Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults

Chirag M. Vyas; Ruslan I. Sadreyev; Jennifer R. Gatchel; Jae H. Kang; Charles F. Reynolds; David Mischoulon; Grace Chang; Aditi Hazra; Joann E. Manson; Deborah Blacker; Immaculata De Vivo; Olivia I. Okereke

doi:10.3233/JAD-230093

Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults

Chirag M. Vyas, Ruslan I. Sadreyev, Jennifer R. Gatchel, Jae H. Kang, Charles F. Reynolds, David Mischoulon, Grace Chang, Aditi Hazra, Joann E. Manson, Deborah Blacker, Immaculata De Vivo, Olivia I. Okereke

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Background: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. Objective: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. Methods: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. Results: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. Conclusion: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition.

Original language	English
Pages (from-to)	1563-1575
Number of pages	13
Journal	Journal of Alzheimer's Disease
Volume	93
Issue number	4
DOIs	https://doi.org/10.3233/JAD-230093
State	Published - 13 Jun 2023
Externally published	Yes

Keywords

Alzheimer's disease
DNA methylation
cognition
epigenetics
neuropsychiatric symptoms

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10.3233/JAD-230093

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Vyas, C. M., Sadreyev, R. I., Gatchel, J. R., Kang, J. H., Reynolds, C. F., Mischoulon, D., Chang, G., Hazra, A., Manson, J. E., Blacker, D., De Vivo, I., & Okereke, O. I. (2023). Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults. Journal of Alzheimer's Disease, 93(4), 1563-1575. https://doi.org/10.3233/JAD-230093

@article{8ae385e90ee84dfb85a5faff0cb04e80,

title = "Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults",

abstract = "Background: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. Objective: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. Methods: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. Results: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. Conclusion: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition.",

keywords = "Alzheimer's disease, DNA methylation, cognition, epigenetics, neuropsychiatric symptoms",

author = "Vyas, {Chirag M.} and Sadreyev, {Ruslan I.} and Gatchel, {Jennifer R.} and Kang, {Jae H.} and Reynolds, {Charles F.} and David Mischoulon and Grace Chang and Aditi Hazra and Manson, {Joann E.} and Deborah Blacker and {De Vivo}, Immaculata and Okereke, {Olivia I.}",

year = "2023",

month = jun,

day = "13",

doi = "10.3233/JAD-230093",

language = "English",

volume = "93",

pages = "1563--1575",

journal = "Journal of Alzheimer's Disease",

issn = "1387-2877",

publisher = "SAGE Publications Ltd",

number = "4",

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Vyas, CM, Sadreyev, RI, Gatchel, JR, Kang, JH, Reynolds, CF, Mischoulon, D, Chang, G, Hazra, A, Manson, JE, Blacker, D, De Vivo, I & Okereke, OI 2023, 'Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults', Journal of Alzheimer's Disease, vol. 93, no. 4, pp. 1563-1575. https://doi.org/10.3233/JAD-230093

TY - JOUR

T1 - Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults

AU - Vyas, Chirag M.

AU - Sadreyev, Ruslan I.

AU - Gatchel, Jennifer R.

AU - Kang, Jae H.

AU - Reynolds, Charles F.

AU - Mischoulon, David

AU - Chang, Grace

AU - Hazra, Aditi

AU - Manson, Joann E.

AU - Blacker, Deborah

AU - De Vivo, Immaculata

AU - Okereke, Olivia I.

PY - 2023/6/13

Y1 - 2023/6/13

N2 - Background: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. Objective: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. Methods: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. Results: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. Conclusion: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition.

AB - Background: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. Objective: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. Methods: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. Results: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. Conclusion: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition.

KW - Alzheimer's disease

KW - DNA methylation

KW - cognition

KW - epigenetics

KW - neuropsychiatric symptoms

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U2 - 10.3233/JAD-230093

DO - 10.3233/JAD-230093

M3 - Article

C2 - 37212116

AN - SCOPUS:85163921301

SN - 1387-2877

VL - 93

SP - 1563

EP - 1575

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 4

ER -

Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults

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Keywords

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