Our present study revealed that patients with COPD had decreased regional GM density confined to the limbic and paralimbic structures. GM density in impaired regions in patients with COPD had significant positive correlation with arterial blood Po2
and negative correlation with disease duration. The decreased WM FA value with increased radial diffusivity value was detected mainly in the visual cortex of the occipital lobe, the posterior parietal lobe as well as the temporal lobe. Decreased FA was associated with compromised myelin structure, changes in axonal morphologic structure and altered interaxonal spacing of fibre bundles.18
Radial diffusivity measures motion of water molecules perpendicular to fibres, and an increase of radial diffusivity is interpreted as abnormalities in myelinated membranes.19
Consequently, decreased FA and increased radial diffusivity in COPD indicated the impairment of WM microstructural integrity.
Previously, Borson et al6
only measured the volume of hippocampus in patients with COPD using region-of-interest analysis and did not find any significant change. The impaired brain regions in COPD have also been found in other chronic hypoxic diseases. For example, decrease in GM volume/concentration in the gyrus rectus, precentral gyrus, anterior cingulate cortex, multiple sites within the temporal lobes, insular cortex, thalamus and caudate nucleus were detected in patients with obstructive sleep apnoea.13
Impairments of WM microstructure in the temporal lobe, parietal lobe, fornix and corona radiata were found in patients with congenital central hypoventilation syndrome.12
In our previous study, the decrease in GM volume in the anterior insula, anterior cingulate cortex and precentral cortex were found in high-altitude residents.10
GM density in impaired regions in patients with COPD had a strongly positive correlation with the arterial blood Po2
, which suggested that the impairment in GM may result from low blood oxygen. Moreover, the GM density in some impaired regions showed negative correlations with disease duration. It is already known that hypoxia can induce metabolic decreases3–5
and cerebral perfusion decline2
in COPD. In addition, patients with COPD often suffer from systemic inflammation, which can exacerbate neuronal injury.1
A greater proportion of regions showing GM loss located in limbic/paralimbic cortex in patients with COPD may be due to the fact that phylogenetically older regions of the brain showed sharper vascular responses to hypoxia than evolutionary younger regions.20
A larger cortical network including the anterior insula and anterior cingulate cortex underlie the perception of dyspnoea,11
and these regions play an important role in regulating the cardiovascular system.21
Posterior thalamus was implicated in suppressing the ventilatory response to hypoxia.22
Hippocampus has been proved to control arterial pressure and heart rate.23
Thus, the morphological impairments in these regions may play a role in respiratory and cardiovascular disturbances, such as higher heart rate and higher respiratory rate, in patients with COPD tested in our study.
In the present study, patients with COPD had poorer performance in MMSE, visuospatial memory and visual construction task. These results were consistent with those found in previous studies in patients with COPD.7
In line with the present findings of COPD, we previously found that long-time living in mild high-altitude hypoxic environment only impaired cognitive performances confined to visual reproduction and short-time complex figure memory.24
In our present study, the decreases in GM density in the frontal precentral cortex, insula/superior temporal cortex/Rolandic operculum and thalamus/pulvinar may be responsible for the performance deficit in visual-related tasks since the GM density in these areas showed a significant positive correlation with figure memory or visual reproduction score. The following data support our findings: (1) recent research has identified the inferior frontal cortex served as a source of top–down modulation underlying attention to visual features25
; (2) studies on patients using fMRI and positron emission tomography demonstrated Rolandic operculum as one of the visual structures26
; (3) the pulvinar region of the thalamus is known to project to posterior parietal lobe and inferior temporal lobe. The pulvinar has been implicated in various visual functions in lesion studies.27
Declines in memory and executive function make contributions to declines in ADL.28
Visual construction tasks reflect executive function. Therefore, the decreases in GM density in the above regions that relate to visual construction may also be responsible for ADL deficits.
Our present study found the impairments of WM limited to the pathways of visual processing, including optic radiation, posterior parietal lobe (superior parietal lobule, supramarginal gyrus and precuneus) and the inferior temporal fusiform and lingual gyri. Visual information enters the primary visual cortex via optic radiation to the visual cortex. Cortical areas along the posterior parietal ‘dorsal stream’ are primarily concerned with spatial localisation and directing attention, while cortical areas along the inferior temporal ‘ventral stream’ are mainly concerned with the recognition and identification of visual stimuli.29
COPD also showed impaired WM in the middle temporal gyrus. Middle temporal cortex is important for the long-term build-up of perceptual memory for ambiguous motion stimuli.30
Based on the above data, our findings in WM may also clarify the mechanisms underlying the deficit in visual-related tasks. In addition, impaired WM in input and output fibres of hippocampus (fornix) may be related to the deficit in MMSE. Previous study on patients with Alzheimer's disease found that the volumes of hippocampus were significantly reduced and the volumes of the left hippocampus correlated significantly with the MMSE score.31
The limitation of our study is the weak statistical power of FA value analysis because the results obtained in the TBSS analysis could not survive multiple comparison correction.