COPD Raises Risk for Mild Cognitive Impairment

Pauline Anderson

March 19, 2014

Chronic obstructive pulmonary disease (COPD) increases the risk for mild cognitive impairment (MCI), especially impairment unrelated to memory, and the risk increases with COPD duration, a new study reports.

The results emphasize the importance of COPD as a risk factor for MCI, the researchers conclude.

"This study shows that COPD patients are at high risk for MCI, which can ultimately lead to dementia," said lead study author Balwinder Singh, MD, a psychiatry resident at University of North Dakota School of Medicine, Grand Forks, and Health Sciences and a research collaborator at the Mayo Clinic Department of Neurology, Rochester, Minnesota.

"If you can get to this population early, and treat them early on, that may prevent or delay the onset of MCI."

Unfortunately, at the primary care level, COPD is underdiagnosed by using spirometry, the gold standard pulmonary function test, leaving many patients untreated, Dr. Singh told Medscape Medical News.

The study was published online March 17 in JAMA Neurology.

Domain-Specific Score

The present analysis included 1425 randomly selected participants with normal cognition aged 70 to 89 years who were involved in the Mayo Clinic Study of Aging (MCSA). Participants underwent a neurologic evaluation and completed neuropsychological testing at baseline and then regularly during a median follow-up of 5.1 years.

Researchers diagnosed MCI using a comprehensive clinical evaluation and through consensus. They considered a domain-specific score of less than 1.0 standard deviation below the age-specific mean among the general population as possible cognitive impairment.

During the study, 370 participants developed incident MCI. Of these, 62.2% had amnestic MCI (A-MCI), 26.2% had nonamnestic MCI (NA-MCI),7.3% had an unknown type of MCI, and 4.3% progressed from normal cognition at one visit to dementia at the next.

With A-MCI, the memory domain is affected and patients may develop Alzheimer's disease (AD), whereas in NA-MCI, the visuospatial and attention domains are more affected and patients tend to develop other dementias, for example dementia with Lewy bodies or frontotemporal lobar degeneration, said Dr. Singh.

Using medical records, researchers, who were blinded to the diagnosis of MCI, identified 171 participants with a possible diagnosis of COPD at baseline.

A COPD diagnosis was associated with an increased risk for MCI (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.07 - 1.91) after adjustment for education, sex, age, depression, and history of stroke. After additional adjustments for apolipoprotein E ε4 genotype, smoking, diabetes, hypertension, coronary artery disease, and body mass index, the result was weaker (HR, 1.33; CI, 0.96 - 1.84) and of borderline nonsignificance, they note.

However, COPD was associated with an almost 2-fold risk for NA-MCI (HR, 1.83; 95% CI, 1.04 - 3.23) after all adjustments. COPD was not associated with an increased risk for A-MCI.

COPD Duration

Researchers also found a dose-response relationship between COPD duration and both MCI and NA-MCI. For MCI, the HRs were 1.11 in study participants who had COPD for 5 years or less and 1.58 in those with a COPD diagnosis of longer than 5 years. The respective HRs for NA-MCI were1.14 and 2.58.

The connection between COPD and MCI could be through inflammation, said Dr. Singh. Patients with COPD have increased levels of inflammatory markers, including interleukin-6, C-reactive protein, and tumor necrosis factor, and these have been associated with cognitive impairment.

Another theory is that hypoxia, which causes decreased oxygen in the brain, is driving the relationship between COPD and MCI. Or, the relationship could be tied to the increased risk for cardiovascular disease (itself a risk factor for MCI) in patients with COPD.

However, the study did factor in stroke history and coronary artery disease. "In our analysis, even after adjustment for vascular disease and confounders, the association remained very robust, suggesting that COPD is an independent predictor of MCI risk," commented Dr. Singh.

Results of the study differ from those of an earlier longitudinal study from Finland reporting that a diagnosis of COPD in midlife (age 39 to 64 years) but not in late life (age 65 to 80 years) was associated with an increased risk for MCI. In fact, the Finnish researchers found a trend for COPD in late life to be associated with a reduced risk for MCI (Curr Alzheimer Res. 2013;10:549-555).

The different outcomes can be explained in part by different study design, said Dr. Singh. Investigators in the Finnish study did a full evaluation for MCI only in participants with a positive screening for COPD, whereas investigators for the current study carried out regular evaluations, said Dr. Singh. "In our study, we evaluated subjects after 12 to 15 months, so we ruled out survivor risk bias."

Comprehensive Examinations

As well, the previous study relied on patient reporting of COPD, and patients with cognitive impairment may not remember being diagnosed, which could have introduced another bias. In contrast, in the newer study, patients were evaluated "very comprehensively" using neurologic examinations and medical record review, said Dr. Singh.

Because there's little in the way of effective treatment for MCI, prevention is key. Research shows that lifestyle choices — for example, maintaining a healthy diet and body weight and avoiding smoking — can help delay or prevent its onset.

Such a lifestyle approach, especially not smoking, may also help prevent COPD. In this study, over 80% of participants were current or former smokers. In developing countries, other environmental factors, such as coal burning, can also contribute to COPD risk, said Dr. Singh.

A limitation of the study was that COPD diagnosis was not based on results of spirometry, which is the recommended diagnostic test for COPD but was not routinely available to study participants. Another limitation is that the study population was mostly white and of European ancestry, which could reduce the generalizability of the study results to other populations.

This study was supported by grants from the National Institutes of Health (NIH); by the Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program; and by Clinical and Translational Science Award UL1TR000135 from the National Center for Advancing Translational Sciences, a component of the NIH. Dr. Singh has disclosed no relevant financial relationships.

JAMA Neurol. Published online March 17, 2014. Abstract

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