Cognitive function in early and later life is associated with blood glucose in older individuals: analysis of the Lothian Birth Cohort of 1936

Abstract

Aims/hypothesis: The aim of this study was to examine whether cognitive function in early and later life, and decline in cognitive function from age 70 to 79 years, are associated with high blood glucose, as measured by HbA_1c, at baseline (age 70), and changes in blood glucose from age 70 to 79.

Methods: Participants (n = 1091) in the Lothian Birth Cohort of 1936 were examined. Fourteen tests were used to assess cognitive functions, grouped into four domains: visuospatial ability, processing speed, memory and crystallised ability. Test results, and measurements of HbA_1c and other health variables, were collected at each of four waves of assessment: at the mean age of 70, 73, 76 and 79 years. Data on cognitive function at age 11 was also available for this cohort. Latent growth curve modelling was performed and statistical controls for known risk factors were introduced.

Results: Higher age 11 cognitive function predicted lower HbA_1c level at age 70 (p < 0.001). Higher cognitive function at age 70 was related to a comparatively smaller increase in HbA_1c levels from age 70 to 79 (p < 0.001). HbA_1c from age 70 to 79 did not have any consistent association with change in cognitive function from age 70 to 79. These associations survived adjustments for age, sex, education, APOE*ε4, smoking history, cardiovascular disease history, hypertension history, BMI and corrections for multiple testing.

Conclusions/interpretation: Our results show that, among older individuals, high blood glucose is consistently predicted by lower cognitive function. Clinical care that examines and tracks cognitive function, while also taking the positive effects of maintaining cognitive function and emulating healthy behaviours associated with higher cognitive function into account, may be one approach for protecting at-risk individuals from elevated blood glucose and subsequent type 2 diabetes mellitus.

Keywords: Blood glucose; Cognitive decline; Cognitive function; HbA1c; Older age; Type 2 diabetes.

Fig. 1

Simplified path diagram of the hierarchical factor of curves growth model of cognitive function and HbA_1c. Circles represent latent variables and squares represent measured variables. Growth curves, including a latent level and slope factor, were estimated for each cognitive test, and the intercepts and slopes were analysed in a hierarchical model which contained domain and overall factors of both level and slope. Basis coefficients (loadings on the individual test slopes) were fixed at 0, 2.96, 6.72 and 9.79 to precisely represent the amount of time passing between assessments. All loadings on latent level were fixed at 1. Dashed lines indicate the relationships between covariates that were fixed across waves and the overall and domain latent variables. Dotted lines indicate the relationships between covariates that differed between waves and individual measurements at different waves. To preserve interpretability, not all covariate relationships are shown. Solid double-arrowed lines indicate correlations between latent variables. Solid single arrowed lines indicate the variables that load on latent variables. Although only two domains and four tests are shown here, the full model used all 14 tests in the four domains, as described in Methods

Fig. 2

Trajectories of overall and domain-specific cognitive abilities in individuals with and without type 2 diabetes in the Lothian Birth Cohort 1936. Diabetes was defined by reported physician diagnosis or HbA_1c level >48 mmol/mol (6.5%) at wave 1. (a) Overall cognitive ability, composed of the four specific cognitive domains: visuospatial ability (b), processing speed (c), memory (d) and crystallised ability (e). Red line and 95% confidence region, individuals without diabetes; blue line and 95% confidence region, individuals with diabetes. These plots only include data from individuals with data available from all four waves of the Lothian Birth Cohort 1936 study, since including data from all individuals in these plots would bias the means towards a positive direction at older ages, making them unrepresentative of the whole sample

Fig. 3

Path diagram of relationships between level and slope estimates of overall cognitive function (CF) and HbA_1c in the Lothian Birth Cohort 1936 from age 70 to 79 years. In (a), the model includes the covariates shown, as well as age. In (b), the model includes the covariates shown, as well as age and history of CVD and high BP, history of smoking and the presence of an APOE*ε4 allele. In (c), the model includes all the covariates shown, age, and history of CVD, history of high BP, smoking and APOE*ε4, as well as BMI (the latter is demonstrated as a time-varying covariate in ESM Table 2). Numbers presented are standardised estimates with SEM in parentheses. Double-headed arrows between latent variables (circles) indicate correlations. Single-headed arrows from covariates (rectangles) indicate regression effects on latent variables. Dashed lines indicate non-significant correlations, whilst solid lines and ^† indicate significance; The false discovery rate correction for multiple testing was applied to all tested relationships. Additional estimates for domains and controls are presented in ESM Table 2