| Background and significanceMedication overuse headache(MOH)was the third most common type of headache following migraine and tension headache.Epidemiological studies have shown that the prevalence of MOH in the general population is about 1%-2%.Up to 30%and 50%of headache patients in the tertiary care centers and headache clinics in Europe and the United States were MOH.As a type of chronic headache,headaches attack almost every day,causing severe disability and a decline in quality of life.The brain structure and function may be continuously affected,resulting in damage to cognitive function,which will further aggravate the economic and mental burden of patients.Understanding the cognitive function and possible influencing factors of patients with MOH is of great significance for the early diagnosis and effective intervention to cognitive impairment.The rapid development of neuroimaging technology,especially the development of magnetic resonance imaging and image processing technology,provides an important means for researchers to observe brain tissue morphology,structural integrity,metabolic changes and functional activities in vitro.VBM(voxel-based morphometry)is a voxel-based whole brain automated analysis technology that quantitatively analyzes the density and volume of gray matter and white matter in the whole brain at the voxel level,thereby accurately showing the changes in whole brain tissue morphology.It is the most commonly used method for comparing gray matter structure differences.DTI(diffusion tensor imaging)technology uses magnetic resonance diffusion-sensitive gradients to quantify the diffusion of water molecules in brain tissue.It can reflect the damage of the fine structure of the white matter fiber bundle in the living human brain tissue.DKI(diffusion kurtosis imaging)technology is an extension of DTI technology,adopting non-Gaussian distribution model,which is more in line with the actual diffusion distribution of water molecules in tissues under high b value.In addition to neurite demyelination and axonal degeneration,kurtosis parameters can also reflect other microstructural changes such as neuroinflammatory changes,neuronal swelling,and gliosis.The sensitivity and specificity of the gray matter and white matter microstructural changes of the brain are higher than those of the DTI parameters.More and more studies have shown that changes in cognitive function are related to abnormalities in brain structure and function.This study was designed to investigate the cognitive function and related influencing factors in patients with MOH.The magnetic resonance technique was used to study the microscopic structure of brain regions of MOH patients,and the correlation with cognitive performance was analyzed to explore the possible neuroanatomical mechanisms of cognitive impairment.And to provide evidence for early detection and early treatment of cognitive impairment.Objective(1)To explore the cognitive function status in patients with MOH and related influencing factors of cognitive impairment.(2)To compare the difference in gray matter volume between MOH patients and healthy controls using the VBM method,and analyze the relationship between the changes of gray matter volume and cognitive function scores.(3)To study the changes in the microstructure of some white matter regions and gray matter regions in MOH patients by using the DKI technique,and analyze their relationship with cognitive function scores.Methods(1)Clinical data of 48 patients with MOH were collected.The primary headache of these patients is migraine.The subjects' overall cognitive performance was assessed using the mini-mental state examination(MMSE)and the Montreal Cognitive Assessment(MoCA).Each subject's cognitive domain was assessed by using MoCA.Then the correlation between cognitive performance and clinical indicators was analyzed.(2)The brain 3D magnetic resonance images of 27 patients with MOH and 16 healthy controls matched with gender,age and years of education were collected.The differences in gray matter volume between the two groups of subjects were compared by VBM method,and correlation with cognitive scores was analyzed.(3)DKI technique was used to collect magnetic resonance images of 24 MOH patients and 16 healthy controls matched with gender,age and years of education.Using the method of region of interest,the differences in DKI parameters(MK,AK,RK values)between the two groups of subjects were compared.The correlation between MK value,RK value and cognitive function scores was analyzed.Results(1)When MMSE was used as the evaluation standard,cognitive impairment occurred in 3 patients(6.25%)with MOH.When MoCA was used as the evaluation standard,31 patients(64.6%)had cognitive impairment in MOH patients.There were significant differences in the visual space and executive function,attention,delayed memory,and orientation power between the cognitive impairment group and the cognitive normal group(P<0.05).The delayed memory impairment was the most extensive in all cognitive domains in MOH patients.Correlation analysis showed that,the MoCA total scores and abnormal cognitive domain scores of MOH patients were negatively correlated with the patient's age and positively correlated with the patient's education years(P<0.05).Partial cognitive domain scores were negatively correlated with duration of headache and duration of medication overuse(P<0.05).The total scores of MoCA and the abnormal cognitive domain scores were not significantly correlated with the patient's headache frequency and the Hospital Depression Scale scores(P>0.05).(2)There was no significant difference in gray matter volume,white matter volume and total volume between the MOH patients and the healthy controls(P>0.05).Gray matter volume of right superior frontal gyrus,right superior temporal gyrus and left middle frontal gyrus/inferior frontal gyrus in MOH patient group was significantly decreased compared with healthy control group(P<0.001).Compared with the healthy control group,there was no brain area with increased gray matter volume in the MOH group.Correlation analysis showed that the decrease of gray matter volume on the right superior frontal gyrus was significantly positively correlated with the total scores of MoCA(P<0.05),mainly in the aspect of visual space and executive function and delayed memory.(3)Compared with the healthy control group,the three parameter values of DKI(MK,AK and RK)were decreased in all brain regions of interest.The MK values of frontal lobe,temporal lobe,splenium of corpus callosum,hippocampus and cerebellum were significantly decreased in MOH patients.The RK values of frontal lobe,temporal lobe,splenium of corpus callosum and hippocampus were significantly decreased in MOH patients.The difference of MK values and RK values between the two groups were statistically significant(P<0.05).There was no significant difference in AK values between the two groups(P>0.05).Correlation analysis showed that the MK value of the frontal lobe was significantly positively correlated with the MoCA total scores,visual space and executive function,and attention scores(P<0.05).The MK value of hippocampus was significantly positively correlated with the MoCA total scores and attention scores(P<0.05).The MK value of cerebellar was significantly positively correlated with the MoCA total scores,visual space and executive function and delayed memory scores(P<0.05).The MK value of temporal lobe was significantly positively correlated with orientation scores(P<0.05).The RK value of frontal lobe was significantly positively correlated with the MoCA total scores and visual space and executive function,delayed memory scores(P<0.05).The RK value of hippocampus was significantly positively correlated with the MoCA total scores,attention and orientation scores(P<0.05).There was significant positive correlation between the RK value of temporal lobe and visual space and executive function scores(P<0.05).Conclusion(1)MOH patients had impairment in multiple cognitive domains such as visual space and executive function,attention,delayed memory,and orientation,only manifest as mild cognitive impairment.The duration of headache and the duration of medication overuse affect the cognitive performance of the patients.(2)MOH patients had brain microstructural damage.The frontal lobe may be the main affected brain area,including the gray matter and white matter areas.Degeneration of these areas may be the main potential neurobiological mechanism of cognitive impairment in MOH patients.The important role of frontal lobe in the pathophysiological process of MOH was further confirmed.(3)DKI technology could detect abnormalities in brain microstructure sensitively,and MK,RK values were more sensitive than AK values.There was significant correlation between MK value,RK value and MoCA total scores and multiple cognitive domain scores.They may play a role in the early assessment of cognitive function status in patients with MOH. |
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