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Background: Cardiometabolic disorders (hypertension, diabetes) are key modifiable risk factors for Alzheimer’s disease and related disorders. They often co-occur; yet, the extent to which they independently affect brain structure and function is unclear. Objective: We hypothesized their combined effect is greater in associations with cognitive function and neuroimaging biomarkers of white matter (WM) health and cerebral perfusion in a diverse older adult cohort. Methods: Participants aged 50-85 years received: clinical evaluation, oral glucose tolerance testing, neuroimaging, cognitive testing, and adjudication. Neuroimaging included: T1 (gray [GM]/WM segmentation, regional volumes/thicknesses); FLAIR (WM hyperintensity volume [WMHv]; arterial spin labeling (cerebral blood flow); diffusion tensor imaging (fractional anisotropy [FA]); and neurite orientation dispersion and density imaging (Free Water). Hypertension (HTN) and impaired glucose tolerance (IGT) were staged and cardiometabolic status was categorized (HTN only, IGT only, IGT+HTN, neither). Multivariable linear regression modeled associations with cognitive and neuroimaging measures (covariates: age, gender, race). Results: MRI was available for 478 participants (35% mild cognitive impairment, 10% dementia) with mean age 70±8 years, 74% with HTN, 61% with IGT, and 15% self-identified as Black/African-American. IGT+HTN was significantly associated with cognitive impairment, higher WM Free Water and WMHv, lower FA, and lower GM perfusion compared to neither factor. HTN alone was associated with poorer cognition and lower GM perfusion. Cardiometabolic factors were not associated with GM macrostructure (volumes, temporal lobe cortical thickness) or cognitive status. Conclusion: HTN and its co-occurrence with IGT (HTN+IGT) were associated with lower global cognitive performance and reduced GM perfusion and impaired WM microstructure.

The objective of the proposed MAQRO mission is to harness space for achieving long free-fall times, extreme vacuum, nano-gravity, and cryogenic temperatures to test the foundations of physics in macroscopic quantum experiments. This will result in the development of novel quantum sensors and a means to probe the foundations of quantum physics at the interface with gravity. Earlier studies showed that the proposal is feasible but that several critical challenges remain, and key technologies need to be developed. These new technologies will open up the potential for achieving additional science objectives. The proposed research campaign aims to advance the state of the art and to perform the first macroscopic quantum experiments in space. Experiments on the ground, in micro-gravity, and in space will drive the proposed research campaign during the current decade to enable the implementation of MAQRO within the subsequent decade., Comment: 9 pages, 2 figures, submitted as a Research Campaign Whitepaper for the BPS2023 Decadal Survey

Systemic mitochondrial dysfunction is reported with AD progression, suggesting that peripheral blood cells may be used to investigate systemic mitochondrial alterations related to cognitive decline. We aimed to identify bioenergetic signatures associated with AD-related dementia and differences in insulin sensitivity associated with AD risk. We analyzed mitochondrial bioenergetics in peripheral blood cells collected from 365 older adults with varying cognitive status (normal, mild cognitive impairment, and AD) and insulin sensitivity. Normoglycemic individuals exhibited lower maximal bioenergetic capacity with AD (PBMCs: 239.6 pmol·min−1, p = 0.02; Platelets: 151.7 pmol·min−1, p = 0.06) compared to normal cognition (PBMCs: 271.5 pmol·min−1; Platelets: 171.7 pmol·min−1). Individuals with impaired insulin sensitivity exhibited lower maximal bioenergetic capacity in platelets with AD (171.6 pmol·min−1, p = 0.008) compared to normal cognition (210.6 pmol.min−1). Participants with impaired insulin sensitivity also exhibited unique bioenergetic profiles exemplified by overall higher levels of mitochondrial respiration, indicating that comorbidities such as diabetes can significantly influence bioenergetic capacity. We observed strong positive associations between maximal respiration in normoglycemic individuals with cognitive function, as measured by Modified Preclinical Alzheimer’s Cognitive Composite (mPACC5) (p = 0.06), and fatty acid oxidation in individuals with impaired insulin sensitivity with cortical thickness (p = 0.05). This study demonstrates that circulating cells may provide a cost-effective and minimally invasive way to monitor systemic bioenergetic changes associated with AD risk, progression, and insulin sensitivity. These findings also suggest that blood-based bioenergetics are related to key features of AD development and progression and should be further developed as a potential biomarker.

We consider the matterwave interferometric measurement of atomic velocities, which forms a building block for all matterwave inertial measurements. A theoretical analysis, addressing both the laboratory and atomic frames and accounting for residual Doppler sensitivity in the beamsplitter and recombiner pulses, is followed by an experimental demonstration, with measurements of the velocity distribution within a 20 $\mu$K cloud of rubidium atoms. Our experiments use Raman transitions between the long-lived ground hyperfine states, and allow quadrature measurements that yield the full complex interferometer signal and hence discriminate between positive and negative velocities. The technique is most suitable for measurement of colder samples., Comment: 16 pages, 6 figures

We propose an interferometric scheme based on an untrapped nano-object subjected to gravity. The motion of the center of mass (c.m.) of the free object is coupled to its internal spin system magnetically, and a free flight scheme is developed based on coherent spin control. The wavepacket of the test object, under a spin-dependent force, may then be delocalized to a macroscopic scale. A gravity induced dynamical phase (accrued solely on the spin state, and measured through a Ramsey scheme) is used to reveal the above spatially delocalised superposition of the spin-nano-object composite system that arises during our scheme. We find a remarkable immunity to the motional noise in the c.m. (initially in a thermal state with moderate cooling), and also a dynamical decoupling nature of the scheme itself. Together they secure a high visibility of the resulting Ramsey fringes. The mass independence of our scheme makes it viable for a nano-object selected from an ensemble with a high mass variability. Given these advantages, a quantum superposition with $100$ nm spatial separation for a massive object of $10^9$ amu is achievable experimentally, providing a route to test postulated modifications of quantum theory such as continuous spontaneous localisation., 7 pages, 3 figures

We describe a dynamic magneto-optical trap (MOT) suitable for the use with vacuum systems in which optical access is limited to a single window. This technique facilitates the long-standing desire of producing integrated atom chips, many of which are likely to have severely restricted optical access compared with conventional vacuum chambers. This "switching-MOT" relies on the synchronized pulsing of optical and magnetic fields at audio frequencies. The trap's beam geometry is obtained using a planar mirror surface, and does not require a patterned substrate or bulky optics inside the vacuum chamber. Central to the design is a novel magnetic field geometry that requires no external quadrupole or bias coils which leads toward a very compact system. We have implemented the trap for $^{85}$Rb and shown that it is capable of capturing 2 million atoms and directly cooling below the Doppler temperature., Comment: 15 pages, 7 figures

The Schr��dinger-Newton equation has been proposed as an experimentally testable alternative to quantum gravity, accessible at low energies. It contains self-gravitational terms, which slightly modify the quantum dynamics. Here we show that it distorts the spectrum of a harmonic system. Based on this effect, we propose an optomechanical experiment with a trapped microdisc to test the Schr��dinger-Newton equation, and we show that it can be realized with existing technology., 13 pages, 4 figures, 1 table, 1 page of supplemental material