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Background: Globally around 50 million people have dementia. Risk factors for dementia such as hypertension and diabetes are more common in Black, Asian, and other ethnic minorities. There are also marked ethnic inequalities in care seeking, likelihood of diagnosis, and uptake of treatments for dementia. Nevertheless, ethnic differences in dementia incidence and prevalence remain under-explored.Objective: To examine published peer-reviewed observational studies comparing age-specific or age-adjusted incidence or prevalence rates of dementia between at least two ethnic groups.Methods: We searched seven databases on 1 September 2019 using search terms for ethnicity, dementia, and incidence or prevalence. We included population-based studies comparing incidence or prevalence of dementia after accounting for age of at least two ethnic groups in adults aged 18 or more. Meta-analysis was conducted for eligible ethnic comparisons.Results: We included 12 cohort studies and seven cross-sectional studies. Thirteen were from the US, and two studies each from the UK, Singapore, and Xinjiang Uyghur Autonomous Region in China. The pooled risk ratio for dementia incidence obtained from four studies comparing Black and White ethnic groups was 1.33 (95% CI 1.07-1.65; I-squared = 58.0%). The pooled risk ratio for dementia incidence comparing the Asian and White ethnic groups was 0.86 (95% CI 0.728-1.01; I-squared = 43.9%). There was no difference in the incidence of dementia for Latino ethnic group compared to the White ethnic group.Conclusion: Evidence to date suggest there are ethnic differences in risk of dementia. Better understanding of the drivers of these differences may inform efforts to prevent or treat dementia. [ABSTRACT FROM AUTHOR]

Background: No studies have been conducted to date on the association between low-density lipoprotein cholesterol (LDL-C), statin use classified into low, medium, and high statin dosages, and dementia in German general practices.Objective: The goal of this retrospective case-control study was to investigate the relationship between elevated LDL-C, statins, and dementia in elderly persons followed in general practices in Germany.Methods: This study included patients aged 65 or older with an initial dementia diagnosis between January 2015 and December 2019 and at least one documented LDL-C value within the year prior to the dementia diagnosis. These patients were treated in one of 963 general practices which document LDL-C in Germany. Dementia cases were matched to non-dementia controls using propensity scores based on age, sex, and comorbidities. Logistic regression models were conducted to assess a possible association between accelerated LDL-C, statins, and dementia.Results: The study included 12,236 patients with dementia and 12,236 non-dementia controls. In total, 2,528 of the dementia patients were diagnosed with vascular dementia. The use of all dosages of statin use was negatively associated with all-cause dementia (OR: 0.80 for low dose, OR: 0.92 for medium dose, and OR: 0.85 for high dose) and with vascular dementia (OR: 0.61 for low dose, OR: 0.77 for medium dose, and OR: 0.74 for high dose). There was no clinically relevant association between elevated LDL-C and dementia.Conclusion: A negative association was found between all dosage use of statin therapy and all-cause dementia and vascular dementia in elderly patients in general practices in Germany. [ABSTRACT FROM AUTHOR]

Background: The Amyloid Tau Neurodegeneration (ATN) framework was proposed to define the biological state underpinning Alzheimer's disease (AD). Blood-based biomarkers offer a scalable alternative to the costly and invasive currently available biomarkers.Objective: In this meta-analysis we sought to assess the diagnostic performance of plasma amyloid (Aβ40, Aβ42, Aβ42/40 ratio), tangle (p-tau181), and neurodegeneration (total tau [t-tau], neurofilament light [NfL]) biomarkers.Methods: Electronic databases were screened for studies reporting biomarker concentrations for AD and control cohorts. Biomarker performance was examined by random-effect meta-analyses based on the ratio between biomarker concentrations in patients and controls.Results: 83 studies published between 1996 and 2020 were included in the analyses. Aβ42/40 ratio as well as Aβ42 discriminated AD patients from controls when using novel platforms such as immunomagnetic reduction (IMR). We found significant differences in ptau-181 concentration for studies based on single molecule array (Simoa), but not for studies based on IMR or ELISA. T-tau was significantly different between AD patients and control in IMR and Simoa but not in ELISA-based studies. In contrast, NfL differentiated between groups across platforms. Exosome studies showed strong separation between patients and controls for Aβ42, t-tau, and p-tau181.Conclusion: Currently available assays for sampling plasma ATN biomarkers appear to differentiate between AD patients and controls. Novel assay methodologies have given the field a significant boost for testing these biomarkers, such as IMR for Aβ, Simoa for p-tau181. Enriching samples through extracellular vesicles shows promise but requires further validation. [ABSTRACT FROM AUTHOR]

Background/objective: The aim of this study was to determine if plasma concentrations of 5 surrogate markers of Alzheimer's disease (AD) pathology and neuroinflammation are associated with disease status in African Americans.Methods: We evaluated 321 African Americans (159 AD, 162 controls) from the Florida Consortium for African-American Alzheimer's Disease Studies (FCA3DS). Five plasma proteins reflecting AD neuropathology or inflammation (Aβ42, tau, IL6, IL10, TNFα) were tested for associations with AD, age, sex, APOE and MAPT genotypes, and for pairwise correlations.Results: Plasma tau levels were higher in AD when adjusted for biological and technical covariates. APOEɛ4 was associated with lower plasma Aβ42 and tau levels. Older age was associated with higher plasma Aβ42, tau, and TNFα. Females had lower IL10 levels. Inflammatory proteins had strong pairwise correlations amongst themselves and with Aβ42.Conclusion: We identified effects of demographic and genetic variants on five potential plasma biomarkers in African Americans. Plasma inflammatory biomarkers and Aβ42 may reflect correlated pathologies and elevated plasma tau may be a biomarker of AD in this population. [ABSTRACT FROM AUTHOR]

Background: African Americans (AA) have a higher Alzheimer's disease (AD) prevalence and report more perceived stress than White Americans. The biological basis of the stress-AD link is unclear. This study investigates the connection between stress and AD biomarkers in a biracial cohort.Objective: Establish biomarker evidence for the observed association between stress and AD, especially in AA.Methods: A cross-sectional study (n = 364, 41.8% AA) administering cognitive tests and the perceived stress scale (PSS) questionnaire. A subset (n = 309) provided cerebrospinal fluid for measurement of Aβ42, Tau, Ptau, Tau/Aβ42 (TAR), and Ptau/Aβ42 (PTAR). Multivariate linear regression, including factors that confound racial differences in AD, was performed.Results: Higher PSS scores were associated with higher Ptau (β= 0.43, p = 0.01) and PTAR (β= 0.005, p = 0.03) in AA with impaired cognition (mild cognitive impairment).Conclusion: Higher PSS scores were associated with Tau-related AD biomarker indices in AA/MCI, suggesting a potential biological connection for stress with AD and its racial disparity. [ABSTRACT FROM AUTHOR]

Background: Increasing research focuses on ethnic differences in Alzheimer's disease, but such efforts in other neurodegenerative dementias are lacking. Currently, data on the ethnic profile of cognitively impaired persons with Lewy body disease (LBD) is limited, despite Lewy body dementia being the second most common neurodegenerative dementia.Objective: The study aimed to investigate presenting characteristics among ethnoracially diverse individuals with cognitive impairment secondary to LBD using the National Alzheimer's Coordinating Center database.Methods: Participants self-identified as African American, Hispanic, or White. We used Kruskal-Wallis and Pearson χ2 analyses to investigate group differences in presenting characteristics and linear regression to compare neuropsychological test performance.Results: Presentation age was similar between groups (median 74-75 years). Compared to Whites (n = 1782), African Americans (n = 130) and Hispanics (n = 122) were more likely to be female and single, have less educational attainment, report more cardiovascular risk factors, describe less medication use, and perform worse on select cognitive tests. Hispanics reported more depressive symptoms.Conclusion: Cohorts differences highlight the need for population-based LBD studies with racial-ethnic diversity. Culturally-sensitive neuropsychological tests are needed to determine whether observed differences relate to cultural, social, testing, or disease-related factors. More research is needed regarding how social and biological factors impact LBD care among diverse populations. [ABSTRACT FROM AUTHOR]

Background: Four prescription drugs (donepezil, galantamine, memantine, and rivastigmine) are approved by the US FDA to treat symptoms of Alzheimer's disease (AD). Even modest effectiveness could potentially reduce the population-level burden of AD and related dementias (ADRD), especially for women and racial/ethnic minorities who have higher incidence of ADRD.Objective: Describe the prevalence of antidementia drug use and timing of initiation relative to ADRD diagnosis among a nationally representative group of older Americans, and if there are disparities in prevalence and timing by sex and race/ethnicity.Methods: Descriptive analyses and logistic regressions of Medicare claims (2008-2016) for beneficiaries who had an ADRD or dementia-related symptom diagnosis, or use of an FDA approved drug for AD. We investigate prevalence of use and timing of treatment initiation relative to ADRD diagnosis across time and beneficiary characteristics (age, sex, race/ethnicity, socioeconomic status, comorbidities).Results: Among persons diagnosed with ADRD or related symptoms, 33.3% used an approved drug over the study period. Odds of use was higher among Whites than non-Whites. Among ADRD drug users, 40% initiated use within 6 months of the initial ADRD or related symptoms diagnosis, and 16% initiated prior to a diagnosis. We observed disparities by race/ethnicity: 28% of Asians, 24% of Hispanics, 16% of Blacks, and 15% of Whites initiated prior to diagnosis.Conclusions: The use of antidementia drugs is relatively low and varies widely by race/ethnicity. Heterogeneity in timing of initiation and use may affect health and cost outcomes, but these effects merit further study. [ABSTRACT FROM AUTHOR]

Background: Black Americans are approximately twice as likely to develop dementia as compared to White Americans and the magnitude of this disparity is often attributed to a variety of factors that include psychosocial and vascular risk factors. However, less is known about the potential contribution of Alzheimer's disease pathological differences.Objective: To examine potential differences incross-sectional and longitudinal cognitive performance in black and white participants who were clinically normal at baseline.Methods: 296 participants (48 African-American/black participants) underwent MRI and amyloid PET at baseline. Linear mixed models were used to examine the main effects of race, years of education, reading ability, Framingham Heart Study cardiovascular risk score (FHS-CVD), white matter hyperintensities (WMH), and amyloid (Aβ) burden on the Preclinical Alzheimer Cognitive Composite-5 (PACC5).Results: Lower levels of educationalattainment and reading ability were found for blacks compared to whites. By contrast, no differences in FHS-CVD, WMH, or Aβ were found by racial group. Baseline differences in PACC5 score were attenuated after adjusting for educationalfactors, vascular factors, and Aβ, but remained lower for blacks compared to whites (β= -0.24, p = 0.014). Further, blacks demonstrated a faster rate of PACC5 decline longitudinally compared to whites (β  = -0.055, p = 0.025) after adjusting for covariates.Conclusion: Accounting for educationalfactors, vascular factors, and Aβ burden diminished, but did not eliminate, racial differences in PACC5 performance longitudinally. Understanding potential differences in longitudinal cognitive outcomes by race may be important for upcoming secondary prevention trials. [ABSTRACT FROM AUTHOR]

Background: Racial disparity in the epidemiology of Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) has been reported. However, less is known about this disparity among Veterans.Objective: To estimate the racial disparity in AD/ADRD among the Veterans.Methods: Of the 5,413,418 Veterans≥65 years receiving care at the Veterans Health Administration (1999-2016), 4,045,269 were free of prevalent AD/ADRD, schizophrenia, or bipolar disorder at baseline. Of these, 432,469 were African American. Race was self-identified and incident AD/ADRD during 20 (median 6.7) years of follow-up was ascertained using International Classification of Diseases codes.Results: Patients had a mean age of 70.4 (±6.6) years and 97.8% were men. Age-sex-adjusted incidence of AD/ADRD per 1,000 person-year was 19.3 and 10.8 for African American and white Veterans, respectively (age-sex-adjusted hazard ratio associated with African American race, 1.77; 95% confidence interval, 1.75-1.79; p < 0.0001). This association remained essentially unchanged after multivariable adjustment (hazard ratio, 1.67; 95% confidence interval, 1.65-1.69; p < 0.0001). Among the key baseline characteristics that were significant predictors of AD/ADRD in both races, stroke was a significantly stronger predictor among African Americans, and Hispanic ethnicity and depression among whites (p-value for all interaction,<0.0001).Conclusion: The findings of a higher incidence of AD/ADRD among African American Veterans is consistent with the findings in the general population reported in the literature, although the overall incidence appears to be lower than that in the general population. Future studies need to examine this disparity in incidence as well as the between-race heterogeneity in AD/ADRD risk. [ABSTRACT FROM AUTHOR]

Background: It is well-documented that African Americans have elevated risk for cognitive impairment and dementia in late life, but reasons for the racial disparities remain unknown. Stress processes have been linked to premature age-related morbidity, including Alzheimer's and related dementias (ADRD), and plausibly contribute to social disparities in cognitive aging.Objective: We examined the relationship between stressful life events and cognitive decline among African American and White participants enrolled in the Wisconsin Registry for Alzheimer's Prevention (WRAP).Methods: Linear mixed models including demographic, literacy, and health-related covariates were used to estimate (1) relationships between a life event index score and decline in cognitive test performance in two domains of executive function (Speed & Flexibility, Working Memory) and one domain of episodic memory (Verbal Learning & Memory) among 1,241 WRAP enrollees, stratified by race, and (2) contributions of stressful life events to racial differences in cognition within the full sample.Results: African Americans (N = 50) reported more stressful life events than Whites (N = 1,191). Higher stress scores associated with poorer Speed & Flexibility performance in both groups, though not with declines across time, and partially explained racial differentials in this domain. Among African Americans only, stressor exposure also associated with age-related decline in Verbal Learning & Memory. Stressor-cognition relationships were independent of literacy and health-related variables.Conclusions: Greater lifetime stress predicted poorer later-life cognition, and, in a small sample of African Americans, faster declines in a key domain of episodic memory. These preliminary findings suggest that future work in large minority aging cohorts should explore stress as an important source of modifiable, socially-rooted risk for impairment and ADRD in African Americans, who are disproportionately exposed to adverse experiences across the life course. [ABSTRACT FROM AUTHOR]

Background: The APOEɛ4 allele is a well-known risk factor for Alzheimer's disease (AD). Previous research argues that higher education helps to preserve cognition in older adults with AD pathology because of its key role in cognitive reserve and resilience.Objective: To test if higher educational level buffers the effect of APOEɛ4 on cognition among older non-Hispanic Blacks.Methods: Participants were 849 non-demented older non-Hispanic Blacks (38.3% APOEɛ4+), who underwent a comprehensive neuropsychological evaluation. Multiple linear regression models tested the relationship between APOEɛ4 status and twelve cognitive measures with education (up to high school and beyond high school) as a moderator.Results: Education buffered the effects of the APOEɛ4 allele, such that there was no impact of APOEɛ4 status on word-list memory retention and working memory among participants with more than a high school degree. This pattern was not observed for ten other cognitive measures of verbal and visual episodic memory, semantic memory, executive function, and processing speed-although a similar trend was observed for switching ability in executive functioning. The buffering effect of education was stronger among women than men.Conclusion: Our findings suggest that genetic effects on late-life cognition may be modified by environmental factors such as educational attainment. These results are consistent with the framework of cognitive reserve such that engaging in cognitively enriching activities and acquiring skills and knowledge with more years of education may increase the capacity to maintain cognitive function despite high genetic risk for impairment. [ABSTRACT FROM AUTHOR]

Background: Both cigarette smoking and diabetes mellitus are well-established risk factors for development of dementia. However, the interaction between smoking and diabetes is yet unknown.Objective: In this study, we clarify association between smoking, diabetes, and dementia risk in older adults.Methods: Participants in this study included community residents aged 65 years and older who had participated in a health checkup in 2006, followed for 10 years (n = 9,403) and had long-term care insurance information data. Furthermore, the risk estimates of smoking status and diabetes diagnosis on dementia adjusted for the competing risk of death prior to dementia were analyzed.Results: During follow-up, 2,647 participants developed dementia. The smoking status-diabetes interaction on development of dementia was statistically significant (p≤0.001). Among those patients exposed to both factors, 17% of risk of development of dementia was attributable to the interaction of these factors. Current smokers with diabetes had significantly greater risks of development of dementia than never smokers without diabetes (reference): multivariable-adjusted risk of dementia in current smokers without diabetes (subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.05-1.48); never smokers with diabetes (1.31, 1.16-1.47); and current smokers with diabetes (1.86, 1.39-2.48). However, no such association was noted for former smokers with and without diabetes.Conclusions: Current smoking, but not former smoking, was associated with increased risk of development of dementia in older adults with and without diabetes. Moreover, the synergistic effect of current smoking and diabetes on dementia was noted. [ABSTRACT FROM AUTHOR]

Social media presents a rich opportunity to gather health information with limited intervention through the analysis of completely unstructured and unlabeled microposts. We sought to estimate the health-related quality of life (HRQOL) of Twitter users using automated semantic processing methods. We collected tweets from 878 Twitter users recruited through online solicitation and in-person contact with patients. All participants completed the four-item Centers for Disease Control Healthy Days Questionnaire at the time of enrollment and 30 days later to measure "ground truth" HRQOL. We used a combination of document frequency analysis, sentiment analysis, topic analysis, and concept mapping to extract features from tweets, which we then used to estimate dichotomized HRQOL ("high" vs. "low") using logistic regression. Binary HRQOL status was estimated with moderate performance (AUC=0.64). This result indicates that free-range social media data only offers a window into HRQOL, but does not afford direct access to current health status. [ABSTRACT FROM AUTHOR]

Social media presents a rich opportunity to gather health information with limited intervention through the analysis of completely unstructured and unlabeled microposts. We sought to estimate the health-related quality of life (HRQOL) of Twitter users using automated semantic processing methods. We collected tweets from 878 Twitter users recruited through online solicitation and in-person contact with patients. All participants completed the four-item Centers for Disease Control Healthy Days Questionnaire at the time of enrollment and 30 days later to measure "ground truth" HRQOL. We used a combination of document frequency analysis, sentiment analysis, topic analysis, and concept mapping to extract features from tweets, which we then used to estimate dichotomized HRQOL ("high" vs. "low") using logistic regression. Binary HRQOL status was estimated with moderate performance (AUC=0.64). This result indicates that free-range social media data only offers a window into HRQOL, but does not afford direct access to current health status. [ABSTRACT FROM AUTHOR]

Longitudinal research suggests that genetic, lifestyle, and environmental factors enhance one's risk for developing Alzheimer's disease and related dementias (ADRD). However, it is not known how an accumulation of such factors impact brain functioning. One barrier to this research is that increased risk for ADRD affects the cerebrovascular system and, therefore, alters the link between neural activity and the fMRI BOLD signal. To better interpret fMRI findings, several steps were taken to adjust fMRI activity thereby reducing such cerebrovascular effects. We hypothesized that as the number of ADRD risk factors increase, brain regions within the medial temporal lobes and the default mode network would exhibit altered brain activity during an episodic memory retrieval task. Middle-aged and older adults (aged 50-74) free of dementia were recruited with varying levels of risk and underwent a neuropsychological battery and fMRI. In the memory task, participants viewed a pair of pictures. In an alternative-forced-choice test, participants viewed a picture cue and had to determine which of four pictures was paired with the cue. Increased dementia risk was positively associated with brain activity in regions of interest within the default mode network, the hippocampus, and the entorhinal cortex during memory retrieval. Whole-brain analyses revealed additional positive associations in prefrontal and occipito-temporal cortices. Risk factors most contributing to these elevated levels of brain activity included hypertension, diabetes, obesity, and cholesterol. We also ruled out confounds due to in-scanner performance and premorbid ability. Cumulative risk might represent early signs of burnout in brain regions underlying episodic memory. [ABSTRACT FROM AUTHOR]

Background: The transition from normal cognition to Alzheimer's disease is considered a continuum, with amnestic mild cognitive impairment (aMCI) an intermediate clinical cognitive state. Although prior work suggests that dementia incidence rates may be declining, there is little information regarding temporal trends in aMCI incidence.Objective: To determine whether age specific rates of aMCI have changed over sequential birth cohorts among individuals included in the population-based Einstein Aging Study (EAS) cohort. A secondary objective was to examine trends in aMCI rates among Blacks and Whites and by sex.Methods: Age specific incidence of aMCI was examined by birth year among 1,233 individuals age 70 years and above enrolled in the population-based EAS cohort between November 1, 1993 and February 22, 2016 and who had at least one annual follow-up assessment (5,321 person years of follow-up). Poisson regression was used to determine whether there has been a change in age specific aMCI rates over sequential years of birth.Results: No significant change in aMCI rates was identified in the overall cohort, among Blacks or Whites, or among males or females born between 1899 and 1946.Conclusions: Despite a trend for decreased dementia incidence in the EAS cohort, rates of incident aMCI have not changed. These apparently conflicting results may indicate a delay or decrease in the rates of transition from aMCI to dementia within the cohort. However, further studies are needed to confirm whether rates of aMCI have changed in other populations, and how aMCI rates are related to secular trends in dementia risk factors. [ABSTRACT FROM AUTHOR]

Population-based clinic-pathological studies have established that the most common pathological substrate of dementia in community-dwelling elderly people is mixed, especially Alzheimer's disease (AD) and cerebrovascular ischemic disease (CVID), rather than pure AD. While these could be just two frequent unrelated comorbidities in the elderly, epidemiological research has reinforced the idea that mid-life (age <65 years) vascular risk factors increase the risk of late-onset (age ≥ 65 years) dementia, and specifically AD. By contrast, healthy lifestyle choices such as leisure activities, physical exercise, and Mediterranean diet are considered protective against AD. Remarkably, several large population-based longitudinal epidemiological studies have recently indicated that the incidence and prevalence of dementia might be decreasing in Western countries. Although it remains unclear whether these positive trends are attributable to neuropathologically definite AD versus CVID, based on these epidemiological data it has been estimated that a sizable proportion of AD cases could be preventable. In this review, we discuss the current evidence about modifiable risk factors for AD derived from epidemiological, preclinical, and interventional studies, and analyze the opportunities for therapeutic and preventative interventions. [ABSTRACT FROM AUTHOR]

This study aimed to determine if patterns of neuropsychological deficits, vascular risk factors, and neuropathology differ in Hispanic and Non-Hispanic patients with autopsy-confirmed Alzheimer's disease (AD). Participants were enrolled in a longitudinal study at the Shiley-Marcos AD Research Center at the University of California, San Diego. Hispanic (n = 14) and Non-Hispanic (n = 20) patients with autopsy-confirmed AD who scored ≥95 on the Dementia Rating Scale (DRS) were included. Patient groups were matched on age, education, global mental status, and severity of functional decline; they were compared to Hispanic (n = 14) or Non-Hispanic (n = 20) cognitively-normal controls of similar age and education. Ethnicity (Hispanic, Non-Hispanic) by disease state (autopsy-confirmed AD or cognitively normal) comparisons were made for cognitive test performance and vascular risk factors. Patient groups were further compared on measures of AD (Braak stage, neuritic plaques, neurofibrillary tangles), vascular neuropathology, and performance across cognitive domains of memory, language, attention, executive functions, and visuospatial abilities after scores were z-transformed based on respective culturally-appropriate control groups. Patient groups had similar overall AD pathology burden, whereas Hispanics with AD had more small parenchymal arteriolar disease and amyloid angiopathy than Non-Hispanics with AD. Despite largely similar pathology, Hispanics with AD were less cognitively impaired (relative to respective NC groups) than Non-Hispanics with AD, and exhibited a different pattern of deficits across cognitive domains. Findings suggest that cognitive deficits that are usually prominent in AD may be less salient in Hispanic patients and this may adversely impact the ability to clinically detect the disease in mild to moderate stages. [ABSTRACT FROM AUTHOR]

The incidence and prevalence of Alzheimer's disease (AD) dementia are higher among Caribbean Hispanics than among non-Hispanic Whites. The causes of this health disparity remain elusive, partially because of the relative limited capacity for biomedical research in the developing countries that comprise Caribbean Latin America. To begin to address this issue, we were awarded a Development Research Award from the US NIH and Fogarty International Center in order to establish the local capacity to integrate magnetic resonance imaging (MRI) into studies of cognitive aging and dementia in Dominican Republic, establish collaborations with Dominican investigators, and conduct a pilot study on the role of cerebrovascular markers in the clinical expression of AD. Ninety older adult participants with and without AD dementia and with and without a strong family history of AD dementia received MRI scans and clinical evaluation. We quantified markers of cerebrovascular disease (white matter hyperintensities [WMH], presence of infarct, and presence of microbleed) and neurodegeneration (entorhinal cortex volume) and compared them across groups. Patients with AD dementia had smaller entorhinal cortex and greater WMH volumes compared with controls, regardless of family history status. This study provides evidence for the capacity to conduct MRI studies of cognitive aging and dementia in Dominican Republic. The results are consistent with the hypothesis that small vessel cerebrovascular disease represents a core feature of AD dementia, as affected participants had elevated WMH volumes irrespective of family history status. [ABSTRACT FROM AUTHOR]

Background: Persons with Alzheimer's disease (AD) are frequently hospitalized from infection-related causes. There are no previous studies investigating hospitalization associated with antibiotic initiation in persons with AD.Objective: To investigate the frequency and risk of hospitalization associated with oral antibiotic initiation among community dwellers with and without AD.Methods: We performed a retrospective register-based study utilizing register-based Medication Use and Alzheimer's disease (MEDALZ) cohort. It includes all community dwellers diagnosed with AD during 2005-2011 in Finland and their matched comparison persons without AD. Antibiotic use was initiated by 34,785 persons with and 36,428 without AD. Drug use data were collected from Prescription Register and comorbidities from Special Reimbursement and Hospital Care Registers. Infection diagnoses were collected from the Hospital Care Register. Factors associated with hospitalization were estimated utilizing logistic regression models.Results: Risk of hospitalization following antibiotic initiation was higher among antibiotic initiators with AD than without AD (adjusted odds ratio, aOR, 1.37, 95% Cl 1.28-1.46).Strongest association with hospitalization was found for oral glucocorticoid use, aOR 1.41 (1.25-1.59); epilepsy, aOR 1.33 (1.10-1.63); and active cancer, aOR 1.30 (1.14-1.49). Among initiators of cephalexin, pivmecillinam, amoxicillin/amoxicillin, and enzyme inhibitor and doxycycline, persons with AD were more frequently hospitalized than persons without AD. A quarter of hospitalized antibiotic initiators had infection diagnosis in their hospital care records.Conclusions: Persons with AD initiating an antibiotic had a higher risk for hospitalization than antibiotic initiators without AD. Further research is needed to determine whether infection-related hospitalization could be reduced. [ABSTRACT FROM AUTHOR]

Background: Aggregation and deposition of amyloid-β (Aβ) in the brain is the main pathological change of Alzheimer's disease (AD). Decreased Aβ42 in the cerebrospinal fluid has been confirmed as a biomarker of AD; however, the relationship between plasma Aβ and cognitive impairment is currently unclear.Objective: The aim was to explore the relationship between plasma Aβ and cognitive impairment in a cross-sectional study.Methods: A total of 1,314 subjects (age above 40) from a village in the suburbs of Xi'an, China were enrolled between October 8, 2014 and March 30, 2015. A validated Chinese version of the Mini-Mental State Examination and neuropsychological battery were used to assess cognition. Levels of plasma Aβ42 and Aβ40 were tested using commercial enzyme-linked immunosorbent assay. Relationship of plasma Aβ and cognitive impairment was analyzed using logistic regression analysis.Results: Of the enrolled subjects, 1,180 (89.80%) had normal cognition, 85 (6.47%) had possible cognitive impairment and 49 (3.73%) had probable cognitive impairment. Logistic regression analysis showed that the Aβ42/Aβ40 ratio (OR = 4.042, 95% CI: 1.248-11.098, p = 0.012) and plasma Aβ42 (OR = 1.036, 95% CI: 1.003-1.071, p = 0.031) was higher in the possible cognitive impairment than that in the normal cognition group. Furthermore, the plasma Aβ42/Aβ40 ratio was higher in the possible cognitive impairment group than that in the probable cognitive impairment group (OR = 0.029, 95% CI: 0.002-0.450, p = 0.011).Conclusions: Levels of plasma Aβ42 and Aβ42/Aβ40 ratio were elevated in patients with possible cognitive impairment, indicating that plasma Aβ42 and Aβ42/Aβ40 ratio increases may be more pronounced in early stage of cognitive impairment. [ABSTRACT FROM AUTHOR]

We present the JaCaMo+ framework for programming multiagent systems (MAS), where agents interact thanks to commitment-based interaction protocols. Commitment protocols are realized as artifacts that maintain a social state and notify to the participating agents those events that are relevant to the interaction. We discuss the advantages, like increased modularity and flexibility, that are brought by commitment-ruled interactions with respect to other proposals. We trace back such advantages to the possibility of relying on a standardized commitment lifecycle. We explain how to use the framework to program interacting agents by using the Netbill protocol as running example, and the Gold Miners scenario as a more complex programming example. [ABSTRACT FROM AUTHOR]

Cerebral amyloid angiopathy (CAA) of the Aβ type is variably present in the brains of patients with Alzheimer's disease (AD). CAA contributes to cognitive decline and increases the risk of lobar hemorrhage; because both AD-typical dementia and lobar hemorrhage are more common in African-Americans than in Caucasians, we postulated that African-Americans with AD might be particularly susceptible to CAA. To test this hypothesis, we analyzed CAA histopathologically in the large vessels and capillaries of autopsy-derived frontal, temporal, parietal, and occipital cortical samples from African-Americans (n = 18) and Caucasians (n = 19) with end-stage AD. In the combined cohort of 37 subjects, 22% of the subjects had severe CAA in large vessels, and 11% had severe CAA in capillaries. However, the prevalence and histopathologic characteristics of CAA were similar in the African-Americans and Caucasians. This conclusion was substantiated in an independent sample from the National Alzheimer's Coordinating Center database, in which the degree of CAA was comparable in 1,554 Caucasians and 68 African-Americans with end-stage AD. These findings support a growing consensus that the fundamental histopathologic features of AD are largely impartial to the race of the afflicted. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) research is at a critical time. The global society is increasingly aware of the frightening rate of growth of the human and financial burden caused by this condition and of the urgent need to halt its progression. Consequently, the scientific community holds great responsibility to quickly put in place and optimize the machinery necessary for testing new treatments or interventions. In this context demand for participants for AD research is at an all-time high. In this review, we will focus on a methodological factor that is increasingly recognized as a key factor that shapes trial populations and affects validity of results in clinical trials: patient engagement, recruitment, and retention. We outline specific problems relevant to patient engagement in AD including recruiting enough participants, difficulties in participant retention, ensuring the recruited sample is representative of the general AD population, the burden of screening failures, and new challenges related to recruiting in preclinical disease. To address the urgent need for more research studying the applicability and cost-effectiveness of different recruitment strategies across different settings and nationalities, we describe the Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project, a public-private partnership promoted by the Innovative Medicine Initiative (IMI), which will provide a large multinational quantitative analysis comparing different innovative recruitment models. We also discuss strategies that address each problem and draw on the experience of Fundació ACE to argue that focusing resources on comprehensive AD centers that offer coordinated clinical and social care and participate in basic and clinical research, is an effective and efficient way of implementing many of the discussed strategies. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a monogenetic disorder marked by hemolytic anemia and vaso-occlusive complications. The hallmark of SCD is the intracellular polymerization of sickle hemoglobin (HbS) after deoxygenation, and the subsequent characteristic shape change (sickling) of red cells. Vaso-occlusion occurs after endothelial activation, expression of adhesion molecules and subsequent adhesion of leucocytes and sickle erythrocytes to the vascular wall. Here we review how oxidative stress from various sources influences this process. Emerging evidence points towards a dominant mechanism in which innate immune receptors, such as Toll like receptor 4, activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidases to produce reactive oxygen species (ROS) which in turn enables downstream pro-inflammatory signaling and subsequent endothelial activation. By serving as an iron donor for the Fenton reaction, heme radically increases the amount of ROS further, thereby increasing the signal originating from the innate immune receptor and downstream effects of innate immune receptor activation. In SCD this results in the production of pro-inflammatory cytokines, endothelial activation and leucocyte adhesion, and eventually vaso-occlusion. Any intervention to stop this cascade, including Toll like receptor blockade, NADPH oxidase inhibition, ROS reduction, heme scavenging, iron chelation, or anti-adhesion molecule antibodies has been successfully used in pre-clinical studies and holds promise for patients with SCD. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) presents with an earlier onset age and increased symptom severity in African Americans and Hispanics.Objective: Although the prevalence of plaques and tangles may not exhibit ethnicity-related differences, levels of neurodegenerative proteins have not been described.Methods: Here, levels of five proteins (i.e., S100B, sRAGE, GDNF, Aβ40, and Aβ42) and the Aβ42/Aβ40 ratio were measured in postmortem samples of the middle temporal gyrus (BA21) from age-matched African Americans and Caucasians with AD (n = 6/gender/ethnicity).Results: S100B levels were increased 17% in African Americans (p < 0.003) while sRAGE was mildly decreased (p < 0.09). Aβ42 levels were increased 121% in African Americans (p < 0.02), leading to a 493% increase in the Aβ42/Aβ40 ratio (p < 0.002). Analysis of GDNF levels did not indicate any significant effects. There were no significant effects of gender and no significant ethnicity with gender interactions on any analyte. Effect size calculations indicated "medium" to "very large" effects.Conclusion: S100B is typically elevated in AD cases; however, the increased levels in African Americans here may be indicative of increased severity in specific populations. Increased Aβ42/Aβ40 ratios in the current study are compatible with increased disease severity and might indicate increased AD pathogenesis in African Americans. Overall, these results are compatible with a hypothesis of increased neuroinflammation in African Americans with AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common type of dementia among individuals 65 or older. There are more than 5 million diagnosed cases in the US alone and this number is expected to triple by 2050. Therefore, AD has reached epidemic proportions with significant socioeconomic implications. While aging in general is the greatest risk factor for AD, several additional demographic factors that have contributed to the rise in AD in the US are under study. One such factor is associated with the relatively fast growth of the Latino population. Several reports indicate that AD is more prevalent among blacks and Latinos. However, the reason for AD disparity among different ethnic groups is still poorly understood and highly controversial. The Latino population is composed of different groups based on nationality, namely South and Central America, Mexico, and Caribbean Hispanics. This diversity among the Latino population represents an additional challenge since there are distinct characteristics associated with AD and comorbidities. In this review, we aim to bring attention to the intersection between social determinants of health and genetic factors associated with AD within the Latino community. We argue that understanding the interplay between identified social determinants of health, co-morbidities, and genetic factors could lead to community empowerment and inclusiveness in research and healthcare services, contributing to improved diagnosis and treatment of AD patients. Lastly, we propose that inserting a neuroethics perspective could help understand key challenges that influence healthcare disparities and contribute to increased risk of AD among Latinos. [ABSTRACT FROM AUTHOR]

We conducted a comprehensive screening of rare coding variants in an African American cohort to identify novel pathogenic mutations within the early-onset Alzheimer's disease (EOAD) genes (APP, PSEN1, and PSEN2) in this understudied population. Whole-exome sequencing of 238 African American subjects identified 6 rare missense variants within the EOAD genes, which were observed in AD cases but never among controls. These variants were analyzed in an independent cohort of 300 African American subjects in which PSEN2:NM_000447:exon5:c.T331C:p.Phe111Leu and PSEN1-minilin rs777923890 variants were again not observed, indicating that these novel rare variants, may contribute to AD risk in this population. [ABSTRACT FROM AUTHOR]

Background: Data on dementia prognosis among ethnic minority groups are limited in Europe.Objective: We assessed differences in short-term (1-year) and long-term (3-year) mortality and readmission risk after a first hospitalization or first ever referral to a day clinic for dementia between ethnic minority groups and the ethnic Dutch population in the NetherlandsMethods: Nationwide prospective cohorts of first hospitalized dementia patients (N = 55,827) from January 1, 2000 to December 31, 2010 were constructed. Differences in short-term and long-term mortality and readmission risk following hospitalization or referral to the day clinic between ethnic minority groups (Surinamese, Turkish, Antilleans, Indonesians) and the ethnic Dutch population were investigated using Cox proportional hazard regression models with adjustment for age, sex, and comorbidities.Results: Age-sex-adjusted short-term and long-term risks of death following a first hospitalization with dementia were comparable between the ethnic minority groups and the ethnic Dutch. Age- and sex-adjusted risk of admission was higher only in Turkish compared with ethnic Dutch (HR 1.57, 95% CI,1.08-2.29). The difference between Turkish and the Dutch attenuated and was no longer statistically significant after further adjustment for comorbidities. There were no ethnic differences in short-term and long-term risk of death, and risk of readmission among day clinic patients.Conclusion: Compared with Dutch patients with a comparable comorbidity rate, ethnic minority patients with dementia did not have a worse prognosis. Given the poor prognosis of dementia, timely and targeted advance care planning is essential, particularly in ethnic minority groups who are mired by cultural barriers and where uptake of advance care planning is known to be low. [ABSTRACT FROM AUTHOR]

Background: Cohort studies have reported that midlife high total serum cholesterol (TC) is associated with increased risk of Alzheimer's disease (AD) in late-life but findings have been based on few studies and previous reviews have been limited by a lack of compatible data.Objective: We synthesized all high quality data from cohort studies reporting on the association between total serum cholesterol measured and late-life cognitive outcomes including Alzheimer's disease (AD), vascular dementia (VaD), any dementia, mild cognitive impairment (MCI), and cognitive decline.Methods: The literature was searched up to October 2016 using a registered protocol. Thirty-four articles meeting study criteria were identified. Seventeen studies published from 1996 to 2014, including 23,338 participants were included in meta-analyses.Results: Relative risk of developing AD for adults with high TC in midlife was 2.14 (95% CI 1.33-3.44) compared with normal cholesterol. Individual studies that could not be pooled also reported high TC in midlife increased the risk of MCI and cognitive decline in late-life. High TC in late-life was not associated with MCI, AD, VaD, any dementia, or cognitive decline. Late-life measured HDL cholesterol and triglycerides were not associated with increased risk of VaD, and HDL was not associated with risk of MCI, AD, or any dementia. There were insufficient data to examine other cholesterol sub-fractions, sex differences, or APOE interactions.Conclusions: Significant gaps in the literature regarding TC and late-life dementia remain. Evidence suggests that high midlife TC increases risk of late-life AD, and may correlate with the onset of AD pathology. [ABSTRACT FROM AUTHOR]

Background: Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-β (Aβ) peptide between cerebrospinal fluid (CSF) and plasma compartments.Objective: To determine whether plasma exchange (PE) with albumin replacement was able to modify Aβ concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD).Methods: In a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein®, Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF Aβ1-40 and Aβ1-42 levels, as well as cognitive, functional, and behavioral measures were determined.Results: CSF Aβ1-42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5 pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma Aβ1-42 levels were lower in the PE-treated group after each treatment period (p < 0.05). Plasma Aβ1-40 levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and Semantic Verbal Fluency (p < 0.05) throughout the study. Neuropsychiatric Inventory scores were higher in controls during the PE phase (p < 0.05).Conclusion: PE with human albumin modified CSF and plasma Aβ1-42 levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued. [ABSTRACT FROM AUTHOR]

Background: Intracellular neurofibrillary tangles are part of the core pathology of Alzheimer's disease (AD), which are mainly composed of hyperphosphorylated tau protein.Objectives: The purpose of this study is to determine whether high molecular weight (HMW) or low molecular weight (LMW) tau protein levels, as well as the ratio HMW/LMW, present in platelets correlates with brain magnetic resonance imaging (MRI) structural changes in normal and cognitively impaired subjects.Methods: We examined 53 AD patients and 37 cognitively normal subjects recruited from two Memory Clinics at the Universidad de Chile. Tau levels in platelets were determined by immunoreactivity and the MRI scans were analyzed using voxel-based morphometry in 41 AD patients.Results: The HMW/LMW tau ratio was statistically different between controls and AD patients, and no associations were noted between HMW or LMW tau and MRI structures. In a multivariate analysis controlled for age and education level, the HMW/LMW tau ratio was associated with reduced volume in the left medial and right anterior cingulate gyri, right cerebellum, right thalamus (pulvinar), left frontal cortex, and right parahippocampal region.Conclusions: This exploratory study showed that HMW/LMW tau ratio is significantly higher in AD patients than control subjects, and that it is associated with specific brain regions atrophy. Determination of peripheral markers of AD pathology can help understanding the pathophysiology of neurodegeneration in AD. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated lower quality diagnostic assessment of dementia in immigrant populations, but knowledge about the quality of treatment and care for dementia is still lacking.Objective: To conduct a nationwide registry-based study to determine whether inequality exists regarding access to anti-dementia treatment and care between immigrant and Danish-born patients with dementia.Methods: A cross-sectional register-based study was conducted in the entire elderly (60≥years) population with dementia in Denmark in 2012 (n = 34,877). The use of anti-dementia drugs and residency in a nursing home were compared among Danish-born and Western and non-Western immigrants with dementia. Logistic regression analysis was done with adjustment for age, sex, comorbidity, marital status, basis of inclusion, and time since dementia diagnosis.Results: Immigrant background was associated with a significantly lower likelihood of receiving anti-dementia drug therapy (odds ratio (OR) [95% confidence interval (CI)]): non-Western = 0.70 [0.56-0.87]; Western = 0.74 [0.63-0.87]). No significant differences were found in type or amount of anti-dementia medication dispensed between the population groups (proxy measure for adherence). Non-Western immigrants were significantly less likely to live in a nursing home (0.52 [0.41-0.65]).Conclusion: This nationwide registry-based study indicated a worrisome difference in access to anti-dementia treatment and care for dementia patients with an immigrant background, but similar levels of adherence compared with the Danish-born population. Further research is necessary to pinpoint barriers to access to suitable healthcare among elderly immigrants with dementia but also to identify and develop culturally sensitive methods for their treatment and care. [ABSTRACT FROM AUTHOR]

The internet has become an important resource to help people search for online medication information. This study aims to report the prevalence and profile of Saudi online medication seeking behavior. Conducted via a web-based survey with Twitter participants between January-February, 2015, the primary outcome measures were the self-reported rates of using the internet to search for medication related information. A valid sample of 4847 participants was collected over the period of the study. Out of the total participants, 68.3% (n=3311) were found to seek online medication related information frequently. Most of the social media users were female 83.5% (n=2766). The majority of respondents 63.6% (n= 3081) used Google, followed by Twitter 28.7% (n= 1392), Snapchat 21%, (n=1019), WhatsApp 13.8% (n= 670), Instagram 11.4%, (n= 553), and Facebook 5.5 % (n= 267), with few searching YouTube 1.3% (n=65) to access online medication information. Findings indicate that the Saudi population actively uses the internet and social media to obtain medication information. Further studies are needed to explore the influence of the internet and social media on user perception, attitude, and behavior with the use of online medication information. [ABSTRACT FROM AUTHOR]

Background: Several studies have shown higher Alzheimer's disease (AD) incidence rates are in African-Americans (AAs) than Caucasians (CCs). If this finding is consistent across studies, it raises important etiologic questions regarding factors responsible for this discrepancy. It also affects the likely public health burden of AD in the US in the future, as the non-Caucasian population becomes the majority.Objective: Estimate the AA/CC rate ratio for AD incidence across all available studies.Methods: We conducted a meta-analysis of population-based studies for the rate ratio (RR) of AD incidence for AAs versus CCs, after identifying six relevant studies from the literature. We calculated an AA/CC rate ratio across all studies using inverse-variance weighting, and assessed inter-study heterogeneity. Using these incidence data, as well as data on survival after diagnosis, and on all-cause mortality, we also estimated the US prevalence of AD among AAs and CCs.Results: There were six population-based studies with data comparing AD incidence between AAs and CCs, with an estimated 370 AA and 640 CC incident cases. The meta-analysis RR showed that the AD rate for AAs was 64% higher than for CCs (RR = 1.64 (95% CI 1.35-2.00)) 1.35-2.00)), with no evidence of heterogeneity. We estimated the current US AD prevalence for ages 65-90 to be 5.5% for CCs, and 8.6% for AAs (prevalence ratio 1.56).Conclusion: AAs have an increased risk of incident and prevalent AD compared to CCs for reasons which are unknown, but are hypothesized to reflect biological, psychological, and socioeconomic factors. [ABSTRACT FROM AUTHOR]

Researchers have shown that immersive Virtual Reality (VR) can serve as an unusually powerful pain control technique. However, research assessing the reported symptoms and negative effects of VR systems indicate that it is important to ascertain if these symptoms arise from the use of particular VR display devices, particularly for users who are deemed "at risk," such as chronic pain patients Moreover, these patients have specific and often complex needs and requirements, and because basic issues such as 'comfort' may trigger anxiety or panic attacks, it is important to examine basic questions of the feasibility of using VR displays. Therefore, this repeated-measured experiment was conducted with two VR displays: the Oculus Rift's head-mounted display (HMD) and Firsthand Technologies' immersive desktop display, DeepStream3D. The characteristics of these immersive desktop displays differ: one is worn, enabling patients to move their heads, while the other is peered into, allowing less head movement. To assess the severity of physical discomforts, 20 chronic pain patients tried both displays while watching a VR pain management demo in clinical settings. Results indicated that participants experienced higher levels of Simulator Sickness using the Oculus Rift HMD. However, results also indicated other preferences of the two VR displays among patients, including physical comfort levels and a sense of immersion. Few studies have been conducted that compare usability of specific VR devices specifically with chronic pain patients using a therapeutic virtual environment in pain clinics. Thus, the results may help clinicians and researchers to choose the most appropriate VR displays for chronic pain patients and guide VR designers to enhance the usability of VR displays for long-term pain management interventions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and stroke are common disorders of aging, but the relationship between these two disorders remains uncertain. Recent evidence recognized that they frequently co-occur and are influenced by each other, while other studies have produced inconsistent results. We conducted this systematic review and meta-analysis of stroke on risk for AD and AD on risk for stroke subtypes to clarify the relation between these two disorders on the basis of the studies published from 1975 to November 2013 in the PubMed, EMBASE, and Cochrane Library databases. In total, 7 cohort studies and 2 nested case-control studies met the inclusion criteria for meta-analysis. For stroke, the pooled effect size for AD risk was 1.59 (95% CI 1.25-2.02; z = 3.76; p = 0.000). For AD dementia, it was not associated with risk of all strokes or ischemic stroke (IS), but the risk of intracerebral hemorrhage (ICH was higher among persons with AD. The pooled RR for AD in relation to incident IS did not indicate a significant association (RR: 1.13; 95% CI 0.75-1.70; z = 0.58; p = 0.565). The pooled effect size for AD and ICH risk was 1.41 (95% CI 1.21-1.66; z = 4.27; p < 0.001). Stroke significantly and independently increased risk for AD and in turn AD increased risk for ICH. These results confirm that AD and ICH may have common pathogenesis and share preventive treatment measures. [ABSTRACT FROM AUTHOR]