Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes

Results from the population-based Mayo Clinic Study of Aging

Alexandra M.V. Wennberg, Clinton E. Hagen, Kelly Edwards, Rosebud O Roberts, Mary Margaret Machulda, David S Knopman, Ronald Carl Petersen, Michelle M Mielke

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics. Methods: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross-sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI. Results: In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7-year follow-up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P <.001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P =.009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P =.014) use were also associated with risk of MCI diagnosis. Conclusions: These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.

Original languageEnglish (US)
Pages (from-to)1114-1120
Number of pages7
JournalInternational Journal of Geriatric Psychiatry
Volume33
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Metformin
Hypoglycemic Agents
Type 2 Diabetes Mellitus
Population
Propensity Score
Insulin
Linear Models
Logistic Models
Sex Education
Exercise Test
Cognitive Dysfunction
Comorbidity
Body Mass Index
Regression Analysis
Diet

Keywords

  • cognition
  • metformin
  • type II diabetes

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

@article{5080ec2d61fd4e67b2a1c5e0240a4df8,
title = "Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes: Results from the population-based Mayo Clinic Study of Aging",
abstract = "Objective: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics. Methods: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross-sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI. Results: In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7-year follow-up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95{\%} CI = 1.64, 4.63, P <.001). Similarly, other oral medications (SHR = 1.96; 95{\%} CI = 1.19, 3.25; P =.009) and insulin (SHR = 3.17; 95{\%} CI = 1.27, 7.92; P =.014) use were also associated with risk of MCI diagnosis. Conclusions: These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.",
keywords = "cognition, metformin, type II diabetes",
author = "Wennberg, {Alexandra M.V.} and Hagen, {Clinton E.} and Kelly Edwards and Roberts, {Rosebud O} and Machulda, {Mary Margaret} and Knopman, {David S} and Petersen, {Ronald Carl} and Mielke, {Michelle M}",
year = "2018",
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T1 - Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes

T2 - Results from the population-based Mayo Clinic Study of Aging

AU - Wennberg, Alexandra M.V.

AU - Hagen, Clinton E.

AU - Edwards, Kelly

AU - Roberts, Rosebud O

AU - Machulda, Mary Margaret

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Mielke, Michelle M

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Objective: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics. Methods: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross-sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI. Results: In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7-year follow-up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P <.001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P =.009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P =.014) use were also associated with risk of MCI diagnosis. Conclusions: These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.

AB - Objective: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics. Methods: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross-sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI. Results: In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7-year follow-up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P <.001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P =.009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P =.014) use were also associated with risk of MCI diagnosis. Conclusions: These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.

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