Asian Americans’ concerns and plans about Alzheimer's disease: The role of exposure,literacy and cultural beliefs

Responding to the increase of the Asian American population and the growing imperative to address issues on Alzheimer's disease (AD) in diverse populations, this study examined Asian Americans’ concerns about AD (both concerns about one's own development of AD and about becoming an AD caregiver) and plans for AD. Focus was given on exploring the role of AD exposure, AD literacy and cultural beliefs about AD in predicting AD‐related concerns and plans. Using data from 2,609 participants in the 2015 Asian American Quality of Life survey (aged 18–98), logistic regression models of three outcome measures (concerns about one's own development of AD, concerns about becoming an AD caregiver and plans about AD) were estimated. AD exposure and literacy (perceived knowledge and awareness of services) were common predictors of all three outcomes. Beliefs that associate AD with a normal part of ageing and a matter of fate increased the odds of having AD concerns. The odds of having AD plans were found to be higher among those with such concerns. Findings not only identified the factors associated with the concerns and plans about AD but also informed ways to develop targeted AD interventions for Asian Americans.     

The immunosuppressant cyclosporin A inhibits recurrent seizures in an experimental model of temporal lobe epilepsy

The immunosuppressant, cyclosporin A (CsA), is neuroprotective following brain injury. Previous studies suggest that CsA treatment ameliorates seizure severity during status epilepticus (SE) or cell death following SE. The antiepileptic effects of CsA on recurrent seizures, however, have not been investigated. In the present study, the effects of CsA on spontaneous recurrent seizures (SRSs) in a kainate (KA)-induced mouse model of mesial temporal lobe epilepsy (TLE) were examined. Moreover, the effects of CsA on epileptiform activity in a 4-aminopyridine (4-AP)-induced in vitro seizure model were investigated. A mesial TLE mouse model was generated with a unilateral intrahippocampal injection of KA. SRSs were determined in the ipsilateral hippocampal CA1 region with a long-term video-EEG. CsA was systemically administrated to the epileptic mice exhibiting a stable occurrence of SRSs. A 1-mg/kg dose of CsA did not have any effect on SRSs in the epileptic mice. However, a 5-mg/kg dose of CsA significantly reduced the number of SRSs and decreased the severity of the seizures in the epileptic mice. Additionally, CsA treatment inhibited spontaneous burst discharges in 4-AP-treated hippocampal slices. The results of the present study demonstrate that CsA inhibits recurrent seizures in a mouse model of mesial TLE and suggest that CsA may afford both neuroprotection against SE and antiepileptic effects during the chronic period of epilepsy.     

Neuropathogenic role of adenylate kinase-1 in Aβ-mediated tau phosphorylation via AMPK and GSK3β

Abnormally hyperphosphorylated tau is often caused by tau kinases, such as GSK3β and Cdk5. Such occurrence leads to neurofibrillary tangle formation and neuronal degeneration in tauopathy, including Alzheimer's disease (AD). However, little is known about the signaling cascade underlying the pathologic phosphorylation of tau by Aβ(42). In this study, we show that adenylate kinase 1 (AK1) is a novel regulator of abnormal tau phosphorylation. AK1 expression is markedly increased in the brains of AD patients and AD model mice and is significantly induced by Aβ(42) in the primary neurons. Ectopic expression of AK1 alone augments the pathologic phosphorylation of tau at PHF1, CP13 and AT180 epitopes and enhances the formation of tau aggregates. Inversely, downregulation of AK1 alleviates Aβ(42)-induced hyperphosphorylation of tau. AK1 plays a role in Aβ(42)-induced impairment of AMPK activity and GSK3β activation in the primary neurons. Pharmacologic studies show that treatment with an AMPK inhibitor activates GSK3β, and a GSK3β inhibitor attenuates AK1-mediated tau phosphorylation. In a Drosophila model of human tauopathy, the retinal expression of human AK1 severely exacerbates rough eye phenotype and increases abnormal tau phosphorylation. Further, neural expression of AK1 reduces the lifespan of tau transgenic files. Taken together, these observations indicate that the neuronal expression of AK1 is induced by Aβ(42) to increase abnormal tau phosphorylation via AMPK-GSK3β and contributes to tau-mediated neurodegeneration, providing a new upstream modulator of GSK3β in the pathologic phosphorylation of tau.     

Dysphagia May Be an Independent Marker of Poor Outcome in Acute Lateral Medullary Infarction

Background and Purpose

The functional recovery after the lateral medullary infarction (LMI) is usually good. Little is known about the prognostic factors associated with poor outcome following acute LMI. The aim of this study was to identify the factors associated with poor long-term outcome after acute LMI, based on experiences at a single center over 11 years.

Methods

A consecutive series of 157 patients with acute LMI who were admitted within 7 days after symptom onset was evaluated retrospectively. Clinical symptoms were assessed within 1 day after admission, and outcomes were evaluated over a 1-year period after the initial event. The lesions were classified into three vertical types (rostral, middle, and caudal), and the patients were divided into two groups according to the outcome at 1 year: favorable [modified Rankin Scale (mRS) score ≤1] and unfavorable (mRS score ≥2).

Results

Of the 157 patients, 93 (59.2%) had a favorable outcome. Older age, hypertension, dysphagia, requirement for intensive care, and pneumonia were significantly more prevalent in the unfavorable outcome group. The frequencies of intensive care (13%) and mortality (16.7%) were significantly higher in the rostral lesion (p=0.002 and p=0.002). Conditional logistic regression analysis revealed that older age and initial dysphagia were independently related to an unfavorable outcome at 1 year [odds ratio (OR)=1.04, 95% confidence interval (95% CI)=1.001-1.087, p=0.049; OR=2.46, 95% CI=1.04-5.84, p=0.041].

Conclusions

These results suggest that older age and initial dysphagia in the acute phase are independent risk factors for poor long-term prognosis after acute LMI.     

The value of video-EEG monitoring to diagnose juvenile myoclonic epilepsy

ObjectiveA diagnostic accuracy of conventional electroencephalography (EEG) is approximately 50% at best. We aimed to determine the accuracy of video-EEG monitoring (VEM) for a correct diagnosis and the feasibility of its clinical application. The data from all 55 patients (M:F = 31:24) with juvenile myoclonic epilepsy (JME) who underwent VEM were reviewed according to the clinical history, brain imaging and video-EEG findings.ResultsAge at seizure onset ranged from 10 to 25 (15.5 ± 2.7 years). The age at VEM ranged from 15 to 46 (21.8 ± 5.8 years) and 57% (29/51) showed seizures. Of those, 20 patients (69%) showed myoclonic jerks alone, whereas 3 (10%) showed generalized seizures alone. Both of these conditions were observed in 6 patients (21%). Interictal abnormalities alone without clinical seizures were detected in 16 patients (31%). Atypical semiologies such as asymmetric myoclonus or versive seizures were observed in 18 patients (35%) during video monitoring. Interestingly three patients complained of visual aura on history. The duration of VEM ranged from 1 to 6 days (1.8 ± 1.1). Overall, 88% of patients showed an EEG abnormality with/without seizure, concordant with JME. Among 10 patients with a normal conventional EEG before VEM, 9 showed interictal or ictal EEG abnormalities during approximately 1-day of VEM.ConclusionsVEM for 1 or 2 days is appropriate for making a correct diagnosis of JME, especially in patients having an atypical semiology and a normal result on the conventional EEG.