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Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia

Sugden, Karen, Caspi, Avshalom, Elliott, Maxwell L., Bourassa, Kyle J., Chamarti, Kartik, Corcoran, David L., Hariri, Ahmad R., Houts, Renate M., Kothari, Meeraj, Kritchevsky, Stephen, Kuchel, George A., Mill, Jonathan S., Williams, Benjamin S., Belsky, Daniel W., Moffitt, Terrie E., for the Alzheimer's Disease Neuroimaging Initiative*·2022·Neurology
DOI 10.1212/wnl.0000000000200898PMC PMC9576288
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Figure 1 Correlations Between the 5 DNA Methylation Measures of Aging in ADNI The matrix above the diagonal plots the Pearson r statistic (with cell color depicting magnitude from light = low to dark = high), while the matrix below the diagonal shows the scatterplots for each comparison. The red dotted line describes the linear regression line. Correlations are adjusted for sex.
Figure 1 Correlations Between the 5 DNA Methylation Measures of Aging in ADNI The matrix above the diagonal plots the Pearson r statistic (with cell color depicting magnitude from light = low to dark = high), while the matrix below the diagonal shows the scatterplots for each comparison. The red dotted line describes the linear regression line. Correlations are adjusted for sex.CC BY · PubMed Central
Figure 2 Mean DNA Methylation Age Advancement Values in Aging in ADNI Within Each of the 3 Diagnostic Categories Values are grouped by diagnostic category at the time of interview: CN (blue bars), MCI (gold bars), and Dementia (grey bars). The 3 diagnostic status groups did not differ significantly from one another on either of the first-generation DNA methylation clocks (Horvath and Hannum clocks) or on the second-generation clocks (PhenoAge and GrimAge). By contrast, individuals with MCI or Dementia had faster DunedinPACE scores than those who were CN. Bars represent means, and whiskers represent 95% CIs. Values are standardized to mean = 0, SD = 1. CN = cognitively normal; MCI = mild cognitive impairment.
Figure 2 Mean DNA Methylation Age Advancement Values in Aging in ADNI Within Each of the 3 Diagnostic Categories Values are grouped by diagnostic category at the time of interview: CN (blue bars), MCI (gold bars), and Dementia (grey bars). The 3 diagnostic status groups did not differ significantly from one another on either of the first-generation DNA methylation clocks (Horvath and Hannum clocks) or on the second-generation clocks (PhenoAge and GrimAge). By contrast, individuals with MCI or Dementia had faster DunedinPACE scores than those who were CN. Bars represent means, and whiskers represent 95% CIs. Values are standardized to mean = 0, SD = 1. CN = cognitively normal; MCI = mild cognitive impairment.CC BY · PubMed Central
Figure 3 DunedinPACE Values by Test Score Quintile for the Rey Auditory Verbal Learning Test, Logical Memory Test, and Trail Making Test Cognitive Assessments in Aging in ADNI Faster DunedinPACE was associated with poorer learning and memory (RAVLT, immediate recall [A] and percent forgotten [B]), episodic memory (Logical Memory test [C]), and executive functioning (Trail Making Test, Part B [D]). Cognitive function scores (x-axis) are binned into quintiles (1–5); grey dots represent mean age advancement value, and whiskers represent 95% CIs. The y-axis represents DunedinPACE (age-residualized, adjusted for sex, and standardized to mean = 0, SD = 1).
Figure 3 DunedinPACE Values by Test Score Quintile for the Rey Auditory Verbal Learning Test, Logical Memory Test, and Trail Making Test Cognitive Assessments in Aging in ADNI Faster DunedinPACE was associated with poorer learning and memory (RAVLT, immediate recall [A] and percent forgotten [B]), episodic memory (Logical Memory test [C]), and executive functioning (Trail Making Test, Part B [D]). Cognitive function scores (x-axis) are binned into quintiles (1–5); grey dots represent mean age advancement value, and whiskers represent 95% CIs. The y-axis represents DunedinPACE (age-residualized, adjusted for sex, and standardized to mean = 0, SD = 1).CC BY · PubMed Central

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Citations

Cites

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Metadata

Authors
Sugden, K., Caspi, A., Elliott, M. L., Bourassa, K. J., Chamarti, K., Corcoran, D. L., Hariri, A. R., Houts, R. M., Kothari, M., Kritchevsky, S., Kuchel, G. A., Mill, J. S., Williams, B. S., Belsky, D. W., Moffitt, T. E., & Initiative*, F. T. A. D. N.
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-09-27
Volume
99
Issue
13
ISSN
  • 0028-3878
  • 1526-632X
DOI
10.1212/wnl.0000000000200898
PMC
PMC9576288
Cited by
156
References
13
Language
en

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