Search

Background: Providing correct information about dementia and people living with dementia and improving the attitude toward the disease have important implications in overcoming prejudice and negative perceptions and strengthening the social support system. However, studies are limited about which aspects of dementia knowledge affect attitudes toward it and the influence of such knowledge on particular aspects of such attitudes. Objective: This study examined which part of dementia knowledge affects attitudes toward dementia and, furthermore, the influence of such knowledge on two aspects of attitudes in the general population. Methods: A population-based cross-sectional survey of 1,200 participants aged 20 years or older was adopted. A landline and wireless telephone survey was conducted from October 12 to October 22, 2021. The survey data included self-report questions about dementia knowledge, dementia attitudes, demographics, and family information. Multiple linear regression analysis was performed. Results: Dementia knowledge was positively associated with global dementia attitudes. In terms of the relationship between the two dimensions of dementia attitudes and knowledge, the latter displayed a significant positive association with accepting attitudes (β= 0.121, p

Amyloid-β (Aβ) is a key protein in Alzheimer's disease (AD) in that its accumulation induces complex pathological changes. Although there has been extensive research on the metabolism of Aβ in AD, new compelling results have recently emerged. Historically, the production and clearance of Aβ have been thought to originate in the central nervous system (CNS). However, recent evidence suggests that the production and clearance of Aβ can also occur in the peripheral system, and that the peripherally driven Aβ migrates to the CNS and induces amyloidopathy with subsequent AD pathologic changes in the brain. This concept implies that AD is not restricted to the CNS but is a systemic disease instead. As such, the development of blood-based biomarkers targeting Aβ is of great interest. Central and peripheral Aβ are both active contributors to the pathology of AD and interact bidirectionally. Measuring peripheral Aβ is not just observing the reflection of the residual Aβ removed from the CNS but also tracking the ongoing process of AD pathology. Additionally, blood-based biomarkers could be a more accessible tool in clinical and research settings. Through arduous research, several blood-based biomarker assays have demonstrated notable results. In this review, we describe the metabolism of Aβ and the amyloid-targeting blood-based biomarkers of AD.

The objective of this study is to investigate the clinical significance of a specific behavior of misplacing items in a refrigerator (i.e., placing extremely unusual things such as remote control and/or cellular phone in a refrigerator) as a symptom of cognitive dysfunction. Patients with memory complaints were asked whether they ever experienced misplacing items in a refrigerator, such as placing a remote control, a cellular phone, or other extremely unusual things inside a refrigerator (referred to as the ‘fridge sign’). Among the 2172 individuals with memory complaints, 55 (2.5%) experienced symptoms of the ‘fridge sign’. We investigated the cognitive profiles of ‘fridge sign’-positive patients and performed follow-up evaluations with neuropsychological tests or telephone interviews. The ‘fridge sign’ was mostly found in individuals diagnosed as subjective cognitive decline (n = 33, 60%) or mild cognitive impairment (MCI, n = 20, 36.4%) with depressive mood and was relatively rare in dementia states (n = 2, 3.5%). Moreover, none of the ‘fridge sign’-positive patients showed significant cognitive decline over the follow-up period. We compared the cognitive profiles and the clinical progression of 20 ‘fridge sign’-positive MCI patients and 40 ‘fridge sign’-negative MCI patients. ‘Fridge sign’-positive MCI patients had worse scores on the Stroop test color reading and had higher scores on the geriatric depression scale than ‘fridge sign’-negative MCI patients, which indicates that the ‘fridge sign’ could be indicative of selective attention deficit in patients with depression rather than indicative of cognitive decline related to dementia.

Background and Purpose There is no specific indicator for monitoring dementia management. We propose an auxiliary indicator called the community management rate, defined as the proportion of dementia patients who receive informal care from close caregivers or themselves within their community population. The 5-year community management rate is the percentage of dementia patients who are receiving community management at 5 years after they were diagnosed. The aim of this study was to identify how the community management rate has changed over time and how the 5-year community management rate differs according to age, sex, income, residence area, and comorbidities. Methods We analyzed customized research database of the Korean National Health Insurance Services from 2003 to 2018. The 5-year community management rate was calculated annually with newly diagnosed dementia patients, and compared among subgroups according to age, sex, income, residence area, and comorbidities. Results This study analyzed 549,297 patients. Among those newly diagnosed with dementia in 2003, the mean duration of community management during the 15-year follow-up was 5.98 years. The community management rate decreased rapidly from 2003 to 2006, after which it increased. A low 5-year community management rate was associated with older age, higher comorbidity burden, nonmetropolitan residence, and low income. Conclusions The community management rate seems to reflect diverse patient factors. Efforts are needed to reduce the comorbidity burden and differences in the 5-year community management rate according to residence area and income. This study indicates the need for further investigations into the use of this indicator to monitor the management of dementia patients.

Gerstmann-Straussler-Scheinker disease (GSS) is a rare prion disease characterized by cerebellar ataxia with progressive cognitive decline.

INTRODUCTION: Oligomeric amyloid ß (Aß) is one of the major contributors to the pathomechanism of AD; Aß oligomerization in plasma can be measured using a Multimer Detection System-Oligomeric Aß (MDS-OAß) after incubation with spiked synthetic Aß. METHODS: We evaluated the clinical sensitivity and specificity of the MDS-OAß values by inBlood TM OAß test using heparin-treated plasma samples from 52 AD patients in comparison with 52 community-based subjects with normal cognition (NC). The inclusion criterion was proposed by the NINCDS-ADRDA and additionally required for the least 6 months of follow-up from the initial clinical diagnosis in the course of AD. RESULTS: The MDS-OAβ values were 1.43 ± 0.30 ng/ml in AD and 0.45 ± 0.19 ( p

Multiple neurological complications have been associated with the coronavirus disease-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. This is a narrative review to gather information on all aspects of COVID-19 in elderly patients with cognitive impairment. First, the following three mechanisms have been proposed to underlie the neurological complications associated with COVID-19: 1) direct invasion, 2) immune and inflammatory reaction, and 3) hypoxic brain damage by COVID-19. Next, because the elderly dementia patient population is particularly vulnerable to COVID-19, we discussed risk factors and difficulties associated with cognitive disorders in this vulnerable population. We also reviewed the effects of the patient living environment in COVID-19 cases that required intensive care unit (ICU) care. Furthermore, we analyzed the impact of stringent social restrictions and COVID-19 pandemic-mediated policies on dementia patients and care providers. Finally, we provided the following strategies for working with elderly dementia patients: general preventive methods; dementia care at home and nursing facilities according to the activities of daily living and dementia characteristics; ICU care after COVID-19 infection; and public health care system and government response. We propose that longitudinal follow-up studies are needed to fully examine COVID-19 associated neurological complications, such as dementia, and the efficacy of telemedicine/telehealth care programs., Graphical Abstract

Introduction Oligomeric amyloid-ß is a major toxic species associated with Alzheimer’s disease pathogenesis. Methods used to measure oligomeric amyloid-β in the blood have increased in number in recent years. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a specific method to measure oligomerization tendencies in the blood. The objective of this study was to determine the association between amyloid-ß oligomerization in the plasma and structural changes of the brain. Methods We studied 162 subjects composed of 92 community-based normal healthy subjects, 17 with subjective cognitive decline, 14 with mild cognitive impairment and 39 with Alzheimer’s disease dementia. All subjects underwent MDS-OAβ and three-dimensional T1 magnetic resonance imaging. To determine the structural changes of the brain that are statistically correlated with MDS-OAβ level, we used voxel-based morphometry with corrections for age and total intracranial volume covariates. Results We found brain volume reduction in the bilateral temporal, amygdala, parahippocampal and lower parietal lobe and left cingulate and precuneus regions (family-wise error, p

Background Approximately 10% to 30% of Alzheimer disease (AD) patients progress rapidly in severity and become more dependent on caregivers. Although several studies have investigated whether imaging biomarkers such as medial temporal atrophy (MTA) and posterior atrophy (PA) are useful for predicting the rapid progression of AD, their results have been inconsistent. Objective The study aims to investigate the association of visually rated MTA and PA with rapid disease progression in AD. Methods This was a retrospective cohort study of 159 AD patients who were initially diagnosed with mild AD and were followed for 1 year to determine whether they progressed rapidly (a decrease of three points or more on the Mini-Mental State Examination over 1 year). We used 5-point and 4-point visual rating scales to assess MTA and PA, respectively. MTA and PA scores for each patient were dichotomized as normal (without atrophy) or abnormal (atrophy). We performed a logistic regression analysis to determine the odds ratios (ORs) of MTA and PA for rapid disease progression with adjustment for covariates. Results Within the study population, 47 (29.6%) patients progressed rapidly. Visual assessment of the magnetic resonance imaging (MRI) scans revealed that 112 patients (70.4%) showed MTA, whereas 80 patients (50.3%) showed PA. The ORs with 95% confidence intervals for MTA and PA were 1.825 (0.819-4.070) and 2.844 (1.378-5.835), respectively. The association of visually assessed PA, but not MTA, with rapid progression was significant after adjustment for covariates. Conclusion In patients with mild AD, visual assessment of PA exhibits independent predictive value for rapid disease progression.

High-throughput label-free measurements of the optical and mechanical properties of single microparticles play an important role in biological research, drug development, and related large population assays. Mechanical detection techniques that rely on the density contrast of a particle with respect to its environment are blind to neutrally bouyant particles. However, neutrally buoyant particles may still have a high compressibility contrast with respect to their environment, opening a window to detection. Here we present a label-free high-throughput approach for measuring the compressibility (bulk modulus) of freely flowing microparticles by means of resonant measurements in an opto-mechano-fluidic resonator., Comment: 4 pages of main text, with 4 figures

Background In patients with amyloid-positive mild cognitive impairment (MCI), neurodegenerative biomarkers such as medial temporal lobe atrophy (MTA) are useful to predict disease progression to dementia. Although posterior atrophy (PA) is a well-known neurodegenerative biomarker of Alzheimer’s disease, little is known about PA as a predictor in patients with amyloid-positive MCI. Methods We included 258 patients with amyloid-positive MCI with at least one follow-up visit, and who had low cerebrospinal fluid (CSF) β-amyloid1–42 concentration. Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative study. We assessed PA and MTA on magnetic resonance imaging (MRI) using visual rating scales and retrospectively determined progression to dementia during the follow-up period of up to 3 years (median 24 months). The Cox proportional hazards model was used to analyze hazard ratios (HRs) of PA and MTA for disease progression. Additionally, subjects were divided into four groups according to brain atrophy pattern (no atrophy, MTA only, PA only, both MTA and PA), and HRs for disease progression were compared with the no atrophy reference group. Analyses were conducted with and without adjustment for CSF phosphorylated tau181p (p-tau) and baseline demographics. Results A total of 123 patients (47.7%) showed MTA and 174 patients (67.4%) showed PA. Of the total cohort, 139 cases (53.9%) progressed to dementia. PA and MTA were associated with an increased risk for progression to dementia (HR 2.244, 95% confidence interval (CI) 1.497–3.364, and HR 1.682, 95% CI 1.203–2.352, respectively). In the analysis according to atrophy pattern, HR (95% CI) for progression was 2.998 (1.443–6.227) in the MTA only group, 3.126 (1.666–5.864) in the PA only group, and 3.814 (2.045–7.110) in both MTA and PA group. These results remained significant after adjustment. Conclusions In patients with amyloid-positive MCI, PA could predict progression to dementia independently of MTA. Electronic supplementary material The online version of this article (doi:10.1186/s13195-017-0326-y) contains supplementary material, which is available to authorized users.

Optical resonators have enabled the label-free measurement of nanoparticles suspended in liquids, down to the resolution of individual viruses and large molecules, but are only able to quantify optical properties (refractive index, scattering, fluorescence). Additionally, these sensors are fundamentally limited by the random diffusion of particles to the sensing region, and thus only measure a tiny fraction of the analyte. We have developed a microfluidic optomechanical resonator capable of sensing freely flowing nanoparticles using the action of phonons that are coupled to light. The phonon mode of the system casts a nearly perfect net for measuring density, viscoelasticity, and compressibility of the particles that flow through, without being limited by random diffusion. Information on the mechanical properties of the particles is encoded in the light scattered from the thermal fluctuations of the phonon mode. We have also developed a new electro-opto-mechanical method for improving the sensing speed achievable with this technique. We demonstrate real-time particle transit measurements as fast as 400 microseconds, without any post-processing. We discuss how this novel technique can be used for ultra-high throughput analysis of mechanical properties of biological particles in liquids, enabling a new form of flow cytometry. (invited by Prof. Giuseppe Leo)

Resonant optical sensors have enabled the label-free measurement of nanoparticles suspended in liquids, down to the resolution of individual viruses and large molecules, but are only able to quantify optical properties (refractive index, scattering, fluorescence). Additionally, these sensors are fundamentally limited by the random diffusion of particles to the sensing region, and thus only quantify a tiny fraction of the analyte. We have developed a microfluidic optomechanical resonator capable of sensing flowing nanoparticles using the action of phonons that are coupled to light. The phonon mode of the system casts a nearly perfect net for measuring density, viscoelasticity, and compressibility of the particles that flow through, without being limited by random diffusion. Information on the particle mechanical properties is encoded in the light scattered from the thermal fluctuations of the phonon mode, and measurements at a timescale of below 20 milliseconds have been demonstrated previously. In this work, we develop a new experimental method for improving the signal-to-noise ratio (SNR) and sensing speed achievable with this technique, by implementing electro-opto-mechanical transduction. We demonstrate real-time particle transit measurements as fast as 400 microseconds, a factor of 50x improvement in speed, without any post-processing. We discuss how this novel technique can be used for ultra-high throughput analysis of mechanical properties of biological particles in liquids, enabling a new form of flow cytometry.

In this study, a novel mutation in APP gene, Val669Leu (“Seoul APP”), was reported in a Korean female patient with Alzheimer's disease. She developed cognitive decline at 56 years of age, and her memory declined rapidly over one-year period from her 1st visit to the hospital. Her Mini-Mental State Examination scores dropped from 25/30 to 13/30. Two years later, she developed parkinsonian features, myoclonic jerk, and generalized seizure. As the disease progressed, aggravated diffuse brain atrophy and small-vessel ischemic lesion was also observed, and she became mute and vegetative in 4 years from the symptom onset. Magnetic resonance imaging showed mild medial temporal lobe and hippocampal atrophy, and 18F-fluoro-deoxyglucose positron emission tomography showed bilateral temporoparietal hypometabolism. Plasma amyloid oligomer analysis revealed highly elevated Aβ oligomers levels in the proband patient. Family history revealed positive without biochemical confirmation because family members testified similar type of cognitive decline from the proband's mother and one of her aunt/uncle. Her half-siblings did not present any signs of memory impairment. Sanger sequencing of the proband patient revealed a novel mutation in APP gene, Val669Leu, but mutation was not found in her unaffected half-sisters. A designed algorithm by Guerreiro et al. on early-onset Alzheimer's disease–associated mutations suggested the mutation as possibly pathogenic mutation. On the other hand, PolyPhen2 and SIFT tools suggested as otherwise. Since the mutation was located nearby the β-secretase cleavage site of APP, right next to the Swedish APP (Lys,Met670/671Asn,Leu) mutation, it was named as “Seoul APP” mutation. 3D modeling revealed that this mutation could result in significant changes in loop orientation of APP and also its intramolecular interactions. Hence, a novel APP Val669Leu mutation could alter the binding interactions between APP and β-secretase, which may influence the Aβ40 and Aβ42 generations.

Inter- and intra-rater reliability. (DOCX 16 kb)

We present a technique for mapping the acoustic pressure fields within microfluidic optomechanical resonators using a single particle probe. These mappings help improve the detection capabilities of high-throughput opto-mechano-fluidic sensors.

Comparison of volumetric measures of temporal and parietal regions according to disease progression to dementia. (DOCX 19 kb)

Visual rating of medial temporal lobe atrophy. (DOCX 14 kb)

Opto-mechano-fluidic resonators (OMFRs) are a new platform for high-throughput sensing of the mechanical properties of freely flowing microparticles in arbitrary media. Experimental extraction of OMFR mode shapes, especially the acoustic pressure field within the fluidic core, is essential for determining sensitivity and for extracting the particle parameters. Here we demonstrate a new imaging technique for simultaneously capturing the spatially distributed acoustic pressure fields of multiple vibrational modes in the OMFR system. The mechanism operates using microparticles as perturbative imaging probes, and potentially reveals the inverse path towards multimode inertial detection of the particles themselves., Comment: 5 pages, 5 figures