Siddiqui, Habeeba

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2 and has caused significant mortality and morbidity since it was first recognized in Wuhan, China in December 2019. Patients may suffer from a constellation of symptoms termed post-acute sequelae of COVID-19 (PASC) . Here we present findings of a retrospective cohort study describing the prevalence and predicting factors of patient-reported post-acute sequelae of COVID-19 (PASC). Categorical variables were summarized as frequency (percentage) and compared between vaccine status groups using Fisher’s exact test. Continuous variables were reported as median (range) and compared between the groups using Kruskal-Wallis test. All tests were two-sided with p value <0.05 considered statistically significant. Survey data from 132 patients with a median age of 45 years, 68% female, 83% Caucasian/Non-Hispanic. The most frequently reported PASC symptoms include fatigue (84.8%), dyspnea (54.5%), cognitive dysfunction (53%), myalgias (37.1%), lightheadedness or vertigo (36.4%), chest pain (34.8%), palpitations (34.8%), headaches (34.1%), arthralgias (31.8%), and unrefreshing sleep (31.1%). There is mounting evidence that supports higher prevalence of PASC in women, White/Caucasian, and middle-aged individuals. This knowledge can provide guidance to clinical practices to anticipate and support healthcare and self-care needs for patients at higher risk to developing PASC.

Background: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes. Objective: Investigate the contributions of vascular factors and cancer to dementia and neuropathology. Methods: Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology. Results: Participants (n = 161; 83% female; 99% non-Hispanic whites)≥95 years (95–106 years-old) with/without dementia did not differ based on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; p = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; p = 0.03) associated with 56% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19–0.98]; p = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39–163]; p = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p = 0.05). Cancer associated with 63% lower dementia odds (OR = 0.37 [CI = 0.17–0.78]; p < 0.01) and lower Braak stage (p = 0.01). Conclusion: Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-β plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old.

Abstract Introduction Alzheimer's disease (AD) biomarkers are increasingly more reliable in predicting neuropathology. To facilitate interpretation of phosphorylated tau sites as an early fluid biomarker, we sought to characterize which neurofibrillary tangle maturity levels (pretangle, intermediary 1, mature tangle, intermediary 2, and ghost tangle) are recognized. Methods We queried the Florida Autopsied Multi‐Ethnic (FLAME) cohort for cases ranging from Braak stages I through VI, excluding non‐AD neuropathologies and tauopathies. Thioflavin‐S staining was compared to immunohistochemical measures of phosphorylated threonine (pT) 181, pT205, pT217, and pT231 in two hippocampal subsectors across n = 24 cases. Results Each phosphorylated tau site immunohistochemically labeled early neurofibrillary tangle maturity levels compared to advanced levels recognized by thioflavin‐S. Hippocampal burden generally increased with each Braak stage. Discussion These results provide neurobiologic evidence that these phosphorylated tau fluid biomarker sites are present during early neurofibrillary tangle maturity levels and may explain why these fluid biomarker measures are observed before symptom onset. Highlights Immunohistochemical evaluation of four phosphorylated tau fluid biomarker sites. Earlier neurofibrillary tangle maturity levels recognized by phosphorylated tau in proline‐rich region. Advanced tangle pathology is elevated in the subiculum compared to the cornu ammonis 1 of the hippocampus. Novel semi‐quantitative frequency to calculate tangle maturity frequency.