Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease.

Background And Objectives: Nicotinamide is a coenzyme involved in cellular oxidation-reduction reactions that can inhibit Class III histone deacetylases (HDACs) or sirtuins. HDAC inhibition can affect numerous therapeutic pathways, including tau phosphorylation. We tested the hypothesis that nicotinamide treatment could reduce tau phosphorylation in early Alzheimer disease (AD).

Medical Histories Associated With Absence of Alzheimer Disease Neuropathologic Changes in the Oldest-Old: The 90+ Study.

Objectives: Exploration of medical histories and medications associated with Alzheimer disease neuropathologic change (ADNC) absence and potential resistance may identify protective factors against ADNC. This was a retrospective examination of data from participants age ≥90 years who enrolled in , a longitudinal study based in California. Participants underwent neuropathologic analysis for the presence of neuritic amyloid plaques (NPs) (any), beta amyloid plaques (Thal phase > 0), and neurofibrillary tangles (>2).

Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer's disease biomarkers in older adults.

The locus coeruleus (LC) is among the first brain structures impacted by Alzheimer's disease (AD), and noradrenergic denervation may contribute to early neurovascular dysfunction in AD. Mechanistic links between the LC and cerebral perfusion have been demonstrated in rodents, but there have been no similar studies in aging humans. Community-dwelling older adults with no history of stroke or dementia (N=66) underwent structural (T1-MPRAGE; T1-FSE) and perfusion (resting pCASL) MRI.

A data-driven, multi-domain brain gray matter signature as a powerful biomarker associated with several clinical outcomes.

Introduction: Characterizing pathological changes in the brain that underlie cognitive impairment, including Alzheimer's disease and related disorders, is central to clinical concerns of prevention, diagnosis, and treatment.

Methods: We describe the properties of a brain gray matter region ("Union Signature") that is derived from four behavior-specific, data-driven signatures in a discovery cohort.

Results: In a separate validation set, the Union Signature demonstrates clinically relevant properties.

Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with its molecular etiology still unclear. Here we present a spatial transcriptomic (ST) and single-nucleus transcriptomic survey of late-onset sporadic AD and AD in Down syndrome (DSAD). Studying DSAD provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD.

Views and Perceptions of Amyloid Imaging in a Preclinical Alzheimer's Disease Trial.

Background: Many cognitively unimpaired older adults are interested in learning their Alzheimer's disease (AD) biomarker status, but little is known about motivations to undergo biomarker testing and result disclosure in the setting of preclinical AD trials.

Objectives: Examine whether motivations to undergo AD biomarker testing and disclosure differ for individuals who have elevated amyloid compared to those with not elevated amyloid, and whether disclosure of amyloid results impacts participants' motivations.

Design, Setting, Participants: We conducted post-hoc analyses using data from the EARLY study, a preclinical AD trial of the beta-secretase inhibitor atabecestat.

Cerebral perfusion and amyloidosis in the oldest-old.

Introduction: In a nested case-control study, we examined how cerebral perfusion relates to cognitive status and amyloid in the oldest-old (i.e., 90 years of age and older).

The Temporal Relation of Physical Function with Cognition and the Influence of Brain Health in the Oldest-Old.

Introduction: Physical function and cognition seem to be interrelated, especially in the oldest-old. However, the temporal order in which they are related and the role of brain health remain uncertain.

Methods: We included 338 participants (mean age 93.

Baseline Impulse Oscillometry Metrics Differentiate Asthmatic Children From Non-Asthmatic Children Across Ethnicity/Race: A Meta-Analysis.

Introduction: Identifying the asthmatic early to prevent permanent airway remodeling and the progression of the disease is desirable. In children, baseline impulse oscillometry has been found effective in identifying asthma in some studies but not others.

Objective: The purpose of our study was to utilize a meta-analysis to determine whether there were significant peripheral airway differences between asthmatic and non-asthmatic children across ethnicity/race, utilizing baseline impulse oscillometry (IOS) to establish its usefulness as a diagnostic tool in this age group.

Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.

Lysosomal storage disorders (LSDs) are a large disease class involving lysosomal dysfunction, often resulting in neurodegeneration. Sandhoff disease (SD) is an LSD caused by a deficiency in the β subunit of the β-hexosaminidase enzyme (). Although expression in the brain is specific to microglia, SD primarily affects neurons.

Inflammation and olfactory loss are associated with at least 139 medical conditions.

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions.

Alzheimer's disease biomarkers and the tyranny of treatment.

Advances in treatment are changing not only the therapeutic options for patients with Alzheimer's disease; they're also changing their diagnostic options. Technologies to detect amyloid such as PET imaging and blood or CSF testing now have a central role in Alzheimer's disease care. Notably, this role has been made possible by regulatory approval and coverage by payers of therapies.

Establishing the Foundations of Emotional Intelligence in Care Companion Robots to Mitigate Agitation Among High-Risk Patients With Dementia: Protocol for an Empathetic Patient-Robot Interaction Study.

Background: An estimated 6.7 million persons are living with dementia in the United States, a number expected to double by 2060. Persons experiencing moderate to severe dementia are 4 to 5 times more likely to fall than those without dementia, due to agitation and unsteady gait.

Evaluating the updated LATE-NC staging criteria using data from NACC.

Introduction: Limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria were updated in 2023. We evaluated this updated staging using National Alzheimer's Coordinating Center data.

Methods: We examined associations of LATE-NC stages with cognition and other neuropathologic changes (NCs), and with cognition while accounting for other NCs, using multilevel regression models.

Subjective cognitive decline and cognitive change among diverse middle-aged and older Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Introduction: The potential utility of subjective cognitive decline (SCD) as an early risk marker of Alzheimer's disease and related dementias is under consideration. We examined associations between SCD and cognitive change among middle-aged and older Hispanic/Latino adults living in the United States.

Methods: The short-form Everyday Cognition Scale (ECog-12) was assessed to generate global, executive function, and memory-related SCD scores.

Prefrontal and lateral entorhinal neurons co-dependently learn item-outcome rules.

The ability to learn novel items depends on brain functions that store information about items classified by their associated meanings and outcomes, but the underlying neural circuit mechanisms of this process remain poorly understood. Here we show that deep layers of the lateral entorhinal cortex (LEC) contain two groups of 'item-outcome neurons': one developing activity for rewarded items during learning, and another for punished items. As mice learned an olfactory item-outcome association, we found that the neuronal population of LEC layers 5/6 (LEC) formed an internal map of pre-learned and novel items, classified into dichotomic rewarded versus punished groups.

DXA-Measured Abdominal Adipose Depots and Structural Brain Integrity in Postmenopausal Women.

Background: This study extends prior research from the MRI substudy of the Women's Health Initiative Memory Study (WHIMS-MRI) linking BMI to reduced brain atrophy and ischemic lesion load by examining DXA-based measurements of total body fat, total abdominal adipose tissue (TAT), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, gynoid fat, and overall leg fat.

Methods: The analytic sample consisted of 61 postmenopausal women (baseline mean age 69.5 [3.

Single-cell spatial transcriptomics reveals distinct patterns of dysregulation in non-neuronal and neuronal cells induced by the Trem2 Alzheimer's risk gene mutation.

The R47H missense mutation of the TREM2 gene is a known risk factor for development of Alzheimer's Disease. In this study, we analyze the impact of the Trem2 mutation on specific cell types in multiple cortical and subcortical brain regions in the context of wild-type and 5xFAD mouse background. We profile 19 mouse brain sections consisting of wild-type, Trem2, 5xFAD and Trem2; 5xFAD genotypes using MERFISH spatial transcriptomics, a technique that enables subcellular profiling of spatial gene expression.

Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin.

The utility of recruitment incentives in early Alzheimer's disease trials.

Introduction: Amid recent approvals, early Alzheimer's disease (AD) remains an active area of treatment development.

Methods: We performed a conjoint experiment to compare preferences among 26 patients with mild cognitive impairment for four trial features including designs incorporating active aducanumab-control (vs. placebo), returning tau positron emission tomography (PET) results (vs.

Reasons for undergoing amyloid imaging among diverse enrollees in the A4 study.

Introduction: Understanding attitudes toward participation among diverse preclinical Alzheimer's disease (AD) trial participants could yield insights to instruct future recruitment.

Methods: Using data from the Anti-Amyloid Treatment in Asymptomatic AD (A4) Study, we examined differences among mutually exclusive racial and ethnic groups in views and perceptions of amyloid imaging (VPAI), a measure of motivations to undergo amyloid biomarker testing in the setting of preclinical AD. We used linear regression to quantify differences at baseline.