Editors' note: Type 2 diabetes mellitus, brain atrophy, and cognitive decline

In the article “Type 2 diabetes mellitus, brain atrophy, and cognitive decline,” Moran et al. examined longitudinal relationships between type 2 diabetes mellitus (T2DM), cortical thickness, and cognitive function in older people with normal cognition, mild cognitive impairment (MCI), and Alzheimer disease (AD) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. They concluded that T2DM contributed to cognitive decline via neurodegeneration (lower baseline cortical thickness) and that previous brain and cognitive reserve (reflected by greater education) may protect against this effect. In response, Ba et al. argue that it is unclear whether the authors properly controlled for other risk factors for cognitive decline such as hypertension, hyperlipidemia, white matter lesion burden, and depression and note that incorporating additional T2DM-related factors such as fasting blood glucose or disease duration would be relevant. They also critique the study’s reliance on clinical diagnoses for determination of MCI and AD, which can often result in misattribution of symptoms to AD when supportive biomarkers are not included. Replying to these comments, Dr. Moran acknowledges the absence of detailed T2DM-specific information as a limitation of repurposing the ADNI dataset for their work but notes that the study reported data on fasting glucose, diabetes medication use, blood pressure, and measures of obesity. Although ADNI participants were selected to have a low burden of cerebrovascular disease, Dr. Moran acknowledges that there are additional potential confounders of the relationship between T2DM and brain health, such as other vascular risk factors, some of which were explored in other work using samples with a greater burden of cerebrovascular disease. He also agrees on the importance of incorporating biomarkers of underlying pathology into future work in this area.

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