Caregivers' attitude toward disclosure of Alzheimer's disease diagnosis in Urban China.

BACKGROUND: Disclosing the diagnosis of Alzheimer's disease (AD) to a patient is controversial. There is significant stigma associated with a diagnosis of AD or dementia in China, but the attitude of the society toward disclosure of such a diagnosis had not been formally evaluated prior to our study. Therefore, we aimed to evaluate the attitude toward disclosing an AD diagnosis to patients in China with cognitive impairment from their caregivers, and the factors that may affect their attitude. METHODS: We designed a 17-item questionnaire and administered this questionnaire to caregivers, who accompanied patients with cognitive impairment or dementia in three major hospitals in Shanghai, China. The caregiver's attitude toward disclosing the diagnosis of AD as evaluated by the questionnaire was compared to that of disclosing the diagnosis of terminal cancer. RESULTS: A majority (95.7%) of the 175 interviewed participants (mean 14.2 years of education received) wished to know their own diagnosis if they were diagnosed with AD, and 97.6% preferred the doctor to tell their family members if they were diagnosed with AD. If a family member of the participants suffered from AD, 82.9% preferred to have the diagnosis disclosed to the patient. "Cognitive impairment" was the most accepted term by caregivers to disclose AD diagnosis in Chinese. CONCLUSION: This study suggests most of the well-educated individuals in a Chinese urban area favored disclosing the diagnosis when they or their family members were diagnosed with AD.

[Progress of research on microRNA and Alzheimer's disease].

MicroRNA are a group of non-coding RNA which, through regulating expression of proteins at post-transcription level, plays an important role in modulating growth and development of nervous system, cell differentiation and functions. Altered expression of microRNA in the brain may influence development and advance of Alzheimer's disease from multiple perspectives. Research on microRNA will facilitate in depth understanding of the pathogenesis of Alzheimer's disease.

An explainable machine learning based prediction model for Alzheimer's disease in China longitudinal aging study.

Alzheimer's disease (AD) is the most common cause of dementia. Accurate prediction and diagnosis of AD and its prodromal stage, i.e., mild cognitive impairment (MCI), is essential for the possible delay and early treatment for the disease. In this paper, we adopt the data from the China Longitudinal Aging Study (CLAS), which was launched in 2011, and includes a joint effort of 15 institutions all over the country. Four thousand four hundred and eleven people who are at least 60 years old participated in the project, where 3,514 people completed the baseline survey. The survey collected data including demographic information, daily lifestyle, medical history, and routine physical examination. In particular, we employ ensemble learning and feature selection methods to develop an explainable prediction model for AD and MCI. Five feature selection methods and nine machine learning classifiers are applied for comparison to find the most dominant features on AD/MCI prediction. The resulting model achieves accuracy of 89.2%, sensitivity of 87.7%, and specificity of 90.7% for MCI prediction, and accuracy of 99.2%, sensitivity of 99.7%, and specificity of 98.7% for AD prediction. We further utilize the SHapley Additive exPlanations (SHAP) algorithm to visualize the specific contribution of each feature to AD/MCI prediction at both global and individual levels. Consequently, our model not only provides the prediction outcome, but also helps to understand the relationship between lifestyle/physical disease history and cognitive function, and enables clinicians to make appropriate recommendations for the elderly. Therefore, our approach provides a new perspective for the design of a computer-aided diagnosis system for AD and MCI, and has potential high clinical application value.

[Hydrogen proton MR spectroscopy of posterior portion cingulate gyrus of patients with Alzheimer's disease: a case control study].

OBJECTIVE: To investigate the characteristics of hydrogen proton magnetic resonance spectroscopy (H-MRS) in posterior portion cingulate gyrus and the correlations thereof with the results of mini-mental state examination (MMSE), Alzheimer disease assessment scale-cognitive (ADAS-cog) in patients with mild-moderate Alzheimer's disease (AD). METHODS: H-MRS in posterior portion cingulate gyrus was conducted in gender, age, and educational background-matched 24 patients with AD, 8 patients with vascular dementia (VD), and 11 normal controls (NC group) to measure the values of NAA (N-acetyl aspartate)myo-inositol (mI), and creatine and phosphocreatine (Cr). All the 4 subjects underwent MMSE and assessment with ADAS-cog as well. The correlations among these results were assessed. RESULTS: The NAA/Cr ratios in posterior portion cingulate gyrus of the AD and VD groups were (1.24 +/- 0.12) and (1.25 +/- 0.15) respectively, both significantly lower than that of the NC group [(1.46 +/- 0.19), P = 0.003, P = 0.017] without significant difference between the AD and VD groups (P = 0.800). The mI/Cr value of the AD group was (0.74 +/- 0.15), not significantly different from that of the VD group [(0.65 +/- 0.15), P = 0.153], and significantly higher than that of the NC group [(0.62 +/- 0.09), P = 0.007], however, the mI/Cr value of the VD group was not significantly different from that of the NC group (P = 0.662). If the NAA/Cr ratio < 1.31 was used as criteria of AD, the positive predictive value of AD was 73% and negative predictive value was 71%. The NAA/Cr ratio was positively correlated with the MMSE score (r = 0.731, P = 0.000), and negatively correlated with the ADAS-cog score (r = -0.541, P = 0.011). CONCLUSIONS: The NAA/Cr ratio decreases in the posterior portion cingulate gyrus of AD patients, and has statistical significant correlations with the score of MMSE and ADAS-cog. The H-MRS characteristics of posterior portion cingulate gyrus cannot effectively differentiate the early AD from early VD.

Cognitive decline is related to high blood glucose levels in older Chinese adults with the ApoE ε3/ε3 genotype.

BACKGROUND: Few studies have investigated the effects of blood glucose (BG) on cognitive function in community-dwelling elderly individuals carrying the apolipoprotein E (APOE) ε3 allele. OBJECTIVE: To explore the effect of high BG levels on cognitive function in APOE ε3-carrying, non-demented, community-dwelling older adults, as compared to their counterparts carrying the APOE ε4 or APOE ε2 alleles. METHODS: Within the China Longitudinal Ageing Study, we recruited 282 elderly adults without dementia. Data collected included demographic information; psychological measures; laboratory test results, including BG and plasma lipid levels; and APOE genotypes. We divided the participants into APOE ε2(ε2/ε2, ε2/ε3), ε3(ε3/ε3), and ε4(ε3/ε4, ε4/ε4) groups. Partial correlation analyses and multivariate linear regression analyses were utilized to compare the cognitive function and laboratory data between the APOE groups. White matter hyperintensity (WMH) was measured on magnetic resonance images in 77 participants. RESULTS: With adjustment for age, sex, education, and diabetes, higher BG in non-demented community-dwelling older adults was associated with cognitive decline in immediate memory and executive function. In the APOE ε3 group, elevated BG was associated with cognitive decline in immediate memory, executive function, and perceptual reasoning. In the APOE ε4 group, higher BG was also correlated with a decline in abstract reasoning. There was a trend for association between higher BG and more severe WMHs. CONCLUSION: Worse cognitive function was correlated withApoEε3/ε3 genotype carriers with higher BG in community-dwelling older adults.

[Brain volume changes of patients with Alzheimer's disease in two years: a case control study].

OBJECTIVE: To study the brain volume changes of patients with Alzheimer's disease (AD). METHODS: 23 patients with (AD and 23 sex, age, and educational background-matched normal controls (NC group) underwent three-dimensional MRI to measure the hippocampus, amygdala, entorhinal cortex (EC), perirhinal cortex (PC), cornu temporale, and uncus distance in the baseline survey. Two years later 10 AD patients and 11 normal controls underwent 3-D MRI once again in the follow-up survey. RESULTS: The baseline survey showed that the levels of uncus distance and total temporal horn volume of the ADS patients were 11 +/- 4 and 1.21 +/- 1.00 respectively, both significantly higher than those of the NC group (7 +/- 3 and 0.59 +/- 0.54 respectively, P < 0.01, P < 0.05), and the levels of total entorhinal cortex volume, total perirhinal cortex volume, and total hippocampus volume were 2.52 +/- 0.86, 2.19 +/- 0.62, and 3.23 +/- 0.75 respectively, all significantly lower than those of the BC group (3.67 +/- 0.54, 3.39 +/- 0.51, and 3.98 0.38, all P < 0.01). The levels of uncus distance and total temporal horn volume of the AD patients during the follow-up survey were 11 +/- 4 and 1.21 +/- 1.00 respectively, both significantly higher than those of the NC group (7 +/- 3 and 0.59 +/- 0.54 respectively, both P < 0.05); and the total entorhinal cortex volume, total perirhinal cortex volume, and total hippocampus volume of the AD patients during the followup survey were. 1.79 +/- 0.56, 1.77 +/- 0.59, and 2.80 +/- 0.80 respectively, all significantly lower than those of the NC group (2.76 +/- 0.50, 2.76 +/- 0.41, and 3.59 +/- 0.38 respectively, all P < 0.01). CONCLUSION: The AD patients have more remarkable atrophy of entorhinal cortex, perirhinal cortex, and have obvious extension of cornu temporale and uncus distance in comparison with the normal controls. The shrinkage rate of hippocampus can be used as a marker for the diagnosis and progress of AD.

Structural alterations in the caudate nucleus and precuneus in un-medicated anorexia nervosa patients.

Anorexia nervosa (AN) is a mental disorder characterized by a preoccupation with thinness and may be associated with brain structural alteration. The aim of the study was to examine the brain structural alteration in AN patients, including subcortical structure volume and cortical thickness. Thirty-five un-medicated AN patients and 20 matched healthy controls underwent structural magnetic resonance imaging brain scans. High resolution structural images were acquired on a SIEMENS 3T scanner and preprocessed using FreeSurfer software. Subcortical structure volume and cortical thickness were compared between the two groups. We found larger percentage of caudate volume relative to total grey matter (GM) volume in the AN group. Reduced cortical thickness at the left precuneus was also observed in AN patients. Moreover, an interaction between group and hemisphere was found, suggesting that cortical thinning was more prominent in the left hemisphere in AN patients. These findings provide further evidence for structural brain abnormalities in patients with AN.

[Change of cerebral metabolism rate of glucose of cerebral white matter in Alzheimer's disease: a study with statistical parametric mapping software].

OBJECTIVE: To study the change of cerebral metabolism rate of glucose (CMRglc) of cerebral white matter in Alzheimer's Disease. METHODS: Positron emission tomography (PET) was performed on 13 AD patients, 6 with behavioral and psychological symptoms of dementia (BPSD) and 7 without BPSD, and 10 healthy controls. The regional cerebral metabolism of glucose (rCMRglc) of some brain regions and nuclei were detected. RESULTS: (1) The rCMRglc of the cerebral white matter decreased extensively in the AD patients, especially in the right frontal lobe, superior gyrus of the left frontal lobe (P = 0.001). (2) The rCMRglc of subcortical white matter of the left medial prefrontal lobe and the left cuneus of occipital lobe increased in the AD patients. (3) The levels of rCMRglc of the subcortical white matter of both side middle occipital lobe, left cuneus of occipital lobe, right inferior parietal lobule, left fusiform gyrus of temporal lobe and the left medial prefrontal lobe were all significantly higher in the AD patients with BPSD than in those without BPSD (P = 0.001). While the levels of rCMRglc of the subcortical white matter of both side paracentral lobule, right superior and middle frontal lobe, and left superior temporal lobe were all significantly lower in the AD patients with BPSD than in those without BPSD (all P = 0.001). CONCLUSION: There is diffuse abnormal rCMRglc in the cerebral white matter in the AD patients: the rCMRglc decreases in the frontal-temporal-occipital association area, and the rCMRglc of the medial prefrontal lobe and cuneus of occipital lobe increases. BPSD is correlated with the abnormal metabolism of related cerebral regions.

[Outcome and cognitive changes of mild cognitive impairment in the elderly: a follow-up study of 47 cases].

OBJECTIVE: To examine the cognitive changes and outcome of mild cognitive impairment (MCI) in the elderly and to explore the predictive factors of development from MCI into dementia. METHOD: A cross-sectional and longitudinal parallel cohort study design was conducted among 47 patients with MCI (MCI group), aged 72.4 +/- 7.1, and 50 sex, marital status, and professional structure-matched normal controls (NC group), aged 67.9 +/- 5.3, using the Neuropsychological Battery of Cognitive Assessment Instruments developed by World Health Organization (WHO-BCAI) and the Wechsler Memory Scale (WMS) to assess the cognitive function. Follow-up was conducted for 34.0 +/- 1.8 months. The diagnosis of dementia was based on the criteria in the Diagnostic and Statistical Manual-IV. RESULTS: Dementia was diagnosed in 13 of the 47 MCI patients with a prevalence rate of 27.7%, significantly higher than that in the NC group (2.0%, 1/50, P < 0.01). The mean total score of mini-mental status examination (MMSE) of the MCI group decreased by 2.2 +/- 3.7, significantly more than that of the NC group (1.0 +/- 1.9, P < 0.01). The mean total mental quotient (MQ) of the MCI group decreased by 12.6 +/- 17.3, significantly more than that of the NC group (3.9 +/- 8.4, P < 0.01). The values of MMSE and MQ of the 13 cases in the MCI group who developed into dementia patients decreased by 5.5 +/- 2.8 and 30.0 +/- 18.0 respectively. The WHO-BCAI assessment demonstrated that the scores of performance of verbal learning, verbal fluency, visual reasoning, trail making, sorting and spatial construct tests of the cases in the MCI group who developed into dementia patients were significantly poorer than those of the NC group (P < 0.01). Logistic analysis based on the baseline assessment suggested that the total score of MMSE and its subtest of orientation, score of orientation memory of WMS, and the scores of performance of trail making, attention, and delayed recall tested by WHO-BCAI were all statistically significant predictive factors for MCI converting into dementia (P < 0.01 or 0.05). The predictive accuracy rates of MMSE, WMS, and WHO-BCAI were 70.3%, 78.4% and 90.7% respectively. CONCLUSION: MCI diagnosed based on the criteria of pure MCI modified by the authors is indeed a transitional state from normal aging to dementia, especially Alzheimer's type of dementia. The cognitive change for MCI converting into dementia is characterized in the areas of orientation, attention, speech and executive function. These predictive factors for MCI to develop dementia are valuable in early detection and prevention of dementia in the elderly.

Clinicians' prescription preferences for treating patients with Alzheimer's disease in Shanghai.

BACKGROUND: China has more cases of Alzheimer's disease (AD) than any other country in the world. As training to recognize and manage dementia is in its early stage, it is important to study clinicians' current prescription preferences for treating patients with AD. METHODS: This study surveyed neurologists, psychiatrists, and general physicians (GPs) in Shanghai who had outpatients with AD, using a questionnaire asking about their prescription preferences for these patients. RESULTS: Among the 148 clinicians in the study, 26.4 % were psychiatrists, 44.6 % were neurologists, and 29.1 % were GPs. The groups did not differ significantly in age, gender, or their monthly cases of new patients with mild or moderate AD (P > 0.05). Most clinicians prescribed Cholinesterase inhibitors (ChEIs), including Huperzine A, but there were significant group-differences in prescribing specific ChEIs (P < 0.05). The daily dosages of ChEI and Memantine prescribed by all three groups were small (P > 0.05), and all three groups prescribed piracetam, ergot, and ginkgo biloba drugs. All three groups also tended to treat AD patients with a combination of antidepressants and anxiolytics, although psychiatrists were significantly more likely than neurologists to combine antipsychotics with other drugs (P < 0.05). CONCLUSION: Clinicians in Shanghai prescribed low doses of ChEIs and Memantine for patients with AD. A relatively high proportion also prescribed cognitive enhancers, which lack evidence-based support of their use, and antipsychotics. There is a need for more training about treating patients with AD and for clinicians to standardize their clinical practice.

Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype.

Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3), APOE ε3 group (ε3/ε3), and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4). Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4%) among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (P<0.05). The APOE ε3 group had slightly higher abnormal fasting plasma glucose values than did the APOE ε2 group (P = 0.065). Furthermore, the APOE3 genotype was significantly correlated with both fasting plasma glucose level and glucose abnormality (P< 0.05) and trended toward statistically significant correlation with diabetes (P = 0.082). The correlation between APOE2 and low low-density lipoprotein levels also approached statistical significance (P = 0.052). Thus, elderly community dwelling residents of Han ethnicity carrying the APOE ε3/ε3 genotype might have higher plasma glucose levels and a higher occurrence of diabetes.

[The neuropsychological test battery for elderly people].

OBJECTIVE: To establish a Chinese T-score norm of neuropsychological test battery for the elderly (NTBE). METHODS: 903 normal elderly people over 60 years old from Shanghai, Beijing, Hebei, Jiangsu, Hubei, Hunan, Zhejiang, Shandong and Liaoning were evaluated by using NTBE which includes tests of auditory verbal learning, sorting, cancellation, language, motor, visual function, construction, trail making 1 and 2, etc. RESULTS: Age and education greatly affected the score of NTBE, but gender did not. Based on these facts, the 903 normal subjects were divided into 12 subgroups, according to the age and the years of education they had received. The raw scores of NTBE were transformed to standard score and normalized standard score, and then these scores were transformed to a total T score (Mean = 100, SD = 10). Using another normal elderly sample (n = 474) to analysis, the correlation between the raw scores and the total T score was significant. Using NTBE to diagnose 110 mild cognitive impairment (MCI) and 63 Alzheimer's disease (AD) patients, the sensitivity and specificity were 66% and 91% for MCI, and 79% and 96% for AD. CONCLUSION: The T norm of the NTBE is suitable for Chinese elderly, and can be a useful instrument for diagnosing mild cognitive impairment and Alzheimer's disease.

[Measurement of regional cerebral metabolism rate of glucose in patients with Alzheimer's disease in different levels of severity].

OBJECTIVE: To measure the changes of regional cerebral metabolism rate of glucose (rCMRglc) in patients with Alzheimer's disease (AD) and explore their value to diagnosis of AD. METHODS: 10 patients with AD who met the diagnostic criteria of DSM-IV and 10 normal controls (NC) were assessed with (18)F-2-fluoro-deoxy-D-glucose positron emission tomography (PET). RESULTS: The two groups were matched in age, gender and education. The mean total scores of the mini-mental status examination (MMSE) were 16.5 +/- 6.1 for AD and 28.7 +/- 1.6 for NC. The mean total memory quotient of Wechsler Memory Scales (MQ) were 32.3 +/- 19.6 for AD and 93.1 +/- 9.0 for NC. Comparing to NC, the AD groups showed statistically significant decline of rCMRglc in frontal lobe, temporal lobe and the hippocampal formation with decreased rates ranged from 3.3% to 28.4% (P < 0.05, P < 0.01). The hypo-metabolism was more salient in the regions of upper and middle frontal gyri, middle temporal gyrus, orbital gyrus and anterior cingulate gyrus, in which areas the metabolism decreased over 20% compared to NC. The hypo-metabolism was correlated to the severity of dementia. Discriminant analysis demonstrated that the variables of right inferior temporal gyrus, left upper temporal gyrus, left hippocampus and right insular lobe were entered into the discriminant functions and the total discriminant accuracy reached 100%. CONCLUSIONS: (18)F-FDG PET is a very sensitive tool in measurement of the changes of rCMRglc in patients with AD. The findings show a frontal-temporal type of metabolism in AD patients and suggest that hypo-metabolism in hippocampal formation and temporal lobe is helpful in early detection of AD.

Induced pluripotent stem cells and neurodegenerative diseases.

Neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Amyotrophic Lateral Sclerosis, are characterized by idiopathic neuron loss in different regions of the central nervous system, which contributes to the relevant dysfunctions in the patients. The application of cell replacement therapy using human embryonic stem (hES) cells, though having attracted much attention, has been hampered by the intrinsic ethical problems. It has been demonstrated that adult somatic cells can be reprogrammed into the embryonic state, called induced pluripotent stem (iPS) cells. It is soon realized that iPS cells may be an alternative source for cell replacement therapy, because it raises no ethical problems and using patient-specific iPS cells for autologous transplantation will not lead to immunological rejection. What's more, certain types of neurons derived from patient-specific iPS cells may display disease-relevant phenotypes. Thus, patient-specific iPS cells can provide a unique opportunity to directly investigate the pathological properties of relevant neural cells in individual patient, and to study the vulnerability of neural cells to pathogenic factors in vitro, which may help reveal the pathogenesis of many neurodegenerative diseases. In this review, the recent development in cellular treatment of neurodegenerative diseases using iPS cells was summarized, and the potential value of iPS cells in the modeling of neurodegenerative disease was discussed.

A double-blind, placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia.

OBJECTIVE To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. METHODS The trial was a double-blind, placebo-controlled, parallel-group design. The eligible patients were randomized into 2 treatment groups: sarsasapogenin group (sarsasapogenin plus risperidone for 8 weeks, n = 41) and placebo group (risperidone only for 8 weeks, n = 39). At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS), Clinical Global Impression (CGI) and Brief Psychiatry Rating Scale (BPRS). The study period for each subject was 8 weeks and duration of overall trial was 2 years. RESULTS Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. CONCLUSION Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.

Association between NMDA receptor subunit 2b gene polymorphism and Alzheimer's disease in Chinese Han population in Shanghai.

OBJECTIVE: N-methyl-D-aspartate (NMDA) receptor has been indicated to be involved in the pathogenesis of Alzheimer's disease (AD). The NMDA receptor subunit 2b (NR2B) has attracted more attention due to its characteristic distribution and selective reduction in AD brain. The present study aimed to explore the association between NMDA gene polymorphism and AD. METHODS: A total of 63 AD patients and 68 normal controls in Shanghai city were employed in this study. Genotype of C2664T variant (rs1806201) in the exon13 of GRIN2B gene was determined by gene sequencing. RESULTS: Among AD patients, 15 (23.6%) subjects were identified as C/C genotype, and 35 (55.6%) were identified as C/T genotype. The left 13 (20.6%) subjects were identified as T/T genotype. In normal controls, 15 (22.1%) subjects were identified as C/C genotype, 39 (57.4%) as C/T genotype and 14 (20.6%) as T/T genotype. The distribution frequency of neither GRIN2B C2664T genotype (P=0.895) nor allele (P=0.790) was significantly different between AD patients and normal controls, even when the subjects were stratified by gender and age of disease onset in AD patients. CONCLUSION: The results suggest that there is no relation between GRIN2B C2664T polymorphism and AD in Chinese Han population of Shanghai City.