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Table 2 Associations between DNA methylation and cognitive impairment

From: Effects of early- and mid-life stress on DNA methylation of genes associated with subclinical cardiovascular disease and cognitive impairment: a systematic review

  Lead Author, Publication Date Exposure Outcome Gene (s) with Greatest Association Regions Analyzed for Methylation Methylation Assessment Summary of Correlations
Human Studies Alelu-Paz et al. 201536 Schizophrenia Memory (MIS), global executive function (FAB), cognitive mental state (MMSE) DISC1, DRD1, GABBR2, HINT1, MB-COMT, RELN, SLC6A4 CpG islands within promoter region of 19 genes analyzed Methylation-specific PCR and bisulfite genomic sequencing No methylated CpGs, regardless of severity of cognitive impairment
Levine et al. 201646 HIV Learning, memory, attention, and motor (battery of tests) Genome-wide HumanMethylation450 Bead Chip Significant positive association between DNA methylation age and diagnosis of HAND
Peter et al. 201645 Postnatal malnourishment Attention (CAARS) ABCF1, COMT, DCTN1-AS1, FOXP2, IFNG, INHBB, MIR200B, RAB3B, SYNGAP1, VARS, VIPR2, WT1 Genome-wide HumanMethylation450 Bead Chip ↑ methylation in 609 and ↓ methylation in 391 CpG sites in autosomal DMRs; < 13 DMRs moderately correlated w/ADHD index; 15 X-linked DMR in males, and 1 in females, associated with attention
Intelligence (WASI) SYNGAP1, ZBTB9 < 3 sites significantly associated with IQ scores; 15 X-linked DMR in males, and 1 in females, associated with IQ scores
Ursini et al. 201147 Obstetric complications and/or stressful life eventss Working memory (n-back task) COMT CpG sites at rs4680 site (C2) analyzed
3 CpG sites within gene promoter analyzed
Pyrosequencing C2 methylation of COMT promoter in Val/Val negatively correlated with stress and positively correlated with working memory accuracy
Animal Studies Cordner et al. 201648 Chronic variable stress Recognition memory (NOR)
Spatial learning and memory (Barnes maze)
Bace1, Bdnf, Gsk3b CpGs within promoter region of Bace1 and Gsk3b analyzed
CpGs in region upstream of Bdnf exon 4 analyzed
Pyrosequencing ↓ methylation of CpGs at TSS-554 and TSS-506 of Bace1 promoter in hippocampus, of TSS-506 and TSS-518 in PFC, and of TSS-506 and TSS-554 in amygdala, and ↑ methylation of TSS-109 of Bdnf exon 4 region all associated with ↓ memory performance; no correlation with CpG sites in Gsk3b
Makhathini et al. 201749 Repetitive stress Recognition memory (NOR) Genome-wide 5-mC DNA Methylation ELISA ↓ global DNA methylation hippocampus in stressed group associated with impairment in memory recall
Zhu et al. 201750 Maternal separation Memory (CFC), spatial learning and memory (MWZ) Nr3c1* 17 CpG sites within promoter region of exon 17 PCR and sequencing ↑ methylation of 14 out of 17 CpG sites within promoter region of exon 17 in hippocampus and induced memory impairment after exposure to anesthesia
  1. sself-report
  2. *reported as GR in Zhu et al. 2017 study
  3. Note: complete list of identified genes is not included for study Peter et al. 2016
  4. ↑ = increased; ↓ = decreased; CAARS Conors Adult Attention Rating Scale; CFC contextual fear conditioning; DLPFC dorsolateral prefrontal cortex; DML differentially methylated loci; FAB frontal assessment battery; MIS Buschke memory impairment screen; MMSE
  5. mini-mental state examination; MWM Morris water maze; NA non-applicable; NOR novel object recognition; PFC prefrontal cortex; RM recognition memory; WASI Wechsler Abbreviated Scale of Intelligence