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Article ; Online: Alzheimer's Disease Biomarkers - Timing Is Everything.

Mayeux, Richard

2024 Volume 390, Issue 8, Page(s) 761–763

MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides ; Biomarkers/analysis ; Disease Progression ; tau Proteins ; Time Factors
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; tau Proteins
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Editorial
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe2400102
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Article ; Online: A global view of the genetic basis of Alzheimer disease.

Reitz, Christiane / Pericak-Vance, Margaret A / Foroud, Tatiana / Mayeux, Richard

Nature reviews. Neurology

2023 Volume 19, Issue 5, Page(s) 261–277

Abstract: The risk of Alzheimer disease (AD) increases with age, family history and informative genetic variants. Sadly, there is still no cure or means of prevention. As in other complex diseases, uncovering genetic causes of AD could identify underlying ... ...

Abstract	The risk of Alzheimer disease (AD) increases with age, family history and informative genetic variants. Sadly, there is still no cure or means of prevention. As in other complex diseases, uncovering genetic causes of AD could identify underlying pathological mechanisms and lead to potential treatments. Rare, autosomal dominant forms of AD occur in middle age as a result of highly penetrant genetic mutations, but the most common form of AD occurs later in life. Large-scale, genome-wide analyses indicate that 70 or more genes or loci contribute to AD. One of the major factors limiting progress is that most genetic data have been obtained from non-Hispanic white individuals in Europe and North America, preventing the development of personalized approaches to AD in individuals of other ethnicities. Fortunately, emerging genetic data from other regions - including Africa, Asia, India and South America - are now providing information on the disease from a broader range of ethnicities. Here, we summarize the current knowledge on AD genetics in populations across the world. We predominantly focus on replicated genetic discoveries but also include studies in ethnic groups where replication might not be feasible. We attempt to identify gaps that need to be addressed to achieve a complete picture of the genetic and molecular factors that drive AD in individuals across the globe.
MeSH term(s)	Middle Aged ; Humans ; Alzheimer Disease/genetics ; Genome-Wide Association Study ; Genetic Predisposition to Disease/genetics ; Mutation ; Ethnicity
Language	English
Publishing date	2023-04-06
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2491514-2
ISSN	1759-4766 ; 1759-4758
ISSN (online)	1759-4766
ISSN	1759-4758
DOI	10.1038/s41582-023-00789-z
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Zs.MG 88: Show issues

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Article: Effects of Vascular Risk Factors on the Association of Blood-Based Biomarkers with Alzheimer's Disease.

Hoost, S S / Brickman, A M / Manly, J J / Honig, L S / Gu, Y / Sanchez, D / Reyes-Dumeyer, D / Lantigua, R A / Kang, M S / Dage, J L / Mayeux, R

Medical research archives

2023 Volume 11, Issue 9

Abstract: Background: Comorbidities may influence the levels of blood-based biomarkers for Alzheimer's disease (AD). We investigated whether differences in risk factors or comorbid conditions might explain the discordance between clinical diagnosis and biomarker ... ...

Abstract	Background: Comorbidities may influence the levels of blood-based biomarkers for Alzheimer's disease (AD). We investigated whether differences in risk factors or comorbid conditions might explain the discordance between clinical diagnosis and biomarker classifications in a multi-ethnic cohort of elderly individuals. Aims: To evaluate the relationship of medical conditions and other characteristics, including body mass index (BMI), vascular risk factors, and head injury, with cognitive impairment and blood-based biomarkers of AD, phosphorylated tau (P-tau 181, P-tau 217), in a multi-ethnic cohort. Methods: Three-hundred individuals, aged 65 and older, were selected from a prospective community-based cohort for equal representation among three racial/ethnic groups: non-Hispanic White, Hispanic/Latino and African American/Black. Participants were classified into four groups based on absence (Asym) or presence (Sym) of cognitive impairment and low (NEG) or high (POS) P-tau 217 or P-tau 181 levels, determined previously in the same cohort: (Asym/NEG, Asym/POS, Sym/NEG, Sym/POS). We examined differences in individual characteristics across the four groups. We performed post-hoc analysis examining the differences across biomarker and cognitive status. Results: P-tau 217 or P-tau 181 positive individuals had lower BMI than P-tau negative participants, regardless of symptom status. Symptomatic and asymptomatic participants did not differ in terms of BMI. BMI was not a mediator of the effect of P-tau 217 or P-tau 181 on dementia. Frequencies of other risk factors did not differ between the four groups of individuals. Conclusions: Participants with higher levels of P-tau 217 or P-tau 181 consistent with AD had lower BMI regardless of whether the individual was symptomatic. These findings suggest that weight loss may change with AD biomarker levels before onset of cognitive decline. They do not support BMI as a confounding variable. Further longitudinal studies could explore the relationship of risk factors with clinical diagnoses and biomarkers.
Language	English
Publishing date	2023-10-04
Publishing country	United States
Document type	Journal Article
ISSN	2375-1916
ISSN	2375-1916
DOI	10.18103/mra.v11i9.4468
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Article ; Online: Clinical practice. Early Alzheimer's disease.

Mayeux, Richard

The New England journal of medicine

2010 Volume 362, Issue 23, Page(s) 2194–2201

MeSH term(s)	Age of Onset ; Aged ; Alzheimer Disease/diagnosis ; Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Alzheimer Disease/psychology ; Cholinesterase Inhibitors/therapeutic use ; Diagnosis, Differential ; Disease Progression ; Humans ; Male ; Memantine/therapeutic use ; Memory Disorders/diagnosis ; Neuropsychological Tests ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
Chemical Substances	Cholinesterase Inhibitors ; Receptors, N-Methyl-D-Aspartate ; Memantine (W8O17SJF3T)
Language	English
Publishing date	2010-06-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcp0910236
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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: Lewis P. Rowland, MD: 1925-2017.

Pedley, Timothy A / Mayeux, Richard

Annals of neurology

2017 Volume 81, Issue 5, Page(s) 620–621

Language	English
Publishing date	2017-05-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.24934
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Article ; Online: CARMA is a new Bayesian model for fine-mapping in genome-wide association meta-analyses.

Yang, Zikun / Wang, Chen / Liu, Linxi / Khan, Atlas / Lee, Annie / Vardarajan, Badri / Mayeux, Richard / Kiryluk, Krzysztof / Ionita-Laza, Iuliana

Nature genetics

2023 Volume 55, Issue 6, Page(s) 1057–1065

Abstract: Fine-mapping is commonly used to identify putative causal variants at genome-wide significant loci. Here we propose a Bayesian model for fine-mapping that has several advantages over existing methods, including flexible specification of the prior ... ...

Abstract	Fine-mapping is commonly used to identify putative causal variants at genome-wide significant loci. Here we propose a Bayesian model for fine-mapping that has several advantages over existing methods, including flexible specification of the prior distribution of effect sizes, joint modeling of summary statistics and functional annotations and accounting for discrepancies between summary statistics and external linkage disequilibrium in meta-analyses. Using simulations, we compare performance with commonly used fine-mapping methods and show that the proposed model has higher power and lower false discovery rate (FDR) when including functional annotations, and higher power, lower FDR and higher coverage for credible sets in meta-analyses. We further illustrate our approach by applying it to a meta-analysis of Alzheimer's disease genome-wide association studies where we prioritize putatively causal variants and genes.
MeSH term(s)	Genome-Wide Association Study/methods ; Bayes Theorem ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2023-05-11
Publishing country	United States
Document type	Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01392-0
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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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: Can estrogen or selective estrogen-receptor modulators preserve cognitive function in elderly women?

Mayeux, R

The New England journal of medicine

2001 Volume 344, Issue 16, Page(s) 1242–1244

MeSH term(s)	Animals ; Cognition/drug effects ; Estrogen Replacement Therapy ; Estrogens/pharmacology ; Estrogens/therapeutic use ; Female ; Humans ; Postmenopause/drug effects ; Postmenopause/psychology ; Raloxifene Hydrochloride/pharmacology ; Raloxifene Hydrochloride/therapeutic use ; Selective Estrogen Receptor Modulators/pharmacology ; Selective Estrogen Receptor Modulators/therapeutic use
Chemical Substances	Estrogens ; Selective Estrogen Receptor Modulators ; Raloxifene Hydrochloride (4F86W47BR6)
Language	English
Publishing date	2001-04-19
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJM200104193441610
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Article: Genomic variation in educational attainment modifies Alzheimer disease risk.

Raghavan, Neha S / Vardarajan, Badri / Mayeux, Richard

Neurology. Genetics

2019 Volume 5, Issue 2, Page(s) e310

Abstract: Objective: To determine the putative protective relationship of educational attainment on Alzheimer disease (AD) risk using Mendelian randomization and to test the hypothesis that by using genetic regions surrounding individually associated single ... ...

Abstract	Objective: To determine the putative protective relationship of educational attainment on Alzheimer disease (AD) risk using Mendelian randomization and to test the hypothesis that by using genetic regions surrounding individually associated single nucleotide polymorphisms (SNPs) as the instrumental variable, we can identify genes that contribute to the relationship. Methods: We performed Mendelian randomization using genome-wide association study summary statistics from studies of educational attainment and AD in two stages. Our instrumental variable comprised (1) 1,271 SNPs significantly associated with educational attainment and (2) individual 2-Mb regions surrounding the genome-wide significant SNPs. Results: A causal inverse relationship between educational attainment and AD was identified by the 1,271 SNPs (odds ratio = 0.63; 95% confidence interval, 0.54-0.74; Conclusions: Educational attainment is an important protective factor for AD. Genomic regions that significantly paralleled the overall causal relationship contain genes expressed in neurons or involved in the regulation of neuronal development.
Language	English
Publishing date	2019-02-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2818607-2
ISSN	2376-7839
ISSN	2376-7839
DOI	10.1212/NXG.0000000000000310
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