At the 61st European Association for the Study of Diabetes in Vienna, Austria, researchers highlighted emerging evidence linking both type 1 diabetes (T1D) and type 2 diabetes (T2D) with dementia and cognitive decline.

Key questions remain unresolved, including whether diabetes directly contributes to neurocognitive disorders, whether cognitive impairment itself increases the risk for diabetes, and whether optimal glycemic control can prevent or delay the onset of dementia.

Jean-Pierre Riveline, MD, PhD, professor at the University Center for Diabetes and Its Complications, Lariboisière Hospital, Paris, France, discussed three studies linking T1D and T2D with dementia, increased mortality, and immune-related mechanisms.

The profile of diabetes-related complications is shifting to include nontraditional conditions, such as dementia, cancer, and liver disease. In several high-income countries, mortality due to dementia is higher among individuals with diabetes than among those without diabetes.

“This first study included several million individuals over 20 years,” explained Riveline. “The key question was whether diabetes increases mortality in patients with dementia compared with those without diabetes.”

Evidence on how diabetes affects dementia-related mortality across age, sex, and time is limited.

A 20-year multinational study in Australia, Denmark, Finland, France, Scotland, and Canada (Alberta and Ontario) reported 114,559 dementia-related deaths in individuals with diabetes and 589,706 in those without diabetes. The study covered more than 61 million and 1.165 billion person-years of follow-up.

Mortality patterns varied according to region and age. The results were inconsistent at 60 and 70 years of age. After the age of 80 years, dementia mortality rose sharply in six countries, with a clear excess among individuals with T2D.

In Scotland, dementia-related deaths increased from 35.5% to 51% in women and from 37.5% to 46.2% in men over successive 5-year periods.

“For the age group between 60 and 70, no clear difference was demonstrated,” Riveline noted. “After 80, there is a distinct excess risk of mortality in individuals with dementia and diabetes compared with those without diabetes.”

T1D Risk

Some studies have estimated that T2D increases the overall risk for dementia by 1.5-2 times, but less is known about T1D.

A 2024 study reported that the incidence of neurodegenerative diseases was 1.7-3.4 times higher in patients with T1D, with diabetic nephropathy and cardiovascular disease further increasing the risk for dementia. Brain MRI studies have also linked T1D to focal cerebral atrophy and cerebral small vessel disease.

A study assessed all-cause dementia risk in 43,440 individuals with T1D from the Swedish National Diabetes Registry, compared with 217,109 age- and sex-matched individuals without T1D, followed for a median of 14.3 years (IQR, 7.9-20.0).

“This study included a large cohort of individuals with T1D compared with individuals without type 1 diabetes,” said Riveline. “Focusing on a younger population with a mean age of 33, the results show that T1D increases the risk of neurodegenerative disease, with ratios from 1.7 to 3.7 up to three times higher than in those without diabetes.”

During follow-up, dementia developed in 530 (1.2%) individuals with T1D and 1867 (0.9%) individuals without T1D. According to lead author Milena Jancev, MD, PhD student, from the Department of Vascular Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, Netherlands, T1D was associated with an increased risk for all-cause dementia (hazard ratio [HR], 2.02; 95% CI, 1.83-2.23), Alzheimer’s disease (HR, 1.38; 95% CI, 1.13-1.69), vascular dementia (HR, 3.73; 95% CI, 3.07-4.52), and non-Alzheimer’s-nonvascular dementia (HR, 1.87; 95% CI, 1.63-2.15).

“The study also examined factors that promote neurodegeneration,” said Riveline. “Expected factors included age, high systolic blood pressure, a history of stroke or transient ischemic attack, cardiovascular disease, and longer diabetes duration. Interestingly, marital status matters; being single increased the risk of cognitive dysfunction in individuals with T1D by 56%. A1c levels also correlate with neurodegenerative diseases, suggesting a link between glycemic control and dementia. However, the causal relationship remains unproven. Intervention studies are needed to determine whether improved diabetes control can preserve cognitive function.”

Immune Markers

Another presentation on dementia in diabetes came from the REVADIAB study, coordinated by Riveline, which analyzed the link between glycemic variability, circulating immune markers, and cognitive function in individuals with T1D. The researchers hypothesized that inflammatory markers could serve as sensitive subclinical indicators of cognitive function, given the higher risk for cognitive impairment in T1D — especially in those with a younger age at diagnosis, longer diabetes duration, or complications — and the known links between inflammation and cognition in other contexts.

Riveline stated that “Inflammation is of great interest because diabetes has a chronic, low-grade inflammatory component. In T2D, this contributes to cardiovascular risk and may also affect cognitive performance.”

A total of 50 participants underwent cognitive assessment using the Wechsler Adult Intelligence Scale, and 23 underwent full peripheral immune phenotyping and a brain MRI. Each assessment took 4-5 hours per participant. The participants were divided according to the median intelligence quotient (IQ; ≤ 121 vs > 121).

This study analyzed immune cell counts, cell frequencies, and expression of the proinflammatory transcription factor IRF5. The median age of the participants was 39 years, 39% were women, the mean BMI was 24.9, mean A1c was 7.85%, and the mean diabetes duration was 23.8 years.

Lower total monocyte counts were associated with higher cognitive performance (IQ > 121; P = .08). Lower nonclassical monocyte frequency is associated with higher cognitive performance (P = .006). Higher expression of IRF5 in innate natural killer cells, myeloid dendritic cells, and monocyte subtypes is associated with better cognitive outcomes. Each percentage point increase in nonclassical monocyte frequency decreased the odds of a high memory index (odds ratio, 0.47; 95% CI, 0.22-0.98; P = .04), which remained significant after adjusting for other immune variables.

“We found significant links between cognitive performance, including processing speed and working memory, and specific immune markers,” Riveline concluded. “Transcription factors associated with inflammation are also correlated with intellectual function, suggesting that some immune markers may reflect cognitive performance. The French SFDT1 cohort, coordinated by Professor Emmanuel Cosson, PhD; Guy Fagherazzi, PhD; and me, is investigating role of inflammation in both cardiovascular and cognitive outcomes in T1D. The exact mechanisms, however, remain unclear.”

Riveline reported having relationships with Sanofi, MSD, Eli Lilly, Novo Nordisk, AstraZeneca, Abbott, Dexcom, Medtronic, Roche, Air Liquide, AlphaLab, Insulet, Amgen, and Timkl.

This story was translated from Medscape’s French edition.