Showing papers by "Jong Ling Fuh published in 2019"

Assessing the therapeutic potential of Graptopetalum paraguayense on Alzheimer's disease using patient iPSC-derived neurons

Abstract: Alzheimer’s disease (AD) is the most common type of dementia and also one of the leading causes of death worldwide. However, the underlying mechanisms remain unclear, and currently there is no drug treatment that can prevent or cure AD. Here, we have applied the advantages of using induced pluripotent stem cell (iPSC)-derived neurons (iNs) from AD patients, which are able to offer human-specific drug responsiveness, in order to evaluate therapeutic candidates for AD. Using approach involving an inducible neurogenin-2 transgene, we have established a robust and reproducible protocol for differentiating human iPSCs into glutamatergic neurons. The AD-iN cultures that result have mature phenotypic and physiological properties, together with AD-like biochemical features that include extracellular β-amyloid (Aβ) accumulation and Tau protein phosphorylation. By screening using a gene set enrichment analysis (GSEA) approach, Graptopetalum paraguayense (GP) has been identified as a potential therapeutic agent for AD from among a range of Chinese herbal medicines. We found that administration of a GP extract caused a significantly reduction in the AD-associated phenotypes of the iNs, including decreased levels of extracellular Aβ40 and Aβ42, as well as reduced Tau protein phosphorylation at positions Ser214 and Ser396. Additionally, the effect of GP was more prominent in AD-iNs compared to non-diseased controls. These findings provide valuable information that suggests moving extracts of GP toward drug development, either for treating AD or as a health supplement to prevent AD. Furthermore, our human iN-based platform promises to be a useful strategy when it is used for AD drug discovery.

Plasma Transthyretin as a Predictor of Amnestic Mild Cognitive Impairment Conversion to Dementia.

Abstract: Amnestic mild cognitive impairment (MCI) is a prodromal stage of dementia, with a higher incidence of these patients progressing to Alzheimer’s disease (AD) than normal aging people. A biomarker for the early detection and prediction for this progression is important. We recruited MCI subjects in three teaching hospitals and conducted longitudinal follow-up for 5 years at one-year intervals. Cognitively healthy controls were recruited for comparisom at baseline. Plasma transthyretin (TTR) levels were measured by ELISA. Survival analysis with time to AD conversion as an outcome variable was calculated with the multivariable Cox proportional hazards models using TTR as a continuous variable with adjustment for other covariates and bootstrapping resampling analysis. In total, 184 MCI subjects and 40 sex- and age-matched controls were recruited at baseline. At baseline, MCI patients had higher TTR levels compared with the control group. During the longitudinal follow-ups, 135 MCI patients (73.4%) completed follow-up at least once. The TTR level was an independent predictor for MCI conversion to AD when using TTR as a continuous variable (p = 0.023, 95% CI 1.001–1.007). In addition, in MCI converters, the TTR level at the point when they converted to AD was significantly lower than that at baseline (328.6 ± 66.5 vs. 381.9 ± 77.6 ug/ml, p < 0.001). Our study demonstrates the temporal relationship between the plasma TTR level and the conversion from MCI to AD.

Topological reorganization of EEG functional network is associated with the severity and cognitive impairment in Alzheimer’s disease

Abstract: Increasing interest is being directed to developing an objective marker that could be used for the assessment of symptom severity in Alzheimer’s disease (AD). This study assessed the utility of graph theory, an emerging topic in statistical physics, to identify the changes of brain topology in AD patients. A total of 108 AD patients were recruited and their scalp electroencephalogram (EEG) recordings were analyzed retrospectively. Weighted and undirected networks were constructed from EEG signals in different frequency bands and two fundamental measures of the whole-brain network, the average clustering coefficient (CC) and global efficiency (GE), were calculated. Meanwhile, the local structure of the network was investigated by nodal CC. We then examined the group differences of those measures and their association with cognitive assessments of AD patients. The results revealed a topological reorganization of alpha band network in AD patients. The nodal CCs from Fz and Pz electrodes seemed to be preserved in AD while those from frontal and central-parietal regions, such as F3, F4, C3, Cz, C4, P3 and P4, were affected significantly by the disease. Furthermore, significant correlations have been found between the global topological measures and the severity of AD, while the altered local structure was revealed to associate with cognitive impairment measured by the verbal fluency and digit-backward tests in AD patients. Overall, topological reorganization of the functional brain network is involved in the evolution of AD. Network measures, i.e., CC and GE, might serve as objective biomarkers for the evaluation of symptom severity in AD.

Adult onset MELAS Syndrome Presenting as A Mimic of Herpes Simplex Encephalitis.

Abstract: Purpose Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome primarily affects the young and may not be considered first in an older adult with infection-like encephalopathy. Here, we present the case of a patient who suffered from the acute onset of fever, delirium, and epilepsy, mimicking herpes simplex encephalitis (HSE). Case report A 52-year-old woman with diabetes and end stage renal disease (ESRD) regularly took oral anti-diabetic drugs (OADs) and received hemodialysis. She presented with an acute onset of fever, delirium, and epilepsy, mimicking HSE. Further investigation showed a persistent elevated lactate level in the cerebrospinal fluid (CSF). A mitochondrial DNA analysis revealed a point mutation at nucleotide 3243. Conclusion The clinical presentation and imaging studies of MELAS in adults are variable and may mimic those of HSE. Antiviral therapy should be administered until the diagnosis of MELAS is definitive. Infection and metformin may have also precipitated MELAS manifestation in this patient. Clinicians should avoid potential mitochondrial-toxic drugs in these patients.

Influence of Climate on the Incidence of RCVS - A Retrospective Study From Taiwan.

Abstract: Background Cold weather is reportedly a precipitator of reversible cerebral vasoconstriction syndrome (RCVS) in a few cases. We systematically investigated whether meteorological factors correlate with the occurrence of RCVS. Methods We conducted a retrospective analysis of a cohort of patients diagnosed with RCVS or probable RCVS, based on International Classification of Headache Disorders, third edition (ICHD-3) criteria, in a hospital-based headache center from March 2005 to February 2014. Monthly averages of local weather data measured in Taipei were obtained from the Central Weather Bureau in Taiwan. Primary weather variables were compared with the number of monthly new-onset cases of RCVS. Results We recruited 226 patients with established RCVS and 72 patients with probable RCVS during a 108-month study period. Incidence of RCVS was higher in winter than summer months (3.3 persons/month [SD: 2.0] vs 2.1 persons/month [SD: 1.5], P = .013). The monthly incidence of RCVS correlated negatively with mean daily temperature (r = -0.231, P = .016) and average precipitation (r = -0.269, P = .005), but positively with barometric pressure (r = 0.274, P = .004). These 3 correlated meteorological factors together explained about 10% of the variance in RCVS monthly incidence (R2 = 0.095, P = .015). Conclusion RCVS was found to be more common in winter months and to be associated with weather variables in Taiwan. Further studies are needed to explore the underlying mechanisms of these associations.

Risk factors and psychological impact of syncope in migraine patients

Abstract: BackgroundMigraine is associated with syncope. We investigated risk factors for syncope and burden of syncope in migraine patients.MethodsParticipants were recruited from a headache clinic. All par...

The Time Sequences of Brain MRI Findings in Spontaneous Intracranial Hypotension (S20.004)

Abstract: Objective: The aim of the present study was to calculate the time sequence of different brain MRI findings in spontaneous intracranial hypotension (SIH). Background: SIH commonly caused by spinal CSF leakage is typically presented as severe orthostatic headaches. Accurate diagnosis of SIH depends largely on brain MRI findings. However, the emergences of brain MRI findings in different disease durations have not been systemically described. Design/Methods: We retrospectively reviewed the medical records and brain MRI findings of consecutive patients with SIH in Taipei Veterans General Hospital. The disease duration was measured as the interval between the onset of the first SIH symptom and the appearance of specified brain MRI findings. We divided our patients into quartiles based on their disease duration. Associations between disease duration and incidences of brain MRI signs were analyzed using chi-square, linear-by-linear association, or exhaustive CHAID algorithms (decision tree analysis). Results: Between January 2007 and December 2016, 176 SIH patients admitted to our hospital were recruited. Except for the venous distension sign, which has an incidence ≥75% in all quartiles, timings of ≥ 40% incidence rate of MRI signs followed a stepwise fashion: diffuse pachymeningeal enhancement ( Conclusions: Our study showed the brain MRI findings in SIH were associated with the disease duration and occurred sequentially. Our findings can be used to help clinicians make accurate diagnosis of SIH in different durations. Disclosure: Dr. Wu has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Hseu has nothing to disclose. Dr. Fuh has nothing to disclose. Dr. Lirng has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Wang has nothing to disclose.