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IntroductionDepression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain.MethodsLongitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics.ResultsA common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates.DiscussionThe results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.

ObjectiveHigh blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.MethodsTo identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.ResultsOver 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.ConclusionOur findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.Clinical trials registrationThe review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.

To acquire larger samples for answering complex questions in neuroscience, researchers have increasingly turned to multi‐site neuroimaging studies. However, these studies are hindered by differences in images acquired across multiple sites. These effects have been shown to bias comparison between sites, mask biologically meaningful associations, and even introduce spurious associations. To address this, the field has focused on harmonizing data by removing site‐related effects in the mean and variance of measurements. Contemporaneously with the increase in popularity of multi‐center imaging, the use of machine learning (ML) in neuroimaging has also become commonplace. These approaches have been shown to provide improved sensitivity, specificity, and power due to their modeling the joint relationship across measurements in the brain. In this work, we demonstrate that methods for removing site effects in mean and variance may not be sufficient for ML. This stems from the fact that such methods fail to address how correlations between measurements can vary across sites. Data from the Alzheimer's Disease Neuroimaging Initiative is used to show that considerable differences in covariance exist across sites and that popular harmonization techniques do not address this issue. We then propose a novel harmonization method called Correcting Covariance Batch Effects (CovBat) that removes site effects in mean, variance, and covariance. We apply CovBat and show that within‐site correlation matrices are successfully harmonized. Furthermore, we find that ML methods are unable to distinguish scanner manufacturer after our proposed harmonization is applied, and that the CovBat‐harmonized data retain accurate prediction of disease group. [ABSTRACT FROM AUTHOR]

Purpose: Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD+) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a 1H MRS pulse sequence for the in vivo, localized 1H MRS detection of NAD+ from the human brain. Methods: Studies were carried out on a 7T Siemens MRI scanner using a 32‐channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E‐BURP‐1 90° pulse. PRESS localization was achieved using optimized Shinnar‐Le Roux 180° pulses and overlapping gradients were used to minimize the TE. The reproducibility of NAD+ quantification was measured in 11 healthy volunteers. The association of cerebral NAD+ with age was assessed in 16 healthy subjects 26–78 years old. Results: Spectra acquired from a voxel placed in subjects' occipital lobe consisted of downfield peaks from the H2, H4, and H6 protons of the nicotinamide moiety of NAD+ between 8.9–9.35 ppm. The mean ± SD within‐session and between‐session coefficients of variation were found to be 6.14 ± 2.03% and 6.09 ± 3.20%, respectively. In healthy volunteers, an age‐dependent decline of the NAD+ levels in the brain was also observed (β = −1.24 μM/y, SE = 0.21, P < 0.001). Conclusion: We demonstrated the feasibility and robustness of a newly developed 1H MRS technique to measure localized cerebral NAD+ at 7T MRI using a commercially available RF head coil. This technique may be further applied to detect and quantify NAD+ from different regions of the brain as well as from other tissues. [ABSTRACT FROM AUTHOR]

A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing antibody pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on serum samples from the NIH IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. Firstly, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Secondly, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Thirdly, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.

Purpose: Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD + ) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a 1 H MRS pulse sequence for the in vivo, localized 1 H MRS detection of NAD + from the human brain., Methods: Studies were carried out on a 7T Siemens MRI scanner using a 32-channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E-BURP-1 90° pulse. PRESS localization was achieved using optimized Shinnar-Le Roux 180° pulses and overlapping gradients were used to minimize the TE. The reproducibility of NAD + quantification was measured in 11 healthy volunteers. The association of cerebral NAD + with age was assessed in 16 healthy subjects 26-78 years old., Results: Spectra acquired from a voxel placed in subjects' occipital lobe consisted of downfield peaks from the H 2 , H 4 , and H 6 protons of the nicotinamide moiety of NAD + between 8.9-9.35 ppm. The mean ± SD within-session and between-session coefficients of variation were found to be 6.14 ± 2.03% and 6.09 ± 3.20%, respectively. In healthy volunteers, an age-dependent decline of the NAD + levels in the brain was also observed (β = -1.24 μM/y, SE = 0.21, P < 0.001)., Conclusion: We demonstrated the feasibility and robustness of a newly developed 1 H MRS technique to measure localized cerebral NAD + at 7T MRI using a commercially available RF head coil. This technique may be further applied to detect and quantify NAD + from different regions of the brain as well as from other tissues., (© 2019 International Society for Magnetic Resonance in Medicine.)