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Younger age at onset of diabetes could be bad news for brain health, a longitudinal British population-based study suggested.

Patients who had type 2 diabetes for over a decade had more than a twofold higher risk for developing dementia compared with those who were diabetes-free at age 70 (HR 2.12, 95% CI 1.50-3.00), reported Archana Singh-Manoux, PhD, of the Université de Paris in France, and colleagues.

At age 70, every additional 5 years younger that a person was diagnosed with diabetes was tied to a 24% (HR 1.24, 95% CI 1.06-1.46) increased risk of incident dementia, even after adjustment for sociodemographic, health-related, and clinical factors including cardiovascular disease, hypertension, body mass index, and use of antidepressant or cardiovascular medications, among others, they noted in .

This equated to a dementia rate of 8.9 per 1,000 person-years among patients age 70 without diabetes versus a rate of 10 to 18.3 for those with diabetes, depending on age at onset:

• Diabetes onset 5 years earlier: 10.0 per 1,000 person-years
• Diabetes onset 6-10 years earlier: 13.0 per 1,000 person-years
• Diabetes onset 10+ years earlier: 18.3 per 1,000 person-years

The strongest association with incident dementia appeared to be younger age at onset of type 2 diabetes. For example, patients age 55 who were diagnosed with diabetes within the past 5 years saw a twofold increased risk for incident dementia (HR 2.14, 95% CI 1.44-3.17), while those age 60 who were diagnosed with diabetes 6 to 10 years prior saw a similar twofold increased risk (HR 2.19, 95% CI 1.48-3.26).

All in all, late-onset diabetes was not found to be tied to incident dementia.

Similarly, prediabetes -- defined as a fasting blood glucose of 110-125 mg/dL -- was also not tied to risk of subsequent dementia. Singh-Manoux and colleagues said that this finding suggested that "a certain threshold of high glucose" might be required to ultimately see hyperglycemia- induced brain injury.

On the other hand, cardiovascular comorbidities played into this link, as patients with diabetes who also suffered a stroke had a significantly elevated risk for dementia (HR 2.17, 95% CI 1.05-4.48). And those with a trifecta of heart conditions -- stroke, coronary heart disease, and heart failure – saw a near fivefold increased risk for subsequent dementia (HR 4.99, 95% CI 2.19-11.37).

Taken together, these findings underscore the importance of age at diabetes onset and cardiovascular comorbidities when determining risk for dementia, the study authors said.

A few possible explanations could shed light on the association between diabetes and dementia, they suggested.

"One hypothesis is that brain metabolic dysfunction is the primary driver of Alzheimer disease, highlighting the role of decreased transport of insulin through the blood-brain barrier, impairments in insulin signaling, and consequently decreased cerebral glucose utilization," they wrote. This idea was supported by findings from the 2019 SNIFF trial, which found some benefit with 40 IU of daily intranasal insulin for Alzheimer's disease patients.

Playing into this hypothesis, the group also suggested that episodes of hypoglycemia, more often experienced by those with a longer diabetes duration, may increase the risk for dementia.

This study drew upon data from the prospective cohort Whitehall II study, which recruited over 10,000 U.K.-based men and women from 1985 to 1988. Type 2 diabetes status was defined as a fasting glucose of 126 mg/dL or higher, a healthcare provider diagnosis of diabetes, use of a diabetes medication, or a hospital record of diabetes. Dementia was identified via ICD-10 codes.

Over a median follow-up of almost 32 years, there were 1,710 cases of diabetes and 639 cases of dementia diagnosed in the cohort.

"Continuing follow-up in the study will allow further examination of the importance of age at onset of type 2 diabetes for dementia," Singh-Manoux and colleagues concluded.

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