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Significant Longitudinal Associations between HbA1c Levels and Cognitive Decline

by Lewis Chang, PhD

Decline in cognitive ability progresses over a long period of time and is a risk factor for dementia. The link between type 2 diabetes (T2D) and dementia has been well documented. Mechanistically, T2D may directly induce amyloid accumulation and indirectly increase microvascular disease of the central nervous system. However, the link between T2D and cognitive decline is much less clear.

HbA1c, a biomarker that reflects blood glucose levels over a prior 2-3 month time frame, is an important tool to help diagnose T2D, identify individuals at risk of T2D, and monitor glucose control. Recently, investigators from Chinese Academy of Sciences and Peking University Health Science Center (Beijing, PRC) as well as Imperial College London and University College London (London, UK) conducted a prospective study to examine the association between HbA1c levels and the trajectory of cognitive decline in an elderly population with normal cognition at the beginning of the study1.

More than 5000 men and women aged 50 years and older were recruited from the English Longitudinal Study of Ageing (ELSA) during 2004-2005. Their baseline HbA1c levels ranged from 3.6% (value < 6.0% was classified as normal) to 13.7% (value ≥ 6.5% was classified as T2D). Cognitive tests were conducted at baseline and every 2 years until 2014-2015, and the data were expressed as z scores to allow longitudinal comparison.

The investigators found that increases in HbA1c levels were significantly associated with an increased rate of decline in global cognitive z scores, memory z scores, and executive function z scores, even after adjustment of various factors including age, sex, BMI, education, marital status, depressive symptoms, blood lipid variables, cigarette and alcohol consumption, and major chronic diseases. Also, the rate of decline in these cognitive scores were greater in individuals with T2D.

Although findings from this observational study cannot prove causal relationship between HbA1c and cognitive decline, having repeated measures of cognitive function over a long follow-up period provides a solid assessment of trajectories of cognitive decline. The study authors acknowledged that their study lacked dementia data and therefore could not assess the temporal relationship between HbA1c and incident dementia.

Why is this Clinically Relevant?

  • Higher HbA1c levels are associated with greater decline in cognitive function over 10 years
  • Currently there is no cure of dementia. It is therefore essential to address modifiable risk factors such as T2D as early as possible

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1. Zheng F, Yan L, Yang Z, Zhong B, Xie W. HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing. Diabetologia. 2018;61(4):839-848.


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