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- 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 in 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.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- 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 in 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

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.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

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

BackgroundEvidence 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.ObjectiveDescribe the characteristics associated with variation in cognition in a sample of cognitively healthy older Panamanian women.MethodsThe 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.ResultsOn 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.DiscussionOur 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

Blood-Based Biomarkers A blood screening test for Alzheimer's disease-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)

Abstract 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, communitybased, 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

Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases

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

Abstract 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

Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer’s disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility as well as an unclear path for moving basic discovery towards clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state-of-the-art. Additionally, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and towards clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional hand-off model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases