Zhihong Shi

Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality.

Background and Purpose— Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality. Methods— A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months. Results— During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 &mgr;mol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03–2.53) compared with patients in the lowest quartile (⩽10 &mgr;mol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05–3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30–2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06–4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01–4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels. Conclusions— Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype.

Apolipoprotein Ε ε4 Frequency Is Increased among Chinese Patients with Frontotemporal Dementia and Alzheimer's Disease

The relationship between the apolipoprotein E (ApoE) ε4 genotype and an increased risk of developing Alzheimers disease (AD) has been well established in Caucasians but is less established among other ethnicities. ApoE ε4 has also been associated with several other neurological disorders. Whether ApoΕ4 ε4 is a risk factor for frontotemporal dementia (FTD) remains controversial. This study examined 432 patients with AD, 62 with FTD, and 381 sex- and age-matched controls. The ApoE ε4 allele frequency was significantly increased among patients in the AD and FTD groups compared with controls. The frequency of the ApoΕ ε4 allele was 24.86% in late-onset AD (p < 0.01), 18.02% in early-onset AD (p < 0.01), 16.13% in FTD (p < 0.01), and 7.34% in controls. ApoΕ ε4 prevalence was similar in the FTD and AD groups. The present study suggests that the ApoE ε4 allele is a risk factor for both disorders.

The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia, Lewy body dementia, and Alzheimer's disease: clinical experience in China

ABSTRACT Background and aims: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimers disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia. Method: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI). Results: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients. Conclusion: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.

Caregiver Burden and Prevalence of Depression, Anxiety and Sleep Disturbances in Alzheimer's Disease Caregivers in China

AIMS AND OBJECTIVESnTo evaluate caregiver burden and factors that influence this burden among caregivers and patients with Alzheimers disease in China.nnnBACKGROUNDnLong-term care can reduce the quality of life for caregivers and result in both mental and physical exhaustion. However, little is known about caregiver burden and associated factors in China.nnnDESIGNnThe study had a quantitative cross-sectional design.nnnMETHODSnA total of 309 caregivers and their patients were included in the study. The patients cognitive, psychological and functional status and their caregivers burden, sleep quality and mental state were evaluated. Descriptive analyses, single-factor regression and stepwise factor regression were used to determine the effects of various factors on caregiver burden.nnnRESULTSnOlder females and spouses still play an important role in providing family care for those with dementia. Most of the caregivers were the sole full-time caregiver and had little time for themselves. Sleepiness was a common physical problem for caregivers, and some of them had moderate to severe depression and anxiety. A lower functional status of the patient was associated with higher caregiver burden. Poorer physical status compared with before caregiving began, lower life satisfaction, and higher degrees of depression and anxiety were associated with higher caregiver burden.nnnCONCLUSIONnDepression, anxiety and sleep problems are the main challenges that are faced by family caregivers of patients with Alzheimers disease. Caregivers functional status, lower life satisfaction, depression and anxiety influenced caregiver burden. Caregiver burden was related to the severity of the patients dementia and the personal factors of the caregivers.nnnRELEVANCE TO CLINICAL PRACTICEnTo provide information about caregivers current status while caring for patients with Alzheimers disease and to understand caregiver burden and its related factors. Professionals who work with Alzheimers disease should pay more attention to caregiver burden, especially those with mental and physical problems.

Prevalence of Dementia and Main Subtypes in Rural Northern China

Background/Aims: The aim of this article was to estimate the prevalence of and to determine the sociodemographic risk factors for dementia, Alzheimers disease (AD) and vascular dementia (VaD) among individuals residing in rural northern China. Methods: Between 2011 and 2012, residents aged ≥60 years and residing in rural areas of northern China were clinically assessed for symptoms of dementia, AD and VaD. Diagnoses were made using established criteria and standard procedures. Results: Among 5,578 enrolled study participants aged ≥60 years, the prevalence rates of dementia, AD and VaD were 7.7, 5.4 and 1.7%, respectively. Older age (OR = 1.17; 95% CI: 1.14-1.19) and female gender (OR = 2.13; 95% CI: 1.51-3.00) were identified as independent risk factors for AD. In turn, a higher educational level (OR = 0.36; 95% CI: 0.21-0.60) and engagement in social activities (OR = 0.219; 95% CI: 0.163-0.295) were protective factors. Risk factors associated with VaD were older age (OR = 1.11; 95% CI: 1.1-1.12) and hypertension (OR = 1.83; 95% CI: 1.18-2.86), while a higher educational level (OR = 0.53, 95% CI: 0.44-0.65) and engagement in social activities (OR = 0.34; 95% CI: 0.29-0.41) were protective factors. Conclusion: High rates of dementia (7.7%) and AD (5.4%) were found in the rural areas of northern China. Older age and female gender were identified as risk factors for AD, while older age and hypertension were risk factors for VaD. A higher educational level and engagement in social activities were identified as protective factors against both AD and VaD.

A Pilot Study on Clinical and Neuroimaging Characteristics of Chinese Posterior Cortical Atrophy: Comparison with Typical Alzheimer’s Disease

Posterior cortical atrophy (PCA) is a clinicoradiologic neurodegenerative syndrome characterized by predominant impairment of higher visual functions. Neuroimaging and neuropathological studies show that PCA is probably an atypical presentation of Alzheimer’s disease. However, in China PCA has rarely been studied and remains largely unknown. Our study therefore aimed to analyze the clinical manifestations and patterns of cerebral atrophy, amyloid beta deposition and regional glucose metabolism in Chinese PCA patients, comparing them directly with those of typical Alzheimer’s disease (TAD). Seven PCA patients, 6 TAD patients and 5 controls underwent neuropsychological assessment, MRI scan, 11C-PIB PET scan and 18F-FDG PET scan. Cerebral atrophy including ventricular enlargement, posterior atrophy and medial temporal lobe atrophy were evaluated with MRI. The uptake of 11C-PIB was quantified at the voxel level using the standardized uptake value ratio. Comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. PCA patients showed significant impairment on visuospatial function in neuropsychological assessment. And PCA patients showed more severe posterior atrophy and less severe left medial temporal lobe atrophy compared with TAD patients. The data from 11C-PIB PET scanning showed that amyloid beta deposition in PCA was comparable to TAD. Moreover, in PCA the results from 18F-FDG PET scanning revealed significant hypometabolism in the temporoparietooccipital region and identified specific hypometabolism in the right occipital lobe, compared with TAD. Our study thus provides a preliminary view of PCA in Chinese patients. A further study with a larger number of subjects would be recommended to confirm these findings.

Prevalence of Cognitive Impairment No Dementia in a Rural Area of Northern China

Objective: Few data are available on the prevalence of cognitive impairment no dementia (CIND) in rural China. The aim of this study was to estimate the prevalence of CIND in individuals aged 60 years and older in a large rural community, and to analyze the associated risk factors. Methods: A two-phase, door-to-door epidemiological study was used for residents aged 60 years and older in Ji County, a rural county near Tianjin in Northern China. In phase 1 of the study, the Mini-Mental State Examination and Clinical Dementia Rating were administered for screening purposes. In phase 2, the subjects who screened positive were further examined by neurologists. A total of 5,744 individuals underwent the home visit interview, where demographic variables and comorbidities were recorded; 5,550 individuals completed the two phases. CIND was diagnosed by the Aging, Demographics and Memory Study on CIND criteria. The odds ratio (OR) for each risk factor was calculated by logistic regression analysis. Results: The prevalence of CIND among those aged 60 years and older was 23.3%. The prevalence of CIND was lower among those with a higher level of education or social involvement. CIND was more prevalent in females, older individuals, those with a past history of stroke, and those living without a partner. Significant risk factors were found by multivariate analyses: past history of stroke (OR = 1.889; 95% CI: 1.437-2.483); being female (OR = 1.546; 95% CI: 1.305-1.832); and having no partner (divorced, widowed or single; OR = 1.250; 95% CI: 1.042-1.499). In turn, level of education (OR = 0.560; 95% CI: 0.460-0.681) and engagement in social activities (OR = 0.339; 95% CI: 0.258-0.404) were protective factors. Conclusions: This is the first large-scale community-based epidemiological study assessing the prevalence of cognitive loss in the rural Chinese population. The total prevalence of CIND observed was 23.3%, which was higher than in other studies in Western and Asian countries. Living without a partner, female gender and previous stroke increased the risk of CIND, whereas a higher level of education and engagement in social activities reduced the risk of CIND.

Prevalence and Clinical Predictors of Cognitive Impairment in Individuals Aged 80 Years and Older in Rural China

Aims: The aim of this study was to estimate the prevalence of cognitive impairment (CI) in individuals aged 80 years and over in rural China and to analyze the associated risk factors. Methods: We conducted a two-phase door-to-door survey of a population in rural Ji County (China). The reference population consisted of individuals aged 80 years or older. A total of 723 individuals were interviewed in their homes, and demographic variables and comorbidities were recorded. Diagnoses were divided into the following 3 categories: normal cognitive function, cognitive impairment no dementia (CIND), and dementia. The odds ratio for each risk factor was calculated by logistic regression analysis. Results: The prevalence of CI among individuals aged 80 years and older was 73.2% (47.4% CIND and 25.7% dementia). The risk of CI decreased with a higher level of education and a higher level of social involvement. The risk of CI was higher in females than in males and among people with a history of stroke (p < 0.01). Conclusions: The observed raw prevalence of CI was 73.2%. Female gender and a history of a previous stroke increased the risk of CI, while a higher educational level and engagement in social activities reduced the risk of CI.

Clinical and Neuroimaging Characterization of Chinese Dementia Patients with PSEN1 and PSEN2 Mutations

Background: Alzheimers disease (AD) and frontotemporal dementia (FTD) are two common forms of primary neurodegenerative dementia. Mutations in 3 genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset AD. Methods: We performed gene sequencing in PSEN1, PSEN2, and APP in 61 AD and 35 FTD Chinese patients. Amyloid load using 11C-labeled Pittsburgh compound B (11C-PIB) positron emission tomography (PET) and cerebral glucose metabolism using 18F-fludeoxyglucose PET were evaluated in patients carrying mutations. Results: We identified 1 known pathogenic PSEN1 (p.His163Arg, c.488A>G) mutation and 3 novel PSEN2 mutations in 6 patients. The novel mutation PSEN2 (p.His169Asn, c.505C>A) was identified in 1 patient with familial late-onset AD and in 1 sporadic FTD patient. The PSEN2 (p.Val214Leu, c.640G>T; p.Lys82Arg, c.245A>G) mutations were identified in 2 early-onset AD patients and 1 early-onset AD patient, respectively. Three patients with PSEN2 mutations were observed to have PIB retention on the cortex and striatum. One patient with the FTD phenotype was not observed to have PIB retention. Conclusion: PSEN2 mutations are common in the Chinese Han population with a history of AD and FTD. Pathogenic mutations or risk variants in the PSEN2 gene can influence both FTD and AD phenotypic traits and show variations in neuroimaging characterization.

Association between the COMT Val158Met Genotype and Alzheimer's Disease in the Han Chinese Population

Background: Alzheimers disease (AD) is the leading cause of dementia worldwide and is associated with individual, familial and social burdens. Catechol-O-methyltransferase (COMT) may have a prominent role in AD pathophysiology by affecting the metabolism of catecholamine neurotransmitters and estrogen. Although the COMT rs4680 gene polymorphism has been investigated as a susceptibility factor for AD, the results are inconsistent. The aim of this study was to examine the influence of the COMT rs4680 gene polymorphism as a risk factor for AD in the Han Chinese population and its synergistic effect with the apolipoprotein E (APOE) gene. Methods: A total of 137 AD patients and 194 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. All subjects were analyzed for the COMT rs4680 polymorphism and APOE genotype. Results: No significant differences were observed between AD and control subjects regarding the COMT genotype frequencies of Val/Val, Val/Met and Met/Met, but Met alleles were higher in AD than in control subjects (35.4 and 28.1%, p = 0.045). A minor synergistic effect between the genotypes GG and APOE ε4 was observed in AD patients (OR: 5.707, 95% CI: 2.505-13.002, p < 0.001). This synergistic effect was greater in women, who showed higher OR of AD (16.007, 95% CI: 4.606-56.118, p < 0.001) versus the AD group with APOE ε4 (11.972, 95% CI: 5.534-25.902, p < 0.001). Furthermore, the COMT Met allele was an independent risk factor for AD without APOE ε4 allele carriers (OR: 1.806, 95% CI: 1.160-2.810, p = 0.009), especially in men (OR: 4.904, 95% CI: 2.381-10.099, p < 0.001). Conclusion: The COMT (Val158Met) polymorphism is not an independent risk factor for AD but shows a synergistic effect between the genotypes GG and APOE ε4 that proves greater in women with AD. The COMT Met allele represents a risk factor in AD without APOE ε4 allele carriers, which is notable in men with AD.