TY - JOUR
T1 - Females with type 2 diabetes are at higher risk for accelerated cognitive decline than males
T2 - CAROLINA-COGNITION study
AU - Verhagen, Chloë
AU - Janssen, Jolien
AU - Biessels, Geert Jan
AU - Johansen, Odd Erik
AU - Exalto, Lieza G
N1 - Funding Information:
This study was sponsored by Boehringer Ingelheim . The manuscript and data analyses have been prepared independently from Boehringer Ingelheim. LG Exalto is supported by Alzheimer Nederland WE.03-2019-15 .
Publisher Copyright:
© 2021 The Author(s)
PY - 2022/2
Y1 - 2022/2
N2 - BACKGROUND AND AIM: Cognitive dysfunction is increasingly recognized as an important comorbidity of type 2 diabetes (T2D). We aimed to establish if the risk of accelerated cognitive decline (ACD) is higher in females with T2D than males.METHODS AND RESULTS: 3163 participants (38% female) with T2D from the cognition substudy of CAROLINA® (NCT01243424) were included (mean age 64.4 ± 9.2 years; T2D duration 7.6 ± 6.1 years). The cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning (Trail Making and Verbal Fluency Test). Potential confounders, were taken into account at an individual patient level. Logistic regression analysis was used to investigate ACD risk by sex. We assessed potential mediators for sex differences in ACD using Causal Mediation Analysis (CMA). After a median follow-up duration of 6.1 ± 0.7 years, 361 (30.0%) females compared to 494 (25.2%) males exhibited ACD (OR 1.27 [95%CI 1.08-1.49], p = .003). Depressive symptoms, which were more common in females (24.3% vs 12.5%), mediated between sex and ACD (mediation effect 20.3%, p = 0.03). There were no other significant mediators.CONCLUSION: Females with T2D had a higher risk of ACD compared to males. This was partly explained by depressive symptoms. After evaluation of vascular and diabetes-related risk factors, complications and treatment, a major share of the higher risk of ACD in females remained unexplained. Our results highlight the need for further research on causes of sex-specific ACD in T2D.
AB - BACKGROUND AND AIM: Cognitive dysfunction is increasingly recognized as an important comorbidity of type 2 diabetes (T2D). We aimed to establish if the risk of accelerated cognitive decline (ACD) is higher in females with T2D than males.METHODS AND RESULTS: 3163 participants (38% female) with T2D from the cognition substudy of CAROLINA® (NCT01243424) were included (mean age 64.4 ± 9.2 years; T2D duration 7.6 ± 6.1 years). The cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning (Trail Making and Verbal Fluency Test). Potential confounders, were taken into account at an individual patient level. Logistic regression analysis was used to investigate ACD risk by sex. We assessed potential mediators for sex differences in ACD using Causal Mediation Analysis (CMA). After a median follow-up duration of 6.1 ± 0.7 years, 361 (30.0%) females compared to 494 (25.2%) males exhibited ACD (OR 1.27 [95%CI 1.08-1.49], p = .003). Depressive symptoms, which were more common in females (24.3% vs 12.5%), mediated between sex and ACD (mediation effect 20.3%, p = 0.03). There were no other significant mediators.CONCLUSION: Females with T2D had a higher risk of ACD compared to males. This was partly explained by depressive symptoms. After evaluation of vascular and diabetes-related risk factors, complications and treatment, a major share of the higher risk of ACD in females remained unexplained. Our results highlight the need for further research on causes of sex-specific ACD in T2D.
KW - Accelerated cognitive decline
KW - Cardiovascular disease
KW - Dementia
KW - Females
KW - Gender
KW - Sex differences
KW - Type 2 diabetes
KW - Women
UR - http://www.scopus.com/inward/record.url?scp=85120827227&partnerID=8YFLogxK
U2 - 10.1016/j.numecd.2021.10.013
DO - 10.1016/j.numecd.2021.10.013
M3 - Article
C2 - 34895804
SN - 0939-4753
VL - 32
SP - 355
EP - 364
JO - NMCD : Nutrition metabolism and cardiovascular diseases
JF - NMCD : Nutrition metabolism and cardiovascular diseases
IS - 2
ER -