HbA1c Levels in Diabetes Linked to Cognitive Decline

Nancy A Melville

January 30, 2018

Patients with diabetes, determined by higher than normal hemoglobin A1c (HbA1c) levels, show greater increases in cognitive decline over 10 years compared to those with normal blood sugar, suggesting that good blood glucose control could help slow possible progression to dementia.

"To the best of our knowledge, this is the first prospective study of the association between diabetes (assessed using HbA1c levels) and cognitive decline that analyzes data from more than three cognitive assessments over time," the authors write.

The association between diabetes and dementia is well known, however evidence of the link between diabetes, the role of HbA1c, and cognitive decline — which can occur years prior to dementia — is lacking.

The study was published online January 25 in Diabetologia, the journal of the European Association for the Study of Diabetes, by Fanfan Zheng, PhD, of the Chinese Academy of Sciences, Beijing, and Institute of Cognitive Neuroscience, University College, London, UK, and colleagues.

Compared with individual fasting or post-load blood glucose measurements, HbA1c has gained ground in the diagnosis and management of diabetes, showing greater reliability in predicting diabetes and indicating average circulating glucose levels over the prior 2 to 3 months, the authors say.

More Than Three Cognitive Assessments Over 10 Years

To take a closer look, researchers evaluated data on 5189 participants aged 50 years and older enrolled in the English Longitudinal Study of Aging (ELSA) who had cognitive function assessed at baseline, between 2004–2005 (wave 2), and every 2 years through to 2014–2015 (wave 7).

Participants were a mean age of 66 years, and 55% were women. Baseline HbA1c ranged from 3.6% to 13.7% (15.9 to 126.3 mmol/mol). Diabetes was defined as HbA1c 6.5% (48 mmol/mol) or greater.

With a mean follow-up of 8.1 years and mean a number of 4.9 cognitive assessments, the results showed that each 1 mmol/mol increment in HbA1c was associated with an increased rate of decline in global cognitive z scores (–0.0009 SD/year), memory z scores (–0.0005 SD/year), and executive function z scores (–0.0008 SD/year).

The declines were seen after adjustment for wide-ranging factors, including age, sex, cholesterol levels, body mass index, education, depressive symptoms, tobacco and alcohol use, hypertension, coronary heart disease, stroke, and cancer.

Compared with cognitive decline seen as part of normal aging over the duration of the study in those without diabetes, the rate of cognitive decline after multivariable adjustment in those with prediabetes (defined as an HbA1c 38.8–46.4 mmol/mol [5.7%–6.4%]) was –0.012 SD/year, while the rate of decline for those with overt diabetes (HbA1c ≥ 6.5%) was –0.031 SD/year (P for trend < .001).

The rates of decline in memory, executive function, and orientation z scores were also greater with diabetes.

"Additionally, HbA1c levels were linearly associated with subsequent cognitive decline in memory and executive function (but not orientation) irrespective of diabetes status at baseline," Dr Zheng and colleagues note.

Early Intervention to Treat Diabetes May Help Prevent Cognitive Decline

In terms of possible underlying mechanisms of the link between diabetes and cognitive decline, some evidence points to glycemic fluctuation as having a stronger effect on cognitive decline compared with sustained hyperglycemia, possibly through effects on endothelial function and induction of oxidative stress.

In addition, diabetes has been linked to subsequent cognitive impairment through direct mechanisms, such as inducing amyloid accumulation, and indirect mechanisms, including increasing microvascular disease of the central nervous system, thereby potentially playing a key role in vascular dementia, the authors note.

"It has been shown that even a modest decrease in cognitive function could result in substantially greater cognitive decline over several years," they say.

While the study adjusted for the numerous known comorbidities of diabetes that could be linked to cognitive performance, such as depression, obesity, and hypertension, research indicates that treatment of modifiable risk factors for dementia, including diabetes, has been linked to prevention of up to a quarter of dementia cases.

"As there is currently no cure for dementia...our findings suggest that interventions that delay diabetes onset, as well as management strategies for glucose control, might help to alleviate the progression of subsequent cognitive decline over the long term," Dr Zheng and colleagues note.  

"Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes," they conclude.

The authors have reported no relevant financial relationships.

Diabetologia.  Published online January 25, 2018. Full article

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