Low Pulmonary Function Associated With Worsened Cognitive Decline, Structural Brain Differences


Patients who were dementia-free with the lowest PF had smaller volumes of total brain, gray matter, and white matter, and had greater white matter hyperintensities.

Weili Xu, PhD

Weili Xu, PhD

Long-term data from the Rush Memory and Aging Project (MAP) suggest that low pulmonary function (PF) is associated with faster decline in global cognition and several domain-specific functions in subjects who are dementia-free. Findings also indicated that both neurodegeneration and vascular lesions in the brain may underlie this association.

To understand the association between baseline PF and cognitive function, senior author Weili Xu, PhD, postdoctoral researcher, Karolinska Institutet, and colleagues used a composite measure that included forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). Global and domain-specific cognitive function was assessed annually using 19 cognitive tests. Investigators also evaluated the relations between baseline PF and structural brain differences such as the total volumes of total brain, total gray matter, total white matter, white matter hyperintensities (WMH), and hippocampus.

Composite PF scores were siloed into 3 categories: lowest PF (tertile 1; PF ≤–0.46), middle PF (tertile 2; –0.46 < PF ≤ 0.33) and highest PF (tertile 3; >0.33). At the conclusion of the study, subsequent analysis showed that better PF was associated with declines in all 5 domain-specific cognitive functions: episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed (all P <.05). Controlling for the estimated intercept at baseline, investigators also concluded that better PF was related to slower decline in global cognition.

"Our findings underscore the detrimental impact of poor pulmonary health on the brain and suggest that interventions designed to maintain pulmonary health may represent significant opportunities for preventing cognitive decline in late life,” Xu and the other study authors wrote.

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When comparing lowest to highest PF, participants with the lowest PF had significantly faster decline in global cognition, as well as all 5 cognitive domains after adjusting for age, sex, education, race, body mass index, stroke, hypertension, diabetes, depression, heart disease, congestive heart failure, COPD, alcohol consumption, smoking, physical activity, and apolipoprotein e4 (APOE e4) carrier status.

In both basic-adjusted models and multivariable-adjusted models, those with moderate level of PF showed significantly faster decline in perceptual speed compared to those with the highest PF. Despite previous associations between APOE e4 and cognitive decline, investigations found no significant interactions with respect to global or domain-specific cognitive decline (all P >.05). They noted that these results may have been because of the small sample size of APOE e4 carriers.

Individuals with the lowest PF also demonstrated smaller volumes of total brain, gray matter, white matter, and greater WMH. These findings remained consistent in a linear regression analysis that adjusting for the same variates mentioned in the cognitive domain assessment. Additionally, investigators found no significant difference in hippocampus volume between the lowest versus highest levels of PF.

There were limitations to the study, including the fact that these were volunteers who were not randomly selected from the community and therefore may have higher scores on cognitive tests compared to the general populations. Additionally, it was noted that the findings may only be generalizable to demographically similar cohorts, which precludes generalizing the findings to the general population.

The investigators wrote that the findings raise the possibility that PF could play a role in the development and progression of dementia. “To assess this, future studies should clarify whether poor PF is associated with the development of mild cognitive impairment and its progression to dementia,” Xu et al wrote. “Furthermore, PF’s relationship to other relevant brain pathology–including biomarkers from cerebrospinal fluid and brain autopsy (eg, total, tau, amyloid beta, neurofibrillary tangles, and plaques)–should be analyzed in large cohort studies with long-term follow-up to better understand the mechanisms linking PF and cognitive function.”

Wang J, Song R, Dove A. et al. Pulmonary function is associated with cognitive decline and structural brain differences. Alzheimers Dement. Published online September 30, 2021. doi:10.1002/alz.12479
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