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Article: Reliability and Validity of self-reported Vascular Risk Factors in a Multi-Ethnic Community Based Study of Aging and Dementia.

Lee, Annie J / Sanchez, Didi / Reyes-Dumeyer, Dolly / Brickman, Adam M / Lantigua, Rafael A / Vardarajan, Badri N / Mayeux, Richard

medRxiv : the preprint server for health sciences

2023

Abstract: Introduction: The reliability and validity of self-reported cardiovascular and cerebrovascular risk factors remains inconsistent in aging research.: Methods: We assessed the reliability, validity, sensitivity, specificity, and percent agreement of ... ...

Abstract	Introduction: The reliability and validity of self-reported cardiovascular and cerebrovascular risk factors remains inconsistent in aging research. Methods: We assessed the reliability, validity, sensitivity, specificity, and percent agreement of self-reported hypertension, diabetes, and heart disease, in comparison with direct measures of blood pressure, hemoglobin A1c (HbA1c), and medication use in 1870 participants in a multiethic study of aging and dementia. Results: Reliability of self-reported for hypertension, diabetes, and heart disease was excellent. Agreement between self-reports and clinical measures was moderate for hypertension (kappa: 0.58), good for diabetes (kappa: 0.76-0.79), and moderate for heart disease (kappa: 0.45) differing slightly by age, sex, education, and race/ethnic group. Sensitivity and specificity for hypertension was 88.6%-78.1%, for diabetes was 87.7%-92.0% (HbA1c > 6.5%) or 92.7%-92.8% (HbA1c > 7%), and for heart disease was 85.8%-75.5%. Discussion: Self-reported history of hypertension, diabetes, and heart disease are reliable and valid compared to direct measurements or medication use.
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.12.23288492
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Article ; Online: Reliability and Validity of Self-Reported Vascular Risk Factors: Hypertension, Diabetes, and Heart Disease, in a Multi-Ethnic Community Based Study of Aging and Dementia.

Lee, Annie J / Sanchez, Didi / Reyes-Dumeyer, Dolly / Brickman, Adam M / Lantigua, Rafael A / Vardarajan, Badri N / Mayeux, Richard

Journal of Alzheimer's disease : JAD

2023 Volume 95, Issue 1, Page(s) 275–285

Abstract: Background: Queries for the presence of cardiovascular and cerebrovascular risk factors are typically assessed through self-report. However, the reliability and validity of self-reported cardiovascular and cerebrovascular risk factors remain ... ...

Abstract	Background: Queries for the presence of cardiovascular and cerebrovascular risk factors are typically assessed through self-report. However, the reliability and validity of self-reported cardiovascular and cerebrovascular risk factors remain inconsistent in aging research. Objective: To determine the reliability and validity of the most frequently self-reported vascular risk factors: hypertension, diabetes, and heart disease. Methods: 1,870 individuals aged 65 years or older among African Americans, Caribbean Hispanics, and white non-Hispanic individuals were recruited as part of a community study of aging and dementia. We assessed the reliability, validity, sensitivity, specificity, and percent agreement of self-reported hypertension, diabetes, and heart disease, in comparison with direct measures of blood pressure, hemoglobin A1c (HbA1c), and medication use. The analyses were subsequently stratified by age, sex, education, and ethnic group. Results: Reliability of self-reported hypertension, diabetes, and heart disease was excellent. Agreement between self-reports and clinical measures was moderate for hypertension (kappa: 0.58), good for diabetes (kappa: 0.76-0.79), and moderate for heart disease (kappa: 0.45) differing slightly by age, sex, education, and ethnic group. Sensitivity and specificity for hypertension was 88.6% -78.1%, for diabetes was 87.7% -92.0% (HbA1c ≥6.5%) or 92.7% -92.8% (HbA1c ≥7%), and for heart disease was 85.8% -75.5%. Percent agreement of self-reported was 87.0% for hypertension, 91.6% -92.6% for diabetes, and 77.4% for heart disease. Conclusion: Ascertainment of self-reported histories of hypertension, diabetes, and heart disease are reliable and valid compared to direct measurements or medication use.
MeSH term(s)	Humans ; Self Report ; Glycated Hemoglobin ; Reproducibility of Results ; Diabetes Mellitus/epidemiology ; Hypertension/epidemiology ; Aging ; Heart Diseases/diagnosis ; Heart Diseases/epidemiology ; Risk Factors ; Dementia/diagnosis ; Dementia/epidemiology
Chemical Substances	Glycated Hemoglobin
Language	English
Publishing date	2023-07-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-230374
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Article ; Online: Risk of Alzheimer's disease is associated with longitudinal changes in plasma biomarkers in the multi-ethnic Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP) cohort.

Gu, Yian / Honig, Lawrence S / Kang, Min Suk / Bahl, Aanya / Sanchez, Danurys / Reyes-Dumeyer, Dolly / Manly, Jennifer J / Dage, Jeffrey L / Lantigua, Rafael A / Brickman, Adam M / Vardarajan, Badri N / Mayeux, Richard

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Volume 20, Issue 3, Page(s) 1988–1999

Abstract: Background: Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination.: ... ...

Abstract	Background: Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination. Methods: In 628 CU individuals from a multi-ethnic cohort, amyloid beta (Aβ)42, Aβ40, phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured in plasma. Results: Higher baseline levels of p-tau181/Aβ42 ratio were associated with an increased risk of incident dementia. A biomarker pattern (with elevated Aβ42/Aβ40 but low p-tau181/Aβ42) was associated with decreased dementia risk. Compared to CU, participants who developed MCI or dementia had a rapid decrease in this protective biomarker pattern reflecting AD-specific pathological change. Discussion: Elevated levels of AD biomarker p-tau181/Aβ42, by itself or combined with a low Aβ42/Aβ40 level, predicts clinically diagnosed AD. Individuals with a rapid change in these biomarkers may need close monitoring for the potential downward trajectory of cognition. Highlights: We discuss a multi-ethnic, urban community study of elderly individuals. The study consisted of a longitudinal assessment over 6 years with repeated clinical assessments. The study used blood-based biomarkers as predictors of mild cognitive impairment and Alzheimer's disease.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease ; Amyloid beta-Peptides ; Washington ; tau Proteins ; Cognitive Dysfunction/diagnosis ; Aging ; Biomarkers
Chemical Substances	Amyloid beta-Peptides ; tau Proteins ; Biomarkers
Language	English
Publishing date	2024-01-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13652
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Article ; Online: Pedigree Selection and Information Content.

Vardarajan, Badri N / Beecham, Gary W / Haines, Jonathan L

Current protocols in human genetics

2018 Volume 97, Issue 1, Page(s) e56

Abstract: In this article, we discuss strategies for selection of families and family members for genetic studies. We will evaluate strategies to sample large families with multiply affected members, sibships, and nuclear families. In addition, we have added a ... ...

Abstract	In this article, we discuss strategies for selection of families and family members for genetic studies. We will evaluate strategies to sample large families with multiply affected members, sibships, and nuclear families. In addition, we have added a section to discuss sub-sampling within pedigrees for large sequencing studies, particularly when genome-wide SNP chips are available on all members of a pedigree. The type of family sampled for a study will determine the statistical analyses and power of discovery of genetic findings. We will evaluate study designs that maximize power and allow for linkage and association analyses to identify genetic loci predisposing to phenotype. © 2018 by John Wiley & Sons, Inc.
MeSH term(s)	Disease/genetics ; Female ; Genetic Linkage ; Genetic Loci ; Genetic Variation ; Genome-Wide Association Study/methods ; Humans ; Linkage Disequilibrium ; Male ; Models, Genetic ; Nuclear Family ; Pedigree ; Phenotype ; Research Design
Language	English
Publishing date	2018-07-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2179054-1
ISSN	1934-8258 ; 1934-8266
ISSN (online)	1934-8258
ISSN	1934-8266
DOI	10.1002/cphg.56
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Article: Rare genetic variation in Fibronectin 1 (

Bhattarai, Prabesh / Gunasekaran, Tamil Iniyan / Reyes-Dumeyer, Dolly / Jülich, Dörthe / Tayran, Hüseyin / Yilmaz, Elanur / Flaherty, Delaney / Lantigua, Rafael / Medrano, Martin / Rivera, Diones / Recio, Patricia / Ertekin-Taner, Nilüfer / Teich, Andrew F / Dickson, Dennis W / Holley, Scott / Mayeux, Richard / Kizil, Caghan / Vardarajan, Badri N

bioRxiv : the preprint server for biology

2024

Abstract: The risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying ... ...

Abstract	The risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying the
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.02.573895
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Article ; Online: Data-Independent Acquisition and Label-Free Quantification for Quantitative Proteomics Analysis of Human Cerebrospinal Fluid.

Makepeace, Karl A T / Rookyard, Alexander W / Das, Lipi / Vardarajan, Badri N / Chakrabarty, Jayanta K / Jain, Anu / Kang, Min Suk / Werth, Emily G / Reyes-Dumeyer, Dolly / Zerlin-Esteves, Marielba / Honig, Lawrence S / Mayeux, Richard / Brown, Lewis M

Current protocols

2024 Volume 4, Issue 3, Page(s) e1014

Abstract: This article presents a practical guide to mass spectrometry-based data-independent acquisition and label-free quantification for proteomics analysis applied to cerebrospinal fluid, offering a robust and scalable approach to probing the proteomic ... ...

Abstract	This article presents a practical guide to mass spectrometry-based data-independent acquisition and label-free quantification for proteomics analysis applied to cerebrospinal fluid, offering a robust and scalable approach to probing the proteomic composition of the central nervous system. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Cerebrospinal fluid sample collection and preparation for mass spectrometry analysis Basic Protocol 2: Mass spectrometry sample analysis with data-independent acquisition Support Protocol: Data-dependent mass spectrometry and spectral library construction Basic Protocol 3: Analysis of mass spectrometry data.
MeSH term(s)	Humans ; Proteomics/methods ; Proteome/analysis ; Mass Spectrometry/methods ; Cerebrospinal Fluid Proteins/chemistry
Chemical Substances	Proteome ; Cerebrospinal Fluid Proteins
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article
ISSN	2691-1299
ISSN (online)	2691-1299
DOI	10.1002/cpz1.1014
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Article: Lysophosphatidylcholines are associated with P-tau181 levels in early stages of Alzheimer's Disease.

Kalia, Vrinda / Reyes-Dumeyer, Dolly / Dubey, Saurabh / Nandakumar, Renu / Lee, Annie J / Lantigua, Rafael / Medrano, Martin / Rivera, Diones / Honig, Lawrence S / Mayeux, Richard / Miller, Gary W / Vardarajan, Badri N

medRxiv : the preprint server for health sciences

2023

Abstract: Background: We investigated systemic biochemical changes in Alzheimer's disease (AD) by investigating the relationship between circulating plasma metabolites and both clinical and biomarker-assisted diagnosis of AD.: Methods: We used an untargeted ... ...

Abstract	Background: We investigated systemic biochemical changes in Alzheimer's disease (AD) by investigating the relationship between circulating plasma metabolites and both clinical and biomarker-assisted diagnosis of AD. Methods: We used an untargeted approach with liquid chromatography coupled to high-resolution mass spectrometry to measure exogenous and endogenous small molecule metabolites in plasma from 150 individuals clinically diagnosed with AD and 567 age-matched elderly without dementia of Caribbean Hispanic ancestry. Plasma biomarkers of AD were also measured including P-tau181, Aβ40, Aβ42, total tau, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Association of individual and co-expressed modules of metabolites were tested with the clinical diagnosis of AD, as well as biologically-defined AD pathological process based on P-tau181 and other biomarker levels. Results: Over 4000 metabolomic features were measured with high accuracy. First principal component (PC) of lysophosphatidylcholines (lysoPC) that bind to or interact with docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AHA) was associated with decreased risk of AD (OR=0.91 [0.89-0.96], p=2e-04). Restricted to individuals without an Conclusions: Our findings indicate that unbiased metabolic profiling can identify critical metabolites and pathways associated with β-amyloid and phosphotau pathology. We also observed an
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.24.23294581
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Article: Risk of Alzheimer's Disease is Associated with Longitudinal Changes in Plasma Biomarkers in the Multiethnic Washington Heights, Inwood Columbia Aging Project Cohort.

Gu, Yian / Honig, Lawrence S / Kang, Min Suk / Bahl, Aanya / Sanchez, Danurys / Reyes-Dumeyer, Dolly / Manly, Jennifer J / Lantigua, Rafael A / Dage, Jeffrey L / Brickman, Adam M / Vardarajan, Badri N / Mayeux, Richard

medRxiv : the preprint server for health sciences

2023

Abstract: Introduction: Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination.: ...

Abstract	Introduction: Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination. Methods: In 628 CU individuals from a multi-ethnic cohort, Aβ42, Aβ40, phosphorylated tau-181 (P-tau181), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL) were measured in plasma. Results: Higher baseline levels of P-tau181/Aβ42 ratio were associated with increased risk of incident dementia. A biomarker pattern (with elevated Aβ42/Aβ40 but low P-tau181/Aβ42) was associated with decreased dementia risk. Compared to CU, participants who developed MCI or dementia had a rapid decrease in the biomarker pattern reflecting AD-specific pathological change. Discussion: Elevated levels of AD biomarker P-tau181/Aβ42, by itself or combined with a low Aβ42/Aβ40 level, predicts clinically diagnosed AD. Individuals with a rapid change in these biomarkers may need close monitoring for the potential downward trajectory of cognition.
Language	English
Publishing date	2023-08-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.11.23293967
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Article: ABCA7-dependent Neuropeptide-Y signalling is a resilience mechanism required for synaptic integrity in Alzheimer's disease.

bioRxiv : the preprint server for biology

2024

Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.02.573893
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Article ; Online: A comparative study of structural variant calling in WGS from Alzheimer's disease families.

Malamon, John S / Farrell, John J / Xia, Li Charlie / Dombroski, Beth A / Das, Rueben G / Way, Jessica / Kuzma, Amanda B / Valladares, Otto / Leung, Yuk Yee / Scanlon, Allison J / Lopez, Irving Antonio Barrera / Brehony, Jack / Worley, Kim C / Zhang, Nancy R / Wang, Li-San / Farrer, Lindsay A / Schellenberg, Gerard D / Lee, Wan-Ping / Vardarajan, Badri N

Life science alliance

2024 Volume 7, Issue 5

Abstract: Detecting structural variants (SVs) in whole-genome sequencing poses significant challenges. We present a protocol for variant calling, merging, genotyping, sensitivity analysis, and laboratory validation for generating a high-quality SV call set in ... ...

Abstract	Detecting structural variants (SVs) in whole-genome sequencing poses significant challenges. We present a protocol for variant calling, merging, genotyping, sensitivity analysis, and laboratory validation for generating a high-quality SV call set in whole-genome sequencing from the Alzheimer's Disease Sequencing Project comprising 578 individuals from 111 families. Employing two complementary pipelines, Scalpel and Parliament, for SV/indel calling, we assessed sensitivity through sample replicates (N = 9) with in silico variant spike-ins. We developed a novel metric, D-score, to evaluate caller specificity for deletions. The accuracy of deletions was evaluated by Sanger sequencing. We generated a high-quality call set of 152,301 deletions of diverse sizes. Sanger sequencing validated 114 of 146 detected deletions (78.1%). Scalpel excelled in accuracy for deletions ≤100 bp, whereas Parliament was optimal for deletions >900 bp. Overall, 83.0% and 72.5% of calls by Scalpel and Parliament were validated, respectively, including all 11 deletions called by both Parliament and Scalpel between 101 and 900 bp. Our flexible protocol successfully generated a high-quality deletion call set and a truth set of Sanger sequencing-validated deletions with precise breakpoints spanning 1-17,000 bp.
MeSH term(s)	Humans ; Alzheimer Disease/genetics ; Whole Genome Sequencing/methods
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202302181
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