Affiliations: Gerontological Nurse Practitioner Program, Northern Kentucky University, Highland Heights, KY,
University Campus Bio-Medico, Rome, Italy,
Italian National Research Center on Aging, Cosenza, Italy,
Federico II University School of Medicine, Naples, Italy
Correspondence to: Perry C. Goldstein, BSN, RN, St. Charles Care Center, 500 Farrell Dr, Covington, KY 41011; e-mail: goldsteinp1@NKU.edu
Antonelli-Incalzi et al1 suggest that drawing ability on a single neuropsychological measure (the copying drawings with landmarks test) is a reliable predictor of mortality among COPD patients. It appears that the conclusions presented are flawed for a number of reasons.
First, the authors present results from a battery of neuropsychological measures and determine the primary mortality predictor to be the copying of drawings with landmarks test, suggesting a specific deficit in higher cortical functions of the right parietal lobe. The authors assume a highly localized “marker” deficit independent of generalized disease or symptom factors such as attention, endurance, and fine and gross motor coordination. In one of the best well-controlled, multicenter studies2 investigating neurocognitive deficits associated with COPD, all patients (mean age, 65 years) with confirmed hypoxemia (Pao2 ≤ 51 mm Hg) and FEV1 ≤ 0.74 performed significantly worse than control subjects on all neuropsychological test measures suggesting diffuse and multifocal deficits; 50% of the patients evidenced impairments in motor speed, strength, and coordination.
Secondly, the pathophysiology of COPD, namely generalized hypoxemia, would suggest generalized, diffuse, or bilateral deficits in cortical and subcortical regions such as the hippocampi and orbitofrontal regions as demonstrated in at least one study.3Thirdly, the authors do not use statistical correction techniques to account for the large number of post hoc statistical comparisons (11 neuropsychological measures) that likely increased type I error, leading to their spurious findings.4
Finally, COPD is a highly variable and heterogeneous disease with multiple deficits and impairments. For this reason, most research has focused on multivariate mortality and morbidity predictor models coupling COPD disease factors with functional impairments. At this time, it appears that the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index represents the most rational, reliable, and valid approach for predicting both mortality and morbidity associated with COPD.5
The author has no conflict of interest to disclose.
The authors have no conflicts of interest to disclose.
We completely agree that cognitive impairment complicating severe COPD affects several domains, as is evident in our study population and, to a greater extent, in the series by Grant et al,1and in the first of our studies on this topic.2However, our study population was characterized by at-rest (n = 97) or effort-induced (n = 37) hypoxemia,3 and this explains why it had a better cognitive profile than populations with hypoxemia at rest had.1 Furthermore, it is well known that COPD-related cerebral dysfunction involves both cortical and subcortical regions.4 Drawing ability is a complex task relying on the integration of several cerebral areas and, thus, is highly representative of diffuse cerebral damage.
We performed the analysis without any a priori assumption for either a biological (we had no reason for focusing on selected cognitive domains) or a procedural (by limiting the analysis to selected cognitive functions, we could have disregarded a potentially important association between cognitive impairment and mortality) reasons. It is true that with multiple comparison the risk of spurious association is higher; however, the main result of the study, reported in Table 4, is still significant using 99.8% confidence intervals, which take into account the multiple comparisons (incidence rate ratio for copy with landmarks, 1.17 to 10.22). Furthermore, several considerations make such an association biologically plausible.5
The observation about the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity index) index seems to the writers to be out of focus. It is clearly evident to the readers (last paragraph of the “Introduction”) that the objective of this study was to assess whether cognitive dysfunction has prognostic implications in COPD. Thus, we did not aim at developing a new prognostic index but only at assessing whether cognitive impairment impact on survival might deserve consideration for further survival studies as well as an indicator of COPD severity.
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