TY - JOUR
T1 - The ApoE4 genotype modifies the relationship of long-term glycemic control with cognitive functioning in elderly with type 2 diabetes
AU - Ravona-Springer, Ramit
AU - Heymann, Anthony
AU - Schmeidler, James
AU - Sano, Mary
AU - Preiss, Rachel
AU - Koifman, Keren
AU - Hoffman, Hadas
AU - Silverman, Jeremy M.
AU - Beeri, Michal Schnaider
N1 - Funding Information:
This study was supported by the American Federation for Aging Research (AFAR), Young Investigator Award 2011 and NIRG-11-205083 Alzheimer׳s Association , 2012 for Dr. Ravona-Springer, NIA grant R01 AG034087 for Dr. Beeri and P50 AG05138 for Dr. Sano as well as the Helen Bader Foundation and the Irma T. Hirschl Scholar Award for Dr. Beeri.
Funding Information:
This study was funded by American Federation for Aging Research (AFAR), Young investigator award 2011 and NIRG-11-205083 Alzheimer׳s Association, 2012 for Dr. Ravona-Springer, NIA grant R01 AG034087 for Dr. Beeri and P50 AG05138 for Dr. Sano as well as the Helen Bader Foundation and the Irma T. Hirschl Scholar Award for Dr. Beeri. The above mentioned organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - ApoE
KW - Cognition
KW - Glycemic control
KW - HbA1c
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84905020513&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2014.05.001
DO - 10.1016/j.euroneuro.2014.05.001
M3 - Article
C2 - 24875283
AN - SCOPUS:84905020513
SN - 0924-977X
VL - 24
SP - 1303
EP - 1308
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 8
ER -