Correlation Between VACS Index and Frailty in HIV+ People and How It Affects Cognition and Brain Volume

The human immunodeficiency virus (HIV) is a retrovirus that causes an infection within the immune system and can lead to acquired immunodeficiency syndrome (AIDS) if not properly addressed. While this disease specifically attacks the immune system, it also affects other systems, such as the brain. One major relationship we will be investigating is between HIV status and the Veterans Aging Cohort Study (VACS) index, which includes race, sex and other biomarkers such as CD4 count, viral load, hepatitis C infection, and hemoglobin. We hypothesize that there will be a strong correlation between the VACS index and frailty in those with HIV; we also predict there will be changes in cognition and brain volumes. Ninety-seven individuals between the ages of 50 and 77 completed neuropsychological testing and neuroimaging. The mean age for males is 57.2 (54% AA) and females is 56.11 (78% AA). The mean years of education for men is 13.8, and 12.4 for women. Individuals were divided into 3 groups based on their severity of frailty (Non-Frail, Pre-Frail, and Frail (N=19). In the present study, we propose to examine potential differences in neuropsychological scores and structural neuroimaging between these groups. Additionally, we will examine whether the VACS index is predictive of more severe frailty and worse cognitive outcomes and structural neuroimaging. Previous studies have shown that the VACS index is more predictive of mortality risks and frailty in older adults than HIV biomarkers alone. We plan to investigate if these indices are correlated to neuropsychological measures and neuroimaging

Amyloid-β and tau deposition influences cognitive and functional decline in Down syndrome

This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET

White matter microstructure associations to amyloid burden in adults with Down syndrome

INTRODUCTION: Individuals with Down syndrome (DS) are at an increased risk of developing Alzheimer\u27s Disease (AD). One of the early underlying mechanisms in AD pathology is the accumulation of amyloid protein plaques, which are deposited in extracellular gray matter and signify the first stage in the cascade of neurodegenerative events. AD-related neurodegeneration is also evidenced as microstructural changes in white matter. In this work, we explored the correlation of white matter microstructure with amyloid load to assess amyloid-related neurodegeneration in a cohort of adults with DS. METHODS: In this study of 96 adults with DS, the relation of white matter microstructure using diffusion tensor imaging (DTI) and amyloid plaque burden using [ RESULTS: TBSS of the DTI maps showed widespread age-by-amyloid interaction with both fractional anisotropy (FA) and mean diffusivity (MD). Further, diffuse negative association of FA and positive association of MD with amyloid were observed. DISCUSSION: These findings are consistent with the white matter microstructural changes associated with AD disease progression in late onset AD in non-DS populations

Impact of the COVID-19 pandemic on daily life, mood, and behavior of adults with Down syndrome

BACKGROUND: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome. OBJECTIVE/HYPOTHESIS: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome. METHODS: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged 22-66 years) located across the United States and in the United Kingdom enrolled in the Alzheimer\u27s Biomarker Research Consortium on Down Syndrome (ABC-DS) completed a survey. RESULTS: The residence of 17% of individuals was altered, and 89% of those who had been employed stopped working during the pandemic. One-third (33%) of individuals were reported to be more irritable or easily angered, 52% were reported to be more anxious, and 41% were reported to be more sad/depressed/unhappy relative to prepandemic. The majority of changes in mood and behavior were of modest severity. CONCLUSIONS: The COVID-19 pandemic has had widespread effects on the daily life and mood and behavior of adults with Down syndrome. In the short term, caregivers and providers should be prepared to help adults with Down syndrome with changes in daily routines, residence, employment, or adult disability day programs as society shifts away from COVID-19 safety protocols

Association of immunosuppression and viral load with subcortical brain volume in an international sample of people living with HIV

Importance: Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date. Objective: To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide. Design, Setting, and Participants: This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019. Main Outcomes and Measures: Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status. Results: After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3 per 100 cells/mm3; P \u3c .001) and thalamic (mean [SE] β = 32.24 [8.96] mm3 per 100 cells/mm3; P \u3c .001) volumes and larger ventricles (mean [SE] β = -391.50 [122.58] mm3 per 100 cells/mm3; P = .001); in participants not taking cART, however, lower current CD4+ cell counts were associated with smaller putamen volumes (mean [SE] β = 57.34 [18.78] mm3 per 100 cells/mm3; P = .003). A dVL was associated with smaller hippocampal volumes (d = -0.17; P = .005); in participants taking cART, dVL was also associated with smaller amygdala volumes (d = -0.23; P = .004). Conclusions and Relevance: In a large-scale international population of HIV-positive individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Our findings extend beyond the classically implicated regions of the basal ganglia and may represent a generalizable brain signature of HIV infection in the cART era

Physical activity affects brain integrity in HIV+ individuals

Prior research has suggested benefits of aerobic physical activity (PA) on cognition and brain volumes in HIV uninfected (HIV−) individuals, however, few studies have explored the relationships between PA and brain integrity (cognition and structural brain volumes) in HIV-infected (HIV +) individuals. Seventy HIV + individuals underwent neuropsychological testing, structural neuroimaging, laboratory tests, and completed a PA questionnaire, recalling participation in walking, running, and jogging activities over the last year. A PA engagement score of weekly metabolic equivalent (MET) hr of activity was calculated using a compendium of PAs. HIV + individuals were classified as physically active (any energy expended above resting expenditure, n = 22) or sedentary (n = 48). Comparisons of neuropsychological performance, grouped by executive and motor domains, and brain volumes were completed between groups. Physically active and sedentary HIV + individuals had similar demographic and laboratory values, but the active group had higher education (14.0 vs. 12.6 years, p = .034). Physically active HIV + individuals performed better on executive (p = .040, unadjusted; p = .043, adjusted) but not motor function (p = .17). In addition, among the physically active group the amount of physical activity (METs) positively correlated with executive (Pearson’s r = 0.45, p = 0.035) but not motor (r = 0.21; p = .35) performance. In adjusted analyses the physically active HIV + individuals had larger putamen volumes (p = .019). A positive relationship exists between PA and brain integrity in HIV + individuals. Results from the present study emphasize the importance to conduct longitudinal interventional investigation to determine if PA improves brain integrity in HIV + individuals

The AT(N) framework for Alzheimer\u27s disease in adults with Down syndrome

The National Institute on Aging in conjunction with the Alzheimer\u27s Association (NIA-AA) recently proposed a biological framework for defining the Alzheimer\u27s disease (AD) continuum. This new framework is based upon the key AD biomarkers (amyloid, tau, neurodegeneration, AT[N]) instead of clinical symptoms and represents the latest understanding that the pathological processes underlying AD begin decades before the manifestation of symptoms. By using these same biomarkers, individuals with Down syndrome (DS), who are genetically predisposed to developing AD, can also be placed more precisely along the AD continuum. The A/T(N) framework is therefore thought to provide an objective manner by which to select and enrich samples for clinical trials. This new framework is highly flexible and allows the addition of newly confirmed AD biomarkers into the existing AT(N) groups. As biomarkers for other pathological processes are validated, they can also be added to the AT(N) classification scheme, which will allow for better characterization and staging of AD in DS. These biological classifications can then be merged with clinical staging for an examination of factors that impact the biological and clinical progression of the disease. Here, we leverage previously published guidelines for the AT(N) framework to generate such a plan for AD among adults with DS

The Alzheimer\u27s Biomarker Consortium-Down Syndrome: Rationale and methodology

Introduction: Adults with Down syndrome (DS) are at exceptionally high risk for Alzheimer\u27s disease (AD), with virtually all individuals developing key neuropathological features by age 40. Identifying biomarkers of AD progression in DS can provide valuable insights into pathogenesis and suggest targets for disease modifying treatments. Methods: We describe the development of a multi-center, longitudinal study of biomarkers of AD in DS. The protocol includes longitudinal examination of clinical, cognitive, blood and cerebrospinal fluid-based biomarkers, magnetic resonance imaging and positron emission tomography measures (at 16-month intervals), as well as genetic modifiers of AD risk and progression. Results: Approximately 400 individuals will be enrolled in the study (more than 370 to date). The methodological approach from the administrative, clinical, neuroimaging, omics, neuropathology, and statistical cores is provided. Discussion: This represents the largest U.S.-based, multi-site, biomarker initiative of AD in DS. Findings can inform other multidisciplinary networks studying AD in the general population