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Background: Carotenoids, potent antioxidants in fruits and vegetables, have recently garnered attention for their potential therapeutic effects against neurodegenerative diseases. This study focuses on the interaction and anti-aggregation properties of conventional and unconventional carotenoids found in red mamey fruit, a nutraceutical fruit that is a rich source of these compounds. Objective: To assess computational the interaction between of amyloid-β (Aβ) peptide with a set of carotenoids and three carotenoids previously explored in experimental assays as well as to assess ADMET prediction of carotenoids selected by computational analysis results. Methods: We analyzed the interaction between these carotenoids and Aβ peptides using molecular docking, a key factor in Alzheimer's disease (AD) pathology. Selected carotenoids were compared with the reference compounds cryptocapsin (1), zeaxanthin (2), lutein (3), and cryptocapsin-5,6-epoxide (24), which previously demonstrated significant anti-aggregation activity against Aβ. Using SwissADME and ADMET Predictor® software to determine the pharmaceutical analysis prediction. Results: Computational analysis identified (5R,8R)-sapotexanthin-5,8-epoxide (19) and (5S,8S)-cryptocapsin-5,8-epoxide (26) as the most promising candidates due to their strong binding affinity and potential anti-aggregation properties against Aβ. The pharmaceutical analysis identified compounds (5S,8S)-cryptocapsin-5,8-epoxide (26) and (5R,8R)-cryptocapsin-5,8-epoxide (28) as the most promising compounds. Our findings suggest that specific modifications in the carotenoid structure, particularly modifications in the type of epoxidation and stereochemistry, can significantly influence the biological activity of carotenoids and biopharmaceutical performance. Conclusions: These results provide valuable insights for future in vitro studies of most potential carotenoids (19 and 26) and the development of potential therapeutic agents for AD. [ABSTRACT FROM AUTHOR]

The population of Hispanic older adults is growing along with the burden of chronic diseases. This cross-sectional study aims to assess the factors associated with frailty among community-dwelling Hispanic women aged ≥60 years (n = 357) enrolled in the Panama Aging Research Initiative—Health Disparities study of cognitive-functional health of older persons in Panama. Cognitive function was assessed with a neuropsychological test battery. Depression was measured with the Geriatric Depression Scale. Frailty was defined using the Fried criteria and participants were classified as non-frail, pre-frail or frail. A subsample (n = 281) provided fasting blood samples for quantification of protein biomarkers. Associations were examined using hierarchical multiple linear regressions. 59.4% and 9.0% of participants (M = 69.2 years, SD = 6.3) were pre-frail and frail, respectively. Having more depression (β =.28, p <.001) was significantly associated with frailty, even after covariate adjustment. Cognitive function was not associated with frailty. Higher pTau181 levels were associated with increased frailty (β =.13, p =.039), whereas higher α2M levels were associated with decreased frailty (β = −.16, p =.004). These findings advance the search for health indicators and biomarkers of frailty and warrant further studies to decrease the burden of frailty among older Hispanic women. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence points to potential risks associated with polypharmacy (using ≥5 medications) in older adults, but most evidence is derived from studies where racial and ethnic minorities remain underrepresented among research participants. Objective: Investigate the association between polypharmacy and cognitive function, subjective health state, frailty, and falls in Hispanic older adults. Methods: Panama Aging Research Initiative–Health Disparities (PARI-HD) is a community-based cohort study of older adults free of dementia at baseline. Cognitive function was measured with a neuropsychological test battery. Frailty assessment was based on the Fried criteria. Subjective health state and falls were self-reported. Linear and multinomial logistic regression analyses were used to examine association. Results: Baseline evaluations of 468 individuals with a mean age of 69.9 years (SD = 6.8) were included. The median number of medications was 2 (IQR: 1–4); the rate of polypharmacy was 19.7% (95% confidence interval [CI] = 16.1–23.3). Polypharmacy was inversely associated with self-rated overall health (b =−5.89, p < 0.01). Polypharmacy users had 2.3 times higher odds of reporting two or more falls in the previous 12 months (odds ratio [OR] = 2.31, 95% CI = 1.06–5.04). Polypharmacy was independently associated with Fried's criteria for pre-frailty (OR = 2.90, 95% CI = 1.36–5.96) and frailty (OR = 5.14, 95% CI = 1.83–14.42). Polypharmacy was not associated with cognitive impairment. Conclusions: These findings illustrate the potential risks associated with polypharmacy among older adults in Panama and may inform interventions to improve health outcomes in this population. [ABSTRACT FROM AUTHOR]

The Panama Aging Research Initiative is a cohort study of 423 adults aged ≥65 years recruited from an outpatient geriatric department of Panama's largest public hospital, the Social Security Fund's Dr Arnulfo Arias Madrid Hospital Complex (Complejo Hospitalario Dr Arnulfo Arias Madrid de la Caja de Seguro Social). The study provides the first reports of modifiable and non-modifiable risk factors of cognitive impairment and dementia, as well as various health conditions common among older adults in Panama, including chronic illnesses, polypharmacy and rates of comorbidity. The initial study, conducted September 2012-May 2016, included a clinical interview; physical assessments of body mass index and handgrip strength; and cognitive testing, plus non-fasting blood draws for measurements of genetic (Apolipoprotein E genotype) and blood-based biological markers. Information was collected regarding limitations in activities of daily living, symptoms of depression and fall incidents. A subsample of participants provided cerebrospinal fluid to measure proteins related to Alzheimer's disease; another subsample underwent ultrasonography and electroencephalography. This report describes the general study design and highlights lessons learned and future directions. In particular, drawing on lessons learned from this clinical research, a community-based prospective cohort study is currently under way among older adults in Panama to validate a blood-based biomarker profile for detecting mild cognitive impairment and Alzheimer's disease, as well as risk factors for cognitive decline. [ABSTRACT FROM AUTHOR]

Vascular pathology and genetic markers such as apolipoprotein E allele ε4 (ApoE ε4) are risk factors for the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). In Panama, a high prevalence of vascular risk factors and an increase in the aging population, generate the need to investigate biomarkers using specific, sensitive, non-invasive and cost-efficient methods that could be used in primary care. The main objective of this study was to explore the association between vascular biomarkers such as intima-media thickness (IMT) and stenosis, ApoΕ ε4 and cognitive function in a sample of older adults, including healthy controls (n = 41), MCI (n = 33), and AD (n = 12). A descriptive and cross-sectional study was conducted. Participants were part of the Panama Aging Research Initiative (PARI), the first prospective study in aging in Panama. Assessments included a neuropsychological battery, ApoΕ ε4 genotyping and a Doppler ultrasound of the left carotid artery to examine the presence of vascular risk factors. Neuropsychological tests were combined to form six cognitive domains: Global cognition, language, visuospatial abilities, learning and memory, attention and executive functions. Multivariable analyses (using age, education, and ApoE ε4 expression as covariates) were conducted. Participants with increased IMT showed poorer performance in memory and those with carotid stenosis showed poorer performance in language, visuospatial abilities and attention, independent of age, education or ApoΕ ε4 expression. The results support the use of vascular markers in cognitive assessments of aged individuals. [ABSTRACT FROM AUTHOR]

Cocaine self-administration increases expression of GluAl subunits in ventral tegmental area (VTA) dopamine neurons, which subsequently enhance the motivation for cocaine. This increase in GluAl may be dependent on concomitant NMDA receptor (NMDAR) activation during self-administration, similar to cocaine-induced long-term potentiation in the VTA. In this study, we used viralmediated expression of a dominant-negative GluNl subunit (HSV-dnGluNl) in VTA neurons to study the effect of transient NMDAR inactivation on the GluAl increases induced by chronic cocaine self-administration in male rats. We found that dnGluNl expression in the VT A limited to the 3 weeks of cocaine self-administration prevents the subsequent increase in tissue GluAl levels when compared with control infusions of HSV-LacZ. Surprisingly, dnGluN 1 expression led to an enhancement in the motivation to self-administer cocaine as measured using a progressive ratio reinforcement schedule and to enhanced cocaine seeking measured in extinction/reinstatement tests following an extended 3 week withdrawal period. Despite blocking tissue GluAl increases in cocaine self-administering animals, the HSV-dnGluN 1 treatment resulted in increased membrane levels of GluA 1 and GluN2B, along with markedly higher locomotor responses to intra-VTA infusions of AMPA, suggesting a paradoxical increase in VTA AMPA receptor responsiveness. Together, these data suggest that NMDARs mediate cocaine-induced increases in VTA GluAl expression, but such transient NMDAR inactivation also leads to compensatory scaling of synaptic AMPA receptors that enhance the motivational for cocaine. [ABSTRACT FROM AUTHOR]

Background: The Panama Aging Research Initiative (PARI) is a longitudinal study of more than 800 adults aged 60 years and older. The objective of this analysis consists of identifying the effects of Apolipoprotein E (ApoE) gene as a risk factor for sporadic Alzheimer's disease (AD), with elevated risk for ε4‐carriers and reduced risk for ε2‐carriers. Method: Our ongoing community‐based cohort (n = 400) has undergone clinical interviews, neuropsychological testing, and assessments of frailty at two time points (14‐29 months apart). Fasting blood draws were obtained for measurements of genetic and blood‐based biological markers. DNA was extracted from whole blood and (ApoE) genotyping (n = 330) was conducted according to standardized PCR procedures. We will examine whether ε2 and ε4 are associated with differential rates of normal cognitive aging, and whether associations of ε4 with cognitive decline are modified by sex, education or other health conditions common among older adults in Panama, including chronic illnesses, polypharmacy and frailty. Result: Our study evaluate whether ApoE ε2, ε3 and ε4 allele frequency is a significant factor associated with cognition and daily function in elderly individuals. Specifically, we focus on evaluating the frequency of ApoE ε4 expression as a risk for cognitive impairment. Together these results contribute to our understanding of the risk factors of cognitive outcomes among Hispanic populations outside the US. Conclusion: Little is known about the factors associated to cognitive health at old age in Central American populations. Genetic biomarkers could be used as a tool for diagnostic testing. It is expected that ApoE‐ε4 polymorphism will correlate with cognitive deficit among the elderly population and those at risk for cognitive impairment. [ABSTRACT FROM AUTHOR]

The population of Hispanic older adults is growing along with the burden of chronic diseases. This cross-sectional study aims to assess the factors associated with frailty among community-dwelling Hispanic women aged ≥60 years ( n  = 357) enrolled in the Panama Aging Research Initiative-Health Disparities study of cognitive-functional health of older persons in Panama. Cognitive function was assessed with a neuropsychological test battery. Depression was measured with the Geriatric Depression Scale. Frailty was defined using the Fried criteria and participants were classified as non-frail, pre-frail or frail. A subsample ( n  = 281) provided fasting blood samples for quantification of protein biomarkers. Associations were examined using hierarchical multiple linear regressions. 59.4% and 9.0% of participants ( M  = 69.2 years, SD  = 6.3) were pre-frail and frail, respectively. Having more depression (β = .28, p  < .001) was significantly associated with frailty, even after covariate adjustment. Cognitive function was not associated with frailty. Higher pTau181 levels were associated with increased frailty (β = .13, p  = .039), whereas higher α2M levels were associated with decreased frailty (β = -.16, p  = .004). These findings advance the search for health indicators and biomarkers of frailty and warrant further studies to decrease the burden of frailty among older Hispanic women., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The Panama Aging Research Initiative is a cohort study of 423 adults aged ≥65 years recruited from an outpatient geriatric department of Panama's largest public hospital, the Social Security Fund's Dr Arnulfo Arias Madrid Hospital Complex (Complejo Hospitalario Dr Arnulfo Arias Madrid de la Caja de Seguro Social). The study provides the first reports of modifiable and non-modifiable risk factors of cognitive impairment and dementia, as well as various health conditions common among older adults in Panama, including chronic illnesses, polypharmacy and rates of comorbidity. The initial study, conducted September 2012-May 2016, included a clinical interview; physical assessments of body mass index and handgrip strength; and cognitive testing, plus non-fasting blood draws for measurements of genetic (Apolipoprotein E genotype) and blood-based biological markers. Information was collected regarding limitations in activities of daily living, symptoms of depression and fall incidents. A subsample of participants provided cerebrospinal fluid to measure proteins related to Alzheimer's disease; another subsample underwent ultrasonography and electroencephalography. This report describes the general study design and highlights lessons learned and future directions. In particular, drawing on lessons learned from this clinical research, a community-based prospective cohort study is currently under way among older adults in Panama to validate a blood-based biomarker profile for detecting mild cognitive impairment and Alzheimer's disease, as well as risk factors for cognitive decline. KEYWORDS: Dementia, biomarkers, Latin America, aging, cognition, chronic disease, Panama.