Year: 2019
Type: article
Abstract: Down syndrome (DS) is the most common genetic cause of neurodevelopmental delay believed due to defects in neurogenesis, neuronal differentiation, and impaired synaptic plasticity and learning. Virtually all adults develop Alzheimer's disease (AD) -associated neuropathology and associated dementia, many by the age of 40, and most will develop dementia by age 60. Recent studies in AD have demonstrated profound white matter (WM) abnormalities including evidence of demyelination, microglial activation, loss of oligodendrocytes and reactive astrocytes. Among participants enrolled in the Biomarkers of Alzheimer's disease in Down Syndrome (ADDS) Study, we examined differences in white matter integrity among DS individuals characterized as no dementia (ND), mild cognitive impairment (MCI) and possible/probable dementia (PRAD). To date, 31 healthy adults with DS, 12 with MCI and 8 with PRAD underwent MRI diffusion weighted imaging. We used a novel diffusion tractography method for the reconstruction of 18 major cerebral white matter fiber bundles. Mean diffusion measures along each tract included: fractional anisotropy (FA), axial (parallel)diffusivity (AD) and radial (perpendicular) diffusivity (RD). Pairwise t-tests were performed to compare differences by group. The discriminatory ability was assessed by regressing the indicator of either MCI or PRAD versus ND onto each measure and summarized using the area under the receiver-operating-characteristic curve (AUC). We found significant reductions in FA in individuals with MCI in several tracts, including the Forceps Major (FMaj), Forceps minor (Fminor) and L/R inferior longitudinal fasciculus (ILF); in AD, additional areas of reduced FA included L/R superior longitudinal fasciculus (SLF), L/R cingulum bundle, and L/R uncinate. Reductions in FA were associated with increases in both RD and AD. ROC curves in these regions were able to distinguish between ND and MCI and between ND and AD, respectively. These results suggest that white matter integrity is lower in select white matter tracts in individuals with DS-MCI, suggesting that DTI may be a promising biomarker for MCI in individuals with DS at risk for AD. The pattern of altered integrity of selected tracts, particularly with early preferential loss of long association fibers, suggests that late myelinating pathways might be particularly vulnerable in DS-AD.
Source: Alzheimer s & Dementia
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980481499