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BackgroundSemantic intrusion errors (SIEs) are associated with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). It is unknown whether accounting for maximum learning capacity still leads to an increase in SIEs when elevated plasma p-tau₂₁₇, a biological indicator of underlying AD, is present. MethodsOne hundred fifty-eight older adult participants completed the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), a sensitive cognitive challenge test designed to elicit SIEs. Of these, 108 were clinically diagnosed with amnestic MCI (aMCI). Fifty-eight individuals met or exceeded a plasma p-tau₂₁₇positivity of >0.55 pg/ml, while 50 individuals scored below this threshold. ResultsAfter adjusting for demographic covariates and maximum learning capacity, the aMCI p-tau₂₁₇+ group evidenced more SIEs compared to aMCI p-tau₂₁₇- on the first (list B1;p= 0.035) and second trials of the competing list (list B2;p= 0.006). Biological predictors such asApoEε4 status, higher p-tau₂₁₇, and older age were predictors of an elevated number of SIEs [list B2:F(3,104) = 10.92;p= 0.001;R= 0.489)]. ConclusionsUnlike previous studies that used amyloid PET or other plasma biomarkers, individuals with aMCI p-tau₂₁₇+ evidenced more SIEs, even after adjusting for their initial learning capacity, a covariate that has not been studied previously. These findings support that SIEs are more prevalent in the presence of underlying AD pathology and occur independent of learning deficits. 

Abstract By utilizing bicontinuous and nanoporous ordered nanonetworks, such as double gyroid (DG) and double diamond (DD), metamaterials with exceptional optical and mechanical properties can be fabricated through the templating synthesis of functional materials. However, the volume fraction range of DG in block copolymers is significantly narrow, making it unable to vary its porosity and surface‐to‐volume ratio. Here, the theoretically limited structural volume of the DG phase in coil‐coil copolymers is overcome by enlarging the conformational asymmetry through the association of mesogens, providing fast access to achieving flexible structured materials of ultra‐high porosities. The new materials design, dual‐extractable nanocomposite, is created by incorporating a photodegradable block with a solvent‐extractable mesogen (m) into an accepting block, resulting in a new hollow gyroid (HG) with the largely increased surface‐to‐volume ratio and porosity of 77 vol%. The lightweight HG exhibits a low refractive index of 1.11 and a very high specific reduced modulus, almost two times that of the typical negative gyroid (porosity≈53%) and three times that of the positive gyroid (porosity≈24%). This novel concept can significantly extend the DG phase window of block copolymers and the corresponding surface‐to‐volume ratio, being applicable for nanotemplate‐synthesized nanomaterials with a great gain of mechanical, catalytic, and optoelectronic properties. 

Neuroimaging and biofluid biomarkers provide a proxy of pathological changes for Alzheimer’s disease (AD) and are useful in improving diagnosis and assessing disease progression. However, it is not clear how race/ethnicity and different prevalence of AD risks impact biomarker levels. In this narrative review, we survey studies focusing on comparing biomarker differences between non-Hispanic White American(s) (NHW), African American(s) (AA), Hispanic/Latino American(s) (HLA), and Asian American(s) with normal cognition, mild cognitive impairment, and dementia. We found no strong evidence of racial and ethnic differences in imaging biomarkers after controlling for cognitive status and cardiovascular risks. For biofluid biomarkers, in AA, higher levels of plasma Aβ42/Aβ40, and lower levels of CSF total tau and p-tau 181, were observed after controlling for APOE status and comorbidities compared to NHW. Examining the impact of AD risks and comorbidities on biomarkers and their contributions to racial/ethnic differences in cognitive impairment are critical to interpreting biomarkers, understanding their generalizability, and eliminating racial/ethnic health disparities. 

Background and Objectives The goal of this work was to determine the relationship between diffusion microstructure and early changes in Alzheimer disease (AD) severity as assessed by clinical diagnosis, cognitive performance, dementia severity, and plasma concentrations of neurofilament light chain. Methods Diffusion MRI scans were collected on cognitively normal participants (CN) and patients with early mild cognitive impairment (EMCI), late mild cognitive impairment, and AD. Free water (FW) and FW-corrected fractional anisotropy were calculated in the locus coeruleus to transentorhinal cortex tract, 4 magnocellular regions of the basal forebrain (e.g., nucleus basalis of Meynert), entorhinal cortex, and hippocampus. All patients underwent a battery of cognitive assessments; neurofilament light chain levels were measured in plasma samples. Results FW was significantly higher in patients with EMCI compared to CN in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus (mean Cohen d = 0.54; p fdr < 0.05). FW was significantly higher in those with AD compared to CN in all the examined regions (mean Cohen d = 1.41; p fdr < 0.01). In addition, FW in the hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus coeruleus to transentorhinal cortex tract positively correlated with all 5 cognitive impairment metrics and neurofilament light chain levels (mean r 2 = 0.10; p fdr < 0.05). Discussion These results show that higher FW is associated with greater clinical diagnosis severity, cognitive impairment, and neurofilament light chain. They also suggest that FW elevation occurs in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus in the transition from CN to EMCI, while other basal forebrain regions and the entorhinal cortex are not affected until a later stage of AD. FW is a clinically relevant and noninvasive early marker of structural changes related to cognitive impairment.