Alzheimer disease in African American individuals: increased incidence or not enough data?

Barnes, Lisa L.

doi:10.1038/s41582-021-00589-3

Cited by 93 publications

(80 citation statements)

References 90 publications

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“… 49 Much larger longitudinal studies of diverse cohorts are needed to evaluate the intersection of race, AD biomarkers, cognitive impairment, medical comorbidities, and social determinants of health. 50 Improved understanding of these complex factors will enable more accurate AD diagnosis and improve patient care for all groups.…”

Section: Discussionmentioning

confidence: 99%

Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light

et al. 2022

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Objective:To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231) and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.Methods:Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age, APOE ε4 carrier status and cognitive status. Each participant underwent blood and cerebrospinal fluid (CSF) collection, and amyloid PET was performed in 103 participants (68%). Plasma Aβ42/Aβ40 was measured by a high-performance immunoprecipitation-mass spectrometry assay. Plasma p-tau181, p-tau231, and NfL were measured by Simoa immunoassays. CSF Aβ42/Aβ40 and amyloid PET status were used as primary and secondary reference standards of brain amyloidosis, respectively.Results:There were 76 matched pairs of AA and NHW participants (n=152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were APOE ε4 carriers and 91% were cognitively normal. AA were less likely than NHW to have brain amyloidosis by CSF Aβ42/Aβ40 (22% versus 43% positive, p = 0.003). The Receiver Operating Characteristic Area Under the Curve (ROC AUC) of CSF Aβ42/Aβ40 status with the plasma biomarkers was as follows: Aβ42/Aβ40, 0.86 (95% confidence intervals [CI] 0.79-0.92); p-tau181, 0.76 (0.68-0.84); p-tau231, 0.69 (0.60-0.78); and NfL, 0.64 (0.55-0.73). In models predicting CSF Aβ42/Aβ40 status with plasma Aβ42/Aβ40 that included covariates (age, sex, APOE ε4 carrier status, race, and cognitive status), race did not affect the probability of CSF Aβ42/Aβ40 positivity. In similar models based on plasma p-tau181, p-tau231 or Nfl, AA had a lower probability of CSF Aβ42/Aβ40 positivity (Odds Ratio [OR] 0.31 [95% CI 0.13-0.73], OR 0.30 [0.13-0.71]) and OR 0.27 [0.12-0.64], respectively. Models of amyloid PET status yielded similar findings.Conclusions:Models predicting brain amyloidosis using a high performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA.

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Section: Discussionmentioning

confidence: 99%

Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light

et al. 2022

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“…Lifestyle, exercise, diet, and environmental factors also appear to influence BDNF signaling and thus appear to play a role in AD ( Pistollato et al, 2018 ). High prevalence in the geriatrics population of African American and Japanese origin points toward the role of lifestyle as a risk/contributory factor in AD ( Barnes, 2022 ). Animal models have reported that chronic stress and sedentary lifestyle negatively influence BDNF signaling ( Perna and Brown, 2013 ; Vassoler et al, 2013 ).…”

Section: Lifestyle Diet Drugs and Bdnf Levelsmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor: A Connecting Link Between Nutrition, Lifestyle, and Alzheimer’s Disease

et al. 2022

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Brain-derived neurotrophic factor (BDNF) involving tropomyosin kinase B and low affinity p75 neurotropin receptors is the most abundant and researched neurotropins in mammal’s brain. It is one of the potential targets for therapeutics in Alzheimer’s disease (AD) owing to its key role in synaptic plasticity. Low levels of BDNF are implicated in the pathophysiology of neurological diseases including AD. However, a healthy lifestyle, exercise, and dietary modifications are shown to positively influence insulin regulation in the brain, reduce inflammation, and up-regulate the levels of BDNF, and are thus expected to have roles in AD. In this review, the relationship between BDNF, mental health, and AD is discussed. Insights into the interrelationships between nutrition, lifestyle, and environment with BDNF and possible roles in AD are also provided in the review. The review sheds light on the possible new therapeutic targets in neurodegenerative diseases.

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“…The majority of research has been conducted in clinical trials or clinical research settings using CSF biomarkers of AD and the vast majority of participants have been non-Hispanic Whites (NHWs). Although Hispanic and African American (AA) communities have significantly higher rates of dementia (16) and therefore may gain significant benefit from the use of AD biomarkers in clinical assessment, there is limited research on blood-based biomarkers of AD in these communities (4,(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Characterizing Plasma Biomarkers of Alzheimer's in a Diverse Community-Based Cohort: A Cross-Sectional Study of the HAB-HD Cohort

et al. 2022

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BackgroundDue to their low cost, less invasive nature, and ready availability, plasma biomarkers of Alzheimer's disease have been proposed as one-time screening tools for clinical trials and research. The impact of ethnoracial factors on these biomarkers has received little attention. The current cross-sectional study investigated the levels of Aβ40, Aβ42, total tau (t tau), and neurofilament light (NfL) across diagnoses for each of the three major ethnoracial groups in the United States in a community-based cohort of older adults.MethodsA total of 1,862 participants (852 Mexican Americans (MAs); 775 non-Hispanic Whites (NHWs), and 235 African Americans (AAs)) drawn from The Health & Aging Brain Study—Health Disparities (HABS-HD) study were included. Diagnoses were assigned using an algorithm (decision tree) verified by consensus review. Plasma samples were assayed using Simoa technology. Levels of each biomarker were compared for the three ethnoracial groups across cognitive diagnoses using ANOVA covarying sex and age.ResultsSignificant differences were found across the groups at each level of cognitive impairment. Cognitively unimpaired (CU) AA had significantly lower levels of each of the biomarkers than cognitively unimpaired MA or NHW and NHW had higher levels of Aβ40, and NfL than the other two groups. MA had higher t tau than AA or NHW. Mild cognitive impairment (MCI) group NHW had the highest levels on all the biomarkers and AA had the lowest. NHW and MA have higher levels of Aβ40, Aβ42, and t tau there was no difference between the groups for Aβ42. NHW had significantly higher levels of Aβ40, t tau, and NfL than AA. AA had a higher Aβ42/Aβ40 ratio than either NHW or MA for CU MCI.ConclusionsThe use of plasma biomarkers of cognitive decline is promising given their advantages over other biomarkers such as CSF and imaging but as the current research shows, ethnoracial differences must be considered to enhance accuracy and utility. Developing ethnoracial-specific cut points and establishing normative ranges by assay platform for each of the biomarkers are needed. Longitudinal research to assess changes in biomarkers during a cognitive decline is ongoing.

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Alzheimer disease in African American individuals: increased incidence or not enough data?

Cited by 93 publications

References 90 publications

Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light

Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light

Brain-Derived Neurotrophic Factor: A Connecting Link Between Nutrition, Lifestyle, and Alzheimer’s Disease

Characterizing Plasma Biomarkers of Alzheimer's in a Diverse Community-Based Cohort: A Cross-Sectional Study of the HAB-HD Cohort

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