Limbic-predominant age-related TDP-43 encephalopathy (LATE-NC): Co-pathologies and genetic risk factors provide clues about pathogenesis.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is detectable at autopsy in more than one-third of people beyond age 85 years and is robustly associated with dementia independent of other pathologies. Although LATE-NC has a large impact on public health, there remain uncertainties about the underlying biologic mechanisms. Here, we review the literature from human studies that may shed light on pathogenetic mechanisms. It is increasingly clear that certain combinations of pathologic changes tend to coexist in aging brains. Although "pure" LATE-NC is not rare, LATE-NC often coexists in the same brains with Alzheimer disease neuropathologic change, brain arteriolosclerosis, hippocampal sclerosis of aging, and/or age-related tau astrogliopathy (ARTAG). The patterns of pathologic comorbidities provide circumstantial evidence of mechanistic interactions ("synergies") between the pathologies, and also suggest common upstream influences. As to primary mediators of vulnerability to neuropathologic changes, genetics may play key roles. Genes associated with LATE-NC include TMEM106B, GRN, APOE, SORL1, ABCC9, and others. Although the anatomic distribution of TDP-43 pathology defines the condition, important cofactors for LATE-NC may include Tau pathology, endolysosomal pathways, and blood-brain barrier dysfunction. A review of the human phenomenology offers insights into disease-driving mechanisms, and may provide clues for diagnostic and therapeutic targets.

Pathologic correlates of aging-related tau astrogliopathy: ARTAG is associated with LATE-NC and cerebrovascular pathologies, but not with ADNC.

Age-related tau astrogliopathy (ARTAG) is detectable in the brains of over one-third of autopsied persons beyond age 80, but the pathoetiology of ARTAG is poorly understood. Insights can be gained by analyzing risk factors and comorbid pathologies. Here we addressed the question of which prevalent co-pathologies are observed with increased frequency in brains with ARTAG. The study sample was the National Alzheimer's Coordinating Center (NACC) data set, derived from multiple Alzheimer's disease research centers (ADRCs) in the United States. Data from persons with unusual conditions (e.g. frontotemporal dementia) were excluded leaving 504 individual autopsied research participants, clustering from 20 different ADRCs, autopsied since 2020; ARTAG was reported in 222 (44.0%) of included participants. As has been shown previously, ARTAG was increasingly frequent with older age and in males. The presence and severity of other common subtypes of pathology that were previously linked to dementia were analyzed, stratifying for the presence of ARTAG. In logistical regression-based statistical models that included age and sex as covariates, ARTAG was relatively more likely to be found in brains with limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and in brains with comorbid cerebrovascular pathology (arteriolosclerosis and/or brain infarcts). However, ARTAG was not associated with severe Alzheimer's disease neuropathologic change (ADNC), or primary age-related tauopathy (PART). In a subset analysis of 167 participants with neurocognitive testing data, there was a marginal trend for ARTAG pathology to be associated with cognitive impairment as assessed with MMSE scores (P = 0.07, adjusting for age, sex, interval between final clinic visit and death, and ADNC severity). A limitation of the study was that there were missing data about ARTAG pathologies, with incomplete operationalization of ARTAG according to anatomic region and pathologic subtypes (e.g., thorn-shaped or granular-fuzzy astrocytes). In summary, ARTAG was not associated with ADNC, whereas prior observations about ARTAG occurring with increased frequency in aging, males, and brains with LATE-NC were replicated. It remains to be determined whether the increased frequency of ARTAG in brains with comorbid cerebrovascular pathology is related to local infarctions or neuroinflammatory signaling, or with some other set of correlated factors including blood-brain barrier dysfunction.

Socio-Demographic, Health, and Transport-Related Factors Affecting the COVID-19 Outbreak in Myanmar: A Cross-Sectional Study.

Introduction The coronavirus disease 2019 (COVID-19) pandemic is a worldwide threat in many aspects, making developing countries with scarce primary health care and medical services more vulnerable. Evaluation of the relationship between the COVID-19 pandemic, sociodemographic variables, and medical services provides useful information to take countermeasures to stop the infection spread and could mitigate the damage. Therefore, this study investigated the relationship between the spread of COVID-19 and sociodemographic variables, medical services, and the transportation system in Myanmar. Methodology This study was a cross-sectional study and was conducted using data on COVID-19 cases from August 20, 2020 to January 31, 2021 in Myanmar. We evaluated the association between the COVID-19 cases and 13 independent variables that were sociodemographic, medical services, and transportation system factors using simple linear regression analysis and multiple linear regression analysis in three phases (increasing (from August 20th to October 10th), stable (from October 11st to December 4th) and decreasing phases (from December 5th to January 31st)) on the infection timeline. Results It was found that the population density was parallelly associated with COVID-19 cases. On the other hand, among the medical services factors, the number of doctors was parallelly associated with COVID-19 cases and the number of nurses was inversely related to COVID-19 cases. Conclusions The result indicated that a high population density area was a risk factor for the increase of COVID-19 cases. This supported the worldwide countermeasures to deal with the spread of the infection, such as social distancing, banning large gatherings, working from home, and implementing quarantine procedures for suspected individuals to reduce person-to-person contact. Finally, at least in Myanmar, employing a large number of nurses could reduce the emergence of new COVID-19 cases. We believe that our study can make valuable contributions to tackling future epidemics like COVID-19 not only in Myanmar but also in other developing countries. This article was previously presented as an abstract at the 91st conference of The Japanese Society for Hygiene (JSH ) on March 08, 2021.