Lior Greenbaum1,2,3, Ramit Ravona-Springer1,4,5, Abigail Livny1,6, Shahar Shelly1,3, Inbal Sharvit-Ginon1,7, Ithamar Ganmore1,3, Anna Alkelai8, Anthony Heymann5,9, Michal Schnaider Beeri1,10. 1. The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel. 2. The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel. 3. Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel. 4. Memory Clinic, Sheba Medical Center, Tel Hashomer, Israel. 5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 6. Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 7. Department of Psychology, Bar-Ilan University, Ramat Gan, Israel. 8. Institute for Genomic Medicine, Columbia University, New York, NY, USA. 9. Maccabi Healthcare Services, Tel Aviv, Israel. 10. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
Objectives: Recent large-scale meta-analysis of genome-wide association studies (GWAS) from multiple cohorts, demonstrated the association of the single nucleotide polymorphism (SNP) rs17518584, with processing speed (measured by the Digit Symbol Substitution Test (DSST) or the Letter Digit Substitution Test (LDST)), at GWAS significance level. This SNP is located within the cell adhesion molecule 2 (CADM2) gene. We aimed to validate this finding in our sample of 944 cognitively normal Jewish elderly individuals with type 2 diabetes (T2D), a population which is at risk for cognitive decline and dementia. Methods: Using linear regression, we studied the association of rs17518584 with DSST performance, adjusting for demographic, T2D-related characteristics and cardiovascular factors. In secondary analyses, associations with performance in four cognitive domains (episodic memory, language/semantic categorisation, attention/working memory and executive function) and overall cognition were examined. Results: Controlling for sex, age at cognitive assessment, years of education and ancestry, we found a significant association of rs17518584 with DSST performance (P = 0.013), consistent with the originally reported effect direction. Results remained significant even when the additional covariates (T2D-related and cardiovascular factors) were included in the analysis (P = 0.034). Moreover, this SNP was significantly associated with performance in the cognitive domains of language/semantic categorisation and executive function, as well as overall cognition.Conclusions: Taken together, irrespective of T2D-related characteristics and cardiovascular factors, our findings provide independent support for the association of CADM2 SNP rs17518584 with processing speed (and demonstrate association with additional cognitive phenotypes), among cognitively normal elderly individuals with T2D.
Objectives: Recent large-scale meta-analysis of genome-wide association studies (GWAS) from multiple cohorts, demonstrated the association of the single nucleotide polymorphism (SNP) rs17518584, with processing speed (measured by the Digit Symbol Substitution Test (DSST) or the Letter Digit Substitution Test (LDST)), at GWAS significance level. This SNP is located within the cell adhesion molecule 2 (CADM2) gene. We aimed to validate this finding in our sample of 944 cognitively normal Jewish elderly individuals with type 2 diabetes (T2D), a population which is at risk for cognitive decline and dementia. Methods: Using linear regression, we studied the association of rs17518584 with DSST performance, adjusting for demographic, T2D-related characteristics and cardiovascular factors. In secondary analyses, associations with performance in four cognitive domains (episodic memory, language/semantic categorisation, attention/working memory and executive function) and overall cognition were examined. Results: Controlling for sex, age at cognitive assessment, years of education and ancestry, we found a significant association of rs17518584 with DSST performance (P = 0.013), consistent with the originally reported effect direction. Results remained significant even when the additional covariates (T2D-related and cardiovascular factors) were included in the analysis (P = 0.034). Moreover, this SNP was significantly associated with performance in the cognitive domains of language/semantic categorisation and executive function, as well as overall cognition.Conclusions: Taken together, irrespective of T2D-related characteristics and cardiovascular factors, our findings provide independent support for the association of CADM2 SNP rs17518584 with processing speed (and demonstrate association with additional cognitive phenotypes), among cognitively normal elderly individuals with T2D.
Entities:
Keywords:
CADM2; Digit Symbol Substitution Test; processing speed; cognition; type 2 diabetes
Authors: Andreas-Christian Hade; Mari-Anne Philips; Ene Reimann; Toomas Jagomäe; Kattri-Liis Eskla; Tanel Traks; Ele Prans; Sulev Kõks; Eero Vasar; Marika Väli Journal: Brain Sci Date: 2021-03-29