivers. The changes of multidimensional burden have deepened our understanding of the psychological characteristics of caregiving beyond a single total score and may be useful for developing interventions to reduce caregiver burden.

Association between Plasma Leptin and Estrogen in Female Patients of Amnestic Mild Cognitive Impairment.

Increasing evidences suggested the association between leptin and cognitive functions. Estrogen is an important factor that regulates the production and metabolism of leptin. However, little is known about the relationship between leptin and estrogen in mild cognitive impairment (MCI). Plasma levels of leptin, total estradiol, and β-amyloid protein (Aβ) were measured in a total of 23 female amnestic MCI (aMCI) patients and 19 female cognitively normal controls. This study showed that female aMCI patients had lower plasma levels of leptin and higher levels of estradiol compared to female normal controls. Leptin and estradiol levels were not correlated with cognitive performances or plasma Aβ levels in either aMCI patients or normal controls. There was a significant negative correlation between leptin and estrogen in female aMCI patients (r = −0.633, p = 0.002) but not in female normal controls. The potential mechanisms of this disease-stage-specific association between leptin and estrogen need further investigations.

Efficacy and safety of the compound Chinese medicine SaiLuoTong in vascular dementia: A randomized clinical trial

No licensed medications are available to treat vascular dementia (VaD).

The efficacy of Cognitive training in patients with VAsCular Cognitive Impairment, No dEmentia (the Cog-VACCINE study): study protocol for a randomized controlled trial

BackgroundVascular cognitive impairment, no dementia (VCIND) refers to cognitive deficits associated with underlying vascular causes that fall short of a dementia diagnosis. There is currently no treatment for VCIND. Computerized cognitive training, which has significantly improved cognitive function in healthy older adults and patients with cognitive impairment has not yet been applied to VCIND.Methods/DesignThe proposed study is a three-center, double-blinded, randomized controlled trial that will include 60 patients with VCIND. The patients will be randomized to either a training or a control group. The intervention is internet-based cognitive training performed for 30 min over 35 sessions. Neuropsychological assessment and functional and structural MRI will be performed before and after 7 weeks training. Primary outcomes are global cognitive function and executive function. Secondary outcome measures are neuroplasticity changes measured by functional and structural MRI.DiscussionApplying an internet-based, multi-domain, adaptive program, this study aims to assess whether cognitive training improves cognitive abilities and neural plasticity in patients with subcortical VCIND. In addition to the comprehensive assessment of the participants by neuropsychological tests, cerebrovascular risk factors and apolipoprotein E genotyping, neuroplasticity will be used as an evaluation outcome in this study for, to our knowledge, the first time. The combination of functional and structural MRI and neuropsychological tests will have strong sensitivity in evaluating the effects of cognitive training and will also reveal the underlying mechanisms at work.Trial registrationClinicalTrials.gov NCT02640716. Retrospectively registered on 21 December 2015.

Validation of the Delayed Matching-to-Sample Task 48 (DMS48) in Elderly Chinese

BACKGROUND Delayed Matching-to-Sample Task 48 (DMS48), a brief tool measuring visual recognition memory, is valid to identify the early stage of Alzheimers disease (AD) in Caucasians. However, little data is available in Chinese. OBJECTIVE To develop norms and optimal cutoff points for the DMS48 in Chinese elders. METHODS A cross-sectional study was conducted in seven memory clinics from five cities across China. DMS48 was applied to 369 Chinese aged 50 or older (138 cognitively normal [CN], 112 mild cognitive impairment due to AD (MCI-A), and 119 mild AD dementia). The demographic factors which influence DMS48 scores were investigated and the norms were established considering those factors. Receiver operating characteristic (ROC) analysis was used to determine the optimal cutoff points. RESULTS Age was shown to influence DMS48 scores (r = -0.36, p < 0.05), and we presented the age-stratified normative data for the DMS48. The optimal cutoff point is 42/43 for identifying cognitive impairment (MCI-A and AD dementia) against CN (sensitivity 97.80% and specificity 89.13%) and MCI-A against CN (sensitivity 86.60% and specificity 94.20%). A cutoff of 39/40 obtained good sensitivity (100.00%) and specificity (94.90%) in discriminating AD dementia from CN. The age-stratified optimal cutoff points for identifying MCI-A were 43/44 for individuals aged 50 to 59 years old, 42/43 for 60 to 69 years old, 41/42 for 70 to 79 years old, and 40/41 for 80 or older, respectively (sensitivity 84.80% and specificity 95.70%). CONCLUSION This study proved that DMS48 is of good validation in screening MCI-A in elderly Chinese.

THE EFFECT OF APOE-ε4 ON THE TRAJECTORY OF ALZHEIMER’S DISEASE RELATED COGNITIVE DECLINE IN CHINESE POPULATION

Background: Patients with dementia, particularly Alzheimer’s disease (AD), are at an increased risk of developing epilepsy. However, the extent of this increased risk has been disputed and remains unclear. We measured the prevalence of epilepsy in a cohort of patients with AD recruited from a memory clinic in secondary care to identify which patients are at a risk of epilepsy, the clinical features of these seizures and the stage of disease at which seizures occur Methods:Patients with a diagnosis of probable AD dementia were recruited from a regional memory clinic. Interviews were conducted with the patient and a reliable informant using a structured proforma designed for this purpose. Using their responses to questions regarding clinical features of epilepsy, patients were categorised into three groups: epilepsy probable, epilepsy possible, or no clinical suspicion of epilepsy. Dementia diagnoses were confirmed using established research criteria. Cognitive function was measured using the Addenbrooke’s Cognitive Examination Version-III (ACE-III). Results: 102 patients were recruited to the study. 12 patients (11.7%) were categorised to the epilepsy probable group and 16 (15.7%) patients to the epilepsy possible group. This group was not significantly different to those in whom there was no suspicion of epilepsy, in terms of age, gender, or duration of memory symptoms. However, there was a significant difference in the Clinical Dementia Rating (CDR) sum of boxes score between those with epilepsy and thosewithout. In the epilepsy probable group, 9 patients (75%) experienced focal impaired awareness / focal behavioural arrest seizures; 2 patients (16.67%) experienced generalised tonicclonic seizures. A range of further seizure features were also seen. The mean duration from onset of memory impairment to seizure onset in this group was 16.4 months (range 0 to 36). Conclusions:Patientswho experience epilepsy as a result of their dementia are demographically and cognitively similar to those that do not have epilepsy, but may experience a broader range of cognitive impairments and increased care needs as evidenced by elevated CDR scores. In our cohort, patients with epilepsy were likely to have experienced a first seizure within 18 months of developing memory symptoms.