Impaired lung function is associated with elevated blood biomarkers of AD/ADRD: Unraveling the interplay with risk of dementia
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Rationale
We hypothesize that impaired lung function contributes to dementia risk via biological mechanisms reflected in AD/ADRD-related protein biomarkers, and aim to evaluate their role in mediating this relationship.
Methods
Serum p-Tau181 and plasma Aβ42/40 ratio, NfL, and GFAP were measured in 4,072 participants (mean age 66 ± 10; 59% women) in the 2016 Health and Retirement Study. Peak Expiratory Flow (PEF) was assessed in 2012/2014, and cognitive function was measured biennially from 2014–2020 to determine dementia status. Impaired lung function (ILF) was defined as PEF <80% predicted. Multivariable regression examined associations between lung function and AD biomarkers; causal mediation analysis evaluated their role in linking lung function to incident dementia.
Results
In total, 881 (21.6%) participants had ILF and 272 (6.8%) participants developed dementia. After adjusting for demographics, education, BMI, smoking, comorbidities, inflammation, eGFR and APOE e4 , ILF was associated with a higher risk of dementia (HR=1.74; 95% CI (1.34, 225)). Individuals with ILF had 0.10 SD higher NfL (SE= 0.03; p= 0.004) and 0.09 SD higher p-Tau 181 (SE= 0.03; p= 0.002) compared to those without ILF. NfL mediated 7.3% (p=0.01) of the total effect of ILF on dementia, while p-Tau 181 mediated 5% (p=0.05) of this association.
Conclusions
ILF was associated with elevated levels of neurodegeneration markers NfL and p-Tau 181, which partially mediated its relationship with dementia risk. These findings highlight the importance of monitoring blood protein biomarkers in individuals with impaired lung health to facilitate early interventions.
