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General slowing of mental processing speed is hallmark of brain and cognitive aging. Thus far it has been limited under-standing in neural mechanisms underlying mental states during fluctuations between efficient versus inefficient cognitiveperformance within individual older adults. Here we examined electrophysiological responses during visual working mem-ory retrieval trials that are fast versus slow reactions. Wireless EEG along with accuracy and reaction times were recordedduring a modified delayed match-to-sample task in 17 cognitively normal older adults (age 65-95) from North America.Compared to trials that are faster than averaged (mean 584 ms), the late positive potentials during trials that are slowerthan average (mean 747 ms) showed increased responses to memory nonmatch distractors than those to object matchingmemory targets in frontal sites, as previously reported in older brains. Interestingly, the brainwaves during efficient andaccurate memory retrievals resemble those typically seen in younger adults.

INTRODUCTION: Protein‐based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia. METHODS: Plasma was obtained from participants (N = 837) in our community‐based University of Kentucky Alzheimer's Disease Research Center cohort. We evaluated six Alzheimer's disease (AD)‐ and neurodegeneration‐related (Aβ40, Aβ42, Aβ42/40, p‐tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF훼, IL6, IL8, IL10, and GFAP) using the SIMOA‐based protein assay platform. Statistics were performed to assess correlations. RESULTS: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD–inflammatory biomarker correlations showed significant associations between AD and inflammatory biomarkers suggesting peripheral inflammatory interactions with increasing AD pathology. Biomarker associations parsed out by clinical diagnosis (normal, MCI, and dementia) reveal changes in strength of the correlations across the cognitive continuum. DISCUSSION: Unique AD–inflammatory biomarker correlations in a community‐based cohort reveal a new avenue for utilizing plasma‐based biomarkers in the assessment of AD and related dementias. Highlights: Large community cohorts studying sex, age, and APOE genotype effects on biomarkers are few.It is unknown how biomarker–biomarker associations vary through aging and dementia.Six AD (Aβ40, Aβ42, Aβ42/40, p‐tau181, total tau, and NfLight) and five inflammatory biomarkers (TNFα, IL6, IL8, IL10, and GFAP) were used to examine associations between biomarkers.Plasma biomarkers suggesting increasing cerebral AD pathology corresponded to increases in peripheral inflammatory markers, both pro‐inflammatory and anti‐inflammatory.Strength of correlations, between pairs of classic AD and inflammatory plasma biomarker, changes throughout cognitive progression to dementia. [ABSTRACT FROM AUTHOR]

Introduction: Clinically, detection of disease‐causing pathology associated with Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) is limited to magnetic resonance imaging and positron emission tomography scans, which are expensive and not widely accessible. Here, we assess angiogenic, inflammatory, and AD‐related plasma biomarkers to determine their relationships with human post mortem neuropathology. Method: Plasma samples were analyzed using a digital immunoassay and pathological evaluation was performed by University of Kentucky Alzheimer's Disease Research Center neuropathologists. The association of plasma markers with neuropathology was estimated via proportional odds and logistic regressions adjusted for age. Results: Included cases (N = 90) showed increased tau/amyloid beta (Aβ)42 ratio, glial fibrillary acidic protein (GFAP), vascular endothelial growth factor A (VEGF‐A), and placental growth factor (PlGF) were positively associated with higher level of AD neuropathological change, while higher Aβ42/Aβ40 ratio was inversely associated. Higher PlGF, VEGF‐A, and interleukin 6 were inversely associated with chronic cerebrovascular disease, while Aβ42/Aβ40 ratio was positively associated. Discussion: Our results provide support for the continued study of plasma biomarkers as a clinical screening tool for AD and VCID pathology. [ABSTRACT FROM AUTHOR]

Sphericalization of the left ventricular (LV) chamber shape in patients with mitral regurgitation (MR) contributes to increased LV wall stress and energy consumption. On the basis of previous observations, we hypothesized the existence of regional differences in the force-frequency relation (FFR) within the LV that may contribute to its shape. Accordingly, in the present study, we assessed regional variation in the FFR in patients undergoing surgery for chronic, nonischemic MR with class II-III heart failure symptoms and related our findings to the in vivo LV shape. FFRs (steady-state isometric twitches, 0.2-3.4 Hz, 37[degrees]C) were evaluated in MR myocardium from the LV subepicardial free wall (MR-FW) and papillary muscle (MR-PM) and from the subepicardial free wall in coronary artery bypass graft patients with normal LV contraction patterns [nonfailing (NF)]. Ascending slope, optimal stimulation frequency, and maximal twitch tension of the FFR were depressed in MR-FW and MR-PM compared with NF (P < 0.05). FFR depression was greater in MR-PM than in MR-FW. Between 107 and 134 beats/min, twitch tension became weaker in MR-PM, whereas it increased in MR-FW. Elevation of intracellular cAMP with forskolin eliminated FFR depression in MR-FW but not in MR-PM. MR-PM also had a 35% lower myosin heavy chain content and slowed twitch kinetics. In MR patients, the echocardiographic end-diastolic LV shape (end-diastolic eccentricity index = long axis/short axis) correlated with the ratio of ascending FFR slopes such that the end-diastolic eccentricity index increased 10% per 15% increase in slope ratio (r = 0.88, P = 0.01). These regional differences in the frequency dependence of contractility between the free wall and papillary myocardium may contribute to changes in LV shape in MR as well as during exercise. human myocardium; ventricular function; regional contractility

Introduction: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia., Methods: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer's Disease Research Center cohort. We evaluated six Alzheimer's disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations., Results: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD-inflammatory biomarker correlations showed significant associations between AD and inflammatory biomarkers suggesting peripheral inflammatory interactions with increasing AD pathology. Biomarker associations parsed out by clinical diagnosis (normal, MCI, and dementia) reveal changes in strength of the correlations across the cognitive continuum., Discussion: Unique AD-inflammatory biomarker correlations in a community-based cohort reveal a new avenue for utilizing plasma-based biomarkers in the assessment of AD and related dementias., Highlights: Large community cohorts studying sex, age, and APOE genotype effects on biomarkers are few. It is unknown how biomarker-biomarker associations vary through aging and dementia. Six AD (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNFα, IL6, IL8, IL10, and GFAP) were used to examine associations between biomarkers. Plasma biomarkers suggesting increasing cerebral AD pathology corresponded to increases in peripheral inflammatory markers, both pro-inflammatory and anti-inflammatory. Strength of correlations, between pairs of classic AD and inflammatory plasma biomarker, changes throughout cognitive progression to dementia., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Clinically, detection of disease-causing pathology associated with Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) is limited to magnetic resonance imaging and positron emission tomography scans, which are expensive and not widely accessible. Here, we assess angiogenic, inflammatory, and AD-related plasma biomarkers to determine their relationships with human post mortem neuropathology., Method: Plasma samples were analyzed using a digital immunoassay and pathological evaluation was performed by University of Kentucky Alzheimer's Disease Research Center neuropathologists. The association of plasma markers with neuropathology was estimated via proportional odds and logistic regressions adjusted for age., Results: Included cases (N = 90) showed increased tau/amyloid beta (Aβ)42 ratio, glial fibrillary acidic protein (GFAP), vascular endothelial growth factor A (VEGF-A), and placental growth factor (PlGF) were positively associated with higher level of AD neuropathological change, while higher Aβ42/Aβ40 ratio was inversely associated. Higher PlGF, VEGF-A, and interleukin 6 were inversely associated with chronic cerebrovascular disease, while Aβ42/Aβ40 ratio was positively associated., Discussion: Our results provide support for the continued study of plasma biomarkers as a clinical screening tool for AD and VCID pathology., (© 2022 the Alzheimer's Association.)