Lung Function Impairment and the Risk of Incident Dementia: The Rotterdam Study

J Alzheimers Dis. 2021;82(2):621-630. doi: 10.3233/JAD-210162.

Abstract

Background: The etiology of dementia may partly be underpinned by impaired lung function via systemic inflammation and hypoxia.

Objective: To prospectively examine the association between chronic obstructive pulmonary disease (COPD) and subclinical impairments in lung function and the risk of dementia.

Methods: In the Rotterdam Study, we assessed the risk of incident dementia in participants with Preserved Ratio Impaired Spirometry (PRISm; FEV1/FVC≥0.7, FEV1 < 80% predicted) and in participants with COPD (FEV1/FVC < 0.7) compared to those with normal spirometry (controls; FEV1/FVC≥0.7, FEV1≥80% predicted). Hazard ratios (HRs) with 95% confidence intervals (CI) for dementia were adjusted for age, sex, education attainment, smoking status, systolic blood pressure, body mass index, triglycerides, comorbidities and Apolipoprotein E (APOE) genotype.

Results: Of 4,765 participants, 110 (2.3%) developed dementia after 3.3 years. Compared to controls, participants with PRISm, but not COPD, had an increased risk for all-type dementia (adjusted HRPRISm 2.70; 95% CI, 1.53-4.75; adjusted HRCOPD 1.03; 95% CI, 0.61-1.74). These findings were primarily driven by men and smokers. Similarly, participants with FVC% predicted values in the lowest quartile compared to those in the highest quartile were at increased risk of all-type dementia (adjusted HR 2.28; 95% CI, 1.31-3.98), as well as Alzheimer's disease (AD; adjusted HR 2.13; 95% CI, 1.13-4.02).

Conclusion: Participants with PRISm or a low FVC% predicted lung function were at increased risk of dementia, compared to those with normal spirometry or a higher FVC% predicted, respectively. Further research is needed to elucidate whether this association is causal and how PRISm might contribute to dementia pathogenesis.

Keywords: Alzheimer’s disease; chronic obstructive pulmonary disease; dementia; forced vital capacity (FVC); preserved ratio impaired spirometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / physiopathology
  • Causality
  • Female
  • Humans
  • Hypoxia / diagnosis
  • Hypoxia / etiology
  • Inflammation / diagnosis
  • Inflammation / etiology
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / epidemiology
  • Pulmonary Disease, Chronic Obstructive* / psychology
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Smoking / epidemiology*
  • Spirometry* / methods
  • Spirometry* / statistics & numerical data
  • Vital Capacity