Cognitive caution: Brain atrophy is evident in pre-diabetes

Brain changes suggestive of cerebral miscrovascular dysfunction are already apparent in patients with prediabetes.

The changes – increased white matter hyperintensities (WHM) and decreased white matter volume – are even more pronounced in subjects with type 2 diabetes, said at the annual meeting of the European Association for the Study of Diabetes. Patients with frank diabetes also showed increase in intracranial cerebrospinal fluid (CSF) – a correlated decrease in the brain volume, said by the University Medical Center.

The changes are probably caused by diabetes-related endothelial dysfunction.

“The brain is highly dependent on properly functioning microcirculation. This is critical, since the brain has high energy demand and no energy reserve. In prediabetes and type 2 diabetes, microvascular endothelial dysfunction occurs. This leads to cerebral hypoperfusion, which in turn causes chronic ischemia. This contributes to small vessel disease leading to brain atrophy and, eventually, cognitive decline and dementia.”

The 2,251 subjects in the analysis were drawn from the Maastricht study, an ongoing observational study of people either type 2 diabetes.

Among the group, 350 had prediabetes, defined as impaired fasting glucose, impaired glucose tolerance, or a combination of the two. Type 2 diabetes was present in 528. The rest had healthy glucose metabolism.

As the cohort progressed from healthy glucose metabolism to prediabetes and then diabetes, they became older (aged 58 years in the healthy group vs. 62 years in the diabetes group), heavier, and displayed worsening cardiovascular risk factors, with increasing systolic blood pressure and progressively poorer lipid profiles. Kidney function was preserved in all patients, however.

The groups were not balanced in terms of sex: 56 percent of those with healthy glucose metabolism were women, compared with 47 percent of those with prediabetes and 31 percent of those with type 2 diabetes.

They examined white matter hyperintensities, white matter volume, gray matter volume, and intracranial CSF. They conducted three linear regression models: a crude unadjusted model; a partially adjusted model that controlled for those factors, plus systolic blood pressure, lipids, smoking, kidney function and education.

There was a clear linear association between WHM volume and healthy glucose metabolism, prediabetes, and type 2 diabetes. In the crude analysis, the healthy subjects carried about 0.75 mL of WHM. Prediabetic subjects carried about 1.25mL, and those with diabetes, about 2mL.

In both the partially and fully adjusted models, this relationship was somewhat attenuated, but it remained significant for both prediabetes and diabetes.

The crude model also found that both diabetes groups had significantly lower white matter volume than the healthy subjects. In healthy subjects, the mean volume was about 480mL. This was about 467mL in those with type 2 diabetes. Again, the partially and fully adjusted models slightly attenuated the relationship, but it remained significant in both disease state.

The crude model showed that gray matter was decreased in both prediabete and type 2 diabetes. In healthy subjects, total gray matter was about 667mL. In those with prediabetes, it was about 655mL, and in those with type 2 diabetes, about 645mL.However, the significant associations disappeared for both diabetes and prediabetes in both adjusted models.

Intracranial CSF was also different among the three groups in the crude model. In the healthy subjects, the total intracranial CSF was about 248mL. In those with prediabetes, it was about 225mL, and in those with type 2 diabetes, about 270mL. The association with prediabetes disappeared in the fully adjusted model – but type 2 diabetes, it remained strongly significant.