Increased Risk of Autopsy-Proven Pneumonia with Sex, Season and Neurodegenerative Disease

Abstract

There has been a markedly renewed interest in factors associated with pneumonia, a leading cause of death worldwide, due to its frequent concurrence with pandemics of influenza and Covid-19 disease. Reported predisposing factors to both bacterial pneumonia and pandemic viral lower respiratory infections are wintertime occurrence, older age, obesity, pre-existing cardiopulmonary conditions and diabetes. Also implicated are age-related neurodegenerative diseases that cause parkinsonism and dementia. We investigated the prevalence of autopsy-proven pneumonia in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study, between the years 2006 and 2019 and before the beginning of the Covid-19 pandemic. Of 691 subjects dying at advanced ages (mean 83.4), pneumonia was diagnosed postmortem in 343 (49.6%). There were 185 subjects without dementia or parkinsonism while clinicopathological diagnoses for the other subjects included 319 with Alzheimer’s disease dementia, 127 with idiopathic Parkinson’s disease, 72 with dementia with Lewy bodies, 49 with progressive supranuclear palsy and 78 with vascular dementia. Subjects with one or more of these neurodegenerative diseases all had higher pneumonia rates, ranging between 50 and 61%, as compared to those without dementia or parkinsonism (40%). In multivariable logistic regression models, male sex and a non-summer death both had independent contributions (ORs of 1.67 and 1.53) towards the presence of pneumonia at autopsy while the absence of parkinsonism or dementia was a significant negative predictor of pneumonia (OR 0.54). Male sex, dementia and parkinsonism may also be risk factors for Covid-19 pneumonia. The apolipoprotein E4 allele, as well as obesity, chronic obstructive pulmonary disease, diabetes, hypertension, congestive heart failure, cardiomegaly and cigarette smoking history, were not significantly associated with pneumonia, in contradistinction to what has been reported for Covid-19 disease.

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19

“…An important issue is whether or not COVID-19 lower respiratory disease elicits more intense systemic repercussions than typical acute pneumonia. Our investigations ( 112 , 156 , 162 ) indicate that acute or subacute ischemic changes, infarctions or hemorrhages are probably not more common in COVID-19 than they are in subjects dying without COVID-19 or with or without non-COVID-19 acute pneumonia. Early adoption of low molecular weight heparin therapy may have reduced thromboembolism in our study subjects, in comparison with COVID-19 decedents in the first few months of the pandemic.…”

“…Although COVID-19 has reportedly caused disproportionate mortality in those with dementia ( 114 ), and the apolipoprotein E-ε4 allele, a genetic risk factor for Alzheimer AD, may be more common in subjects with severe COVID-19 disease ( 113 , 115–119 ), in the set of subjects that we examined in these studies, there was no apparent predilection of COVID-19 for AD or other major aging-associated neuropathological diagnoses, or an association with the apolipoprotein E-ε4 allele. This may be due to insufficient subject numbers and statistical power, as in a much larger set of AZSAND subjects, we have reported that autopsy-confirmed acute pneumonia is significantly more common in those with concurrent neuropathologically diagnosed major neurodegenerative conditions ( 112 ). It is acknowledged, however, that all of these studies have not considered whether it is specific neurodegenerative processes or just being institutionalized, critically ill and bedbound that is linked to the increased COVID-19 and pneumonia risk.…”

Dementia and autopsy-verified causes of death in racially-diverse older Brazilians

“…The finding of an association of dementia with a higher odds of an infectious disease as cause of death, especially of pneumonia is supported by prior literature [ 34 ]. Pneumonia is particularly more common in advanced stages of dementia when dysphagia is present increasing the risk of aspiration pneumonia [ 35 , 36 ]. Our finding that dementia is associated with a lower odds of cancer as cause of death is also consistent with the findings from other studies [ 16 – 18 ].…”

Associated Factors of Pneumonia in Individuals with Chronic Obstructive Pulmonary Disease (COPD) Apart from the Use of Inhaled Corticosteroids

“…Patients with these conditions are often bedridden and may experience dysphagia, altered mental states, or respiratory muscle weakness, all of which can increase the risk of pneumonia. Additionally, the causes of pneumonia in patients with neurological conditions who also have COPD may be different from those in the general population, which can lead to differences in the distribution of pathogens causing the infection [62].…”