Abstract
BackgroundHyperglycemia is believed to be a risk factor for cognitive decline, but the longitudinal relationship between hyperglycemia and cognitive decline in the Japanese population is unclear. The present study aimed to clarify the association between blood glucose levels and information processing ability in middle-aged and older adults.MethodsThe subjects were 866 men and 815 women aged 40–79 years not taking medication for diabetes who participated in the first study wave (1997–2000) and then participated at least once in the subsequent six study waves (2000–2012) of the National Institute for Longevity Sciences—Longitudinal Study of Aging, Japan. Hemoglobin A1c (HbA1c) levels were categorized into four groups (< 5.6, 5.6 to < 6.0, 6.0 to < 6.5, ≥ 6.5%), and a mixed-effects model was used to evaluate the effects of the HbA1c level (four groups) on repeated measures of information processing speed. The models also included baseline age, body mass index, ethanol intake, smoking status, educational level, family income, and history of stroke, hypertension, heart disease, and dyslipidemia as covariates.ResultsMean (standard deviation) HbA1c and follow-up time in participants were 5.2 (0.5) % and 10.0 (3.6) years, respectively. A linear mixed model showed that the main effect of the four HbA1c groups on information processing ability was not significant in either men or women, but the interaction of HbA1c and time with information processing speed in the higher HbA1c level groups (≥ 6.5% group in men, 6.0 to < 6.5% and ≥ 6.5% groups in women) was significant compared to the lower HbA1c level (< 5.6%) group (P < 0.05). When the slope of information processing speed by HbA1c level at baseline was examined, the slope of information processing speed in the higher HbA1c level (≥ 6.5%) group was higher than in the lower HbA1c level (< 5.6%) group, both in men (− 0.31/year) and in women (− 0.30/year), as well as in women with an HbA1c level of 6.0 to < 6.5% (− 0.40/year).ConclusionsHigher baseline HbA1c was associated with greater subsequent decline in information processing ability in Japanese community dwellers, even with the pre-clinical HbA1c level (6.0 to < 6.5%) in women. The results suggest that good glycemic control or prevention of hyperglycemia may contribute to maintaining information processing ability.
Highlights
Hyperglycemia is believed to be a risk factor for cognitive decline, but the longitudinal relationship between hyperglycemia and cognitive decline in the Japanese population is unclear
A persistent condition of high blood glucose levels might increase the risk of cognitive decline through the mediation of factors such as arteriosclerosis or glucotoxicity [3], and a cross-sectional study has reported a negative relationship between high Hemoglobin A1c (HbA1c) levels and cognitive function in diabetic patients [4]
In the Atherosclerosis Risk in Communities (ARIC) study with 6-year follow-up, there was a reduction in the digit symbol substitution test (DSST) score in diabetic patients, which was similar to the present study, while no significant relationship was found in the non-diabetic group from which self-reported diabetic patients were excluded [2]
Summary
Hyperglycemia is believed to be a risk factor for cognitive decline, but the longitudinal relationship between hyperglycemia and cognitive decline in the Japanese population is unclear. A persistent condition of high blood glucose levels might increase the risk of cognitive decline through the mediation of factors such as arteriosclerosis or glucotoxicity [3], and a cross-sectional study has reported a negative relationship between high HbA1c levels and cognitive function in diabetic patients [4]. A recent study conducted in the USA reported that a higher HbA1c was associated with poor executive function in persons with cognitive impairment, but not with performance in other cognitive domains [6] Another English longitudinal study of aging (ELSA) reported a significant linear association between HbA1c and the increase in the rate of decline of global cognitive z scores [7]. A Finnish nationwide population-based study with 11-year follow-up reported that higher baseline HOMA-IR and fasting insulin levels predicted poorer verbal fluency performance and verbal fluency, but not word-list learning or word-list delayed recall scores [8]
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