Plasma proteomic signatures of dual cognitive and mobility decline in older adults.

Background: The simultaneous memory and gait decline is linked to greater dementia risk than memory decline alone. We aim to identify dual decline-related protein changes that may offer valuable insights into biological processes.

Methods: We compared longitudinal changes in 7268 plasma proteomic markers in older adults experiencing dual decline, memory decline, and gait decline from no decline (reference) using linear mixed-effects regression and related to brain MRI and blood biomarkers.

Plasma GDF15 affects long-term dementia risk and alters neuro-immune signaling.

Growth/differentiation factor-15 (GDF15) is a secreted peptide hormone and cytokine that is strongly associated with dementia risk. However, the extent to which plasma GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15-to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular dementia compared to Alzheimer's disease (AD).

Risk Factors for Early Poor Outcomes in In-hospital Intracranial Hemorrhage: A Retrospective Cohort Study.

Background: Compared to in-hospital ischemic stroke, the prognosis of in-hospital intracranial hemorrhage (IH-ICH) remains poorly understood. We aimed to analyze the risk factors for early poor outcomes and propose a novel predictive nomogram for in-hospital ICH.

Methods: We retrospectively analyzed data of patients with in-hospital ICH treated in our hospital between 2014 and 2022.

Olfaction and diabetes among older adults.

Both poor olfaction and diabetes are common in older adults. It is biologically plausible that they may be related and interact to affect the health of older adults. We examined the association between poor olfaction and diabetes and their joint associations with mortality among 2,416 older adults from the Health, Aging, and Body Composition Study.

Prediction of future aging-related slow gait and its determinants with deep learning and logistic regression.

Background: Identification of accelerated aging and its biomarkers can lead to more timely therapeutic interventions and decision-making. Therefore, we sought to predict aging-related slow gait, a known predictor of accelerated aging, and its determinants.

Methods: We applied a deep learning neural network (NN) and compared it to conventional logistic regression (LR) analysis.

Proteomic signatures of corona and herpes viral antibodies identify IGDCC4 as a mediator of neurodegeneration.

Mechanisms underlying the dynamic relationships of viral infections and neurodegeneration warrant examination. Using a community-based cohort of older adults, the current study characterized the neurocognitive (cognitive functioning, brain volumes, Alzheimer's disease positron emission tomography, and plasma biomarkers) and plasma proteomic (7268 proteins) profiles of four common coronavirus and six herpesvirus antibody titers. Genetic inference techniques demonstrated the associations between viral antibody titers and neurocognitive outcomes may be attributed to altered expression in a subset of mechanistically relevant proteins in plasma.

Plasma proteomic analysis of intermuscular fat links muscle integrity with processing speed in older adults.

Introduction: More intermuscular fat (IMF) has been associated with lower cognitive performance through mechanisms that are not fully elucidated.

Methods: The associations of 7628 plasma proteins with IMF were assessed in the Baltimore Longitudinal Study on Aging (n = 941, mean age = 66.7 ± 15.

Physical activity complexity, cognition, and risk of cognitive impairment and dementia in the Baltimore Longitudinal Study of Aging.

Introduction: Studies on physical activity (PA) and dementia mainly focus on activity quantity or intensity. Yet PA requires neuro-coordination of movement, and it is unclear whether complexity of daily activity varies by cognitive status. Thus, we examined the association between PA complexity, using multiscale entropy, and cognitive function, mild cognitive impairment (MCI), and dementia in older adults in the Baltimore Longitudinal Study of Aging (BLSA).

Directionality between cognitive function and daily physical activity patterns.

Introduction: Physical activity is a modifiable risk factor for dementia, but cognitive function is also important for physical activity engagement. This study evaluated the directionality of associations between daily physical activity and cognitive function in a sample of cognitively and physically intact older adults.

Methods: Cognitive factor scores for domains including global cognition, memory, language, executive function/attention, and visuospatial processing, and physical activity patterns from wrist accelerometry were measured at two visits (mean: 1.

Qualitative and quantitative lipidomic profiling of cardiolipin, oxidized cardiolipin, and monolysocardiolipin from human skeletal muscle by UPLC-Orbitrap-MS.

Background: Cardiolipins (CL) are a mitochondria-specific family of phospholipids that play central roles in mitochondrial function. Imbalance in CL metabolism, especially excessive CL oxidation, leads to mitochondrial dysfunction, apoptosis, and inflammation, contributing to age-related diseases. As of yet no comprehensive methods have been developed to assess CL, oxidized CL (oxCL), and monolyso-CL (MLCL) species.

Metabolomic Pathways of Inflammation and Mitochondrial Dysfunction Are Related to Worsening Healthy Aging Index and Mortality.

Background: Metabolic-inflammatory states are central to multiorgan mechanisms of aging, but precise functional biomarkers of physiological aging remain less clear.

Methods: In the Health, Aging, and Body Composition study, we defined metabolomic profiles of the Healthy Aging Index (HAI), a composite of cardiovascular, lung, cognitive, metabolic, and renal function (0-10, with higher scores indicating poorer health) in a split set design from 2015 older participants (mean age 73.6 years; 50% women; 35% Black).

Longitudinal patterns of brain aging and neurodegeneration among older adults with dual decline in memory and gait.

Introduction: Dual cognitive and mobility decline is more strongly associated with dementia risk than cognitive decline only. It remains unknown whether this syndrome is associated with brain atrophy patterns, white matter (WM) damage, or pathology.

Methods: In the Baltimore Longitudinal Study of Aging participants with and without dual decline, we used linear mixed-effects models to compare up to 13-year longitudinal changes in MRI-derived atrophy patterns, WM hyperintensities (n = 339), microstructure (n = 307), plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid beta 42/40 (Aβ) ratio (n = 349), and phosphorylated tau 181 (pTau181) (n = 258).

Metabolomic insight into the link of intermuscular fat with cognitive performance: the Health ABC Study.

There is growing evidence that higher intermuscular fat (IMF) is associated with worse processing speed, measured by the digit symbol substitution test (DSST) in older adults. However, the underlying biological mechanisms are not well understood. Considering that both muscle and the brain are metabolically active organs, we sought to identify metabolites that may explain the IMF-DSST association.

Plasma proteomic analysis of intermuscular fat links muscle integrity with processing speed in older adults.

Introduction: More intermuscular fat (IMF) has been associated with lower cognitive performance and faster age-associated decline in cognitive function however, the mechanisms driving this relationship have not been fully elucidated. We utilized proteomic analyses to identify the molecular mediators of the association between IMF and cognition to gain further insight into the mechanisms underlying this association.

Methods: In this cross-sectional study, the plasma proteomic profile of IMF was assessed in the Baltimore Longitudinal Study on Aging (BLSA; n=941, age=66.

TERTp Mutation and its Prognostic Value in Glioma Patients Under the 2021 WHO Classification: A Real-World Study.

Background: The 2021 WHO Classification of Central Nervous System Tumors introduces more molecular markers for glioma reclassification, including TERT promoter (TERTp) mutation as a key feature in glioblastoma diagnosis.

Aims: Given the changes in the entities included in each subtype under the new classification, this research investigated the distribution, prognostic value, and correlations with other molecular alterations of TERTp mutation in different subgroups under this latest classification.

Methods: All glioma patients admitted to Peking Union Medical College Hospital for surgical resection or biopsy from 2011 to 2022 were included.

Higher skeletal muscle mitochondrial oxidative capacity is associated with preserved brain structure up to over a decade.

Impaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer's disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, k) is associated with less ventricular enlargement and brain aging progression, and less atrophy in specific regions, notably primary sensorimotor cortex, temporal white and gray matter, thalamus, occipital areas, cingulate cortex, and cerebellum white matter.

Metabolite signatures of chronological age, aging, survival, and longevity.

Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk.

Proteomic analysis of APOEε4 carriers implicates lipid metabolism, complement and lymphocyte signaling in cognitive resilience.

Background: Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer's disease (AD). This case-cohort study used targeted plasma biomarkers and large-scale proteomics to examine the biological mechanisms that allow some APOEε4 carriers to maintain normal cognitive functioning in older adulthood.

Methods: APOEε4 carriers and APOEε3 homozygotes enrolled in the Women's Health Initiative Memory Study (WHIMS) from 1996 to 1999 were classified as resilient if they remained cognitively unimpaired beyond age 80, and as non-resilient if they developed cognitive impairment before or at age 80.

Mitochondrial DNA copy number associated dementia risk by somatic mutations and frailty.

Mitochondrial dysfunction is linked to physical impairment and dementia. Mitochondrial DNA copy number (mtDNAcn) from blood may predict cognitive decline and dementia risk, but the effect of somatic mutations or frailty is unknown. We estimated mtDNAcn using fastMitoCalc and microheteroplasmies using mitoCaller, from Whole Genome Sequencing (WGS) data.

Clinical features, MRI, molecular alternations, and prognosis of astrocytoma based on WHO 2021 classification of central nervous system tumors: A single-center retrospective study.

Background: The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification.

Methods: Patients diagnosed with astrocytoma, IDH-mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included.

Shared plasma metabolomic profiles of cognitive and mobility decline predict future dementia.

Experiencing decline in both cognition and mobility is associated with a substantially higher dementia risk than cognitive decline only. Metabolites associated with both cognitive and mobility declines may be early predictors of dementia and reveal specific pathways to dementia. We analyzed data from 2450 participants initially free of dementia who had 613 metabolites measured in plasma in 1998-1999 (mean age = 75.

Relationship between skeletal mitochondrial function and digital markers of free-living physical activity in older adults.

This study examined the association between in vivo skeletal mitochondrial function and digital free-living physical activity patterns-a measure that summarizes biological, phenotypic, functional, and environmental effects on mobility. Among 459 participants (mean age 68 years; 55% women) in the Baltimore Longitudinal Study of Aging, mitochondrial function was quantified as skeletal muscle oxidative capacity via post-exercise phosphocreatine recovery rate (τ) in the vastus lateralis muscle of the left thigh, using 31P magnetic resonance spectroscopy. Accelerometry was collected using a 7-day, 24-h wrist-worn protocol and summarized into activity amount, intensity, endurance, and accumulation patterning metrics.

MRI-derived brain iron, grey matter volume, and risk of dementia and Parkinson's disease: Observational and genetic analysis in the UK Biobank cohort.

Background: Iron overload is observed in neurodegenerative diseases, especially Alzheimer's disease (AD) and Parkinson's disease (PD). Homozygotes for the iron-overload (haemochromatosis) causing HFE p.C282Y variant have increased risk of dementia and PD.