Predictors of cognitive change in cognitively healthy older women in Panama: the PARI-HD study.

Background: Evidence suggests that a combination of biological and social factors influence risk of dementia differently for women and men. In healthy older women, several factors may contribute to changes in cognition. Objective: Describe the characteristics associated with variation in cognition in a sample of cognitively healthy older Panamanian women. Methods: The study includes cross-sectional analyses of cognitive domains at baseline (n = 357) and 17-month (SD = 2.0) follow-up (n = 200) for women aged 60 years and older enrolled in the Panama Aging Research Initiative-Health Disparities (PARI-HD) study. Instruments included clinical questionnaires, physiological measures, and a neuropsychological test battery assessing global cognition and seven cognitive domains. Multiple regression analyses examined the associations between demographic and clinical characteristics and cognition at baseline. Repeated measures analyses were used to investigate changes in cognition from baseline to follow-up. Results: On average, participants were 68.6 years of age (SD = 5.9) with 16.1 years of education (SD = 4.7). Age, income, and education showed robust associations with baseline cognition. Subjective cognitive impairment was associated with lower performance in global cognition, verbal learning, and memory domains. Only performance in the attention domain decreased at follow-up, and subjective health state and depressive symptoms significantly predicted the change in attention. Discussion: Our study findings contribute to the investigation of cognitive health in older Hispanic women and to the understanding of sociodemographic and health-related factors associated with cognitive decline and the progression to cognitive impairment and dementia.

Polypharmacy and Associated Health Outcomes in the PARI-HD Study.

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.

Digital phenotyping: An equal opportunity approach to reducing disparities in Alzheimer's disease and related dementia research.

A rapidly aging world population is fueling a concomitant increase in Alzheimer's disease (AD) and related dementias (ADRD). Scientific inquiry, however, has largely focused on White populations in Australia, the European Union, and North America. As such, there is an incomplete understanding of AD in other populations. In this perspective, we describe research efforts and challenges of cohort studies from three regions of the world: Central America, East Africa, and East Asia. These cohorts are engaging with the Davos Alzheimer's Collaborative (DAC), a global partnership that brings together cohorts from around the world to advance understanding of AD. Each cohort is poised to leverage the widespread use of mobile devices to integrate digital phenotyping into current methodologies and mitigate the lack of representativeness in AD research of racial and ethnic minorities across the globe. In addition to methods that these three cohorts are already using, DAC has developed a digital phenotyping protocol that can collect ADRD-related data remotely via smartphone and/or in clinic via a tablet to generate a common data elements digital dataset that can be harmonized with additional clinical and molecular data being collected at each cohort site and when combined across cohorts and made accessible can provide a global data resource that is more racially/ethnically represented of the world population.

Depression Mediates the Association Between Occupational Complexity and Late-Life Cognition in Hispanics.

There is a dearth of research in Latin America regarding risk and protective factors affecting older adults' cognition. This study aimed to investigate the factors mediating the association between occupational complexity and late-life cognition and daily function in a sample of Hispanic older adults. Participants (n = 588) aged 65 years and older underwent clinical, functional, and cognitive assessments. Mediation analyses revealed that depressive symptoms mediated the relationship between occupational complexity and cognitive as well as functional outcomes. Results provide evidence that depression may act as a risk factor for worse outcomes, even if older adults had a cognitively demanding occupation.

Apolipoprotein ɛ4 Affects Multiple Domains of Neuropsychological Functioning in a Sample of Elderly Hispanics.

Apolipoprotein ɛ4 allele (APOEɛ4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), but inconsistencies have arisen in studies with Hispanics. The objective of this study was to explore APOEɛ4 expression and cognitive function in a sample of Panamanian older adults, including healthy controls, mild cognitive impairment, and AD. Participants with at least one copy of APOEɛ4 had a significantly lower performance in global cognition, verbal memory, executive functions, visuospatial abilities, regardless of diagnosis. The present study contributes to the understanding of the association of APOEɛ4 and impairment in specific cognitive domains in elderly Hispanics.

The Panama Aging Research Initiative Longitudinal Study.

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.

Inflammatory Biomarkers, Depressive Symptoms and Falls Among the elderly in Panama.

BACKGROUND: Falls are common among elderly adults, and are predictors of hospitalization, institutionalization and mortality. OBJECTIVE: The objective of the present study was to examine the relationship between blood-based markers of inflammation and fall events in a sample of elderly Hispanic adults. METHOD: Data were collected from 190 participants enrolled in the Panama Aging Research Initiative study who completed baseline clinical and cognitive assessments. A non-fasting blood sample was obtained. Self-reported falls were classified as no falls, single falls or recurrent (two or more) falls reported in the 12 months prior to baseline evaluations. Serum levels of C Reactive Protein (CRP), T-lymphocyte secreting protein (I-309), interleukin 10 (IL-10), interleukin 6 (IL-6) and interleukin 7 (IL-7) were measured. Global cognition was assessed with the Mini Mental State Examination and depressive symptoms were assessed with the Geriatric Depression Scale (GDS-30). Multinomial logistic regression was used to assess the link between inflammation and fall events. RESULTS: Depressive symptoms, limitations in Instrumental Activities of Daily Living (IADL), IL-7 and I-309 were significantly related to fall events. Elevated levels of IL-7 increased the likelihood of single and recurrent falls, while increased levels of I-309 were associated only with recurrent falls. Greater IADL limitations and depressive symptoms were associated with an increased likelihood of recurrent falls. CONCLUSION: There is a lack of research investigating the relationship between inflammatory biomarkers and fall events. These results provide evidence of risk factors for falls in Hispanic older adults, and could serve to guide public health professionals to establish clinical guidelines to reduce fall risks.

Vascular biomarkers and ApoE4 expression in mild cognitive impairment and Alzheimer's disease.

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 Îµ4 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 Îµ4 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 Îµ4 expression. The results support the use of vascular markers in cognitive assessments of aged individuals.

Serum-based protein profiles of Alzheimer's disease and mild cognitive impairment in elderly Hispanics.

AIM: To describe the biomarker profiles in elderly Panamanians diagnosed with Alzheimer's disease (AD), mild cognitive impairment (MCI) or no impairment using serum-based biomarkers. METHODS: Twenty-four proteins were analyzed using an electrochemiluminescence-based multiplex biomarker assay platform. A biomarker profile was generated using random forest analyses. RESULTS: Two proteins differed among groups: IL-18 and T-lymphocyte-secreted protein I-309. The AD profile was highly accurate and independent of age, gender, education and Apolipoprotein E ε4 status. AD and MCI profiles had substantial overlap among the top markers, suggesting common functions in AD and MCI but differences in their relative importance. CONCLUSION: Our results underscore the potential influence of genetic and environmental differences within Hispanic populations on the proteomic profile of AD.

A blood screening test for Alzheimer's disease.

INTRODUCTION: This study combined data across four independent cohorts to examine the positive and negative predictive values of an Alzheimer's disease (AD) blood test if implemented in primary care. METHODS: Blood samples from 1329 subjects from multiple independent, multiethnic, community-based, and clinic-based cohorts were analyzed. A "locked-down" referent group of 1128 samples was generated with 201 samples randomly selected for validation purposes. Random forest analyses were used to create the AD blood screen. Positive (PPV) and negative (NPV) predictive values were calculated. RESULTS: In detecting AD, PPV was 0.81, and NPV was 0.95 while using the full AD blood test. When detecting mild cognitive impairment, PPV and NPV were 0.74 and 0.93, respectively. Preliminary analyses were conducted to detect any "neurodegenerative disease". The full 21-protein AD blood test yielded a PPV of 0.85 and NPV of 0.94. DISCUSSION: The present study creates the first-ever multiethnic referent sample that spans community-based and clinic-based populations for implementation of an AD blood screen.

Characterization of Alzheimer's Disease and Mild Cognitive Impairment in Older Adults in Panama.

Research on age-related cognitive impairment is scarce in Central America. We report factors associated with cognitive impairment among a sample of older adults in Panama diagnosed with Alzheimer's disease (AD, n = 31), mild cognitive impairment (MCI, n = 43), or no cognitive impairment (controls, n = 185). Apolipoprotein E (ApoE) genotype was assessed in a subset of cases (n = 135). Age (OR = 2.53, 95% CI = 1.03-6.17) and ApoE ɛ4 (OR = 5.14, 95% CI = 2.11-12.52) were significantly related to cognitive impairment (AD/MCI combined). Results underscore the potential of genetic screening in Panama for identifying those at risk of dementia.

Cognitive Impairment, Depression, and Cooccurrence of Both among the Elderly in Panama: Differential Associations with Multimorbidity and Functional Limitations.

Cognitive impairment and depression are common mental health problems among the elderly, although few studies have examined their cooccurrence in older adults in Latin America. The purpose of this study was to examine cognitive impairment, depression, and cooccurrence of the two conditions and associated factors in a sample of older adults in Panama. This study included 304 community-dwelling elderly (≥ 65 years) individuals. Participants underwent a clinical interview and assessments of cognitive function by the Minimental State Examination and depressive symptoms by the Geriatric Depression Scale. Limitations in basic (BADL) and instrumental (IADL) activities in daily living and the presence of chronic illnesses were recorded. Multinomial regression analysis revealed that cooccurrence of cognitive impairment and depressive symptoms was explained by increasing age (OR: 3.2, 95% CI: 1.20, 8.30), low education (OR: 3.3, 95% CI: 1.33, 8.38), having four or more chronic conditions (OR: 11.5, 95% CI: 2.84, 46.63), and BADL limitations (OR: 5.0, 95% CI: 1.26, 19.68). Less education and limitations in BADL and IADL increased the odds of cognitive impairment alone, while less education and three or more chronic conditions increased the odds of depression alone. These findings underscore the relevance of assessing cognitive impairment in the elderly as part of a long-term approach to managing depression and vice versa.

The effects of impaired cerebral circulation on Alzheimer's disease pathology: evidence from animal studies.

Persistent systemic hypoxia, a direct consequence of alterations in vascular function, can compromise the brain by increasing the risk of developing dementias such as Alzheimer's disease (AD). Vascular contributions to cognitive impairment and AD in aged individuals are common, and several vascular risk factors for AD are linked to hypoxia. Clinical evidence confirms that structural and functional changes characteristic of AD pathology also occur following hypoxic-ischemic events such as stroke and traumatic brain injury. Studies with transgenic and non-transgenic mouse models reliably show that hypoxia increases the levels of amyloid-ß peptides that form the characteristic plaques in AD brains. Moreover, some studies suggest that vascular lesions also promote tau phosphorylation, modulate apolipoprotein E expression, and have more profound effects in aged animals, but additional evidence is needed to establish these findings. Although the mechanisms underlying hypoxia-related effects remain unclear, controlled animal studies continue to reveal mechanistic aspects of the relationship between hypoxia and AD pathology that are necessary for therapeutic developments. The present review summarizes evidence from rodent studies regarding the effects of hypoxia on AD-related pathology and evaluates its impact on understanding human disease.