Globally, the burden of dementia profoundly affects low- and middle-income countries (LMICs), with a greater burden and risk for late-life women than men. Structural and social determinants of health, crucial constructs conferring risk and protection from later-life dementia, are relatively understudied, yet essential in LMICs. Typical neuroscience studies have historically been small, with highly selected samples that do not generalize well to target populations in LMICs. To better understand gender and sex differences in dementia risk in LMICs, this Perspective lays out a guiding framework for a global dementia research plan—the Population Neuroscience-Dementia Syndemics Framework. Population neuroscience considers the brain in a multilevel context, from a lifecourse perspective, using tools to enhance internal and external validity, while syndemics suggest that diseases and social conditions may cluster and interact in populations with syndemic risk factors—sociocultural, political, economic, and environmental factors that promote stress pathways and disease. This Perspective proposes the Population Neuroscience-Dementia Syndemics Framework and model to develop knowledge of how multiple factors may interact to perpetuate inequities in dementia, especially for women in low- and middle-income countries.

(1) Substance use disorder (SUD) is a global issue, which affects people for their physical and mental health. However, it remains unclear about how SUD is associated with cognitive impairment. (2) A literature search was performed across PubMed, Web of Science, and Google Scholar using keywords: cognitive impairment, cognitive dysfunction/prevention and control, behavior, addictive/prevention and control, substance use disorder, addictive/rehabilitation, and recovery. Data from 20 original research studies were extracted to analyze how SUD is associated with cognitive functions. (3) All substances, including tobacco, are associated with a measured decrease in cognitive function in at least one domain. The longer the duration of substance use, especially if multiple substances were used concurrently, the worse the cognitive performance. Abstinence, targeted medication, or cognitive remediation therapy can be used to treat SUD and associated cognitive impairments. (4) Cognitive function should be a focus for rehabilitation programs. For people with SUD, cognitive impairments may hinder them from seeking available treatment options. On the other hand, improved cognitive function may increase the possibility of successful rehabilitation for people with SUD.

Cognitive impairment still occurs despite well-controlled HIV but with milder symptoms. People with and without HIV have different neuronal protein changes that may differentiate the asymptomatic neurocognitive impairment (ANI) condition from normal cognition (NPN) and mild neurocognitive disorder (MND). Plasma neuronal-enriched extracellular vesicles (nEVs) were isolated from people with HIV (PWH) with NPN, ANI, or MND, and HIV seronegative controls with NPN (HIV−). Two different platforms were used to delineate protein patterns between sexes and cognitive conditions. When combining results from men and women, the nEV cargo in many cases showed little difference between cognitive conditions. However, when separated, there were different patterns between the sexes for some nEV cargo that distinguished the HIV− groups and HIV+ cognition groups. PWH with NPN had higher nEV toxic proteins compared to individuals without HIV. Women with HIV showed perfect separation between NPN and ANI with Aβ42 and NCAM-1 and perfect separation between ANI and MND with Aβ40 and NCAM-1. Men with HIV with MND had significantly higher NCAM-1 when compared to ANI, and lower GLRX when compared to NPN. This study shows distinct markers for different HIV cognitive categories, many of which differed between men and women.

Background/Objectives: Individual plasma protein biomarkers have been shown to correlate with cognitive performance in people with HIV (PWH). This study aimed to investigate the association between plasma proteomic signatures and attention/working memory in virologically well-controlled women with HIV (WWH). Methods: Seventy-seven WWH from three Women’s Interagency HIV Study (WIHS) sites completed neuropsychological (NP) testing and a blood draw. Selected protein biomarkers (200 total) were analyzed using a multiplexing method. Results: Random forest analysis was used to identify the top 10 biomarkers that were each positively or negatively associated with attention/working memory. Ingenuity pathway analysis (IPA) was used to facilitate data interpretation. Tumor necrosis factor receptor 1 (TNF RI), TNF RII, interleukin 1 receptor 1 (IL-1RI), and IL-6R were negatively associated with attention/working memory. Conclusions: Based on the IPA, two gene signaling networks were proposed for associating these plasma protein biomarkers with attention/working memory function. This novel methodology demonstrates how gene networks can be identified using blood draws in conjunction with cognitive assessment, and then used in random forest analysis, to derive value that can be put in IPA.

Individual plasma protein biomarkers have been shown to correlate with cognitive performance in people with HIV. This study aimed to investigate the association between plasma proteomic signatures and cognition in virologically well-controlled women with HIV. 77 women with HIV from three Women's Interagency Study (WIHS) sites completed neuropsychological testing and a blood draw. Targeted protein biomarkers were analyzed using a multiplexing method. Random forest analysis was used to identify the top 10 biomarkers that positively or negatively associated with domain-specific or global neuropsychological function. Next, ingenuity pathway analysis was used to facilitate data interpretation. Plasma protein biomarkers are either related to domain-specific or overall cognition: tumor necrosis factor receptor 1 (TNF RI), TNF-RII, interleukin 1 receptor 1 (IL-1RI), and IL-6R are negatively associated with attention/working memory; IL-7 and CD40 are positively associated with executive function; IL-1RI, hepatocyte growth factor (HGF), transforming growth factor beta-1(TGFβ1), TGFβ2, and sonic hedgehog (SHH) are negatively associated but IL-7 is positively associated with fluency; IL-9, IL-15, and IL-21R are positively associated with motor function; Brain-derived neurotrophic factor (BDNF), HGF, SHH, and vascular endothelial growth factor (VEGF) are negatively associated with processing speed. HGF, VEGF, and insulin are negatively associated with global neuropsychological function. Based on the ingenuity pathway analysis, one to three signaling networks were proposed for associating plasma biomarkers with each domain-specific or global neuropsychological function. It is likely that a panel of plasma protein biomarkers can be used to predict domain-specific or global neuropsychological function. Multiple signaling networks might explain cognitive functions in Women with HIV.

Cognitive intra-individual variability (IIV) is a sensitive marker of neuropathology and is increased in people with HIV (PWH). In a sample of PWH from the United States Deep South, we examined the relationship of cognitive IIV with cognitive impairment and social determinants of health (SDoH). This secondary analysis included 131 PWH from a larger cognitive training protocol. Our primary outcome measure was the coefficient of variation (CoV). We also included the individual standard deviation (iSD), with both calculated from demographically adjusted T-scores and unadjusted sample-based scores. Mixed-effects models investigated the relationship between IIV and cognitive impairment severity (i.e., Global Rating Score), SDoH, and clinical variables. Bivariate correlations were used to further explore these relationships. Greater cognitive IIV was associated with greater cognitive impairment in PWH, when accounting for demographic factors. When IIV is calculated from the sample, then IIV is no longer associated with cognitive impairment, but is associated with race (>IIV in Black and African American participants). Demographically adjusted IIV is associated with global cognition, Wide Range Achievement Test-Fourth Edition reading score, and viral load (iSD only). No correlations were significant when using the unadjusted sample-based IIV metrics. In PWH from the Deep South, greater cognitive variability is seen in those with greater cognitive impairment, in Black participants, and in those with lower reading scores. Further research on the psychometric properties of IIV in HIV and other populations is needed, as results varied depending on the normative adjustments.

Substance use recovery is a multifaceted process influenced by psychological, physiological, and social factors. Stress remains a critical barrier to sustained recovery, particularly among elderly individuals who may face compounded challenges due to age-related vulnerabilities. Understanding age-related stress in recovery populations can inform targeted interventions and improve program efficacy. Demographic information and vital signs were collected from participants aged from 20 to 80 years old. Stress was assessed using a standardized questionnaire. Correlation analyses was done between demographic factors or vital signs and stress scores using the SPSS. p < 0.05 was considered significant. Age was positively correlated with systolic blood pressure (r = 0.235, p = 0.03) and diastolic blood pressure (r = 0.258, p = 0.017), indicating higher blood pressure levels in older participants. Conversely, heart rate showed a negative correlation with age (r = −0.216, p = 0.046). Psychological stress negatively correlated with age and older individuals reported lower levels of perceived stress as indicated by the following negative correlations: 1. feeling nervous or stressed (r=-0.369, p < 0.001); 2. feeling unable to control important things (r=-0.256, p = 0.017); 3. perceived helplessness (r=-0.286, p = 0.008); Total stress score (r=-0.25, p = 0.02). In conclusion, age is a significant factor influencing stress in individual enrolled in a local substance abuse recovery program. These findings underscore the need for age-sensitive approaches in substance use recovery services and highlight the importance of continuous psycho-social support.

Background Cognitive impairments have been reported among disadvantaged populations. Objective We aimed to ascertain how demographic factors are associated with cognitive performance in individuals enrolled in a local substance abuse recovery program. Methods In total, 106 participants were included in the study. Besides demographic information, vital signs and cognitive function, measured by Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA), were collected from each participant. Welch's t-test and regression analysis were used to analyze how different demographic factors are associated with cognitive assessment scores. Results The mean age of African American (AA) participants (n = 43) were 48.35 ± 1.65 years, which are older than that for the White participants of 38.95 ± 1.36 (n = 63) years. Compared to the AA participants, the White participants had a larger variance in attained education levels. The average MMSE scores were 27.09 ± 0.40 for AA participants, which is lower than that for the White participants of 28.52 ± 0.33 ( p < 0.05). The average MoCA scores were 23.71 ± 0.54 for AAs, which is lower that for the White participants of 26.65 ± 0.44 ( p < 0.001). The AA and White participant groups had cognitive impairment rate of 18.6% and 6.35%, respectively. The regression analysis indicates age and education are two significant predictors for the cognitive performance difference between the two racial groups. Conclusions Significant disparities in cognitive performance exist between two racial groups of enrolled in a local substance abuse recovery program. The older age and lower levels of attained education in AA participants can explain the poorer cognitive function than the White participants.

Differentiation of human embryonic stem cells (hESCs) into human embryonic stem cells-derived parathyroid-like cells (hESC-PT) has clinical significance in providing new therapies for congenital and acquired parathyroid insufficiency conditions. However, a highly reproducible, well-documented method for parathyroid differentiation remains unavailable. By imitating the natural process of parathyroid embryonic development, we proposed a new hypothesis about the in vitro differentiation of parathyroid-like cells. Transcriptome, differentiation marker protein detection and parathyroid hormone (PTH) secretion assays were performed after the completion of differentiation. To optimize the differentiation protocol and further improve the differentiation rate, we designed glial cells missing transcription factor 2 (GCM2) overexpression lentivirus transfection assays and constructed hESCs-derived parathyroid organoids. The new protocol enabled hESCs to differentiate into hESC-PT. HESC-PT cells expressed PTH, GCM2 and CaSR proteins, low extracellular calcium culture could stimulate hESC-PT cells to secrete PTH. hESC-PT cells overexpressing GCM2 protein secreted PTH earlier than their counterpart hESC-PT cells. Compared with the two-dimensional cell culture environment, hESCs-derived parathyroid organoids secreted more PTH. Both GCM2 lentiviral transfection and three-dimensional cultures could make hESC-PT cells functionally close to human parathyroid cells. Our study demonstrated that hESCs could differentiate into hESC-PT in vitro, which paves the road for applying the technology to treat hypoparathyroidism and introduces new approaches in the field of regenerative medicine.

BACKGROUND:Alcohol use disorder (AUD) is a worldwide problem. The AUD can take the form of hazardous drinking, binge drinking, or alcohol dependence. The effects of alcohol on cognition can be diverse and complex.OBJECTIVE:Our study aimed to assess AUD as a risk factor for cognitive impairment.METHODS:A literature search was conducted using major electronic databases of PubMed, EMBASE, and Web of Science. Abstracts were screened independently to include data from original research reports. The following keywords were used: alcohol abuse, cognitive impairment, Alzheimer's disease, and dementia. In total, 767 abstracts were retrieved. After removing the duplicates, 76 articles met the criteria for full-text review, of which 41 were included in this report.RESULTS:People with AUD are seen from different geographical areas and cultures. AUD is associated with an increased risk of cognitive impairments, Alzheimer's disease, and dementia, especially vascular dementia. In addition, AUD interacts with comorbidities increasing the risk of cognitive impairment.CONCLUSION:AUD is associated with an increased risk of cognitive impairments, which may have more than one underlying mechanism.

Mild to moderate forms of neurocognitive impairment persist among people living with HIV (PLWH), despite being virally suppressed on antiretroviral therapy. PLWH are disproportionally impacted by physiological and psychosocial comorbidities compared to those without HIV. As adults live longer with HIV, the neurocognitive burden of physiological and psychosocial stressors can impair everyday functioning and may contribute to the development of neurodegenerative diseases such as Alzheimer's disease. This article outlines neurocognitive consequences of everyday stressors in PLWH. While some lifestyle factors can exacerbate inflammatory processes and promote negative neurocognitive health, novel interventions including the use of cannabinoids may be neuroprotective for aging PLWH who are at risk for elevated levels of inflammation from comorbidities. Studies of integrated neurocognitive rehabilitation strategies targeting lifestyle factors are promising for improving neurocognitive health, and may over time, reduce the risk of Alzheimer's disease in PLWH.

Subjective and objective cognitive impairments in Breast Cancer Survivors (BCS) often do not correlate. One important contribution to the reported disparities may be the reliance on mean-based cognitive performance. Cognitive intra-individual variability (IIV) may provide important insights into these reported disparities. Cognitive IIV refers to the fluctuation in performance for an individual on either one cognitive task across a trial or dispersed across tasks within a neuropsychological test battery. The purpose of this systematic review was to search for and examine the literature on cognitive IIV in BCS. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach was used to search for all articles related to cognitive IIV in BCS. MEDLINE (via PubMed), Embase, and Scopus databases were searched using detailed search terms and strategies. Initially, 164 articles were retrieved but only 4 articles met the criteria for this systematic review. BCS differed from healthy controls in similar ways across the four studies, generally demonstrating similar performance but showing increased cognitive IIV for the more difficult tasks. Differences were enhanced later during chemotherapy. The four studies provide support for cognitive IIV as a useful measure to detect the subtle objective cognitive change often reported by BCS but frequently not detected by standard normed-based cognitive testing. Unexpectedly, measures of cognitive IIV were not consistently associated with self-reported measures of cognition.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

Background and Purpose An active lifestyle is important for health maintenance and disease prevention. This study was to examine what factors predict an active lifestyle in HIV+ and HIV- adults from the United States Deep South. Methods The sample included 279 participants (174 HIV+ and 105 HIV-) who completed a comprehensive assessment. An active lifestyle composite was created using variables of employment status, level of social support, level of physical activity, and diet. Correlations and regression analyses were conducted between the active lifestyle composite and possible predictors for all (HIV+ and HIV-), HIV+, and HIV- participants, respectively. Results Lower levels of depression, higher socioeconomic status (SES), and younger age were significant predictors of a more active lifestyle for the full sample, HIV+, and HIV- participants, respectively. Conclusion SES and depression represent important factors influencing engagement in an active lifestyle in PLWH. Such factors should be considered when developing and implementing lifestyle interventions.

Cognitive impairments have been endemic to the HIV epidemic since its beginning and persist to this day. These impairments are attributed to HIV-induced neuroinflammation, the long-term effects of combination antiretroviral therapy, lifestyle factors (e.g., sedentary behavior, substance use), neuro-comorbidities (e.g., depression), age-associated comorbidities (e.g., heart disease, hypertension), and others causes. Normal aging and lifestyle also contribute to the development of cognitive impairment. Regardless of the etiology, such cognitive impairments interfere with HIV care (e.g., medication adherence) and everyday functioning (e.g., driving safely, financial management). With more than half of people with HIV (PWH) 50 years and older, and similar to 45% of all PWH meeting the criteria for HIV-Associated Neurocognitive Disorder (HAND), those aging PWH are more vulnerable for developing cognitive impairment. This article provides an update to a social work model to identify and monitor PWH for cognitive impairment. Within this update, the state of the science on protecting brain health and cognitive reserve within the context of neuroHIV is also presented. From this, implications for practice and policy to promote successful cognitive functioning in older PWH are provided.

Background: Lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) are collectively called macular pigment. MZ can be converted from L in the macula. In the recent decade, many studies have been performed to investigate the effects for taking carotenoids, especially L and Z or L, Z, and MZ, as diet supplements on human health. Objective: We examined if diet supplements of L+ Z or L+ Z+ MZ have effects on cognitive function in adults. Methods: A systemic literature search was performed in March 2021 with the following keywords: lutein, zeaxanthin, meso-zeaxanthin, cognition, cognitive, and macular pigment. The searched databases included Medline EBSCOhost, Scopus, Elsevier, Cochrane Library, ProQuest, and ClinicalTrials.gov. Findings from eight clinical trials were presented as the strongest evidence on the studied topic. Results: Most studies have found that macular pigments (L + Z) in blood or macula are positively correlated with cognitive performance. As an index of the amount of macular pigments in the brain, macular pigment optical density is related to cognitive performance in adults. In addition, there is an inverse relationship between a higher amount of macular pigment in the blood and lower risk of mild cognitive impairments or Alzheimer's disease. Based on the findings from the clinical trials, diet supplements of L+ Z or L+ Z+ MZ are associated with improved cognition in adults. Conclusion: The diet supplements of L+ Z or L + Z+MZ are associated with better cognitive functioning, which may be via their beneficial effects on the vision.

Byun, Jun Y. MSN; Azuero, Andres PhD; Fazeli, Pariya L. PhD; Li, Wei PhD; Chapman Lambert, Crystal PhD, CRNP; Del Bene, Victor A. PhD; Triebel, Kristen PsyD, ABPP; Jacob, Alexandra MS; Vance, David E. PhD, MGS Author Information

Introduction Homelessness is associated with an increased risk of cardiometabolic morbidities. However, few studies have been performed to evaluate the racial differences on these morbidities commonly seen in the homeless. Methods A retrospective chart review was conducted to examine the racial differences in the prevalence of cardiometabolic morbidities among the homeless men served at a local health care screening clinic. Medical information was extracted and collated into a single Excel spreadsheet. Racial differences in cardiometabolic morbidities were evaluated using multivariable binary or ordinal logistic regression analyses, adjusting for age, body mass index, and smoking status. Results Of the 551 homeless men, 377 (68.4%) were Black, and 174 (31.6%) were White. The mean age (47.8±11.9 years) of Black homeless men was significantly older than that (45.4±13.0 years) of White homeless men ( p =0.03). Blacks were 2.7 (95% CI = 1.75, 4.16) times more likely to be in the less desirable HbA1c categories than Whites. By contrast, Blacks were less likely to have non-desirable lipid profile than Whites. Blacks were 0.42 (95% CI = 0.29, 0.62) times and 0.51 (95% CI = 0.28, 0.94) times likely to be in the non-desirable high-density lipoprotein (HDL) and low-density lipoprotein (LDL) categories than Whites, respectively. Conclusion Black homeless men are more likely to have pre-diabetes or diabetes than White counterparts. On the other hand, Black homeless men have better lipid profiles of HDL or LDL than their White counterparts. Our findings reveal the health challenges of the homeless men and can provide guidance on policy changes related to diet and nutrition of meal programs provided by homeless shelters and congregate meal program to address the health disparities by race in this population.

Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are two commonly used cognitive screening and diagnostic tools. At baseline, participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were divided into four groups based on their cognitive diagnoses: healthy control (HC), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and Alzheimer’s Disease (AD). MMSE or MoCA scores were compared among the four groups using one-way analysis of variance (ANOVA) model with post-hoc Bonferroni correction. For those participants who had both MMSE and MoCA assessments done, a Pearson correlation analysis was performed between the two assessments for each visit. The MMSE scores were significantly different among the four groups at baseline, which was true for each of the three annual follow-up visits. By contrast, the MoCA scores were not significantly different between HC and EMCI groups at either baseline or any of the follow-up visits. For participants with a diagnosis of LMCI, the cognitive performance deteriorated in a linear manner 12 months after the baseline, which was independent of MMSE or MoCA. At last, the MMSE scores were moderately related to MoCA scores, which got stronger along with the time of follow-up. MMSE and MoCA are comparable as cognitive assessment tools to monitor cognitive changes. In addition, the measurements of MMSE and MoCA are moderately correlated for the follow-up visits.