Project description:The myriad of neuropsychiatric manifestations reported in myotonic dystrophy type 1 may have its origin in alterations of complex brain network interactions at the structural level. In this study, we tested the hypothesis that altered white matter microstructural integrity and network organisation were present in a cohort of individuals with DM1 compared to unaffected controls, which was expected to be associated with CNS related disease manifestations of DM1. We performed a cross-sectional neuropsychological assessment and brain MRI in 25 myotonic dystrophy type 1 (DM1) patients and 26 age, sex and educational level matched unaffected controls. Patients were recruited from the Dutch cohort of the OPTIMISTIC study, a concluded trial which had included ambulant, genetically confirmed DM1 patients who were severely fatigued. We applied graph theoretical analysis on structural networks derived from diffusion tensor imaging (DTI) data and deterministic tractography to determine global and local network properties and performed group-wise comparisons. Furthermore, we analysed the following variables from structural MRI imaging: semi-quantitative white matter hyperintensity load andwhite matter tract integrity using tract-based spatial statistics (TBSS). Structural white matter networks in DM1 were characterised by reduced global efficiency, local efficiency and strength, while the network density was compatible to controls. Other findings included increased white matter hyperintensity load, and diffuse alterations of white matter microstructure in projection, association and commissural fibres. DTI and network measures were associated (partial correlations coefficients ranging from 0.46 to 0.55) with attention (d2 Test), motor skill (Purdue Pegboard test) and visual-constructional ability and memory (copy subtest of the Rey-Osterrieth Complex Figure Test). DTI and network measures were not associated with clinical measures of fatigue (checklist individual strength, fatigue subscale) or apathy (apathy evaluation scale - clinician version). In conclusion, our study supports the view of brain involvement in DM1 as a complex network disorder, characterised by white matter network alterations that may have relevant neuropsychological correlations. This work was supported by the European Community's Seventh Framework Programme (FP7/2007-2013; grant agreement n° 305,697) and the Marigold Foundation.

Project description:ObjectiveThe Alzheimer's continuum is biologically defined by beta-amyloid deposition, which at the earliest stages is superimposed upon white matter degeneration in aging. However, the extent to which these co-occurring changes is characterized is relatively underexplored. The goal of this study was to use diffusional kurtosis imaging (DKI) and biophysical modeling to detect and describe amyloid-related white matter changes in preclinical Alzheimer disease.MethodsCognitively unimpaired participants ages 45 to 85 years completed brain magnetic resonance imaging, amyloid positron emission tomography (florbetapir), neuropsychological testing, and other clinical measures at baseline in a cohort study. We tested whether beta-amyloid-negative (AB-) and -positive (AB+) participants differed on DKI-based conventional (ie, fractional anisotropy [FA], mean diffusivity [MD], mean kurtosis) and modeling (ie, axonal water fraction [AWF], extra-axonal radial diffusivity [De,⊥ ]) metrics, and whether these metrics were associated with other biomarkers.ResultsWe found significantly greater diffusion restriction (higher FA/AWF, lower MD/De,⊥ ) in white matter in AB+ than AB- (partial η2 =0.08-0.19), more notably in the extra-axonal space within primarily late myelinating tracts. Diffusion metrics predicted amyloid status incrementally over age (area under the curve = 0.84) with modest yet selective associations, where AWF (a marker of axonal density) correlated with speed/executive functions and neurodegeneration, whereas De,⊥ (a marker of gliosis/myelin repair) correlated with amyloid deposition and white matter hyperintensity volume.InterpretationThese results support prior evidence of a nonmonotonic change in diffusion behavior, where an early increase in diffusion restriction is hypothesized to reflect inflammation and myelin repair prior to an ensuing decrease in diffusion restriction, indicating glial and neuronal degeneration. ANN NEUROL 2022;91:864-877.

Dataset Information

Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders.

Publications

Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets