The Bio‐Hermes Study: Biomarker database developed to investigate blood‐based and digital biomarkers in community‐based, diverse populations clinically screened for Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(4), P. 2752 - 2765

Published: Feb. 28, 2024

Abstract INTRODUCTION Alzheimer's disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many not positive. Use of blood‐based biomarkers may reduce screen failures. METHODS We recruited 755 non‐Hispanic White, 115 Hispanic, 112 Black, and 19 other minority across groups cognitively normal ( n = 417), mild cognitive impairment 312), or AD 272) participants. Plasma beta (Aβ)40, Aβ42, Aβ42/Aβ40, total tau, phosphorylated tau (p‐tau)181, p‐tau217 were measured; PET/CSF 956) determined positivity. Clinical, blood biomarker, ethnicity/race differences associated with status evaluated. RESULTS Greater impairment, older age, carrying an apolipoprotein E (apoE) ε4 allele greater burden. Areas under the receiver operating characteristic curve plasma p‐tau181, positivity ≥ 0.7117 all ethnoracial (p‐tau217, ≥0.8128). Age apoE adjustments imputation biomarker values outside limit quantitation provided small improvement in predictive power. DISCUSSION Blood‐based highly results diverse populations enrolled at clinical sites. Highlights Amyloid (Aβ)42/Aβ40, p‐tau 217 predicted P‐tau was strongest predictor Biomarkers from ethnic, racial, cohorts Community‐based have similar levels populations. A prescreen process assays number

Language: Английский

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Alzheimer’s disease biomarkers and their current use in clinical research and practice

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Language: Английский

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Diagnosis of Alzheimer’s disease using plasma biomarkers adjusted to clinical probability

Nature Aging, Journal Year: 2024, Volume and Issue: 4(11), P. 1529 - 1537

Published: Nov. 12, 2024

Abstract Recently approved anti-amyloid immunotherapies for Alzheimer’s disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need PET CSF testing; however, their interpretation at individual level and circumstances requiring confirmatory testing are poorly understood. Individual-level diagnostic test results requires knowledge prevalence in relation clinical presentation (clinical pretest probability). Here, a study 6,896 individuals evaluated 11 cohort studies six countries, we determined positive negative predictive value five plasma cognitively impaired probability. We observed that p-tau217 could rule with probable AD dementia (positive above 95%). In mild cognitive impairment, depended on patient age. Negative out non-AD syndromes (negative between 90% 99%). Our findings provide framework individual-level biomarkers, suggesting combined phenotyping can identify patients where be ruled without testing.

Language: Английский

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Cognivue Clarity^® characterizes amyloid status and preclinical Alzheimer's disease in biomarker confirmed cohorts in the Bio-Hermes Study

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

Cognivue Clarity® is an FDA-cleared computerized cognitive test to screen for impairment included in the Bio-Hermes Study blood-based and digital biomarkers' ability mild (MCI) Alzheimer's disease (AD). A subset of cognitively normal individuals have amyloid deposition (Preclinical AD) but no current assessment can identify these absence expensive biomarkers. We examined differences Clarity performance between positive negative whether could differentiate True Controls (cognitively normal/amyloid negative), Preclinical AD positive), MCI due (MCI-AD, impaired/amyloid positive). was administered all participants who also had PET Performance compared biomarker-defined groups: (n = 297), 95), MCI-AD 113). global scores distinguished from (p < 0.001) differentiated versus 0.014) 0.001). Three subtests [Shape Discrimination 0.004), Visual Salience 0.008), Adaptive Motor Control 0.004)] 3-test mean AD. The composite correlated with Amyloid (r -0.433) pTau217 -0.400). identified both White Black participants. Clarity, a 10-min battery, screens impairment, characterizes individuals, identifies This has great potential as cost- time-effective strategy enroll prevention trials.

Language: Английский

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Influence of cognitive impairment and race on plasma p‐Tau₂₁₇ in two diverse cohorts

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION Factors influencing plasma Alzheimer's disease (AD) biomarkers remain incompletely understood. Here we evaluated Fujirebio p‐Tau 217 in two diverse cohorts among whom 91% underwent cerebrospinal fluid (CSF) analysis. METHODS Non‐Hispanic White (NHW, n = 113), Black/African American (B/AA, 66), and Chinese (ChA, 38) participants recruited from universities were included. We examined if correlated with CSF clinical factors, differed between racial groups, associated novel proteins. RESULTS 181 strongly ( R 2 0.912) which moderately 0.694). Plasma levels higher greater cognitive impairment but lower B/AA than NHW even after adjusting for . This resulted positive predictive value participants, could be mediated by complement or lysosomal pathways. DISCUSSION Severity of race both influence beyond race‐associated differences Highlights Cognitive associates independent biomarkers. Americans had non‐Hispanic Americans. not explain difference results more false cases according to race. Novel processes race‐related difference.

Language: Английский

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Effect of long-term physical exercise and multidomain interventions on cognitive function and the risk of mild cognitive impairment and dementia in older adults: a systematic review with meta-analysis

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 100, P. 102463 - 102463

Published: Aug. 23, 2024

Language: Английский

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Cognitive Assessment with Cognivue Clarity®: Psychometric Properties and Normative Ranges in a Diverse Population

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 100(2), P. 509 - 523

Published: June 14, 2024

Detecting cognitive impairment in clinical practice is challenging as most instruments do not perform well diverse samples of older adults. These same are often used for eligibility into trials making it difficult to recruit minoritized adults Alzheimer's disease (AD) studies. Cognivue Clarity® an FDA-cleared computerized 10-minute screening platform using adaptive psychophysics detect impairment.

Language: Английский

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Digital Clock and Recall: a digital, process-driven evolution of the Mini-Cog

Frontiers in Human Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Aug. 26, 2024

Introduction Alzheimer’s disease and related dementias (ADRD) represent a substantial global public health challenge with multifaceted impacts on individuals, families, healthcare systems. Brief cognitive screening tools such as the Mini-Cog© can help improve recognition of ADRD in clinical practice, but widespread adoption continues to lag. We compared Digital Clock Recall (DCR), next-generation process-driven adaptation Mini-Cog, original paper-and-pencil version well-characterized trial sample. Methods DCR was administered 828 participants Bio-Hermes-001 (age median ± SD = 72 6.7, IQR 11; 58% female) independently classified cognitively unimpaired ( n 364) or having mild impairment (MCI, 274) dementia likely due AD (DLAD, 190). MCI DLAD cohorts were combined into single impaired group for analysis. Two experienced neuropsychologists rated verbal recall accuracy digitally drawn clocks using Mini-Cog scoring rules. Inter-rater reliability scores computed subset data 508) concordance between rule-based calculated. Results good excellent, Rater 2’s significantly higher than 1’s variation clock p &lt; 0.0001). correlated τ B 0.71, However, cut score 4, identified more cases 47; χ 2 13.26, 0.0005) missed 87). In addition, correctly by 44) vice versa 4; 21.69, Discussion Our findings demonstrate sensitivity DCR, an automated, process-driven, process-based digital Mini-Cog. metrics capture drawing dynamics increase detection diagnosed cohort older individuals.

Language: Английский

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Diagnostic and discriminative accuracy of plasma phosphorylated tau 217 for symptomatic Alzheimerʼs disease in a Chinese cohort

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100092 - 100092

Published: Feb. 1, 2025

Plasma phosphorylated tau at threonine 217 (p-tau217) measured with an ultrasensitive immunoassay method has been demonstrated to be optimal biomarker for Alzheimer's disease (AD). The aim of this study was establish the reference interval plasma p-tau217 in Chinese individuals and evaluate its diagnostic value symptomatic AD. We recruited 150 cognitively unimpaired (CU) individuals, 60 patients AD dementia, 30 mild cognitive impairment (MCI) due AD, 40 frontotemporal lobar degeneration (FTLD), 70 subcortical ischaemic vascular dementia (SIVD). concentrations p-tau217, total tau, amyloid-beta (Aβ)42 Aβ40 were a single-molecule array. outperformed other biomarkers discriminating from CU controls, FTLD patients, SIVD (AUC = 0.983, 0.936, 0.892) MCI controls 0.943). level negatively correlated memory accuracy exceptional even early stages, population.

Language: Английский

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The Cognivue Amyloid Risk Measure (CARM): A Novel Method to Predict the Presence of Amyloid with Cognivue Clarity

Neurology and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

At the present time, clinical detection of individuals who have amyloid in their brain is not possible without expensive biomarkers. The objective study was to test whether Cognivue Clarity® can differentiate True Controls, preclinical Alzheimer's disease (pAD), mild cognitive impairment (MCI) due (MCI-AD), AD, and MCI dementia non-AD etiologies enrolled Bio-Hermes Study. A total 887 completed Clarity, PET scan, blood-based AD Three Clarity subtests differentiated between Controls pAD, versus processes. This finding leveraged develop an amyloid-specific marker, combining three with age using machine learning create 4-point Amyloid Risk Measure (CARM). discriminated cognitively normal from impaired (p < 0.001, Cohen's d = 0.732). CARM by 0.618) biomarkers (p's 0.001). positivity increased across four thresholds Dichotomizing into low (CARM1/CARM2) high (CARM3/CARM4) likelihood provided excellent discrimination for (OR: 3.67; 95% CI 2.76-4.89). categories MCI-AD, (χ2 137.6, p 0.001) majority being CARM1/CARM2, CARM3/CARM4. detects impairment, a derivation benchmarked against used predict presence amyloid. Combining overall score could help identify or etiologies, screen treatment protocols anti-amyloid therapies, enrich trial recruitment, pAD prevention studies. ClinicalTrials. gov identifier, NCT04733989.

Language: Английский

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