Type 2 Diabetes Can Accelerate Natural Brain Aging

Botand Antal, BSc

Presence of type 2 diabetes could accelerate natural brain aging by 26%, according to the results of a new study.

Using data from the UK Biobank cohort and meta-analyses, investigators from Stony Brook University sought to characterize the neurocognitive effects of type 2 diabetes and found a diagnosis of type 2 diabetes was a significantly associated with gray matter atrophy at a rate approximately 26% faster than seen with normal aging, with disease duration associated with increased neurodegeneration.

“Routine clinical assessments for diagnosing diabetes typically focus on blood glucose, insulin levels and body mass percentage,” said lead investigator Botond Antal, BSc, a PhD student in the Department of Biomedical Engineering at Stony Brook University, in a statement. “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.”

Although most of the focus regarding adverse outcomes in an aging population with type 2 diabetes have revolved around the risk of adverse cardiovascular and renal outcomes, recent revelations regarding its potential impact on cognitive decline have contributed to heightened awareness.The current study was conducted by Antal and colleagues from Stony Brook University and Massachusetts General Hospital to further explore associations between type 2 diabetes and long-term neurological health in aging patients.

To do so, investigators designed their study as an analysis of cross-sectional neuroimaging and cognitive data from the UK Biobank cohort, with additional plans for a meta-analysis to confirm the findings of their analyses in published reports. In their analysis of UK Biobank data, investigators hoped to estimate the extent of overlap between effects of type 2 diabetes and aging through use of correlation measures to separately characterized neurocognitive changes. Investigators also noted plans for further analysis to evaluate potential impact of disease duration and metformin treatment with neurocognitive effects.

From the UK Biobank cohort, investigators obtained data related to 20,314 patients with cognitive and neuroimaging data aged between 50-80 years for inclusion in their analyses. Of these, 1012 had type 2 diabetes and 19,302 were considered healthy controls. Among those with type 2 diabetes, the duration of diabetes ranged from 0-31 years (mean, 8.5±6.1 years), 498 were treated with metformin alone, and 352 were unmedicated.

For their meta-analysis, investigators identified 34 cognitive studies and 60 neuroimaging studies for inclusion in their meta-analysis. These 34 cognitive studies included a population of 22,231 patients. The neuroimaging studies included 30 with neuroimaging of patients with type 2 diabetes and 30 examining the effects of aging, with total study populations of 866 and 1088, respectively.

Upon analysis, results indicated the strongest type 2 diabetes-related effects were also observed in executive function, which saw an additional 13.1±6.9% decrease in performance beyond age-related effects (T=-3.7, P=.001), and processing speed, which saw an additional 6.7±3.2% decrease in performance, beyond age-related effects (T=-4.1, P=.0002)In their meta-analysis, investigators confirmed those with type 2 diabetes exhibited lower performance when compared to age and education-matched controls for these domains and for numeric memory (P=.05), abstract reasoning (P=1e–7), immediate verbal memory (P=.001), delayed verbal memory (P=.005), verbal fluency (P=2e–8), visuospatial reasoning (P=4e–7), and working memory (P=.002).

When assess neurobiological correlates with age and type 2 diabetes, investigators found patients with type 2 diabetes experienced additional decreases in gray matter, beyond age-related effects. The greatest degree of atrophy beyond age-related effects was observed in the ventral striatum, which saw an additional mean decrease of 6.2±1.6% in volume (P <1e-10), in the cerebellum, which saw an additional mean decrease of 4.9±1.1% in volume(P <1e-10), and in the putamen, which saw an additional mean decrease of 4.7±2.3% in volume (P=.002). Further analysis by disease duration revealed neurocognitive effects of type 2 diabetes appeared to exacerbate neurocognitive decline, with type 2 diabetes progression associated with a 26±14% acceleration of age-related effects.

“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,” added senior investigator Lilianne Mujica-Parodi, director of the Laboratory for Computational Neurodiagnostics at Stony Brook University, in the aforementioned statement. “By the time diabetes is formally diagnosed, this damage may already have occurred. But 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 and treatment strategies that specifically target its neurocognitive effects.”

This study, “Type 2 diabetes mellitus accelerates brain aging and cognitive decline: complementary findings from UK Biobank and meta-analyses,” was published in eLife.