COVID-19 in a rural health system in New York - case series and an approach to management.

INTRODUCTION: Many rural hospitals and health systems in the USA lack sufficient resources to treat COVID-19. St Lawrence Health (SLH) developed a system for managing inpatient COVID-19 hospital admissions in St Lawrence County, an underserved rural county that is the largest county in New York State. METHODS: SLH used a hub-and-spoke system to route COVID-19 patients to its flagship hospital. It further assembled a small clinical team to manage admitted COVID-19 patients and to stay abreast of a quickly changing body of literature and standard of care. A review of clinical data was completed for patients who were treated by SLH's inpatient COVID-19 treatment team between 20 March and 22 May 2020. RESULTS: Twenty COVID-19 patients were identified. Sixteen patients (80%) met National Institutes of Health criteria for severe or critical disease. One patient died. No patients were transferred to other hospitals. CONCLUSION: During the first 2 months of the pandemic, the authors were able to manage hospitalized COVID-19 patients in their rural community. Development of similar treatment models in other rural areas should be considered.

Dynamic Amyloid and Metabolic Signatures of Delayed Recall Performance within the Clinical Spectrum of Alzheimer's Disease.

Associations between pathophysiological events and cognitive measures provide insights regarding brain networks affected during the clinical progression of Alzheimer's disease (AD). In this study, we assessed patients' scores in two delayed episodic memory tests, and investigated their associations with regional amyloid deposition and brain metabolism across the clinical spectrum of AD. We assessed the clinical, neuropsychological, structural, and positron emission tomography (PET) baseline measures of participants from the Alzheimer's Disease Neuroimaging Initiative. Subjects were classified as cognitively normal (CN), or with early (EMCI) or late (LMCI) mild cognitive impairment, or AD dementia. The memory outcome measures of interest were logical memory 30 min delayed recall (LM30) and Rey Auditory Verbal Learning Test 30 min delayed recall (RAVLT30). Voxel-based [18F]florbetapir and [18F]FDG uptake-ratio maps were constructed and correlations between PET images and cognitive scores were calculated. We found that EMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake on the right parieto-occipital region. LMCI individuals had LM30 scores positively associated with left lateral temporal lobe [18F]FDG uptake, and RAVLT30 scores positively associated with [18F]FDG uptake in the left parietal lobe and in the right enthorhinal cortex. Additionally, LMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake in the right frontal lobe. For the AD group, [18F]FDG uptake was positively correlated with LM30 in the left temporal lobe and with RAVLT30 in the right frontal lobe, and [18F]florbetapir uptake was negatively correlated with LM30 scores in the right parietal and left frontal lobes. The results show that the association between regional brain metabolism and the severity of episodic memory deficits is dependent on the clinical disease stage, suggesting a dynamic relationship between verbal episodic memory deficits, AD pathophysiology, and clinical disease stages.

[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the brain accumulation of amyloid-ß and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the brain deposition of amyloid-ß and tau proteins. Using positron emission tomography (PET) tracers selective for amyloid-ß, tau, and class I histone deacetylase (HDAC I isoforms 1-3), we find that HDAC I levels are reduced in patients with AD. HDAC I PET reduction is associated with elevated amyloid-ß PET and tau PET concentrations. Notably, HDAC I reduction mediates the deleterious effects of amyloid-ß and tau on brain atrophy and cognitive impairment. HDAC I PET reduction is associated with 2-year longitudinal neurodegeneration and cognitive decline. We also find HDAC I reduction in the postmortem brain tissue of patients with AD and in a transgenic rat model expressing human amyloid-ß plus tau pathology in the same brain regions identified in vivo using PET. These observations highlight HDAC I reduction as an element associated with AD pathophysiology.

Topographical distribution of Aß predicts progression to dementia in Aß positive mild cognitive impairment.

INTRODUCTION: Abnormal brain amyloid beta (Aß) is typically assessed in vivo using global concentrations from cerebrospinal fluid and positron emission tomography (PET). However, it is unknown whether the assessment of the topographical distribution of Aß pathology can provide additional information to identify, among global Aß positive individuals, those destined for dementia. METHODS: We studied 260 amnestic mild cognitive impairment (MCI) subjects who were Aß-PET positive with [18F]florbetapir. Using [18F]florbetapir, we assessed the percentage of voxels sowing Aß abnormality as well as the standardized uptake value ratio (SUVR) values across brain regions. Regressions tested the predictive effect of Aß on progression to dementia over 2 years. RESULTS: Neither global nor regional [18F]florbetapir SUVR concentrations predicted progression to dementia. In contrast, the spatial extent of Aß pathology in regions comprising the default mode network was highly associated with the development of dementia over 2 years. DISCUSSION: These results highlight that the regional distribution of Aß abnormality may provide important complementary information at an individual level regarding the likelihood of Aß positive MCI to progress to dementia.

Aß-induced vulnerability propagates via the brain's default mode network.

The link between brain amyloid-ß (Aß), metabolism, and dementia symptoms remains a pressing question in Alzheimer's disease. Here, using positron emission tomography ([18F]florbetapir tracer for Aß and [18F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that Aß aggregation within the brain's default mode network leads to regional hypometabolism in distant but functionally connected brain regions. Moreover, we found that an interaction between this hypometabolism with overlapping Aß aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic Aß rats that do not form neurofibrillary tangles, which support these findings as an independent mechanism of cognitive deterioration. These results suggest a model in which distant Aß induces regional metabolic vulnerability, whereas the interaction between local Aß with a vulnerable environment drives the clinical progression of dementia.