Hyperglycemia Tied to Cognitive Decline, Vascular Dementia
Elevated HbA1c is associated with increased risk of vascular dementia, cognitive decline and structural brain changes, an analysis of data from the UK Biobank study suggests.

The study included 210,309 participants in the UK Biobank who had low HbA1c levels (less than 35 mmol/mol); 198,969 people who were normoglycemic (35 - 42 mmol/mol); 15,229 participants with prediabetes (42 - 48 mmol/mol); 3,279 individuals with undiagnosed diabetes (48 mmol/mol or more); and 22,187 people with a known diabetes diagnosis based on primary care records or prescription data.

Compared to normoglycemic individuals, people with pre-diabetic HbA1c levels had a significantly higher risk of developing vascular dementia and cognitive decline, the analysis found.

Known diabetes carried a significantly higher risk of vascular dementia and cognitive decline, as well as all-cause dementia and Alzheimer's disease.

In addition, researchers found higher white matter hyper-intensity volumes with prediabetes (3%), undiagnosed diabetes (22%) and known diabetes (7%) than with normoglycemia, and lower hippocampal volumes. By contrast, individuals with low HbA1c had 1% lower level of white matter hyper-intensity volumes than those with normoglycemia and larger hippocampal volumes.

"Associations appeared to be somewhat driven by antihypertensive medication, which implies that certain cardiovascular drugs may ameliorate some of the excess risk," the researchers from the Institute of Cardiovascular Science at University College London note.

"While the results for diagnosed diabetes were less surprising, the particularly strong associations of prediabetes and worse brain health outcomes are novel," they said.

"We are the first to find that blood sugar levels that are somewhat high, but preclude a diabetes diagnosis, may negatively affect our brain health," they mentioned. "However, we still have a very incomplete picture when it comes to the underlying biological mechanisms of exactly how long-term elevated blood sugar affects associates with worse brain health."

One limitation of the study is that validated algorithms to define diabetes and dementia can still lead some individuals to be misclassified, they commented.

Not everyone with prediabetes or diagnosed diabetes will go on to develop dementia, they also noted.

"For many people who have elevated blood sugar levels in the pre-diabetic range, it's very likely that lifestyle changes could ameliorate their blood sugar levels and confer health benefits, preventing or delaying the development of diabetes and associated health risks," they said.

However, the study offers fresh evidence that prediabetes and diabetes are both risk factors for vascular disease in general and for small vessel disease in the brain, researchers added.

Source: https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.14321
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