Neuroimaging and biomarker evidence of neurodegeneration in asthma

Rosenkranz, Melissa A.; Dean, Douglas C.; Bendlin, Barbara B.; Jarjour, Nizar N.; Esnault, Stéphane; Zetterberg, Henrik; Heslegrave, Amanda; Evans, Michael D.; Davidson, Richard J.; Busse, William W.

doi:10.1016/j.jaci.2021.09.010

Cited by 31 publications

(21 citation statements)

References 101 publications

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“… 16 , 17 With data from a large human sample, we recently demonstrated that widespread subcortical white matter alterations occur in asthma and show significant associations with blood‐based biomarkers of glial activation and axonal injury. 13 Further, findings from several epidemiological studies indicate that asthma is associated with increased risk of mild cognitive impairment (MCI) and dementia. 18 , 19 , 20 More generally, patients with chronic peripheral inflammation, who also carry the APOE ε4 allele, are at greater risk of AD dementia, relative to those with only chronic inflammation or APOE ε4.…”

Section: Introductionmentioning

confidence: 99%

“…Asthma is a complex heterogeneous disorder with multiple etiologies and molecular phenotypes (eosinophilic, neutrophilic, paucigranulocytic, based on the nature of airway inflammation) 9–11 . A growing body of research suggests that the adverse effects of asthma on the brain 12,13 are mediated by neuroinflammatory processes, potentially via the interleukin‐17 pathway, 14 though hypoxia and changes to the neurovasculature 15 are additional possible mechanisms. Allergen exposure in mouse models of asthma, for example, activates microglial cells and evokes pro‐inflammatory cytokine expression, as well as deleterious structural brain changes, in regions relevant to dementia and Alzheimer's disease (AD) 16,17 .…”

Section: Introductionmentioning

confidence: 99%

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Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Nair

Hulle

Bendlin

et al. 2022

A&D Transl Res & Clin Interv

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Introduction Evidence from epidemiology, neuroimaging, and animal models indicates that asthma adversely affects the brain, but the nature and extent of neuropathophysiological impact remain unclear. Methods We tested the hypothesis that asthma is a risk factor for dementia by comparing cognitive performance and cerebrospinal fluid biomarkers of glial activation/neuroinflammation, neurodegeneration, and Alzheimer's disease (AD) pathology in 60 participants with asthma to 315 non‐asthma age‐matched control participants (45–93 years), in a sample enriched for AD risk. Results Participants with severe asthma had higher neurogranin concentrations compared to controls and those with mild asthma. Positive relationships between cardiovascular risk and concentrations of neurogranin and α‐synuclein were amplified in severe asthma. Severe asthma also amplified the deleterious associations that apolipoprotein E ε4 carrier status, cardiovascular risk, and phosphorylated tau 181 /amyloid beta 42 have with rate of cognitive decline. Discussion Our data suggest that severe asthma is associated with synaptic degeneration and may compound risk for dementia posed by cardiovascular disease and genetic predisposition. Highlights Those with severe asthma showed evidence of higher dementia risk than controls evidenced by: higher levels of the synaptic degeneration biomarker neurogranin regardless of cognitive status, cardiovascular or genetic risk, and controlling for demographics. steeper increase in levels of synaptic degeneration biomarkers neurogranin and α‐synuclein with increasing cardiovascular risk. accelerated cognitive decline with higher cardiovascular risk, genetic predisposition, or pathological tau.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Nair

Hulle

Bendlin

et al. 2022

A&D Transl Res & Clin Interv

Self Cite

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“…Finally, the referral process in this study, which was enriched with study subjects with elevated PCL and PHQ-9 scores, potentially reduced the mediation effect of PCL and PHQ-9 scores on the association between WTC dust cloud exposure and the reduced MoCA scores, warranting further studies in WTC Survivors. Other important variables that were not included in the study can also impact cognitive functioning such as comorbid respiratory symptoms that can be caused by diseases such as asthma [ 57 , 58 ]. Chronic persistent lower respiratory symptoms and severe lung function impairment are very common among patients at WTC EHC and a large portion of WTC Survivors, and it is therefore of clinical relevance to further study the relationship between WTC exposures, persistent respiratory symptoms and lung function impairments with potential cognitive decline among WTC Survivors.…”

Section: Discussionmentioning

confidence: 99%

Cognitive Function among World Trade Center-Exposed Community Members with Mental Health Symptoms

Rosen

Shao

Zhang

et al. 2022

IJERPH

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The World Trade Center Environmental Health Center (WTC EHC), is a federally designated clinical center of excellence for surveillance and treatment of WTC disaster exposed community members (WTC Survivors). Cognitive impairment (CI) has been extensively described in WTC responders and a concern for progressive impairment in all WTC disaster exposed groups has been raised. Cognitive status, however, has not been systematically characterized in the WTC Survivor population. We describe cognitive status in a subgroup of the Survivor population referred for mental health evaluation (N = 480) in the WTC EHC as measured by scores on the Montreal Cognitive Assessment (MoCA) instrument, and examine their association with WTC exposures and individual-level covariates including PTSD and depression screening inventory scores. In regression analyses, probable cognitive impairment (MoCA score < 26) was found in 59% of the study subjects and was significantly associated with age, race/ethnicity, education, income, depression and PTSD scores. Being caught in the dust cloud on 11 September 2011 was significantly associated with cognitive impairment even after controlling for the above. These data suggest an association with cognitive dysfunction in WTC Survivors with exposure to the toxic dust/fumes and psychological stress from the 9/11 terrorist attack and warrant further systematic study.

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“…60 For this review, however, we will focus on recent data on circulating molecular markers of the risk of cardiovascular disease in obstructive sleep apnoea. Biomarkers are important assessable indicators that can provide complementary information for many diseases, including obstructive sleep apnoea, 61 cardiovascular diseases, 62 diabetes mellitus, 63 hypertension, 64 stroke, 65 asthma, 66 and heart failure. 63 Intermittent hypoxia and consequent reoxygenation injury are a hallmark of obstructive sleep apnoea.…”

Section: Advanced Polysomnographic Metricsmentioning

confidence: 99%

Role of precision medicine in obstructive sleep apnoea

Liu

Ghafoor

Hajipour

et al. 2023

bmjmed

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Obstructive sleep apnoea is a substantial clinical and public health problem because it contributes to harmful effects on quality of life, daytime symptoms, road traffic incidents, and cardiometabolic disease. Increasingly, obstructive sleep apnoea is recognised as a heterogeneous disease, and patients have varied susceptibility to long term complications and different responses to treatment. This narrative review summarises the current knowledge of precision medicine in obstructive sleep apnoea, particularly the role of symptom clusters, polysomnogram phenotypes, physiological endotypes, and circulating biomarkers in defining subtypes. In the near future, the prognostic accuracy of these measures in predicting long term complications in obstructive sleep apnoea will likely be improved, together with better matching of treatments to disease subtypes.

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Neuroimaging and biomarker evidence of neurodegeneration in asthma

Cited by 31 publications

References 101 publications

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Cognitive Function among World Trade Center-Exposed Community Members with Mental Health Symptoms

Role of precision medicine in obstructive sleep apnoea

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