Abstract
BackgroundMild cognitive impairment is a common systemic manifestation of chronic obstructive pulmonary disease (COPD). However, its pathophysiological origins are not understood. Since, cognitive function relies on efficient communication between distributed cortical and subcortical regions, we investigated whether people with COPD have disruption in white matter connectivity.MethodsStructural networks were constructed for 30 COPD patients (aged 54–84 years, 57% male, FEV1 52.5% pred.) and 23 controls (aged 51–81 years, 48% Male). Networks comprised 90 grey matter regions (nodes) interconnected by white mater fibre tracts traced using deterministic tractography (edges). Edges were weighted by the number of streamlines adjusted for a) streamline length and b) end-node volume. White matter connectivity was quantified using global and nodal graph metrics which characterised the networks connection density, connection strength, segregation, integration, nodal influence and small-worldness. Between-group differences in white matter connectivity and within-group associations with cognitive function and disease severity were tested.ResultsCOPD patients’ brain networks had significantly lower global connection strength (p = 0.03) and connection density (p = 0.04). There was a trend towards COPD patients having a reduction in nodal connection density and connection strength across the majority of network nodes but this only reached significance for connection density in the right superior temporal gyrus (p = 0.02) and did not survive correction for end-node volume. There were no other significant global or nodal network differences or within-group associations with disease severity or cognitive function.ConclusionCOPD brain networks show evidence of damage compared to controls with a reduced number and strength of connections. This loss of connectivity was not sufficient to disrupt the overall efficiency of network organisation, suggesting that it has redundant capacity that makes it resilient to damage, which may explain why cognitive dysfunction is not severe. This might also explain why no direct relationships could be found with cognitive measures. Smoking and hypertension are known to have deleterious effects on the brain. These confounding effects could not be excluded.
Highlights
Mild cognitive impairment is a relatively common feature of a number of chronic diseases, including diabetes, kidney disease and rheumatoid arthritis [1,2,3]
Group comparison of global network measures using the total area under the metric curves
Group means ± standard deviations are presented for Gaussian data, and medians for non-Gaussian data. 1Gaussian and 2log10-transformed to Gaussian data were assessed using parametric ANCOVAs and non-Gaussian data by 3non-parametric permutation ANCOVAs (10000 permutations)
Summary
Mild cognitive impairment is a relatively common feature of a number of chronic diseases, including diabetes, kidney disease and rheumatoid arthritis [1,2,3]. Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease which is one of the leading causes of morbidity and mortality worldwide. It is associated with a number of extra-pulmonary co-morbid conditions, which occur more frequently in COPD than in smokers or never smokers, suggesting an intrinsic link to the disease [4]. One such co-morbidity is cognitive dysfunction, with estimates of its prevalence ranging from 10–61% [5]. Cognitive function relies on efficient communication between distributed cortical and subcortical regions, we investigated whether people with COPD have disruption in white matter connectivity
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