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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood–brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin–angiotensin–aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID. [ABSTRACT FROM AUTHOR]

Acute hemorrhagic encephalomyelitis (AHEM) is the most severe form of acute disseminated encephalomyelitis (ADEM). Patients with AHEM usually have unfavorable outcomes with high mortality rate. We reported a middle-aged male, who was diagnosed with AHEM and died 35 days after admission even under intensive immune therapy. Clinical courses were recorded and serial MR images were demonstrated to illustrate the rapidly changes in brain parenchyma. By highlighting these aspects, we hope to provide valuable insights for future studies and potential advancements in the management of AHEM. [ABSTRACT FROM AUTHOR]

Background and Purpose: Small vessel disease (SVD) imaging markers are related to ischemic and hemorrhage stroke and to cognitive dysfunction. This study aimed to clarify the relationship between SVD imaging markers and subcortical vascular dementia in severe SVD burden. Methods: A total of 57 subjects with multiple lobar cerebral microbleeds (CMBs) and four established SVD imaging markers were enrolled from the dementia and stroke registries of a single center. Visual rating scales that are used to semi-quantify SVD imaging changes were analyzed individually and compositely to make correlations with cognitive domains and subcortical vascular dementia. Results: Dementia group had higher subcortical and total white matter hyperintensities (WMHs) and SVD composite scores than non-dementia group. Individual imaging markers correlated differently with one another and had distinct cognitive correlations. After adjusting for demographic factors, multivariate logistic regression indicated associations of subcortical WMHs (odds ratio [OR] 2.03, CI 1.24–3.32), total WMHs (OR 1.43, CI 1.09–1.89), lacunes (OR 1.18, CI 1.02–1.35), cerebral amyloid angiopathy-SVD scores (OR 2.33, CI 1.01–5.40), C1 scores (imaging composite scores of CMB and WMH) (OR 1.41, CI 1.09–1.83), and C2 scores (imaging composite scores of CMB, WMH, perivascular space, and lacune) (OR 1.38, CI 1.08–1.76) with dementia. Conclusions: SVD imaging markers might have differing associations with cognitive domains and dementia. They may provide valuable complementary information in support of personalized treatment planning against cognitive impairment, particularly in patients with a heavy SVD load. [ABSTRACT FROM AUTHOR]

This document is a reply to a comment made on a previous article about a case of acute hemorrhagic encephalomyelitis (AHEM) in a middle-aged male patient. The comment suggested a possible link between AHEM and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), which the authors found intriguing and worthy of further investigation. The authors clarified that they had conducted MOG antibody testing on the patient, and the results were negative. They expressed appreciation for the comment and stated that it would influence their future research. [Extracted from the article]

Background and Purpose: Pyroglutamate-modified β-amyloid peptide (AβpE) is crucial for AD pathophysiological process. The potential associations of plasma AβpE and total tau (t-tau) with brain Aβ burden and cognitive performance remain to be clarified. Methods: Forty-six subjects with unimpaired cognition, mild cognitive impairment, or very mild dementia were enrolled. Plasma levels of AβpE3−40, t-tau, and Aβ42 were quantified by immunomagnetic reduction (IMR) assays. We analyzed individual and combined biomarker correlations with neuropsychological scores and Aβ positivity determined by 18F-florbetapir positron emission tomography (PET). Results: Both plasma AβpE3−40 levels and AβpE3−40/t-tau ratios correlated negatively with short-term memory and global cognition scores, while correlating positively with PET standardized uptake value ratios (SUVRs). Among the biomarkers analyzed, the combination of AβpE3−40 in a ratio with t-tau had the best discriminatory ability for Aβ PET positivity. Likewise, logistic regression analysis showed that AβpE3−40/t-tau was a highly robust predictor of Aβ PET positivity after controlling for relevant demographic covariates. Conclusion: Plasma AβpE3−40/t-tau ratios correlate with cognitive function and cerebral Aβ burden. The suitability of AβpE3−40/t-tau as a candidate clinical biomarker of AD pathology in the brain should be examined further in larger studies. [ABSTRACT FROM AUTHOR]

Introduction: The current study aimed to provide data on the effectiveness of the 10 cm2 rivastigmine patch in patients with Alzheimer's disease (AD) in a real-world setting in Taiwan. Methods: This was a 48-week, single-arm, open-label, observational, and post-marketing study conducted across seven centers in Taiwan between May 5, 2016 and July 10, 2017. Eligible patients (aged 55–95 years) treated with the 10 cm2rivastigmine patch were enrolled based on physicians' judgment and according to the Taiwan reimbursement criteria of the drug. Data were prospectively collected at Week 0 (baseline), Week 24, and Week 48. The primary endpoint was the change in the cognitive assessment screening instrument (CASI) scores at Week 48 versus baseline. The changes from baseline in clinical dementia rating (CDR), mini-mental state examination (MMSE), and neuropsychiatric inventory (NPI) scores were evaluated, as were treatment persistence and the safety profile. Results: Of the 285 eligible patients [full analysis set (FAS)], 216 (75.8%) completed the study protocol while 180 (63.2%) persisted on the 10 cm2 rivastigmine patch for the full 48 weeks. At baseline, 89.8% of patients had a CDR score of 0.5 or 1, while the change in CDR score at Week 48 was not significant. In the FAS, both the CASI and MMSE scores had numerical improvement at Week 24 but declined by 2.1 and 0.4 points, respectively, at Week 48 (p = 0.005 and p = 0.022). The increment in NPI scores was not significant. The most common drug-related adverse events (AEs) were pruritus (11.2%), nausea (3.5%), rash (3.2%), and vomiting (2.8%). Conclusions: The use of the 10 cm2 rivastigmine patch in the mild stage of AD maintained cognitive function at Week 24 and neuropsychiatric function at Week 48. The treatment persistency and safety profile support the clinical tolerability of the rivastigmine patch in the management of mild-to-moderate AD in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Changes in cerebrospinal fluid, neuroimaging, and cognitive functions have been used as diagnostic biomarkers of Alzheimer's disease (AD). This study aimed to investigate the temporal trajectories of plasma biomarkers in subjects with mild cognitive impairment (MCI) and patients with AD relative to healthy controls (HCs). Methods: In this longitudinal study, 82 participants (31 HCs, 33 MCI patients, and 18 AD patients) were enrolled. After 3 years, 7 HCs had transitioned to MCI and 10 subjects with MCI had converted to AD. We analyzed plasma amyloid beta (Aβ) and tau proteins at baseline and annually to correlate with biochemical data and neuropsychological scores. Results: Longitudinal data analysis showed an evolution of Aβ-related biomarkers over time within patients, whereas tau-related biomarkers differed primarily across diagnostic classifications. An initial steady increase in Aβ42 in the MCI stage was followed by a decrease just prior to clinical AD onset. Hyperphosphorylated tau protein levels correlated with cognitive decline in the MCI stage, but not in the AD stage. Conclusion: Plasma Aβ and tau levels change in a dynamic, nonlinear, nonparallel manner over the AD continuum. Changes in plasma Aβ concentration are time-dependent, whereas changes in hyperphosphorylated tau protein levels paralleled the clinical progression of MCI. It remains to be clarified whether diagnostic efficiency can be improved by combining multiple plasma markers or combining plasma markers with other diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Background: In Taiwan, the causes of death and related factors in the oldest old people with Alzheimer disease (AD) are not well characterized. We investigated the factors associated with mortality in the oldest old patients with newly diagnosed AD admitted to a long-stay residential facility. Methods: We performed a prospective study of newly diagnosed AD patients at a veterans' home between 2012 and 2016. At admission, all eligible participants received a comprehensive geriatric assessment, including demographic variables, lifestyle habits, cognitive evaluations, medical conditions (comorbidities, Age-Adjusted Charlson Comorbidity Index score, and polypharmacy), nutritional status evaluated by the Mini Nutritional Assessment-Short Form and body mass index (BMI), and global functional status. A Cox proportional hazards model was used to evaluate the predictive values of clinical parameters for all-cause mortality. Results: The cohort comprised 84 newly diagnosed AD patients (mean age 86.6 ± 3.9 years) with a mean follow-up period of 2.1 ± 1.2 years. The overall median survival was 3.5 years from the time of AD diagnosis (95% confidence interval, 3.1–3.9 years). BMI was significantly lower in the deceased group than in the alive group (20.7 ± 2.9 vs. 22.6 ± 3.4, p = 0.023). Logistic regression demonstrated that the clinical parameters significantly associated with mortality were high global comorbidity, low nutritional status (malnutrition and underweight), and impaired physical function at the time of AD diagnosis. Conclusion: Comorbidity burden, nutritional status, and physical functional status at the time of dementia diagnosis are important contributors to poor outcome in the oldest old. Efforts to control concurrent chronic disorders, nutritional interventions, and physical independency as a long-term care strategy for dementia may provide survival benefit. [ABSTRACT FROM AUTHOR]

Background: Dementia due to Alzheimer's disease (AD) is the major type of dementias in the world. In addition to amyloid plaques and neurofibrillary tangles, cerebrovascular disease is another important pathophysiological cause of AD. Cerebrovascular disease is highly associated with vascular risk factors (VRFs). Well‐treated VRFs might decrease the risk and progression of AD. However, findings on the impact of VRFs treatment status on cognitive decline after the diagnosis of AD established are unclear, and there is no direct evidence supporting well‐treated VRFs can slow down the AD progression. Method: This study recruited mild cognitive impairment (MCI) and mild AD patients (CDR = 0.5 or 1) with at least one VRF from at Taichung Veteran General Hospital. The treatment status of the VRFs was identified and all participants were evaluated by a standard neuropsychological test battery. We collected the participants' brain MRI done within one year and performed Apolipoprotein E genotyping. FreeSurfer was used for structural MRI reconstruction and calculated total gray matter volume, hippocampus volume, and AD signature cortical thickness. Cerebrovascular lesions, including perivascular spaces in centrum semiovale, basal ganglia and presence of lobar cerebral microbleeds (LCMBs), and the volume of white matter hyperintensities were estimated by visual rating scales and Lesion Segmentation Tool for Statistical Parametric Mapping. We analyzed the relationships among the treatment status of VRFs, neuropsychological tests, and brain MRI. Result: We recruited 61 patients in this study. Four patients refused to keep involving the study, 6 patients were not compatible with the criteria of MCI and AD after neuropsychiatric testing, and 4 patients' brain MRI images cannot be analyzed after quality checked. The remaining 47 patients (15 MCI patients and 32 AD patients) constituted the final sample for analysis. The patients with well‐controlled VRFs present with similar cognitive function compared to the patients with partially‐controlled VRFs even though the more severe hippocampal atrophy was noted in the patients with well controlled VRFs. The severity of white matter hyperintensities and other cerebrovascular lesions are not correlated with the cognitive function in MCI and AD patients. Conclusion: Brain reserve in the AD and MCI patients with well‐controlled VRFs might contribute cognitive function [ABSTRACT FROM AUTHOR]

Background: Comorbid medical diseases are highly prevalent in the geriatric population, imposing hardship on healthcare services for demented individuals. Dementia also complicates clinical care for other co-existing medical conditions. This study investigated the comorbidities associated with dementia in the elderly population aged 65 years and over in Taiwan. Methods: We conducted a nationwide, population-based, cross-sectional survey; participants were selected by computerized random sampling from all 19 Taiwan counties between December 2011 and March 2013. After exclusion of incomplete or erroneous data, 8,456 subjects were enrolled. Of them, 6,183 were cognitively normal (control group), 1,576 had mild cognitive impairment (MCI), and 697 had dementia. We collected information about types of comorbidities (i.e., vascular risk factors, lung diseases, liver diseases, gastrointestinal diseases, and cancers), Charlson comorbidity index score, and demographic variables to compare subjects with normal cognition, MCI, and dementia. Results: Regardless of the cognitive condition, over 60% of the individuals in each group had at least one comorbid disease. The proportion of subjects possessing at least three comorbidities was higher in those with cognitive impairment (MCI 20.9%, dementia 27.3%) than in control group (15%). Hypertension and diabetes mellitus were the most common comorbidities. The mean number of comorbidities and Charlson comorbidity index score were greater in MCI and dementia groups than in control group. Logistic regression demonstrated that the comorbidities significantly associated with MCI and dementia were cerebrovascular disease (OR 3.35, CI 2.62–4.28), cirrhosis (OR 3.29, CI 1.29–8.41), asthma (OR 1.56, CI 1.07–2.27), and diabetes mellitus (OR 1.24, CI 1.07–1.44). Conclusion: Multiple medical comorbid diseases are common in older adults, especially in those with cognitive impairment. Cerebrovascular disease, cirrhosis, asthma, and diabetes mellitus are important contributors to cognitive deterioration in the elderly. Efforts to lower cumulative medical burden in the geriatric population may benefit cognitive function. [ABSTRACT FROM AUTHOR]

Background/Aims: Impairment in visual interpretation, semantic conception, or word retrieval may contribute to the naming errors identified in the Boston Naming Test (BNT). We investigated the possible cognitive mechanism of the naming difficulty in Alzheimer's disease (AD) by analyzing the error patterns presented in the BNT. Methods: The Chinese version of the 30-item BNT (BNT-30) was performed on 115 normal control (NC) subjects and 104 mild-to-moderate AD patients. Accurate rates after semantic and phonemic cues were analyzed. The frequencies of 7 types of error patterns in the AD patients and the NC subjects were compared. Results: The accurate rate after semantic cues was significantly lower in the AD than in the NC groups, but phonemic cues were more helpful than semantic cues to achieve accurate naming in both groups. The AD patients made more errors in all error patterns. Particularly, the frequency of nonresponse errors (n = 806) in the AD group significantly exceeded that in the NC group (n = 382). However, the distribution of the error patterns did not differ between the two groups. Conclusion: Naming difficulties in AD might be attributed to progressive semantic knowledge degradation. The AD and the NC groups differ quantitatively but not qualitatively in the error patterns in confrontation naming. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]