Becky McCall

September 16, 2015

STOCKHOLM — Higher HbA1c levels are associated with an increased risk of dementia among patients with type 2 diabetes, indicating potential for prevention of dementia with improved glycemic control, concludes the largest study of its kind.

Lead investigator Dr Aidin Rawshani, MD, from the National Diabetes Register and Institute of Medicine, Gothenburg, Sweden, presented the findings here at the European Association for the Study of Diabetes (EASD) 2015 Meeting.

Dr Rawshani and colleagues found that patients with poor blood glucose control (HbA1c ≥10%) have a 50% higher risk of being admitted to the hospital for dementia at some point in the future than those with good control.

"We noticed a J-shaped relationship between HbA1c levels and risk of developing dementia, so as glycemic levels increase gradually, so does the risk of dementia in these individuals," Dr Rawshani told Medscape Medical News.

"Also, very low HbA1c levels were associated with increased risk of developing dementia."

"HbA1c is a modifiable risk factor, and this growing evidence…[of an association]…means we have an opportunity to decrease the risk of developing dementia by optimizing HbA1c," he added.

Commenting on the findings, moderator of the session, Nita Forouhi, MD, from the MRC Epidemiology Unit, University of Cambridge, United Kingdom, said these are good preliminary data with a clear hypothesis.

"They show an association between hyperglycemia and dementia risk, but right now it is just an association. However, this should stimulate more research…to better understand the balance between episodes of hypoglycemia and hyperglycemia in terms of dementia risk.

"As well as looking at dementia, we also need to look at links with cognitive decline, because it can be informative in terms of leading to dementia," she added.

Largest Observational Study of Glycemic Control and Dementia

Dr Rawshani and his colleagues looked at glycemic control and the incidence of dementia in Sweden in the largest observational study of its kind among 353,214 patients with type 2 diabetes. They also examined other predictors of dementia in relation to diabetes.

"These are two huge public-health challenges [type 2 diabetes and dementia], and previous work has shown that those with type 2 diabetes are at increased risk of developing dementia, by up to 50%," said Dr Rawshani.

"Glycemia has also been associated with risk of dementia, but there are gaps in the knowledge, because most studies have been hampered by cross-sectional design or used a composite of random/fasting glucose and HbA1c. We need to disentangle these associations," he added, explaining the motivation for the study.

Patients in the study had type 2 diabetes and no known hospitalization for dementia (vascular, Alzheimer's, or unspecified). They were registered in the Swedish National Diabetes Registry between January 2003, and December 2012.

This information was merged with data on socioeconomic variables, an outpatient registry (detailing discharge diagnoses), an inpatient registry, and a cause-of-death registry.

All patients were over 50 years of age at first observation and were followed until a first event (hospital admission for dementia), death, or end of study.

The association between patients' characteristics, including HbA1c, and dementia was assessed, adjusted for a wide range of confounding factors.

These included age, sex, duration of diabetes, marital status, income, education, smoking status, systolic blood pressure, body mass index, estimated glomerular filtration rate, statin use, albuminuria, type of glucose-lowering treatment, atrial fibrillation, stroke, and antihypertensive medication.

A total of 13,159 events of any dementia type were observed, including 3499 of Alzheimer's dementia and 3377 of vascular dementia over a mean follow-up of 4.8 years. The mean age across all categories of HbA1c (<6% to >10%) was 68 years, and duration of diabetes was 4 to 10 years.

Event rates per 1000 years for any type of dementia were 7.25 for HbA1c of less than 6% and 8.47 for HbA1c of at least 10%, reported Dr Rawshani.

Patients with HbA1c greater than 10% had a hazard ratio for dementia of 1.5 compared with HbA1c of 6.7% (the guideline target level used as the reference value), added the researcher.

"We see that patients with an HbA1c of 6.7% have no increased risk of developing dementia, but as this [HbA1c] increases, so too does the risk of dementia," reported Dr Rawshani.

"We also found that patients with very low levels of HbA1c have an increased risk of dementia," he noted — those with very low HbA1c (<6%) had around a 50% increased risk of dementia as well.

Dr Rawshani also highlighted that individuals with microalbuminuria have a greater risk of developing dementia compared with those without any microalbuminuria.

And the complete absence of physical exercise was found to be associated with an increased risk of dementia compared with those patients reporting daily activity.

A linear relationship was identified between dementia risk and increasing diastolic blood pressure. Likewise, stroke, atrial fibrillation, and heart disease were also found to be risks for developing dementia, while antihypertensive therapy and statin use were associated with a lower risk of developing dementia.

Survival Affected After Dementia Diagnosis

The researchers also examined survival — patients who received a diagnosis of dementia had a 10-year survival of 40%, compared with 70% in those without such a diagnosis.

Adding further insight, Dr Forouhi remarked on the potential clinical usefulness of the association between raised HbA1c and dementia, pointing out that "with any new link we find the ultimate interpretative question is, 'So what? And where do we go with this?'

"If this is a true link, then having this knowledge means we could pick up signs early and offer advice and support before the event," she suggested.

She noted that alcohol intake was not considered in the analysis and that it would be beneficial to also account for this.

"I think alcohol is particularly important, because we know that other work points to an association between alcohol intake and dementia, [and] also with diabetes and chronic disease. I think it would be important to add this in."

Dr Rawshani and Dr Forouhi have declared no relevant financial relationships.

European Association for the Study of Diabetes 2015 Meeting; Stockholm, Sweden, Abstract 10, presented September 15, 2015.


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