Resonant Coupling Parameter Estimation with Superconducting Qubits

Today’s quantum computers are composed of tens of qubits interacting with each other and the environment in increasingly complex networks. To achieve the best possible performance when operating such systems, it is necessary to have accurate knowledge of all parameters in the quantum computer Hamiltonian. In this paper, we demonstrate theoretically and experimentally a method to efficiently learn the parameters of resonant interactions for quantum computers consisting of frequency-tunable superconducting qubits. Such interactions include, for example, those with other qubits, resonators, two-level systems, or other wanted or unwanted modes. Our method is based on a significantly improved swap spectroscopy calibration and consists of an offline data collection algorithm, followed by an online Bayesian learning algorithm. The purpose of the offline algorithm is to detect and coarsely estimate resonant interactions from a state of zero knowledge. It produces a quadratic speedup in the scaling of the number of measurements. The online algorithm subsequently refines the estimate of the parameters to accuracy comparable with that of traditional swap spectroscopy calibration but in constant time. We perform an experiment implementing our technique with a superconducting qubit. By combining both algorithms, we observe a reduction of the calibration time by 1 order of magnitude. Our method will improve present medium-scale superconducting quantum computers and will also scale up to larger systems. Finally, the two algorithms presented here can be readily adopted by communities working on different physical implementations of quantum computing architectures

Diagnosis of prodromal and Alzheimer's disease dementia in adults with Down syndrome using neuropsychological tests

We aimed to define prodromal Alzheimer's disease (AD) and AD dementia using normative neuropsychological data in a large population-based cohort of adults with Down syndrome (DS). Cross-sectional study. DS participants were classified into asymptomatic, prodromal AD and AD dementia, based on neurologist's judgment blinded to neuropsychological data (Cambridge Cognitive Examination for Older Adults with Down's syndrome [CAMCOG-DS] and modified Cued Recall Test [mCRT]). We compared the cutoffs derived from the normative data in young adults with DS to those from receiver-operating characteristic curve (ROC) analysis. Diagnostic performance of the CAMCOG-DS and modified Cued Recall Test (mCRT) in subjects with mild and moderate levels of intellectual disability (ID) was high, both for diagnosing prodromal AD and AD dementia (area under the curve [AUC] 0.73-0.83 and 0.90-1, respectively). The cutoffs derived from the normative data were similar to those derived from the ROC analyses. Diagnosing prodromal AD and AD dementia in DS with mild and moderate ID using population norms for neuropsychological tests is possible with high diagnostic accuracy

APP-derived peptides reflect neurodegeneration in frontotemporal dementia

Altres ajuts: The Catalan frontotemporal initiative (CATFI) is funded by the Health Department of the Government of Catalonia (grant PERIS SLT002/16/00408 to Alberto Lleó and Raquel Sánchez-Valle). This work was also supported by research grants from the CIBERNED Program (Program 1, Alzheimer Disease to Alberto Lleó and SIGNAL study, file://www.signalstudy.es), partly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa." This work has also been supported by a "Marató TV3" grant (20141210 to Juan Fortea, 044412 to Rafael Blesa, 20143710 to Ricard Rojas-García and 20143810 to Raquel Sánchez-Valle) and Fundación BBVA (grant to A. Lleó) and a grant from the Fundació Bancaria La Caixa to Rafael Blesa. Ignacio Illán-Gala and Sergi Borrego-Écija are supported by the Rio Hortega grant from "Acción estratégica en Salud 2013-2016" and the European Social Fund. Ignacio Illán-Gala is supported by the Global Brain Health Institute (Atlantic Fellow for Equity in Brain Health). We acknowledge all the participants in this study and all the collaborators of the SPIN cohort. We also acknowledge Soraya Torres and Laia Muñoz for technical assistance. We thank EUROIMMUN for providing Aβ1-38 and Aβ1-40 ELISA assays for this study.Objective: We aimed to investigate the relationship between cerebrospinal fluid levels (CSF) of amyloid precursor protein (APP)-derived peptides related to the amyloidogenic pathway, cortical thickness, neuropsychological performance, and cortical gene expression profiles in frontotemporal lobar degeneration (FTLD)-related syndromes, Alzheimer's disease (AD), and healthy controls. Methods: We included 214 participants with CSF available recruited at two centers: 93 with FTLD-related syndromes, 57 patients with AD, and 64 healthy controls. CSF levels of amyloid β (Aβ)1-42, Aβ1-40, Aβ1-38, and soluble β fragment of APP (sAPPβ) were centrally analyzed. We compared CSF levels of APP-derived peptides between groups and, we studied the correlation between CSF biomarkers, cortical thickness, and domain-specific cognitive composites in each group. Then, we explored the relationship between cortical thickness, CSF levels of APP-derived peptides, and regional gene expression profile using a brain-wide regional gene expression data in combination with gene set enrichment analysis. Results: The CSF levels of Aβ1-40, Aβ1-38, and sAPPβ were lower in the FTLD-related syndromes group than in the AD and healthy controls group. CSF levels of all APP-derived peptides showed a positive correlation with cortical thickness and the executive cognitive composite in the FTLD-related syndromes group but not in the healthy control or AD groups. In the cortical regions where we observed a significant association between cortical thickness and CSF levels of APP-derived peptides, we found a reduced expression of genes related to synaptic function. Interpretation: APP-derived peptides in CSF may reflect FTLD-related neurodegeneration. This observation has important implications as Aβ1-42 levels are considered an indirect biomarker of cerebral amyloidosis

IC-P-082: ASSOCIATION OF PERCEIVED MEMORY DECLINE WITH MULTIMODAL NEUROIMAGING AT DIFFERENT STAGES OF ALZHEIMER'S DISEASE

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Distinct relationships of self-reported subjective memory decline to neurodegeneration across the Alzheimer's clinical continuum: Neuroimaging/Optimal neuroimaging measures for tracking disease progression

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Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome

IMPORTANCE Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established. OBJECTIVE To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments. DESIGN, SETTING, AND PARTICIPANTS This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia. Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia. EXPOSURES Neurological and neuropsychological assessments. MAIN OUTCOMES AND MEASURES The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test. RESULTS A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age = 50 years; P < .001), and 94.1% (95% CI. 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline. CONCLUSIONS AND RELEVANCE This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD

Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly

Altres ajuts: This study was supported by [...], and the CIBERNED program (Program 1, Alzheimer Disease to Alberto Lleó and SIGNAL study, www.signalstudy.es); and partly jointly funded by Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa. This work was also supported by the National Institutes of Health (NIA grants 1R01AG056850 - 01A1; R21AG056974, and R01AG061566 to Juan Fortea), Fundació La Marató de TV3 (20141210 to Juan Fortea, 044412 to Amanda Jiménez and Rafael Blesa). This work was also supported by [...] and a grant from the Fundació Bancaria La Caixa to Rafael Blesa. The work of Adriana Pané is supported by the " Ajut a la Recerca Josep Font" (Hospital Clinic de Barcelona). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). [...]. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org).Midlife obesity is a risk factor for dementia. We investigated the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) core Alzheimer's disease (AD) biomarkers in healthy elderly. We selected controls from ADNI2 with CSF AD biomarkers and/or fluorodeoxyglucose positron emission tomography (FDG-PET) and 3T-MRI. We measured cortical thickness, FDG uptake, and CSF amyloid beta (Aβ)1-42, p-tau, and t-tau levels. We performed regression analyses between these biomarkers and body mass index (BMI). We included 201 individuals (mean age 73.5 years, mean BMI 27.4 kg/m 2). Higher BMI was related to less cortical thickness and higher metabolism in brain areas typically not involved in AD (family-wise error [FWE] <0.05), but not to AD CSF biomarkers. It is notable that the impact of obesity on brain metabolism and structure was also found in amyloid negative individuals. In the cognitively unimpaired elderly, obesity has differential effects on brain metabolism and structure independent of an underlying AD pathophysiology

P3-381: IMPACT OF THE RECRUITMENT SETTING ON THE CHARACTERISTICS OF PATIENTS WITH SUBJECTIVE COGNITIVE DECLINE

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Neural correlates of episodic memory in adults with Down syndrome and Alzheimer’s disease

Background Adults with Down syndrome are at an ultra-high risk of developing early-onset Alzheimer's disease. Episodic memory deficits are one of the earliest signs of the disease, but their association with regional brain atrophy in the population with Down syndrome has not been explored. We aimed to investigate the neuroanatomical correlates of episodic memory in adults with Down syndrome and symptomatic Alzheimer's disease. Methods Single-center, cross-sectional study. A total of 139 adults with Down syndrome (85 asymptomatic and 54 with symptomatic Alzheimer's disease) were included in the study (mean age 43.6 +/- 10.9 years, 46% female). Episodic memory was assessed using the modified Cued Recall Test. Immediate (trial 1 free immediate recall, trial 3 free immediate recall, total free immediate recall score, and total immediate score) and delayed scores (free delayed recall score and total delayed score) were examined. Cortical thickness from magnetic resonance imaging was determined with surface-based morphometry using the FreeSurfer 6.0 software package. The clusters of reduced cortical thickness were compared between symptomatic and asymptomatic participants to create a cortical atrophy map. Then, the correlation between cortical thickness and the modified Cued Recall Test subscores were separately assessed in symptomatic and asymptomatic subjects, controlling for age, sex, and severity of intellectual disability. Results Compared with asymptomatic participants, those with symptomatic Alzheimer's disease showed a pattern of cortical atrophy in posterior parieto-temporo-occipital cortices. In symptomatic subjects, trial 1 immediate free recall significantly correlated with cortical atrophy in lateral prefrontal regions. Trial 3 free immediate recall and total free immediate recall were associated with the most widespread cortical atrophy. Total immediate score was related to posterior cortical atrophy, including lateral parietal and temporal cortex, posterior cingulate cortex, precuneus, and medial temporal lobe areas. Delayed memory scores were associated with cortical atrophy in temporoparietal and medial temporal lobe regions. No significant relationships were observed between episodic memory measures and cortical atrophy in asymptomatic subjects. Conclusions Different episodic memory measures were associated with cortical atrophy in specific brain regions in adults with Down syndrome and Alzheimer's disease. These results overlap with those described in sporadic Alzheimer's disease and further support the similarities between Down syndrome-associated Alzheimer's disease and that in the general population

VAMP-2 is a surrogate cerebrospinal fluid marker of Alzheimer-related cognitive impairment in adults with Down syndrome

Altres ajuts: Fundació la Marató de TV3/20141210There is an urgent need for objective markers of Alzheimer's disease (AD)-related cognitive impairment in people with Down syndrome (DS) to improve diagnosis, monitor disease progression, and assess response to disease-modifying therapies. Previously, GluA4 and neuronal pentraxin 2 (NPTX2) showed limited potential as cerebrospinal fluid (CSF) markers of cognitive impairment in adults with DS. Here, we compare the CSF profile of a panel of synaptic proteins (Calsyntenin-1, Neuroligin-2, Neurexin-2A, Neurexin-3A, Syntaxin-1B, Thy-1, VAMP-2) to that of NPTX2 and GluA4 in a large cohort of subjects with DS across the preclinical and clinical AD continuum and explore their correlation with cognitive impairment. We quantified the synaptic panel proteins by selected reaction monitoring in CSF from 20 non-trisomic cognitively normal controls (mean age 44) and 80 adults with DS grouped according to clinical AD diagnosis (asymptomatic, prodromal AD or AD dementia). We used regression analyses to determine CSF changes across the AD continuum and explored correlations with age, global cognitive performance (CAMCOG), episodic memory (modified cued-recall test; mCRT) and CSF biomarkers, CSF Aβ ratio, CSF Aβ, CSF p-tau, and CSF NFL. P values were adjusted for multiple testing. In adults with DS, VAMP-2 was the only synaptic protein to correlate with episodic memory (delayed recall adj.p =.04) and age (adj.p =.0008) and was the best correlate of CSF Aβ (adj.p =.0001), p-tau (adj.p < .0001), and NFL (adj.p < .0001). Compared to controls, mean VAMP-2 levels were lower in asymptomatic adults with DS only (adj.p =.02). CSF levels of Neurexin-3A, Thy-1, Neurexin-2A, Calysntenin-1, Neuroligin-2, GluA4, and Syntaxin-1B all strongly correlated with NPTX2 (p <.0001), which was the only synaptic protein to show reduced CSF levels in DS at all AD stages compared to controls (adj.p <.002). These data show proof-of-concept for CSF VAMP-2 as a potential marker of synapse degeneration that correlates with CSF AD and axonal degeneration markers and cognitive performance