Biomarkers.

Background: Traumatic encephalopathy syndrome (TES) is the proposed clinical syndrome of the neurodegenerative disease chronic traumatic encephalopathy (CTE). As part of the 2021 TES NINDS consensus diagnostic criteria, certainty levels of underlying CTE neuropathology can be determined (i.e.

Biomarkers.

Background: A decline in gait has been associated with an escalated risk of cognitive decline and changes in Alzheimer's disease (AD) biomarkers, thus offering prognostic insight. However, the utility of gait analysis in preclinical stages of AD is unclear, and prior studies have primarily used qualitative or gross measures of gait. Furthermore, gait analysis has predominantly been performed in cohorts of non-Hispanic Whites.

Biomarkers.

Background: Cognitive dysfunction is more common in individuals with type 1 diabetes (T1D) compared to the general population. Blood-based biomarkers are accurate in identifying early signs of neurodegeneration. However, studies using these biomarkers in T1D are lacking.

Biomarkers.

Background: AD-NeuroScore is a validated metric that summarizes Alzheimer's disease (AD)-specific atrophy and can detect AD early, benchmark disease severity, predict and monitor AD progression, and can aid in testing the efficacy of therapeutic interventions using a single number (Kress, 2023). It meets criteria for translatability by using clinically available regional brain volumes as input (Ahdidan, 2015; Cavedo, 2022) and having patient and model-level interpretability (Pinto, 2022). Also, features can be reviewed by a neuroradiologist (Larson, 2019).

Biomarkers.

Background: White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted MRI scans. They vary in size, location, and intensity, suggesting different underlying conditions like small vessel disease and inflammation. This variation potentially links WMH to outcomes ranging from normal aging to severe neurological disorders.

Biomarkers.

Background: Bilingualism can stimulate brain plasticity (Jafari et al. Ann N Y Acad Sci. 2021;1505(1):8-22) and is also associated with better executive function (Grundy.

Biomarkers.

Background: Alzheimer's disease (AD) is associated with impaired lipid metabolism in the brain. To identify the specific regions where pathological change to cell functionality occurs, a spatial investigation of regional lipid dysregulation is needed.

Method: We measured untargeted spatial lipidomics using Desorption Electrospray Ionization (DESI) mass spectrometry in the brains of mice from two genotypes, wild type (WT) and APPsw, an AD mouse model overexpression amyloid precursor protein (APP).

Biomarkers.

Background: There is an urgent need for neuropsychological screening tests that are easily deployed and reliable. We have developed a digital neuropsychological screening protocol that is administered on a tablet, automatically scored using artificial intelligence, and requires approximately 10 minutes to administer. This tablet-administered protocol assesses the requisite neurocognitive constructs associated with emergent neurodegenerative illness METHOD: The digital protocol was administered to 77 ambulatory care/ memory clinic patients (Table 1).

Biomarkers.

Background: Familial Alzheimer's disease research necessitates innovative methodologies to disentangle the intricate relationships between genetic factors and neuroimaging measures. Traditional frequentist approaches, often hampered by small sample sizes in this population and challenges in incorporating prior knowledge transparently, may limit the robustness of findings.

Methods: We analyzed neuroimaging data of preclinical PSNE1 single mutation carriers, utilizing the software JASP to test effects of carrier status on measures of basal forebrain functional connectivity using both frequentist and Bayesian approach.

Biomarkers.

Background: Greater adherence to the Mediterranean Diet (MeDi) is associated with lower risk for cardiovascular disease, slower cognitive decline, and reduced risk for Alzheimer's Disease (AD). However, its association with AD biomarkers is not well known. We hypothesized that greater MeDi adherence is associated with reduced amyloid and tau PET burden in a community-based sample of older adults in Northern Manhattan.

Biomarkers.

Background: Subjective cognitive decline (SCD) is thought to be a preclinical stage of Alzheimer's disease (AD), associated with faster disease progression and with imaging and cerebrospinal fluid biomarkers. However, it is unclear whether and how the degree of SCD correlates with plasma biomarkers. To address this, we investigated the association of plasma biomarkers of AD with established validated measures of SCD.

Biomarkers.

Background: Cognitive reserve (CR) is a property of the brain trait that allows for better-than-expected cognitive performance, relative to the degree of brain change over the life course. However, the neurophysiological markers of CR require further investigation. Electroencephalography (EEG) may provide an appropriate neurophysiological marker of CR.

Biomarkers.

Background: Myelin integrity is central to healthy brains and is increasingly shown to be compromised in neurodegenerative diseases. Diffusion- and susceptibility-based MRI metrics can detect myelin changes. We show advanced diffusion and susceptibility metrics can detect degenerative myelin changes in ex vivo AD and HD mouse models.

Biomarkers.

White matter hyperintensities (WMH) are areas of increased lucency visualized on T2-weighted magnetic resonance imaging (MRI), including fluid attenuated inversion recovery (FLAIR) sequences. Over the past 15 years we have been examining WMH in studies of cognitive aging among clinical, community-based, and populations at genetic risk to understand the role of vascular brain injury in Alzheimer's disease (AD) onset, symptom progression, and pathogenesis. Our findings suggest that regional WMH, particularly when distributed in posterior areas, increase risk for clinical AD and contribute to the clinical course of the disease, even among genetic population with relatively low rates of vascular risk factor, like adults with Down syndrome and with autosomal dominant genetic mutations for AD.

Biomarkers.

Background: Brain-predicted age estimates are used to quantify an individual's brain age compared to a normative trajectory. We have recently shown that brain age from structural MRI is elevated in autosomal dominant Alzheimer disease (ADAD), a unique sample that allows the study of AD progression independently of age-related confounds. Resting-state functional connectivity (FC) may capture a biphasic response to sporadic AD, and thus may complement structural measures of brain aging in ADAD.

Street Pharmacology: Toxico-Dermatology of Injection Drug Use.

Street medicine is a point-of-care, mobile approach that services the needs of unhoused individuals who are otherwise unable to access medical care in traditional settings. The prevalence of injection drug use combines with the pipeline of illicit substances, to produce a constellation of severe, potentially life-threatening dermatological disorders unique to this population. This review applies principles of clinical pharmacology to clarify the mechanisms underlying the dermatological toxicity of xylazine, desomorphine, and 3,4-methylenedioxymethamphetamine (MDMA).

Biomarkers.

Background: Inexpensive, non-invasive tests may improve the identification of persons at increased risk for cognitive decline and dementia. We compared impairment in odor identification and global cognition with neuro-imaging biomarkers to predict cognitive decline and dementia in the population-based Mayo Clinic Study of Aging (MCSA).

Method: At the 2008 assessment, 647 participants who were ≥ 55 years old with at least one follow-up had the following procedures: modified Blessed Information-Memory-Concentration Test (BIMCT), 12-item Brief Smell Identification Test (BSIT), brain magnetic resonance imaging (MRI), and Positron Emission Tomography (PET) amyloid imaging with 11C-Pittsburgh compound B (11C-PiB).

Biomarkers.

Background: Inflammation is a risk factor for cognitive decline, mild cognitive impairment (MCI), and Alzheimer's disease (AD). While past research in laboratory settings suggests that inflammation relates to cognitive decline and MCI status, more research is needed to examine such associations in everyday life. The present work addressed this gap by examining MCI and gender stratified links between circulating inflammatory biomarkers and self-reported prospective memory (PM; i.

Biomarkers.

Background: In prior work we identified cortical resilience proteins associated with the linear trajectories of cognitive decline independent of the effects of neuropathology. Some of these proteins were associated with slower and some with faster cognitive decline. We tested the hypothesis that the temporal onset and duration of effects of cortical resilience proteins associated with cognitive trajectories may vary in aging adults.

Biomarkers.

Background: Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB), and other neurodegenerative diseases (NDD) develop over an extended preclinical period, sharing common risk factors and underlying pathophysiological mechanisms. Plasma proteins, including Amyloid-beta peptides (Aβ) and Tau isoforms, facilitate differential diagnosis of NDD in their earliest stages, allowing for timely delivery of targeted interventions. Blood-based biomarkers may also serve as a reliable means of monitoring disease progression and evaluating the effectiveness of individualized interventions across the spectrum of disease.

Biomarkers.

Background: Alzheimer disease (AD) related cognitive decline occurs at relatively young ages in individuals with Down syndrome (DS, early-mid 50s) and in those with autosomal dominant mutations (ADAD, 40-50s). Both groups show similar patterns of amyloid accumulation. We examined if brain volumes are similarly affected by AD pathology in individuals with DS and ADAD.

Biomarkers.

Background: Motoric Cognitive Risk (MCR) syndrome is a predementia syndrome characterized by slow gait and subjective cognitive concerns. Individuals with MCR are at high risk of transitioning to both Alzheimer's disease (AD) and vascular dementia. With chronological age, the incidence of MCR increases and MCR cases exhibit a higher prevalence of age-associated diseases.

Biomarkers.

Background: The hippocampus and its subfields in the human brain play a pivotal role in forming new memories and spatial navigation. The automated assessment of the hippocampus and its subfields are useful tools for the early diagnosis of Alzheimer's disease and other neurodegenerative diseases such as primary age-related tauopathy, Lewy body dementia, limbic-predominant age-related TDP-43 encephalopathy (LATE), and frontotemporal lobar Dementia. Postmortem brain magnetic resonance imaging plays a crucial role in neuroscience and clinical research, providing valuable insights into the structural and pathological features of the brain after death.

Biomarkers.

Background: Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia. Its underlying mechanisms remain elusive and specific mechanism-based drugs are lacking.

Method: We integrated more than 2,800 CSF and 4,600 plasma pQTL, derived from the largest proteomic studies so far (SOMAscan 7k and 4k; in up to 35,559 individuals), and the two most prevalent MRI-markers of cSVD (MRI-cSVD, white matter hyperintensities and perivascular spaces burden; in up to 48,454 individuals) in a Mendelian Randomization (MR) framework to identify causal and druggable targets for cSVD.

Biomarkers.

Background: Cardiovascular disease and dementia often co-exist at advanced stages. Yet, midlife longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health are scarce. We aimed to determine the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis and cardiovascular risk factors in middle-aged asymptomatic individuals.