INS NYC 2024 Program

Poster	Poster Session 06 Program Schedule 02/15/2024 04:00 pm - 05:15 pm Room: Majestic Complex (Posters 61-120) Poster Session 06: Aging \| MCI \| Neurodegenerative Disease - PART 2 Final Abstract #94 Faster DunedinPACE, an Epigenetic Clock for Pace of Biological Aging, is Associated with Accelerated Cognitive Aging Among Older Adults in the Framingham Heart Study Micah Savin, Butler Columbia Aging Center, New York City, United States Stephanie Assuras, Columbia University Irving Medical Center, New York City, United States Calen Ryan, Butler Columbia Aging Center, New York City, United States Daniel Belsky, Butler Columbia Aging Center, New York City, United States Category: Aging Keyword 1: aging (normal) Keyword 2: cognitive functioning Keyword 3: genetic neuropsychology Objective: Biomarkers that predict the heterogenous nature and late onset of cognitive decline are needed to: 1) advance research identifying risk and resiliency, and 2) to evaluate geroscience interventions designed to delay or prevent the progression of Alzheimer’s Disease and related dementias (ADRD). The DunedinPACE epigenetic clock is designed to measure pace of biological aging, a major risk factor for cognitive decline, and is therefore a promising candidate biomarker. In prior studies, we showed that the DunedinPACE epigenetic clock was predictive of general cognition in mid-life adults and dementia in older adults. Here we (1) investigate if DunedinPACE is longitudinally associated with cognitive aging, (2) the extent to which these associations are independent of education and (3) explore if education modifies DunedinPACE’s associations with cognitive aging. Participants and Methods: We analyzed data from the Framingham Heart Study Offspring Cohort. Our analysis sample included participants with neuropsychological testing data and blood DNA methylation data collected within 14 months of their baseline cognitive assessment (n=2,296 non-Hispanic White adults, 46% male; M age=61.6 ± 9.0 [25-101y]). Comprehensive cognitive assessments were performed annually for up to 12 years (Mdn follow up visits=3 visits; Mdn visit interval duration=362 days). The DunedinPACE epigenetic clock was measured from Illumina 450k microarray DNA methylation data (Belsky et al., 2022). Global cognition was calculated according to the methods described in Au et al. (2004) and Downer et al. (2015). Education was measured as years of completed schooling. A series of growth curve models tested the interactive effects of DundeinPACE and education upon baseline and longitudinal changes in global unadjusted T scores. All models included covariates to adjust for cellular composition of blood samples, smoking status, gender, age at baseline (specified as a quadratic term), and date of blood draw. Results: A faster DunedinPACE was associated with worse global cognition, and steeper decline in cognition over time (Bs=-.37 - -.45; ps<.001). After adjusting for education, DunedinPACE remained robustly associated with global cognition and steeper decline in cognition over time (Bs=-.33 - -38; ps<.01). In effect modification analyses, higher education buffered the effect of faster DunedinPACE upon global cognition at baseline (B=-.21; p<.01), but did not significantly modify the effect of DunedinPACE upon cognitive decline over time (p=.95). Conclusions: The presented findings support prior work that highlight the role of systemic biological aging in cognitive decline, and further validates the utility of the epigenetic clock, DunedinPACE, as a potential biomarker for decline in cognitive aging. Further validation of DunedinPACE and its clinical utility as a biomarker for geroscience interventions targeting ADRD is warranted. Greater years of education appears to mitigate some of the deleterious effect of biological aging upon cognition, consistent with the available literature suggesting that education remains an important area of potential intervention. Future studies should critically examine these relationships among nationally representative samples and diverse samples disproportionately impacted by ADRD.

Poster

02/15/2024
04:00 pm - 05:15 pm
Room: Majestic Complex (Posters 61-120)

Poster Session 06: Aging | MCI | Neurodegenerative Disease - PART 2

Final Abstract #94

Faster DunedinPACE, an Epigenetic Clock for Pace of Biological Aging, is Associated with Accelerated Cognitive Aging Among Older Adults in the Framingham Heart Study

Micah Savin, Butler Columbia Aging Center, New York City, United States
Stephanie Assuras, Columbia University Irving Medical Center, New York City, United States
Calen Ryan, Butler Columbia Aging Center, New York City, United States
Daniel Belsky, Butler Columbia Aging Center, New York City, United States

Category: Aging

Keyword 1: aging (normal)
Keyword 2: cognitive functioning
Keyword 3: genetic neuropsychology

Objective:

Biomarkers that predict the heterogenous nature and late onset of cognitive decline are needed to: 1) advance research identifying risk and resiliency, and 2) to evaluate geroscience interventions designed to delay or prevent the progression of Alzheimer’s Disease and related dementias (ADRD). The DunedinPACE epigenetic clock is designed to measure pace of biological aging, a major risk factor for cognitive decline, and is therefore a promising candidate biomarker. In prior studies, we showed that the DunedinPACE epigenetic clock was predictive of general cognition in mid-life adults and dementia in older adults. Here we (1) investigate if DunedinPACE is longitudinally associated with cognitive aging, (2) the extent to which these associations are independent of education and (3) explore if education modifies DunedinPACE’s associations with cognitive aging.

Participants and Methods:

We analyzed data from the Framingham Heart Study Offspring Cohort. Our analysis sample included participants with neuropsychological testing data and blood DNA methylation data collected within 14 months of their baseline cognitive assessment (n=2,296 non-Hispanic White adults, 46% male; M age=61.6 ± 9.0 [25-101y]). Comprehensive cognitive assessments were performed annually for up to 12 years (Mdn follow up visits=3 visits; Mdn visit interval duration=362 days). The DunedinPACE epigenetic clock was measured from Illumina 450k microarray DNA methylation data (Belsky et al., 2022). Global cognition was calculated according to the methods described in Au et al. (2004) and Downer et al. (2015). Education was measured as years of completed schooling. A series of growth curve models tested the interactive effects of DundeinPACE and education upon baseline and longitudinal changes in global unadjusted T scores. All models included covariates to adjust for cellular composition of blood samples, smoking status, gender, age at baseline (specified as a quadratic term), and date of blood draw.

Results:

A faster DunedinPACE was associated with worse global cognition, and steeper decline in cognition over time (Bs=-.37 - -.45; ps<.001). After adjusting for education, DunedinPACE remained robustly associated with global cognition and steeper decline in cognition over time (Bs=-.33 - -38; ps<.01). In effect modification analyses, higher education buffered the effect of faster DunedinPACE upon global cognition at baseline (B=-.21; p<.01), but did not significantly modify the effect of DunedinPACE upon cognitive decline over time (p=.95).

Conclusions:

The presented findings support prior work that highlight the role of systemic biological aging in cognitive decline, and further validates the utility of the epigenetic clock, DunedinPACE, as a potential biomarker for decline in cognitive aging. Further validation of DunedinPACE and its clinical utility as a biomarker for geroscience interventions targeting ADRD is warranted. Greater years of education appears to mitigate some of the deleterious effect of biological aging upon cognition, consistent with the available literature suggesting that education remains an important area of potential intervention. Future studies should critically examine these relationships among nationally representative samples and diverse samples disproportionately impacted by ADRD.