{"doi":"10.3233/jad-230093","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.","journal":"Journal of Alzheimer s Disease","year":2023,"id":342695,"datarank":0.5862507268094338,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.18004319664410226,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.18004319664410226,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":14,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9299,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01169259","NCT01696435"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260528,"name":"Ruslan I. Sadreyev","orcid":"0000-0002-4240-5466","position":1,"is_corresponding":false},{"id":467491,"name":"Jennifer R. Gatchel","orcid":"0000-0002-3892-9742","position":2,"is_corresponding":false},{"id":6854,"name":"Jae H. Kang","orcid":"0000-0003-4812-0557","position":3,"is_corresponding":false},{"id":303746,"name":"Charles F. Reynolds","orcid":"0000-0002-2605-7887","position":4,"is_corresponding":false},{"id":320517,"name":"David Mischoulon","orcid":"0000-0001-7233-5860","position":5,"is_corresponding":false},{"id":323419,"name":"Grace Chang","orcid":"0000-0002-5508-3013","position":6,"is_corresponding":false},{"id":238430,"name":"Aditi Hazra","orcid":"0000-0003-2563-0239","position":7,"is_corresponding":false},{"id":11268,"name":"JoAnn E. Manson","orcid":"0000-0002-9426-7595","position":8,"is_corresponding":false},{"id":19607,"name":"Deborah Blacker","orcid":"0000-0001-6107-7376","position":9,"is_corresponding":false},{"id":55318,"name":"Immaculata De Vivo","orcid":"0000-0002-7185-7402","position":10,"is_corresponding":false},{"id":323420,"name":"Olivia I. Okereke","orcid":"0000-0002-9523-2693","position":11,"is_corresponding":false},{"id":323417,"name":"Chirag M. Vyas","orcid":"0000-0002-4262-2786","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:11:17.288563Z","pmid":"37212116","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}