African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older ...African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD.
We prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for β-amyloid (Aβ42, Aβ40), total and phosphorylated tau (t-tau and p-tau
, respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), α-synuclein, and neurodegeneration (neurofilament light chain NfL), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity WMH volume).
Sixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau
(difference of 7.4 pg/ml; 95% CI, 3.7-11.2 pg/ml; p < 0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5-37.7; p = 0.001), and Aβ40 (difference of 1.35 ng/ml; 95% CI, 0.29-2.42 ng/ml; p = 0.013) despite similar levels of Aβ42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/Aβ42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100-0.409; p = 0.001) and p-tau
/Aβ42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031-0.122; p = 0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH.
Despite comparable levels of CSF Aβ42 and Aβ42/Aβ40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans.
ClinicalTrials.gov, NCT02089555 . Retrospectively registered on 14 March 2014.
Background
“Super‐agers” are adults aged ≥80 with cognitive performance similar to persons two to three decades younger. Characteristics such as larger hippocampal volume, APOE‐ε4 allele absence, ...higher educational attainment, female sex, and lifelong cognitive stimulation are associated with cognitive performance compatible with super‐aging. These findings are based on predominantly white research samples. Limited data are available on African‐American super‐agers. To fill this gap, we explored potential factors associated with super‐aging in older African‐American adults.
Methods
Data from African‐American participants aged ≥80 in the National Alzheimer's Coordinating Center (NACC) dataset were analyzed. Using global Clinical Dementia Rating (CDR) scores, participants were first categorized as impaired (score ≥0.5) or non‐impaired/normal cognition (NC) (score = 0). From the NC group, super‐agers were identified using NACC‐data‐driven cutoffs. Participants were considered super‐agers if their memory performance was similar to persons aged 50–60 with NC, and their performance on other domains was within one standard deviation of the mean for persons aged ≥80. We examined group characteristics (NC, super‐ager, impaired) using chi‐square and ANOVA with pairwise comparisons. Multinomial logistic regression, adjusted for sex and education, evaluated correlates of super‐ager group assignment.
Results
Data for 1285 African‐American participants aged ≥80 were analyzed. We identified 24.7% (n = 316) NC, 4.8% (n = 61) super‐agers, and 70.6% (n = 905) impaired. Super‐agers were mostly female and more educated, had similar vascular comorbidities as the other groups, and had less sleep disorders, depression, and alcohol use. After adjusting for sex and education, super‐ager group assignment was associated with less sleep disorders, less depression, and moderate alcohol use.
Conclusions
Participants with controlled vascular risk, mental health, alcohol use, and sleep disorders tended to be in the super‐ager group. These factors may be important focus areas in clinical practice to support cognitive resilience with aging in older African‐American adults.
Objective
Compared to older Caucasians, older African Americans have higher risks of developing Alzheimer disease (AD) and lower cerebrospinal fluid (CSF) tau biomarker levels. It is not known ...whether tau‐related differences begin earlier in life or whether race modifies other AD‐related biomarkers such as inflammatory proteins.
Methods
We performed multiplex cytokine analysis in a healthy middle‐aged cohort with family history of AD (n = 68) and an older cohort (n = 125) with normal cognition (NC), mild cognitive impairment, or AD dementia. After determining baseline interleukin (IL)‐9 level and AD‐associated IL‐9 change to differ according to race, we performed immunohistochemical analysis for proteins mechanistically linked to IL‐9 in brains of African Americans and Caucasians (n = 38), and analyzed postmortem IL‐9–related gene expression profiles in the publicly available Mount Sinai cohort (26 African Americans and 180 Caucasians).
Results
Compared to Caucasians with NC, African Americans with NC had lower CSF tau, p‐Tau181, and IL‐9 levels in both living cohorts. Conversely, AD was only correlated with increased CSF IL‐9 levels in African Americans but not Caucasians. Immunohistochemical analysis revealed perivascular, neuronal, and glial cells immunoreactive to IL‐9, and quantitative analysis in independent US cohorts showed AD to correlate with molecular changes (upstream differentiation marker and downstream effector cell marker) of IL‐9 upregulation only in African Americans but not Caucasians.
Interpretation
Baseline and AD‐associated IL‐9 differences between African Americans and Caucasians point to distinct molecular phenotypes for AD according to ancestry. Genetic and nongenetic factors need to be considered in future AD research involving unique populations. ANN NEUROL 2019;86:407–418
African Americans living with dementia are considered less likely to seek formal institutionalized elder care and more likely to be managed in the home by family-member caregivers. Assistive ...technologies (the use of smart visual devices like tablets and phones) can be used effectively to guide memory-impaired individuals with a sequence of pictures showing steps to complete activities of daily living, e.g., bathing, toileting, dressing. Assistive technology so far has not been generally embraced in African American communities.
Determine, if African American family caregivers, given the opportunity, would embrace the use of assistive technology and if they would perceive its use beneficial.
We assessed a group of eight family caregivers' overall care-burden scores, and their user-satisfaction scores after using assistive technology for three months.
We found significant reduction in caregiver burden, positive changes in behavior and emotion scores, and high ratings on user satisfaction.
The findings reported here comprise the first systematic study of the use of assistive technology by caregivers in an underserved population. They set the stage for exploring meaningful strategies and variables that will better engage underserved populations to take advantage of assistive technologies available in healthcare.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This guidance can help shape the conversations you have with patients who want to understand the results of their gene and biomarker testing for Alzheimer disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date ...examining cerebrospinal fluid AD biomarkers in AA individuals. Methods We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non‐AD cases, including 495 (16.5%) self‐identified black/AA and 2,456 (81.7%) white/European individuals using cutoffs derived from the Alzheimer's Disease Neuroimaging Initiative, and using a data‐driven multivariate Gaussian mixture of regressions. Results Distinct effects of race were found in different groups. Total Tauand phospho181‐Tau were lower among AA individuals in all groups ( p < 0.0001), and Aβ 42 was markedly lower in AA controls compared with white controls ( p < 0.0001). Gaussian mixture of regressions modeling of cerebrospinal fluid distributions incorporating adjustments for covariates revealed coefficient estimates for AA race comparable with 2‐decade change in age. Using Alzheimer's Disease Neuroimaging Initiative cutoffs, fewer AA controls were classified as biomarker‐positive asymptomatic AD (8.0% vs 13.4%). After adjusting for covariates, our Gaussian mixture of regressions model reduced this difference, but continued to predict lower prevalence of asymptomatic AD among AA controls (9.3% vs 13.5%). Interpretation Although the risk of dementia is higher, data‐driven modeling indicates lower frequency of asymptomatic AD in AA controls, suggesting that dementia among AA populations may not be driven by higher rates of AD. ANN NEUROL 2024
Older African Americans are more likely to develop Alzheimer's disease (AD) than older Caucasians, and this difference cannot be readily explained by cerebrovascular and socioeconomic factors alone. ...We previously showed that mild cognitive impairment and AD dementia were associated with attenuated increases in the cerebrospinal fluid (CSF) levels of total and phosphorylated tau in African Americans compared to Caucasians, even though there was no difference in beta-amyloid 1-42 level between the two races.
We extended our work by analyzing early functional magnetic resonance imaging (fMRI) biomarkers of the default mode network in older African Americans and Caucasians. We calculated connectivity between nodes of the regions belonging to the various default mode network subsystems and correlated these imaging biomarkers with non-imaging biomarkers implicated in AD (CSF amyloid, total tau, and cognitive performance).
We found that race modifies the relationship between functional connectivity of default mode network subsystems and cognitive performance, tau, and amyloid levels.
These findings provide further support that race modifies the AD phenotypes downstream from cerebral amyloid deposition, and identifies key inter-subsystem connections for deep imaging and neuropathologic characterization.
The brain changes of Alzheimer's disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle ...to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline. Researchers often hesitate to share DRE data, either because they are insufficiently validated or reliable for use in individuals, or there are concerns about assuring responsible use and ensuring adequate understanding of potential problems when one's biomarker status is known. Concerns include warning people receiving DRE about situations in which they might be compelled to disclose their risk status potentially leading to discrimination or stigma. The Advisory Group on Risk Evidence Education for Dementia (AGREEDementia) welcomes all concerned with how best to share and use DRE. Supporting understanding in clinicians, stakeholders, and people with or at risk for dementia and clearly delineating risks, benefits, and gaps in knowledge is vital. This brief overview describes elements that made this group effective as a model for other health conditions where there is interest in unfettered collaboration to discuss diagnostic uncertainty and the appropriate use and communication of health-related risk information.
African Americans are under-represented in Alzheimer's disease (AD)-related biomarker studies, and it has been speculated that mistrust plays a major factor in the recruitment of African Americans ...for studies involving invasive procedures such as the lumbar puncture (LP). We set out to determine factors associated with non-participation in a biomarker study aiming to explore cerebrospinal fluid (CSF) AD biomarker differences between older African Americans and Caucasians. We also surveyed participants' procedure-related perception (a standard medical procedure vs. a frightening invasive procedure) and reluctance, as well as the rate and type of post-procedure discomfort and complications. Among 288 subjects approached for study participation, 145 (50.3%) refused participation with concerns over LP being the most commonly reported reason. Relatively more African Americans than Caucasians reported concerns over LP as the main reason for non-participation (46% vs. 25%,
= 0.03), but more African Americans also did not provide a specific reason for non-participation. Among those who completed study participation (including the LP), African Americans and Caucasians were similar in pre-LP perceptions and reluctance, as well as post-LP rates of discomfort or complication. Perceiving LP as a frightening invasive procedure, not race, is associated with increased likelihood of post-LP discomfort or complication (RR 6.2, 95% confidence interval 1.1-37.0). Our results indicate that LP is a well perceived procedure in a cohort of African American and Caucasian research participants, and is associated with few serious complications. The pre-procedure perception that the LP is a frightening invasive procedure significantly increases the risk of self-reported discomfort of complications, and African Americans may be more likely to turn down study participation because of the LP. Future studies will need to address factors associated with negative LP perceptions to further assure participants and reduce complication rates.
Underrepresentation of African American women as research participants contributes to health disparities. Contemporary studies have focused on clinical trial (CT) participation; epidemiologic and ...genetic studies utilizing medical records and/or biological samples have received less attention. In partnership with The Links, Incorporated (The Links), a national service organization of professional African American women, this study sought to examine attitudes regarding chart review (CR) studies, genetic studies/biobanking (GEN), and CTs; develop; and evaluate an online education-to-action program.
In phase 1, focus groups were convened with members of The Links to inform the content and format of the program. Phases 2 and 3 involved designing and evaluating the program, respectively.
Thirty-four women across three focus groups shared attitudes and perceptions regarding research and provided guidance for program development. Subsequently, 244 women completed the program (77% response rate), including pre- and post-assessments. Participants indicating that they "definitely" or "probably" (responses combined) intend to participate in research increased from 36.5% to 69.3% (pre/post-program). Agreement with the statement "research in the U.S. is ethical" increased (52.9% to 74.4%) as did factual knowledge regarding each of the study types. There was a decrease in reporting "little or no understanding" of study types (Pre/Post: GEN: 66%/24.9%, CR: 62.9%/18.4%, CTs: 40.7%/15.5%). Pre-program, few were "very positive" about the study types (14.3% GEN, 15.0% CR, 28.6% CTs); post-program ratings increased and equalized (42.8% GEN, 43.0% CR, 42.5% CTs).
An online education-to-action program targeting professional African American women improved knowledge, perceptions of ethics, and intent to participate in biomedical research.
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