Impaired Lung Function, Lung Disease, and Risk of Incident Dementia

Lutsey, Pamela L.; Chen, Nemin; Mirabelli, Maria C.; Lakshminarayan, Kamakshi; Knopman, David S.; Vossel, Keith A.; Gottesman, Rebecca F.; Mosley, Thomas H.; Alonso, Álvaro

doi:10.1164/rccm.201807-1220oc

Cited by 92 publications

(92 citation statements)

References 37 publications

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“…Evidence before this study Our results indicate that there is minimal evidence of a causal association between lung function or liability to COPD and risk of Alzheimer's disease. This is in contrast to two large observational studies (12,13) , which do report an association between COPD and Alzheimer's disease. The observed associations may be due to unmeasured confounding by risk factors common to both COPD and Alzheimer's disease such as smoking, physical inactivity, social deprivation and lower educational attainment (30) .…”

Section: Discussioncontrasting

confidence: 99%

“…(9) Alzheimer's disease (AD) is the most common type of dementia (10) , its association with COPD is less well defined than general cognitive ability, but reports of a potential link between COPD and AD was first described nearly 30 years ago (11) . Large retrospective observational case-control cohorts have reported increased risk of AD in patients with both COPD and reduced lung function (12,13) . For example, Lutsey et al reviewed hospitalisation codes (13) in the Atherosclerosis Risk In Communities Study for AD-related outcomes and reported that an Odds Ratio of 1.24 for AD-type dementia or mild cognitive impairment (MCI) in patients with COPD and OR 1.79 for those with a restrictive impairment compared to controls.…”

Section: Introductionmentioning

confidence: 99%

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Examining the possible causal relationship between Lung Function, COPD and Alzheimer’s Disease. A Mendelian Randomization Study

Higbee¹,

Granell²,

Walton³

et al. 2020

Preprint

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Rationale: Large retrospective case-control studies have reported an association between COPD, reduced lung function and an increased risk of Alzheimers disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required. Objectives: To examine a causal relationship between COPD, lung function and Alzheimers disease. Methods: Using two-sample Mendelian randomization, we utilised single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimers disease (outcome) were taken from a GWAS based on a sample of 24,807 patients and 55,058 controls. Results: We found minimal evidence for an effect of either lung function (odds ratio [OR]:1.02 per SD; 95% confidence interval [CI]: 0.91, 1.13; p value 0.68). or liability for COPD on Alzheimers disease (OR: 0.97 per SD; 95% CI: 0.92, 1.03; p value 0.40). Conclusion: Neither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimers, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimers disease by targeting impaired lung function or COPD directly.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Examining the possible causal relationship between Lung Function, COPD and Alzheimer’s Disease. A Mendelian Randomization Study

Higbee¹,

Granell²,

Walton³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Future research using biomarkers of neurodegeneration and vascular brain pathology could confirm this possibility. Other potential biological factors that could be on the causal pathway between WTC exposure intensity and cognitive change include sleep disorders, pulmonary function impairment [ 46 ], and inflammatory serum biomarkers associated with cognitive impairment [ 47 ]. Longitudinal analyses would be needed to confirm cross-sectional results to support causality.…”

Section: Discussionmentioning

confidence: 99%

PTSD and Depressive Symptoms as Potential Mediators of the Association between World Trade Center Exposure and Subjective Cognitive Concerns in Rescue/Recovery Workers

Singh

Zeig‐Owens

Schwartz

et al. 2020

IJERPH

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We observed that World Trade Center (WTC) exposure, post-traumatic stress disorder (PTSD) symptoms and depressive symptoms were associated with subjective cognitive concerns in Fire Department of the City of New York (FDNY) rescue/recovery workers. This follow-up study examined whether PTSD symptoms and/or depressive symptoms mediate the observed association between WTC exposure and subjective cognitive concerns. We included WTC-exposed FDNY workers who completed the Cognitive Function Instrument (CFI), measuring self-perceived cognitive decline (N = 9516). PTSD symptoms and depressive symptoms were assessed using the PCL-S and CES-D, respectively. Multivariable linear regression estimated the association between WTC exposure and CFI score, adjusting for confounders. Mediation analyses followed the methods of Vanderweele (2014). Participants’ average age at CFI assessment was 56.6 ± 7.6 years. Higher-intensity WTC exposure was associated with worse CFI score, an effect that was entirely mediated by PTSD symptoms (%mediated: 110.9%; 95%CI: 83.1–138.9). When substituting depressive symptoms for PTSD symptoms, the WTC exposure–CFI association was largely mediated (%mediated: 82.1%; 95%CI: 60.6–103.7). Our findings that PTSD symptoms and depressive symptoms mediate the association between WTC exposure and subjective cognitive concerns indicate that in the absence of these symptoms, WTC exposure in rescue/recovery workers would not be associated with subjective cognition. Interventions targeting PTSD and depression may have additional value in mitigating cognitive decline in WTC-exposed populations.

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“…Finally, while we found that high‐intensity WTC exposure was modestly associated with subjective cognitive concerns 17 years later, we believe that the observed effect may be due to the high prevalence of WTC exposure‐related illnesses among the most exposed. Several chronic physical health illnesses, ranging from acid reflux to asthma, have been linked to greater WTC exposure and some of these illnesses or their treatments could be risk factors for cognitive impairment in WTC rescue/recovery workers. Future research examining risk factors for cognitive impairment in WTC‐exposed rescue/recovery workers should evaluate the association between WTC‐related health conditions and cognitive function using mediation analyses.…”

Section: Discussionmentioning

confidence: 99%

World Trade Center exposure, post‐traumatic stress disorder, and subjective cognitive concerns in a cohort of rescue/recovery workers

Singh

Zeig‐Owens

Hall

et al. 2019

Acta Psychiatr Scand

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Objective To determine whether World Trade Center (WTC)‐exposure intensity and post‐traumatic stress disorder (PTSD) are associated with subjective cognitive change in rescue/recovery workers. Method The population included 7875 rescue/recovery workers who completed a subjective cognition measure, the Cognitive Function Instrument (CFI), between 3/1/2018 and 2/28/2019 during routine monitoring, indicating whether they had experienced cognitive and functional difficulties in the past year. Higher scores indicated greater self‐perceived cognitive change. Probable PTSD, depression, and alcohol abuse were evaluated by validated mental health screeners. Logistic regression assessed the associations of WTC exposure and current PTSD with top‐quartile (≥2) CFI score, and of early post‐9/11 PTSD with top‐quartile CFI in a subpopulation (N = 6440). Models included demographics, smoking, depression, and alcohol abuse as covariates. Results Mean age at CFI completion was 56.7 ± 7.7 (range: 36–81). Participants with high‐intensity WTC exposure had an increased likelihood of top‐quartile CFI score (odds ratio[OR] vs. low exposure: 1.32, 95%CI: 1.07–1.64), controlling for covariates. Current and early PTSD were both associated with top‐quartile CFI (OR: 3.25, 95%CI: 2.53–4.19 and OR: 1.56, 95%CI: 1.26–1.93) respectively. Conclusions High‐intensity WTC exposure was associated with self‐reported cognitive change 17 years later in rescue/recovery workers, as was PTSD. Highly WTC‐exposed subgroups may benefit from additional cognitive evaluation and monitoring of cognition over time.

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Impaired Lung Function, Lung Disease, and Risk of Incident Dementia

Abstract: Contributions: PLL, NC and AA developed the research idea. DSK, RFG and THM were involved with outcome ascertainment. NM and AA conducted the analysis. PLL drafted the manuscript.

Cited by 92 publications

References 37 publications

Examining the possible causal relationship between Lung Function, COPD and Alzheimer’s Disease. A Mendelian Randomization Study

Examining the possible causal relationship between Lung Function, COPD and Alzheimer’s Disease. A Mendelian Randomization Study

PTSD and Depressive Symptoms as Potential Mediators of the Association between World Trade Center Exposure and Subjective Cognitive Concerns in Rescue/Recovery Workers

World Trade Center exposure, post‐traumatic stress disorder, and subjective cognitive concerns in a cohort of rescue/recovery workers

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