Ramit Ravona-Springer1, Anthony Heymann2, James Schmeidler3, Mary Sano3, Rachel Preiss4, Keren Koifman5, Hadas Hoffman4, Jeremy M Silverman3, Michal Schnaider Beeri6. 1. Memory clinic, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Electronic address: ramit.ravona@sheba.health.gov.il. 2. Department of Family Medicine, University of Tel Aviv, Israel. 3. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA. 4. Maccabi Health Services, Israel. 5. Memory clinic, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 6. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA; Josef Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Abstract
AIM: To assess whether the APOE4 genotype affects the relationship of long-term glycemic control with cognitive function in elderly with type 2 diabetes (T2D). METHODS: Participants were cognitively normal and pertained to a Diabetes Registry which provided access to HbA1c levels and other T2D related factors since 1998. Glycemic control was defined as the mean of all HbA1c measurements available (averaging 18 measurements) per subject. Four cognitive domains (episodic memory, semantic categorization, attention/working memory and executive function), based on factor analysis and an overall cognitive score (the sum of the 4 cognitive domains) were the outcome measures. RESULTS: The analysis included 808 subjects; 107 (11.9%) subjects had ≥1ApoE4 allele. In ApoE4 carriers, higher mean HbA1c level was significantly associated with lower scores on all cognitive measures except attention/working memory (p-values ranging from 0.047 to 0.003). In ApoE4 non-carriers, higher mean HbA1c level was significantly associated with lower scores on executive function, but not with other cognitive measures-despite the larger sample size. Compared to non-carriers, there were significantly stronger associations in ApoE4 carriers for overall cognition (p=0.02), semantic categorization (p=0.03) and episodic memory (p=0.02), and the difference for executive function approached statistical significance (p=0.06). CONCLUSION: In this cross-sectional study of cognitively normal T2D subjects, higher mean HbA1c levels were generally associated with lower cognitive performance in ApoE4 carriers, but not in non-carriers, suggesting that ApoE4 affects the relationship between long-term glycemic control and cognition, so APOE4 carriers may be more vulnerable to the insults of poor glycemic control.
AIM: To assess whether the APOE4 genotype affects the relationship of long-term glycemic control with cognitive function in elderly with type 2 diabetes (T2D). METHODS:Participants were cognitively normal and pertained to a Diabetes Registry which provided access to HbA1c levels and other T2D related factors since 1998. Glycemic control was defined as the mean of all HbA1c measurements available (averaging 18 measurements) per subject. Four cognitive domains (episodic memory, semantic categorization, attention/working memory and executive function), based on factor analysis and an overall cognitive score (the sum of the 4 cognitive domains) were the outcome measures. RESULTS: The analysis included 808 subjects; 107 (11.9%) subjects had ≥1ApoE4 allele. In ApoE4 carriers, higher mean HbA1c level was significantly associated with lower scores on all cognitive measures except attention/working memory (p-values ranging from 0.047 to 0.003). In ApoE4 non-carriers, higher mean HbA1c level was significantly associated with lower scores on executive function, but not with other cognitive measures-despite the larger sample size. Compared to non-carriers, there were significantly stronger associations in ApoE4 carriers for overall cognition (p=0.02), semantic categorization (p=0.03) and episodic memory (p=0.02), and the difference for executive function approached statistical significance (p=0.06). CONCLUSION: In this cross-sectional study of cognitively normal T2D subjects, higher mean HbA1c levels were generally associated with lower cognitive performance in ApoE4 carriers, but not in non-carriers, suggesting that ApoE4 affects the relationship between long-term glycemic control and cognition, so APOE4 carriers may be more vulnerable to the insults of poor glycemic control.
Authors: Lenore J Launer; Michael E Miller; Jeff D Williamson; Ron M Lazar; Hertzel C Gerstein; Anne M Murray; Mark Sullivan; Karen R Horowitz; Jingzhong Ding; Santica Marcovina; Laura C Lovato; James Lovato; Karen L Margolis; Patrick O'Connor; Edward W Lipkin; Joy Hirsch; Laura Coker; Joseph Maldjian; Jeffrey L Sunshine; Charles Truwit; Christos Davatzikos; R Nick Bryan Journal: Lancet Neurol Date: 2011-09-28 Impact factor: 44.182
Authors: José R Carrión-Baralt; Josefina Meléndez-Cabrero; Heide Rodríguez-Ubiñas; James Schmeidler; Michal Schnaider Beeri; Gary Angelo; Mary Sano; Jeremy M Silverman Journal: J Alzheimers Dis Date: 2009 Impact factor: 4.472
Authors: Kristine Yaffe; Cherie Falvey; Nathan Hamilton; Ann V Schwartz; Eleanor M Simonsick; Suzanne Satterfield; Jane A Cauley; Caterina Rosano; Lenore J Launer; Elsa S Strotmeyer; Tamara B Harris Journal: Arch Neurol Date: 2012-09
Authors: R J Caselli; A C Dueck; D E C Locke; M N Sabbagh; G L Ahern; S Z Rapcsak; L C Baxter; R Yaari; B K Woodruff; C Hoffman-Snyder; R Rademakers; S Findley; E M Reiman Journal: Neurology Date: 2011-02-16 Impact factor: 9.910
Authors: A Sugawara; K Kawai; S Motohashi; K Saito; S Kodama; Y Yachi; R Hirasawa; H Shimano; K Yamazaki; H Sone Journal: Diabetologia Date: 2012-05-12 Impact factor: 10.122
Authors: Abigail Livny; Ramit Ravona-Springer; Anthony Heymann; Rachel Priess; Tammar Kushnir; Galia Tsarfaty; Leeron Rabinov; Reut Moran; Hadass Hoffman; Itzik Cooper; Lior Greenbaum; Jeremy Silverman; Mary Sano; Sterling C Johnson; Barbara B Bendlin; Michal Schnaider Beeri Journal: Diabetes Care Date: 2016-04-08 Impact factor: 19.112
Authors: Lior Greenbaum; Ramit Ravona-Springer; Irit Lubitz; James Schmeidler; Itzik Cooper; Mary Sano; Jeremy M Silverman; Anthony Heymann; Michal Schnaider Beeri Journal: Eur Neuropsychopharmacol Date: 2015-11-14 Impact factor: 4.600
Authors: Ana B Martínez-Martínez; Elena Torres-Perez; Nicholas Devanney; Raquel Del Moral; Lance A Johnson; Jose M Arbones-Mainar Journal: Neurobiol Dis Date: 2020-02-19 Impact factor: 5.996
Authors: Christopher S Y Benwell; Paula Davila-Pérez; Peter J Fried; Richard N Jones; Thomas G Travison; Emiliano Santarnecchi; Alvaro Pascual-Leone; Mouhsin M Shafi Journal: Neurobiol Aging Date: 2019-10-14 Impact factor: 4.673
Authors: Timothy M Hughes; Suzanne Craft; Laura D Baker; Mark A Espeland; Stephen R Rapp; Kaycee M Sink; Alain G Bertoni; Gregory L Burke; Rebecca F Gottesman; Erin D Michos; José A Luchsinger; Annette L Fitzpatrick; Kathleen M Hayden Journal: Alzheimers Dement (Amst) Date: 2017-03-31