No abstract

BackgroundWe longitudinally assessed Down syndrome individuals at the age of risk of developing dementia to measure changes in brain anatomy and their relationship to cognitive impairment progression.MethodsForty-two Down syndrome individuals were initially included, of whom 27 (mean age 46.8 years) were evaluable on the basis of completing the 2-year follow-up and success in obtaining good quality MRI exams. Voxel-based morphometry was used to estimate regional brain volumes at baseline and follow-up on 3D anatomical images. Longitudinal volume changes for the group and their relationship with change in general cognitive status and specific cognitive domains were mapped.ResultsAs a group, significant volume reduction was identified in the substantia innominata region of the basal forebrain, hippocampus, lateral temporal cortex and left arcuate fasciculus. Volume reduction in the substantia innominata and hippocampus was more prominent in individuals whose clinical status changed from cognitively stable to mild cognitive impairment or dementia during the follow-up. Relevantly, longitudinal memory score change was specifically associated with volume change in the hippocampus, prospective memory with prefrontal lobe and verbal comprehension with language-related brain areas.ConclusionsResults are notably concordant with the well-established anatomical changes signaling the progression to dementia in Alzheimer's disease, despite the dense baseline pathology that developmentally accumulates in Down syndrome. This commonality supports the potential value of Down syndrome as a genetic model of Alzheimer's neurodegeneration and may serve to further support the view that Down syndrome patients are best candidates to benefit from treatment research in Alzheimer's disease.

Our results contribute to characterizing the expression of white matter structural alterations in adult Down syndrome. However, an accelerated aging effect was not demonstrated, which may suggest that the FA measurements used are not sufficiently sensitive or, alternatively, age-related white matter neurodegeneration is not obvious prior to overt clinical dementia.

BackgroundDown syndrome (DS) is considered the most frequent cause of early-onset Alzheimer’s disease (AD), and the typical pathophysiological signs are present in almost all individuals with DS by the age of 40. Despite of this evidence, the investigation on the pre-dementia stages in DS is scarce. In the present study we analyzed the complexity of brain oscillatory patterns and neuropsychological performance for the characterization of mild cognitive impairment (MCI) in DS.Materials and methodsLempel-Ziv complexity (LZC) values from resting-state magnetoencephalography recordings and the neuropsychological performance in 28 patients with DS [control DS group (CN-DS) (n = 14), MCI group (MCI-DS) (n = 14)] and 14 individuals with typical neurodevelopment (CN-no-DS) were analyzed.ResultsLempel-Ziv complexity was lowest in the frontal region within the MCI-DS group, while the CN-DS group showed reduced values in parietal areas when compared with the CN-no-DS group. Also, the CN-no-DS group exhibited the expected pattern of significant increase of LZC as a function of age, while MCI-DS cases showed a decrease. The combination of reduced LZC values and a divergent trajectory of complexity evolution with age, allowed the discrimination of CN-DS vs. MCI-DS patients with a 92.9% of sensitivity and 85.7% of specificity. Finally, a pattern of mnestic and praxic impairment was significantly associated in MCI-DS cases with the significant reduction of LZC values in frontal and parietal regions (p = 0.01).ConclusionBrain signal complexity measured with LZC is reduced in DS and its development with age is also disrupted. The combination of both features might assist in the detection of MCI within this population.