Brain development in aging patients with Duchenne muscular dystrophy

Patients with Duchenne muscular dystrophy (DMD) lack the full-length dystrophin protein. In muscle this protein contributes to membrane integrity. It is also found in the brain, but its function there is unclear. Patients with DMD experience a number of cognitive and behavioral problems, and MRI studies have shown reduced gray matter and total brain volume. The current study aimed to assess whether these MRI findings are progressive and whether neural correlates of psychological problems in DMD are similar to those in healthy controls. Previously-acquired pediatric data was combined with newly-acquired data from adult DMD patients and age- and sex-matched healthy controls. Subjects underwent a magnetic resonance imaging scan and a neuropsychological evaluation. Linear mixed models were used to assess the effect of age and DMD on the ratio of gray matter to cerebrospinal fluid volume (GMV:CSFV) and total brain volume corrected for intracranial volume (TBV:ICV). An independent-samples...Show morePatients with Duchenne muscular dystrophy (DMD) lack the full-length dystrophin protein. In muscle this protein contributes to membrane integrity. It is also found in the brain, but its function there is unclear. Patients with DMD experience a number of cognitive and behavioral problems, and MRI studies have shown reduced gray matter and total brain volume. The current study aimed to assess whether these MRI findings are progressive and whether neural correlates of psychological problems in DMD are similar to those in healthy controls. Previously-acquired pediatric data was combined with newly-acquired data from adult DMD patients and age- and sex-matched healthy controls. Subjects underwent a magnetic resonance imaging scan and a neuropsychological evaluation. Linear mixed models were used to assess the effect of age and DMD on the ratio of gray matter to cerebrospinal fluid volume (GMV:CSFV) and total brain volume corrected for intracranial volume (TBV:ICV). An independent-samples t-test and a voxel-based morphometry analysis were used to compare gray matter volume in patients with psychological problems to patients without such problems, to identify global or local gray matter reductions in patients with psychological problems. Patients with DMD had reduced GMV:CSFV and TBV:ICV compared to healthy controls (b=-0.43, p<0.001; b=-0.02, p<0.001 respectively). Both GMV:CSFV and TBV:ICV linearly decreased in both groups (b=-0.09, p<0.001; b=-0.003, p<0.001 respectively), but this was not different between-groups (p>0.05). No global (p>0.05) or localized gray matter volume reductions were found in patients with DMD with psychological problems compared to patients without such problems. In both patients and healthy controls gray matter was displaced by cerebrospinal fluid over time, suggesting this process is not a pathological mechanism in DMD. Patients with DMD did have a lower GMV:CSFV and TBV:ICV ratio, suggesting this is a diseased mechanism. No global or local GM reductions were found in patients with DMD with psychological problems compared to patients without such problems.Show less

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Brain development in aging patients with Duchenne muscular dystrophy