Abstract Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and ...density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white matter damage in thirty-seven patients with YOAD (twenty-two, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in four white matter regions of interest. White matter disruption was more widespread in ε4+ individuals, but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occiptal white matter correlated with visual object and spatial perception battery performance (right and left, both p=0.02), and performance (non-verbal) intelligence (WASI matrices, right, p=0.04). NODDI provides tissue-specific microstructural metrics of white matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white matter neurodegeneration.
Objective To describe the normative course of maternal sleep during the first 4 months postpartum. Study Design Sleep was objectively measured using continuous wrist actigraphy. This was a ...longitudinal, field-based assessment of nocturnal sleep during postpartum weeks 2 through 16. Fifty mothers participated during postpartum weeks 2 through 13; 24 participated during postpartum weeks 9 through 16. Results Maternal nocturnal sleep time was 7.2 (SD ± 0.95) hours and did not change significantly across postpartum weeks 2 through 16. Maternal sleep efficiency did improve across weeks 2 (79.7%; SD ± 5.5) through 16 (90.2%; SD ± 3.5) as a function of decreased sleep fragmentation across weeks 2 (21.7; SD ± 5.2) through 16 (12.8; SD ± 3.3). Conclusion Though postpartum mothers' total sleep time was higher than expected during the initial postpartum months, this sleep was highly fragmented (similar to fragmenting sleep disorders) and inefficient. This profile of disturbed sleep should be considered in intervention designs and family leave policies.
Background Coronary computed tomographic angiography (CTA) allows for noninvasive identification of anatomic coronary artery disease (CAD) severity but does not discriminate whether a stenosis causes ...ischemia. Computational fluid dynamic techniques applied to CTA images now permit noninvasive computation of fractional flow reserve (FFR), a measure of lesion-specific ischemia, but the diagnostic performance of computed FFR (FFRCT ) as compared with measured FFR at the time of invasive coronary angiography remains unexplored. Objective We determined the diagnostic accuracy of noninvasive FFRCT for the detection and exclusion of ischemia-causing stenoses. Methods DeFACTO (NCT01233518) is a prospective, international, multicenter study of 238 patients designed to evaluate the diagnostic performance of FFRCT for the detection of hemodynamically significant coronary artery stenoses identified by CTA, compared with invasive FFR as a reference standard. FFR values ≤ 0.80 will be considered hemodynamically significant. Patients enrolled in the DeFACTO study will undergo CTA, invasive coronary angiography, and 3-vessel FFR in the left anterior descending artery, left circumflex artery, and right coronary artery distributions. FFRCT will be computed with acquired CTA images, without modification to CTA image acquisition protocols and without additional image acquisition. Blinded core laboratory interpretation will be performed for CTA, invasive coronary angiography, FFR, and FFRCT. Results The primary endpoint of the DeFACTO study is the per-patient diagnostic accuracy of FFRCT for noninvasive assessment of the hemodynamic significance of CAD, compared with FFR during invasive coronary angiography as a reference standard. The secondary endpoints include additional per-patient as well as per-vessel diagnostic performance characteristics, including sensitivity, specificity, positive predictive value, and negative predictive value. Conclusion The DeFACTO study will determine whether the addition of FFRCT to conventional CTA improves the diagnosis of hemodynamically significant CAD.
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