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Faster Cognitive Decline Tied to Hyperglycemia

Faster Cognitive Decline Tied to Hyperglycemia

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Action Points

  • Note that this longitudinal study found that diabetes and prediabetes were associated with more rapid subsequent cognitive decline.
  • Be aware that cognitive decline was assessed via standard instruments; clinical diagnoses of dementia were not evaluated.

Diabetes may speed up cognitive decline over time, a new study reported.

Both prediabetes (-0.012 SD/year, 95% CI -0.022 to -0.002) and diabetes (-0.031 SD/year, -0.046 to -0.015) were tied to a faster rate of global cognitive decline over time when compared with people with normoglycemia, according to Fanfan Zheng, PhD, of the Chinese Academy of Sciences in Beijing and University College London, and colleagues (P-trend <0.001, for both).

In the study, published online in Diabetologia, those with prediabetes and diabetes also showed a similarly fast trend of cognitive decline versus those with normoglycemia, as reported in memory, executive function, and orientation cognitive tests.

The results also showed that a 2.2% increase in HbA1c (1 mmol/mol) was directly associated with a more rapid rate of cognitive decline over time, in a fully adjusted model:

  • Global cognitive z-scores: -0.0009 SD/year (95% CI -0.0014 to -0.0003) (P=0.002)
  • Memory: -0.0005 SD/year (-0.0009 to -0.0001) (P=0.025)
  • Executive function: -0.0008 SD/year (-0.0013 to -0.0004) (P<0.001)

“Dementia is one of the most prevalent psychiatric conditions strongly associated with poor quality of later life,” the study’s senior author, Wuxiang Xie, PhD, of Imperial College London and Peking University Health Science Center in Beijing, told MedPage Today via email. “Currently, dementia is not curable, which makes it very important to study risk factors of dementia so that we could intervene on modifiable risk factors in the very early stage.

“The associations between dementia and diabetes mellitus have been supported by previous researchers. However, the associations of glycated hemoglobin with the trajectory of cognitive decline were not well-established. Therefore, we decided to conduct this study to find out whether high levels of glycated hemoglobin A1c were associated with faster cognitive decline.”

To assess this potential relationship, he and his colleagues collected data on 5,189 individuals who participated in the English Longitudinal Study of Ageing between 2004 and 2015.

All participants were given cognitive evaluations, which included a memory assessment of two independent tests of immediate and delayed word recall and an executive function assessment measured via a verbal fluency task. An orientation test was also included, which asked questions about the current calendar date. HbA1c was measured at the same time as the initial cognitive assessment, and the cognitive assessments were repeated during a follow-up period of up to 10 years.

Exclusion criteria for the study included having a confirmed diagnosis of dementia or Alzheimer’s disease. Diabetes was defined as having an HbA1c of 6.5% of greater, while prediabetes was defined as a level between 5.7% and 6.4%. Among the total cohort, 8.6% of participants had diabetes and 22.9% were considered to be prediabetic.

At baseline, those with diabetes were more likely to have higher blood pressure and body mass index and cardiovascular disease. Both memory (9.4 ± 3.3 versus 10.5 ± 3.4) and executive functioning scores (19.4 ± 6.7 versus 20.8 ± 6.3) at baseline also tended to be lower among those with diabetes compared with those with normoglycemia (P-trend<0.001, for both).

A sensitivity analysis also showed similar findings, in a model excluding 261 individuals who developed diabetes during the follow-up period.

“We were not surprised by the findings of the significant longitudinal association, given previous research on relationships of diabetes mellitus with dementia, but we were kind of surprised by the linear associations between HbA1c levels, regardless of diabetic status, and long-term cognitive decline, which provides further evidence that HbA1c is a very important biomarker for management of glucose control,” Xie noted.

One limitation of the study included a lack of a clinical diagnosis of dementia during the follow-up period, so the findings are only limited to a link with cognitive decline, the researchers wrote.

“We want to carry on with research related to this aspect,” added Xie. “For the present study, we identified linear associations between HbA1c levels and cognitive decline when [considering only HbA1c]; when we also considered diabetic status, we divided our diabetes participants into two groups according to the levels of HbA1c to examine the effect of glucose management on subsequent cognitive decline, but no significant difference was observed.

“In this case,” he continued, “we think there must be some underlying mechanisms that we don’t understand yet, and it is worth trying to find new markers to study those mechanisms.”

Click here for the American Association of Clinical Endocrinologists’ 2018 type 2 diabetes management algorithm.

The study was funded by the National Natural Science Foundation of China and the Newton International Fellowship from the Academy of Medical Sciences.

Xie and co-authors reported having no conflicts of interest.

  • Reviewed by
    F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner


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