CSF Biomarkers in Longitudinal Alzheimer Disease Cohorts: Pre-Analytic Challenges.

Background: The sensitivity of amyloid to pre-analytic factors complicates cerebrospinal fluid (CSF) diagnostics for Alzheimer disease. We report reliability and validity evidence for automated immunoassays from frozen and fresh CSF samples in an ongoing, single-site research program.

Methods: CSF samples were obtained from 2 Wisconsin cohorts (1256 measurements; 727 participants).

Lamotrigine use and potential for adverse cardiac effects: A retrospective evaluation in a Veteran population.

Objective: To identify the impact of lamotrigine (LTG) on cardiac rhythm and conduction abnormalities for Veterans, an especially vulnerable population.

Background: In October 2020 the US Food and Drug Administration (FDA) added a new warning to the label of lamotrigine (Lamictal™) regarding its potential to cause cardiac rhythm and conduction abnormalities [1]. This warning came following in vitro data which suggested Class IB antiarrhythmic effects occurring at clinically achievable concentrations of lamotrigine [2].

Prevalence and Clinical Implications of a β-Amyloid-Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease.

Importance: Knowledge is lacking on the prevalence and prognosis of individuals with a β-amyloid-negative, tau-positive (A-T+) cerebrospinal fluid (CSF) biomarker profile.

Objective: To estimate the prevalence of a CSF A-T+ biomarker profile and investigate its clinical implications.

Design, Setting, And Participants: This was a retrospective cohort study of the cross-sectional multicenter University of Gothenburg (UGOT) cohort (November 2019-January 2021), the longitudinal multicenter Alzheimer Disease Neuroimaging Initiative (ADNI) cohort (individuals with mild cognitive impairment [MCI] and no cognitive impairment; September 2005-May 2022), and 2 Wisconsin cohorts, Wisconsin Alzheimer Disease Research Center and Wisconsin Registry for Alzheimer Prevention (WISC; individuals without cognitive impairment; February 2007-November 2020).

Plasma phosphorylated tau 217 in preclinical Alzheimer's disease.

An accurate blood test for Alzheimer's disease that is sensitive to preclinical proteinopathy and cognitive decline has clear implications for early detection and secondary prevention. We assessed the performance of plasma phosphorylated tau 217 ( ) against brain PET markers of amyloid [ -labelled Pittsburgh compound B (PiB)] and tau ( MK-6240) and its utility for predicting longitudinal cognition. Samples were analysed from a subset of participants with up to 8 years follow-up in the Wisconsin Registry for Alzheimer's Prevention (WRAP; 2001-present; plasma 2011-present), a longitudinal cohort study of adults from midlife, enriched for parental history of Alzheimer's disease.

Subjective Cognitive Decline Associated with Discrimination in Medical Settings among Transgender and Nonbinary Older Adults.

Background: Transgender and nonbinary (TNB) individuals report greater subjective cognitive decline (SCD) compared to non-TNB people. SCD involves self-reported problems with memory and thinking and is a potential risk for Alzheimer's disease and related dementias (ADRD). We explored psychosocial factors, such as discrimination in medical settings, associated with SCD in a sample of TNB older adults.

Crosswalk study on blood collection-tube types for Alzheimer's disease biomarkers.

Introduction: Blood-based Alzheimer's disease (AD) biomarkers show promise, but pre-analytical protocol differences may pose problems. We examined seven AD blood biomarkers (amyloid beta [ , , , total tau [t-tau], neurofilament light chain [NfL], and ) in three collection tube types (ethylenediaminetetraacetic acid [EDTA] plasma, heparin plasma, serum).

Methods: Plasma and serum were obtained from cerebrospinal fluid or amyloid positron emission tomography-positive and -negative participants (N = 38) in the Wisconsin Registry for Alzheimer's Prevention.

Sex differences in off-target binding using tau positron emission tomography.

Purpose: Off-target binding in the skull and meninges is observed in some subjects undergoing tau positron emission tomography (PET) and could potentially differ between men and women. In this study we elucidate sex differences in tau off-target binding using three different tau PET tracers.

Methods: 541 cognitively unimpaired amyloid-β negative participants underwent tau PET using [F]flortaucipir (n = 165), [F]RO948 (n = 189) and [F]MK6240 (n = 187).

Cognitive Changes with Reproductive Aging, Perimenopause, and Menopause.

This article reviews the role of endogenous estrogen in neural and cognitive processing, followed by an examination of longitudinal cognitive data captured in various stages of the menopausal transition. The remaining text reviews the contradictory results from major hormone therapy trials to date, evidence for the "timing hypothesis," and closes with recommendations for future research and for practicing clinicians.

Cerebrospinal Fluid and Plasma Levels of Inflammation Differentially Relate to CNS Markers of Alzheimer's Disease Pathology and Neuronal Damage.

Inflammatory markers have been shown to predict neurocognitive outcomes in aging adults; however, the degree to which peripheral markers mirror the central nervous system remains unknown. We investigated the association between plasma and cerebrospinal fluid (CSF) markers of inflammation, and explored whether these markers independently predict CSF indicators of Alzheimer's disease (AD) pathology or neuronal damage. Plasma and CSF samples were analyzed for inflammatory markers in a cohort of asymptomatic older adults (n = 173).

Relatedness Matters.

Today, nurses are confronted with much more in their day-to-day activities than 40 years ago. Not only are nurses caring for more patients during their shifts, patients are acute and complex and have shorter hospital stays. The nurse-patient relationship has been a focus of nursing since the profession began.

Cerebrospinal Fluid Markers of Alzheimer's Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer's Disease.

Background: The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-β (Aβ). However, overproduction of inflammatory compounds may exacerbate neural damage in AD. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown.

Insulin Resistance is Associated with Higher Cerebrospinal Fluid Tau Levels in Asymptomatic APOEɛ4 Carriers.

Background: Insulin resistance (IR) is linked with the occurrence of pathological features observed in Alzheimer's disease (AD), including neurofibrillary tangles and amyloid plaques. However, the extent to which IR is associated with AD pathology in the cognitively asymptomatic stages of preclinical AD remains unclear.

Objective: To determine the extent to which IR is linked with amyloid and tau pathology in late-middle-age.

Insulin resistance predicts brain amyloid deposition in late middle-aged adults.

Background: Insulin resistance (IR) increases Alzheimer's disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD. No studies have examined if IR is associated with an in vivo index of amyloid in the human brain in late middle-aged participants at risk for AD.

Effect of age and calorie restriction on corpus callosal integrity in rhesus macaques: a fiber tractography study.

The rhesus macaque exhibits age-related brain changes similar to humans, making an excellent model of normal aging. Calorie restriction is a dietary intervention that reduces age-related comorbidities in short-lived animals, and its effects are still under study in rhesus macaques. Here, using deterministic fiber tracking method, we examined the effects of age and calorie restriction on a diffusion tensor imaging measure of white matter integrity, fractional anisotropy (FA), within white matter tracks traversing the anterior (genu) and posterior (splenium) corpus callosum in rhesus monkeys.

Interleukin-8 and interleukin-10, brain volume and microstructure, and the influence of calorie restriction in old rhesus macaques.

Higher systemic levels of the proinflammatory cytokine interleukin-6 (IL-6) were found to be associated with lower gray matter volume and tissue density in old rhesus macaques. This association between IL-6, and these brain indices were attenuated by long-term 30 % calorie restriction (CR). To extend these findings, the current analysis determined if a CR diet in 27 aged rhesus monkeys compared to 17 normally fed controls reduced circulating levels of another proinflammatory cytokine, interleukin-8 (IL-8), and raised levels of anti-inflammatory interleukin-10 (IL-10).

Dysphagia.

Swallowing is one of the primary functions that enable humans to sustain life. Likewise, it is an important element of healthy life and contributes to quality of life and well-being. When the ability to swallow is lost or impaired, the risk of disability or even death is greatly increased.

A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using magnetic resonance imaging, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n=24, 13 males, 11 females) and standard (n=17, 8 males, 9 females) diets. Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex.

A generalized form of context-dependent psychophysiological interactions (gPPI): a comparison to standard approaches.

Functional MRI (fMRI) allows one to study task-related regional responses and task-dependent connectivity analysis using psychophysiological interaction (PPI) methods. The latter affords the additional opportunity to understand how brain regions interact in a task-dependent manner. The current implementation of PPI in Statistical Parametric Mapping (SPM8) is configured primarily to assess connectivity differences between two task conditions, when in practice fMRI tasks frequently employ more than two conditions.

Calorie restriction reduces psychological stress reactivity and its association with brain volume and microstructure in aged rhesus monkeys.

Background: Heightened stress reactivity is associated with hippocampal atrophy, age-related cognitive deficits, and increased risk for Alzheimer's disease. This temperament predisposition may aggravate age-associated brain pathology or be reflective of it. This association may be mediated through repeated activation of the stress hormone axis over time.

Low HDL Cholesterol is Associated with Lower Gray Matter Volume in Cognitively Healthy Adults.

Dyslipidemia is common in adults and contributes to high rates of cardiovascular disease and may be linked to subsequent neurodegenerative and neurovascular diseases. This study examined whether lower brain volumes and cognition associated with dyslipidemia could be observed in cognitively healthy adults, and whether apolipoprotein E (APOE) genotype or family history of Alzheimer's disease (FHAD) alters this effect. T1-weighted magnetic resonance imaging was used to examine regional brain gray matter (GM) and white matter (WM) in 183 individuals (58.

Effects of aging and calorie restriction on white matter in rhesus macaques.

Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of caloric restriction likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue.

Role of arachidonic acid, lipoxygenase, and mitochondrial depolarization in reperfusion arrhythmias.

We have sought evidence that arachidonic acid (AA) induces mitochondrial depolarization in isolated myocytes by a lipoxygenase (LOX)-dependent mechanism and that such depolarization might contribute to arrhythmogenesis following ischemia-reperfusion injury. A method was developed for measuring mitochondrial depolarization in isolated adult rat myocytes in suspension, using tetramethylrhodamine ethyl ester. The addition of AA to myocytes resulted in mitochondrial depolarization that was inhibited by the LOX inhibitor baicalein, by the reactive oxygen species (ROS) scavenger mercaptoproprionylglycine, and by the anion channel inhibitor diisothiocyanatostilbene-disulfonic acid (DIDS).

Rhesus macaque brain morphometry: a methodological comparison of voxel-wise approaches.

Voxel-based morphometry studies have become increasingly common in human neuroimaging over the past several years; however, few studies have utilized this method to study morphometry changes in non-human primates. Here we describe the application of voxel-wise morphometry methods to the rhesus macaque (Macaca mulatta) using the 112RM-SL template and priors (McLaren et al. (2009) [42]) and as an illustrative example we describe age-associated changes in grey matter morphometry.