Faculty Bibliography

INTRODUCTION/BACKGROUND:We assessed plasma biomarkers for the diagnosis of early Alzheimer's disease (AD). METHODS: = 45). Plasma assays for amyloid beta (Aβ) 40, Aβ42, neurofilament light chain protein, glial fibrillary acidic protein, and phosphorylated tau181 levels were measured using single molecule array (Simoa) technology. Neuroinflammation and blood-brain barrier (BBB) biomarkers were measured using the Corplex cytokine 10-Plex kit and the angiogenesis 6-Plex kit, respectively. RESULTS:Biomarker levels were regressed by cognitive group, age, sex, race, and apolipoprotein E apoE ε4 status, yielded significant positive associations between age and numerous AD, neuroinflammation, cytokine, and BBB plasma markers. DISCUSSION/CONCLUSIONS:Linear regression analysis, adjusted for age, sex, race, and ApoE status, revealed significant differences between cognitive groups in levels of several plasma biomarkers and associations with age and sex. Neuroinflammation and BBB dysfunction showed significant positive associations with age across different stages of AD.

BackgroundSubjective cognitive decline (SCD) is increasingly recognized in some cases as an early clinical stage in the Alzheimer's disease continuum, yet the factors that predict which individuals will progress to objective impairment remain poorly understood.ObjectiveWe evaluated risk factor differences and cognitive domain markers associated with progression in participants with subjective cognitive decline (SCD) at baseline from the NYU Alzheimer's Disease Research Center.MethodsWe included SCD non-decliners (n = 27), who remained stable, and decliners (n = 24), who progressed to mild cognitive impairment or worse, between the second to sixth yearly follow-up visits. Adjusted mixed-effects models examined group differences and associations between demographic, APOE status, psychometric test performance and comorbidities with longitudinal-decline.ResultsOverall, mean (SD) age was 67.4 (9.2) and total follow-up time was 5.1 (1.8) years. Lower education (14.9 (3.2) versus 17.3 (2.1)), Hispanic ethnicity (50.0% versus 11.0%), and hypercholesterolemia (adjusted odds ratio: 6.67) were risk factors for progression in SCD, p ≤ 0.05, whereas APOE status was not. Notably, SCD decliners were at increased risk for both amnestic and non-amnestic cognitive-decline with psychometric changes in memory, executive, and language domains (p < 0.001 for all).ConclusionsThese findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.

INTRODUCTION/BACKGROUND:Blood-brain barrier (BBB) dysfunction is an early feature of Alzheimer's disease (AD). Fibrinogen represents a sensitive marker of BBB leakage, but whether it modifies longitudinal tau progression in cognitively unimpaired (CU) individuals remains unknown. METHODS:CU older adults underwent clinical evaluation and cerebrospinal fluid (CSF) assessment of fibrinogen, Aβ42, total tau (tTau), phosphorylated tau 181 (pTau181), and YKL-40. Linear regression tested baseline associations. Linear mixed-effects models tested whether baseline fibrinogen predicted longitudinal pTau181 change. RESULTS:Among 169 CU participants with baseline fibrinogen, 87 had longitudinal pTau181 measurements (mean follow-up 2.5-years). Higher fibrinogen was associated with elevated YKL-40 (β = 0.28, 95% confidence interval [CI] [0.11, 0.45]) but not Aβ42, tTau, or pTau181 at baseline. Baseline fibrinogen modified longitudinal pTau181 trajectories (interaction β = 0.11, 95% CI [0.04, 0.19]), with only participants above the median showing significant pTau181 increases (β = 0.13, 95% CI [0.08, 0.18]). DISCUSSION/CONCLUSIONS:CSF fibrinogen associates cross-sectionally with glial inflammation and predicts accelerated tau accumulation in preclinical AD.

BACKGROUND/UNASSIGNED:Lifestyle interventions are effective in reducing cardiovascular disease (CVD) risk, but few target mothers of toddlers and preschool-aged children. Cardiovascular risk factors may emerge or worsen during this life stage due to high child-rearing demands, with the potential to persist long-term. We scoped the literature to synthesize findings and highlight future research opportunities regarding CVD prevention interventions among mothers of young children. METHODS/UNASSIGNED:We searched PubMed, Scopus, Web of Science, CINAHL, Embase, and APA PsycINFO for 2010-2024 peer-reviewed, English-language articles about CVD risk reduction lifestyle interventions for mothers with young children aged 1-5 years. Due to limited initial results, we broadened this demographic criterion to include mothers with children either <1-5 years (infants to young children) or 1-12 years (young to school-age children). RESULTS/UNASSIGNED:= 2). None addressed nicotine exposure nor sleep. Five studies reported statistically significant results for at least one of their outcomes. CONCLUSION/UNASSIGNED:Very few studies discuss lifestyle interventions for CVD prevention among mothers of young children, highlighting a salient gap and opportunities for additional research in this population.

INTRODUCTION/UNASSIGNED:Young Black children experience poorer sleep health than children from other racial/ethnic groups. Tailored family-centered interventions are needed to improve sleep health among young Black children. Tailoring requires information about parent perceptions, practices and context. The purpose of this study was to (1) understand the contextual definition of sleep health for Black families; (2) bedtime routines and sleep practices among Black families; and (3) parent preferences that may inform intervention design. METHODS/UNASSIGNED:We engaged 30 Black parents of 3-8-year-old children with mild sleep problems (e.g., child takes >30 min to fall asleep at bedtime) in this study. Parents completed three ratings scales about sleep health practices and child bedtime behavior and a semi-structured interview. Statistical analysis included descriptive statistics and correlations. We used an implementation science rapid qualitative analysis approach to analyze qualitative data from the interviews. RESULTS/UNASSIGNED:The final sample identified as 52% African-American, 14% Jamaican, 10% Haitian, and 26% mixed multi-ethnic groups. Parent mean age was 41 years and child mean age were 5 years old. About 80% of responders were women. About one-third of the sample held a doctoral degree, and half the sample had a bachelor's or Master's degree. Parents answered 56% of sleep knowledge questions accurately (ranging from 32 to 100%) and reported an average of two sleep problems. Parents described healthy sleep as involving flexibility in sleep timing and bedtime routines. More than half of parents reported co-sleeping practices, with reasons ranging from a strategy to address night wakings, to a way to preserve bonding. Later child bedtime (after 9 pm) was associated with bedtime resistance, permissive parenting, and parent stress. Many parents reported that they had poor sleep quality and duration. DISCUSSION/UNASSIGNED:Findings elucidate a range of factors to consider in tailoring sleep health interventions for Black families of young children. These include the common practice of co-sleeping, parents' value for flexibility related to bedtime and bedtime routines, and parents' own challenges with getting enough and good quality sleep. Tailored family-centered interventions will benefit from considering these factors.

Alzheimer's disease (AD) is characterised by the intraneuronal aggregation of phosphorylated Tau (pTau) into neurofibrillary tangles and by the extracellular deposition of β-amyloid (Aβ). Tau pathology restricted to the hippocampal formation is frequently observed in the elderly brain in the absence of any Aβ deposition and considered as "primary age-related tauopathy" (PART). Here, we applied an unbiased proteomic approach to determine how concomitant Aβ pathology modifies the neurofibrillary tangle proteome. Neurofibrillary tangles were isolated by dissecting Tau pSer202/pThr205 "AT8" immunopositive neuronal profiles, combining chromogenic immunohistochemistry with laser capture microdissection, from hippocampal sections of 17 post-mortem brains spanning three groups: PART (n = 5; A0, B1-2, C0 scores), intermediate AD (n = 6; A1-2, B2-3, C1-2 scores) and advanced AD (n = 6; A3, B3, C3 scores). A label-free quantitative liquid chromatography-mass spectrometry based proteomic analysis, using data independent acquisition (DIA) on a Bruker timsTOF, was performed. A conserved core of 63 proteins was identified as enriched in tangles across all groups, mostly associated with "RNA binding" and "regulation of mRNA metabolic process", based on the Gene Ontology database. Group-specific signatures were also observed: 33 proteins were significantly enriched only in tangles collected from PART cases and were predominantly linked to "structural molecule activity", whereas Aβ-positive cases showed specific enrichment of "RNA binding" and "cytoplasmic translation" pathways-with intermediate AD cases displaying a transitional profile. Our findings are consistent with PART having distinct tangle proteomic features; however, the majority of its proteomic signature is in common with tangles within the AD continuum. By addressing how Aβ accumulation alters the tangle proteome, this study provides mechanistic insights into the expansion of Tau pathology, paving the way towards the identification of biomarkers and therapeutic strategies that would allow for stabilisation of Tau pathology in the elderly.

Local community populations ("survivors") exposed to the World Trade Center (WTC) disaster experienced complex exposures to mixtures of dust and combustion products with potential carcinogenic effects. Survivors with certifiable WTC-related conditions are eligible for inclusion in the federally funded WTC Health Program. We provide an updated description of cancers in the WTC Environmental Health Center (EHC), a program for WTC survivors, through 31 December 2024. Using data from the WTC EHC Pan Cancer Database, we summarized demographics, exposure history, and tumor characteristics among enrollees with pathologically confirmed primary cancers meeting WTC Health Program certification criteria. Among 17,449 members, 7274 had a certifiable cancer diagnosis; excluding non-melanoma skin cancers, 6588 patients with 7643 eligible cancers were analyzed. Women comprised 50.3% of the cohort and 47.5% of diagnoses. Solid tumors accounted for 87% of certifications, with breast (22%) and prostate (19%) cancers most frequent, followed by lung (8%), thyroid (6%), colorectal (6%), and melanoma (4.5%). Lymphoproliferative and hematopoietic malignancies represented 13% of cases. Fourteen percent developed multiple primary cancers, and median latency clustered around 14-16 years. Compared with our previous report in 2020, the enrolled number of cancers increased 2.5-fold. These findings support the need for sustained surveillance and additional epidemiologic studies to improve cancer prevention and survivorship in this uniquely exposed population.

BackgroundPeople with subjective cognitive decline (SCD) are at increased risk of Alzheimer's disease. Prior research has suggested that amygdala volume may be more sensitive than hippocampal volume in detecting differences between SCD and age-matched controls, as well as in predicting SCD conversion to mild cognitive impairment. However, the microstructure underlying this volumetric change remains unclear.ObjectiveThis study evaluated amygdala microstructural differences in SCD versus control participants as well as associations between amygdala microstructure and volume, age, memory performance, anxiety, and depression using diffusion imaging.MethodsDiffusion tensor imaging, diffusion kurtosis imaging, and neurite orientation dispersion and density imaging were fit to diffusion MRI images. Group differences and correlations between diffusion metrics, age, memory, anxiety, and depression were assessed in 123 SCD versus 194 age-matched controls over age 55.ResultsIn the left amygdala, SCD participants had significantly lower fractional anisotropy (FA), lower kurtosis fractional anisotropy (KFA), and higher free water fraction (FWF). KFA was lower in the right amygdala in SCD. There were no significant group differences in the amygdala volume. Bilateral KFA negatively correlated with FWF, a marker of neuroinflammation and neurodegeneration. Left FA negatively correlated with orientation dispersion index, a marker of neuritic branching. Right KFA correlated with age only in SCD, while left FA correlated with anxiety only in controls.ConclusionsKFA is sensitive to group differences between SCD and controls in bilateral amygdala. KFA may reflect neuroinflammation and increased sensitivity to aging in the amygdala in SCD.

BACKGROUND:While there is evidence of the benefits of healthy maternal lifestyle behaviors (eg, physical activity plus a healthy diet) on cardiometabolic health, there are limited data on the independent association between physical activity and cardiometabolic health among women with a history of gestational diabetes mellitus (GDM). OBJECTIVE:In this study, our aim was to explore the association between device-assessed physical activity and cardiometabolic outcomes in Chinese American women, a group disproportionately affected by GDM and type 2 diabetes. METHODS:A cross-sectional study was conducted among 33 Chinese American women (0.5-5 years after delivery) with a history of GDM in New York City in 2023 to 2024, in which we collected their device-assessed physical activity data, online survey data (in Mandarin and English), and cardiometabolic data (via fasting blood samples). Descriptive, unadjusted, and adjusted regression analyses were performed. RESULTS:Participants' mean age was 38.2 ± 3.3 years (2.6 ± 1.5 years after delivery), and body mass index was 23.5 (interquartile range: 21.7-25.1) kg/m 2 . Among the 33 participants, 27.3% had prediabetes, 51.5% had lipid dysregulation, and 21.2% had elevated blood pressure. The duration of moderate-to-vigorous physical activity per week was 132.4 (interquartile range: 90.5-272.0) minutes, and 46.9% of the cohort met the physical activity recommendation of ≥150 minutes moderate-to-vigorous physical activity per week. In regression models, meeting the physical activity recommendations was inversely associated with total cholesterol (-27.6 ± 12.7 mg/dL) and low-density lipoprotein cholesterol (-25.5 ± 10.6 mg/dL) levels (both P <.04). CONCLUSIONS:The majority of participants engaged in suboptimal physical activity levels. However, meeting physical activity recommendations was associated with better total and low-density lipoprotein cholesterol levels. Targeting physical activity may be a key strategy for improving cardiometabolic health in Chinese American women recently diagnosed with GDM.

OBJECTIVES/OBJECTIVE:There is increased recognition of the importance of hearing ability in social connectedness and healthy aging. Hearing loss is common among Veterans, and hearing rehabilitation is prioritized within the Veterans Administration (VA). Despite the attention to hearing care in the VA, limited data on cochlear implant (CI) utilization raises concern about whether this transformative and accessible treatment is reaching Veterans who could be helped with communication to improve their quality of life. The overall hypothesis is that Veterans with severe hearing loss, despite having unique rehabilitative needs, are not consistently treated as a distinct population. In this article, we identify patterns associated with specific management strategies for Veterans with severe hearing loss and describe the utilization of CIs in the VA as an evidence-based strategy when hearing aids provide limited benefit. DESIGN/METHODS:We investigated rehabilitation strategies used for Veterans with severe hearing loss. We defined a population-based cohort of 213,285 United States Veterans with newly diagnosed bilateral severe or worse hearing loss from January 1, 2006, to December 31, 2023. Severe hearing loss was defined as having a 4-frequency pure tone average (0.5, 1, 2, and 4 kHz) ≥70 dB HL in both ears. Speech perception abilities were also collected. We related hearing rehabilitation treatment of Veterans to factors hypothesized to impact care, including audiologic results, sociodemographic characteristics, comorbidities, and geography. Main outcomes included the receipt of CI and the cumulative incidence of CI. We used a competing risks framework to determine the factors associated with CI receipt. RESULTS:Of the 213,285 Veterans with bilateral severe or poorer hearing loss (mean age [SD], 80.3 [9.7]), 202,949 (95.2%) were fit with hearing aids, 5335 (2.5%) had a CI procedure, and 5001 (2.3%) had no evidence of receiving hearing rehabilitation. The 5- and 10-yr cumulative incidence (95% confidence interval) of receipt of CI was 1.9% (1.8 to 2.0%) and 2.9% (2.8 to 3.0%), respectively (death treated as a competing risk). In competing risks regression, age, race and ethnicity, VA priority group, word recognition score (WRS), hearing loss severity, the year hearing loss was first identified, and a greater number of comorbidities were all significantly associated with the receipt of CI. Patient age, word recognition score, and hearing loss severity were found to be the most important predictors of CI receipt based on concordance loss. CONCLUSIONS:Most Veterans with severe hearing loss and poor speech understanding, who are likely to be audiologic candidates for CIs, are treated with hearing aids, whereas relatively few receive CIs. The treatment approach may be driven by several different factors specific to the Veteran, site of care, and VA policies. A multifaceted strategy and care delivery may be required to improve evidence-based care for those with severe hearing loss.