For this study, Dove and her team studied MRI brain scans of more than 31,000 people between the ages of 40 and 70 from the UK Biobank. At baseline, about 43% of study participants had prediabetes, and almost 4% had diabetes.

All participants received up to two MRI brain scans over 11 years of follow-up. Researchers calculated each participant’s brain age using a machine-learning model.

Upon analysis, researchers discovered that both prediabetes and diabetes were associated with brains that were 0.5 and 2.3 years older, respectively, than a person’s chronological age.

“There are several potential biological pathways through which (pre)diabetes may impact brain health,” Dove explained.

“Hyperglycemia, the defining pathophysiological feature of diabetes, can promote endothelial dysfunction, oxidative stress, systemic inflammation, and the accumulation of advanced glycation end products. Together, these contribute to disruption of blood-brain barrier permeability — exposing the brain to potentially toxic substances, leading to abnormal neuronal activity — demyelination, and loss of axons leading to brain atrophy and disruptions in neurotransmitter signaling, and alterations in Ca2+ signaling leading to excitotoxicity and disruptions in gene expression.”
— Abigail Dove

“Additionally, the micro- and macrovascular complications of diabetes can contribute to brain atherosclerosis and cerebrovascular pathologies that may lower the threshold for neurodegeneration,” she continued. “Finally, the insulin resistance that characterizes diabetes has been linked to Alzheimer’s disease related processes including amyloid-β generation, tau hyperphosphorylation, and impaired amyloid-β clearance.”

During the study, researchers also found that the gap between brain age and chronological age increased slightly over time in people with diabetes.

However, these associations were reduced in participants who participated in high physical activity, did not smoke, and abstained from heavy alcohol drinking.

“In this analysis, we were curious whether the negative influence of diabetes on brain health could be mitigated in part by healthy lifestyle behaviors,” Dove detailed. “We divided participants into six groups according to glycemic status — normoglycemia, prediabetes, diabetes — and lifestyle — optimal (i.e., no smoking, no heavy alcohol, high physical activity) vs. not.”

“The gap between brain and chronological age was significantly smaller in the diabetes + optimal lifestyle group compared to the diabetes + non-optimal lifestyle group, indicating that lifestyle can compensate against the detrimental influence of diabetes. Importantly, all the lifestyle factors we considered — smoking, drinking, physical activity — are things that are readily modifiable, so these findings provide actionable strategies people with diabetes could consider taking to improve their brain health.”
— Abigail Dove

After reviewing this study, Scott Kaiser, MD, a board certified geriatrician and Director of Geriatric Cognitive Health for the Pacific Neuroscience Institute in Santa Monica, CA, told MNT this is an important, well-done study that reinforces much of what we know in terms of the importance of a healthy lifestyle and effectively managing diabetes with regard to brain health and reducing dementia risk.

“There’s really little doubt that diabetes, among its many potential negative effects, increases the risk and severity of dementia — that’s pretty well established. So it’s important to think about how we can mitigate that risk — how a brain-healthy lifestyle, including being physically active, avoiding smoking, avoiding excessive alcohol, … diet … and a variety of other factors are really just so important for maintaining brain health and reducing dementia risk.”
— Scott Kaiser, MD

“We have an aging population (and) with that comes a rising dementia risk, so over 150 million people (are) predicted to have dementia by 2050. So we really need to start thinking now and on a massive scale about the best possible strategies and approaches to preventing dementia,” he added.

Kaiser pointed out that this study showed associations and that causality is not yet 100% established.

“I think more prospective studies that prove the direct causal impact and pathways are important, but much more importantly interventions that can leverage this information (could) have a huge impact,” he continued. “This study provides really great targets for lifestyle interventions to promote brain health and that’s really important, again, when you think about this not just (at) an individual level, but at a population level.”