Interactive effects of hearing aid use and cognitive function in patients with hearing loss.

Background: There has been a significant increase in scientific investigations of the hearing-dementia association among the research on potentially modifiable risk factors for cognitive impairment. We tested two clinical questions. Analysis 1: does persistent hearing aid (HA) use decrease the decline in cognitive function caused by ageing? Analysis 2: does cognitive function at the time of HA fitting predict future persistent HA use?

Methods: This case-control study performed at two referral centres reported data obtained over a 4.

Resident Memory-like CD8 T Cells Are Involved in Chronic Inflammatory and Neurodegenerative Diseases in the CNS.

Background And Objectives: Resident memory T (Trm) cells are a unique population that can survive and function in a compartmentalized tissue with inflammatory potential. We aim to investigate the alteration of Trm population in acute/chronic inflammatory and neurodegenerative diseases in the CNS.

Methods: The frequencies of CD4 and CD8 T cells expressing both CD69 and CD103, the markers for Trm cells, were quantified in the peripheral blood and CSF (n = 80 and 44, respectively) in a cross-sectional manner.

Acute inhibition of AMPA receptors by perampanel reduces amyloid β-protein levels by suppressing β-cleavage of APP in Alzheimer's disease models.

Hippocampal hyperexcitability is a promising therapeutic target to prevent Aβ deposition in AD since enhanced neuronal activity promotes presynaptic Aβ production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as a therapeutic agent for AD. Using transgenic AD mice combined with in vivo brain microdialysis and primary neurons under oligomeric Aβ-evoked neuronal hyperexcitability, the acute effects of PER on Aβ metabolism were investigated.

Predictive Diagnostic Approach to Dementia and Dementia Subtypes Using Wireless and Mobile Electroencephalography: A Pilot Study.

Background: Developing a screening method for mild cognitive impairment in the aging population and intervening early in the progression of dementia based on such a method, remains challenging. Electroencephalography (EEG) is a noninvasive and sensitive tool to assess the functional activity of the brain, and wireless and mobile EEG (wmEEG) could serve as an alternative screening technique that is widely tolerable in patients with dementia from the preclinical to severe stage.

Materials And Methods: Using wmEEG, we recorded bioelectrical activity (BA) from the forehead in 101 individuals with dementia and nondementia controls (NCs) during 4 tasks and investigated which task could differentiate dementia from NC.

[Non-convulsive status epilepticus manifesting as ictal catatonia: a case report].

A 66 year-old right-handed female was admitted to our hospital presenting with recurrent episodes of catatonic symptoms consisting of stupor, waxy flexibility, and catalepsy lasting about 5-20 minutes. A brain MRI showed no significant abnormalities. An scalp-electroencephalography (EEG) concurrent with the symptoms showed ictal EEG activities arising from the left fronto-central area, which evolved into the bilateral frontal and bilateral parietal areas together.

Synaptic Vesicle Protein 2B Negatively Regulates the Amyloidogenic Processing of AβPP as a Novel Interaction Partner of BACE1.

Background: Given that amyloid-β (Aβ) peptide is produced and released at synapses, synaptic Aβ is one of the promising therapeutic targets to prevent synaptic dysfunction in Alzheimer's disease (AD). Although Aβ production begins with the cleavage of the amyloid-β protein precursor (AβPP) by β-site AβPP cleaving enzyme 1 (BACE1), the mechanism on how BACE1 is involved in AβPP processing at synapses remains unclear.

Objective: This study aimed to identify novel BACE1 interacting proteins regulating Aβ production at the synapse.

Development of the Reading Cognitive Test Kyoto (ReaCT Kyoto) for Early Detection of Cognitive Decline in Patients with Hearing Loss.

Background: Early detection of cognitive decline allows timely intervention to delay progression of dementia. However, current cognitive evaluation tools often include items delivered via verbal forms of instruction, which can cause poor performance in patients with hearing loss.

Objective: To develop and validate a cognitive screening battery, the Reading Cognitive Test Kyoto (ReaCT Kyoto), comprising test items given through non-verbal instruction.

Two-Point Dynamic Observation of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus.

Background: Extensive research into cerebrospinal fluid (CSF) biomarkers was performed in patients with idiopathic normal pressure hydrocephalus (iNPH). Most prior research into CSF biomarkers has been one-point observation.

Objective: To investigate dynamic changes in CSF biomarkers during routine tap test in iNPH patients.

Increase in direct social care costs of Alzheimer's disease in Japan depending on dementia severity.

Aim: With the aging population, costs of direct social support for patients with Alzheimer's disease have grown and will continue to increase. The purpose of the present study was to estimate the cost of direct social support for Alzheimer's disease under long-term care insurance in Japan.

Methods: This cross-sectional study included 169 patients with Alzheimer's disease or mild cognitive impairment who visited a memory clinic and were followed over time.

Hashimoto's Encephalopathy Presenting with Smoldering Limbic Encephalitis.

Hashimoto's encephalopathy (HE) is a steroid-responsive autoimmune encephalopathy associated with Hashimoto thyroiditis. We herein report a case of HE manifesting "smoldering" limbic encephalitis with persisting symptoms and abnormalities on examinations. Although our patient experienced partial clinical remission after treatment, hippocampal hypermetabolism on [F] fluorodeoxyglucose positron emission tomography (FDG-PET) and subclinical seizures on video electroencephalography persisted.

[An adult female with proline-rich transmembrane protein 2 related paroxysmal disorders manifesting paroxysmal kinesigenic choreoathetosis and epileptic seizures].

A 21-year-old woman presented with a chief complaint of generalized tonic-clonic seizures occurring once a month at night since the age of 14. The patient was treated with clonazepam plus levetiracetam, but seizure frequency was not reduced. After the detailed re-examination of her history of illness, it was revealed that she has been suffering from transient and recurrent choreoathetoid attacks triggered by sudden voluntary movements since she was a junior high school student, and it recently increased in frequency.

Fibronectin type III domain-containing protein 5 interacts with APP and decreases amyloid β production in Alzheimer's disease.

The deposition of Amyloid-beta peptides (Aβ) is detected at an earlier stage in Alzheimer's disease (AD) pathology. Thus, the approach toward Aβ metabolism is considered to play a critical role in the onset and progression of AD. Mounting evidence suggests that lifestyle-related diseases are closely associated with AD, and exercise is especially linked to the prevention and the delayed progression of AD.

A comparative study: visual rating scores and the voxel-based specific regional analysis system for Alzheimer's disease on magnetic resonance imaging among subjects with Alzheimer's disease, mild cognitive impairment, and normal cognition.

Aim: Hippocampal atrophy shown on magnetic resonance imaging can differentiate Alzheimer's disease (AD) patients from subjects with normal cognition (NC). Simplified automated methods that use volumetric analysis, such as as the voxel-based specific regional analysis system for AD, have become widely used in Japan. However, the diagnostic value of the voxel-based specific regional analysis system compared with visual rating scores for clinical diagnosis is unclear.

Degradation of amyloid β peptide by neprilysin expressed from Borna disease virus vector.

Accumulation of amyloid β (Aβ40 and Aβ42) in the brain is a characteristic of Alzheimer's disease (AD). Because neprilysin (NEP) is a major Aβ-degrading enzyme, NEP delivery in the brain is a promising gene therapy for AD. Borna disease virus (BoDV) vector enables long-term transduction of foreign genes in the central nerve system.

An acute functional screen identifies an effective antibody targeting amyloid-β oligomers based on calcium imaging.

Soluble amyloid β oligomers (AβOs) are widely recognized neurotoxins that trigger aberrant signaling in specific subsets of neurons, leading to accumulated neuronal damage and memory disorders in Alzheimer's disease (AD). One of the profound downstream consequences of AβO-triggered events is dysregulation of cytosolic calcium concentration ([Ca]), which has been implicated in synaptic failure, cytoskeletal abnormalities, and eventually neuronal death. We have developed an in vitro/in vivo drug screening assay to evaluate putative AβO-blocking candidates by measuring AβO-induced real-time changes in [Ca].

Identification of the novel activity-driven interaction between synaptotagmin 1 and presenilin 1 links calcium, synapse, and amyloid beta.

Background: Synaptic loss strongly correlates with memory deterioration. Local accumulation of amyloid β (Aβ) peptide, and neurotoxic Aβ42 in particular, due to abnormal neuronal activity may underlie synaptic dysfunction, neurodegeneration, and memory impairments. To gain an insight into molecular events underlying neuronal activity-regulated Aβ production at the synapse, we explored functional outcomes of the newly discovered calcium-dependent interaction between Alzheimer's disease-associated presenilin 1 (PS1)/γ-secretase and synaptic vesicle proteins.

Exercise is more effective than diet control in preventing high fat diet-induced β-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice.

Accumulating evidence suggests that some dietary patterns, specifically high fat diet (HFD), increase the risk of developing sporadic Alzheimer disease (AD). Thus, interventions targeting HFD-induced metabolic dysfunctions may be effective in preventing the development of AD. We previously demonstrated that amyloid precursor protein (APP)-overexpressing transgenic mice fed HFD showed worsening of cognitive function when compared with control APP mice on normal diet.

Gain of function by phosphorylation in Presenilin 1-mediated regulation of insulin signaling.

We have recently reported that Presenilin 1 (PS1), a causative gene of familial Alzheimer disease (AD), down-regulates the expression level of insulin receptor (IR) as well as its signaling through a γ-secretase-independent pathway. PS1 is phosphorylated by glycogen synthase kinase 3 β at the serine 353 and 357 residues. The main purpose of the present study was to clarify the effect of PS1 phosphorylation on IR/insulin signaling.

Environmental enrichment ameliorated high-fat diet-induced Aβ deposition and memory deficit in APP transgenic mice.

The pathogenesis of Alzheimer's disease (AD) is tightly associated with metabolic dysfunctions. In particular, a potential link between type 2 diabetes (T2DM) and AD has been suggested epidemiologically, clinically, and experimentally, and some studies have suggested that exercise or dietary intervention reduces risk of cognitive decline. However, there is little solid molecular evidence for the effective intervention of metabolic dysfunctions for prevention of AD.

N-cadherin enhances APP dimerization at the extracellular domain and modulates Aβ production.

Sequential processing of amyloid precursor protein (APP) by β- and γ-secretase leads to the generation of amyloid-β (Aβ) peptides, which plays a central role in Alzheimer's disease pathogenesis. APP is capable of forming a homodimer through its extracellular domain as well as transmembrane GXXXG motifs. A number of reports have shown that dimerization of APP modulates Aβ production.

Presenilin regulates insulin signaling via a gamma-secretase-independent mechanism.

Presenilin (PS), a causative molecule of familial Alzheimer disease, acts as a crucial component of the γ-secretase complex, which is required to cleave type I transmembrane proteins such as amyloid precursor protein and Notch. However, it also functions through γ-secretase-independent pathways. Recent reports suggested that PS could regulate the expression level of cell surface receptors, including the PDGF and EGF receptors, followed by modulating their downstream pathways via γ-secretase-independent mechanisms.