Abstract
AbstractBackgroundIndividuals with type 2 diabetes (T2D) are at particularly high risk for cognitive decline and dementia. Finding early, pre‐clinical biomarkers for detecting and tracking cognitive impairment and dementia in this population is important for personalized medicine approach. Our study aims to find blood DNA methylation biomarkers for cognitive decline among elderly T2D patients.MethodTwo groups of 30 T2D subjects each, from the Israel Diabetes and Cognitive Decline (IDCD) cohort, were included. One group (converters) was cognitively normal at baseline, yet at 36‐54 months follow‐up deteriorated from a Clinical Dementia Rating scale CDR = 0 (no dementia) to CDR≥0.5 (questionable dementia or frank dementia). The control group (non‐converters) was cognitively normal at baseline and maintained normal cognition during the follow‐up period (CDR = 0). We performed an epigenome‐wide association study, using the Illumina Infinium MethylationEPIC microarray, and searched for differentially methylated positions (DMPs) with significant methylation alterations (≥ 2 fold and FDR corrected p value <0.05) between the baseline and the follow‐up time points for each of the two groups.ResultParticipants were 65‐83 years of age (mean‐73.6 ± 4.1), 72% were men. The mean hemoglobin A1C value was 6.9 ± 0.8%, and T2D duration was 9.4 ± 4.7 years. Converters and non‐converters did not differ in any of these characteristics. Results show significant changes in multiple DMPs among the converters, but only in a few DMPs in the non‐converters. Gene ontology analyses indicates primarily involvement of central nervous system‐related pathways, mainly neurodevelopmental disorders.ConclusionThese preliminary results, employing a high‐throughput approach for methylation profile in blood, suggest methylomic alterations as a potential biomarker for cognitive decline in T2D elderly. A priori identification of patients at risk for cognitive decline may lead to early intervention in modifiable risk factors in this population, which is highly susceptible to dementia.
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