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Age-related cognitive decline shown to be accelerated by type 2 diabetes

According to a newly published study, age-related cognitive decline occurs at an increased rate of 26% in those with type 2 diabetes (T2D) compared to people without the disease. (Credit: Goldsmiths, University of London)

The researchers looked at the association between regular brain aging and T2D, finding that T2D has a similar neurodegenerative pattern to normal aging, but it proceeds faster. This study has several major implications, one of which is that even normal brain aging might reflect changes in insulin-regulated glucose levels in the brain.

The findings also show, however, that by the time T2D is properly diagnosed, severe brain damage may have already occurred. As a result, sensitive methods for detecting diabetes-related brain abnormalities are necessary.

Although there is significant evidence that T2D is related to decreases in cognitive functioning, most patients do not have a full cognitive evaluation as part of their therapeutic care. It can be difficult to tell the difference between the patterns of typical middle-age neurodegeneration and diabetes-related neurodegeneration. Until now, no studies have explicitly compared brain-aging in healthy individuals to brain-aging in people with diabetes of the same age.

First author and Stony Brook University PhD student, Botond Antal, told eLife, “Routine clinical assessments for diagnosing diabetes typically focus on blood glucose, insulin levels and body mass percentage. However, the neurological effects of type 2 diabetes may reveal themselves many years before they can be detected by standard measures, so by the time type 2 diabetes is diagnosed by conventional tests, patients may have already sustained irreversible brain damage.”

The team used the UK Biobank, which contains data from 20,000 adults aged 50 to 80 years old to identify the impact of diabetes on the brain over and above normal aging. This resource contains neuroimaging and cognitive function assessments for both healthy people and people with T2D. The researchers utilized this data in order to identify which structural and cognitive changes are specific to T2D patients as opposed to healthy patients.

The research team found that both aging and T2D induced alterations in executive skills including working memory, learning, and flexible thinking, as well as changes in brain processing speed. When compared to adults of the same age without diabetes, people with diabetes experienced an additional 13.1% decline in executive function beyond age-related effects, and a 6.7% decline in their processing speed. Their meta-analysis of over 100 studies verified that people with type 2 diabetes had consistently and significantly worse cognitive function than healthy people of similar age and education.

The findings imply that the characteristics of T2D-related brain aging closely resemble those of normal aging, but that neurodegeneration occurs at a faster pace. Furthermore, the impairments on brain function were more significant as diabetes duration rose. Diabetic progression was associated with a 26% faster rate of brain aging.

One of the authors of the study, Lilianne Mujica-Parodi, shared her remarks, “Our findings suggest that type 2 diabetes and its progression may be associated with accelerated brain aging, potentially due to compromised energy availability causing significant changes to brain structure and function….brain imaging could provide a clinically valuable metric for identifying and monitoring these neurocognitive effects associated with diabetes. Our results underscore the need for research into brain-based biomarkers for type 2 diabetes.”

The study was published in eLife on May 24th, 2022.

Abstract. Type 2 diabetes mellitus (T2DM) is known to be associated with neurobiological and cognitive deficits; however, their extent, overlap with aging effects, and the effectiveness of existing treatments in the context of the brain are currently unknown. We characterized neurocognitive effects independently associated with T2DM and age in a large cohort of human subjects from the UK Biobank with cross-sectional neuroimaging and cognitive data. We then proceeded to evaluate the extent of overlap between the effects related to T2DM and age by applying correlation measures to the separately characterized neurocognitive changes. Our findings were complemented by meta-analyses of published reports with cognitive or neuroimaging measures for T2DM and healthy controls (HCs). We also evaluated in a cohort of T2DM-diagnosed individuals using UK Biobank how disease chronicity and metformin treatment interact with the identified neurocognitive effects.

Botond Antal, Liam P McMahon, Syed Fahad Sultan, Andrew Lithen, Deborah J Wexler, Bradford Dickerson, Eva-Maria Ratai, Lilianne R Mujica-Parodi (2022) Type 2 diabetes mellitus accelerates brain aging and cognitive decline: Complementary findings from UK Biobank and meta-analyses eLife 11:e73138. DOI: https://doi.org/10.7554/eLife.73138

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