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How Type 2 Diabetes is Linked with Alzheimer’s Disease

Brains of patients with Alzheimer’s dementia often feature key physiologic abnormalities: beta-amyloid plaques and tau-protein tangles. A study lead by Dr. Velandai Srikanth, a geriatrician at Monash University in Melbourne, Australia, suggests that type 2 diabetes may contribute to the development of these physiological changes. The study looked at data from 124 older adults with type 2 diabetes and nearly 700 who did not have type 2 diabetes. Results were reported in the journal Neurology.

The participants in the study all had MRI brain scans. Half of the participants had cerebrospinal fluid samples drawn to assess beta-amyloid and tau-protein levels. The brain scans revealed that the brains of type 2 diabetes patients had more thinning in the cortex (the part of the brain with the highest nerve cell concentration). The spinal fluid samples revealed that type 2 diabetes patients had higher tau levels, which is correlated with more tau-protein tangles in the brain. Both of these changes are indicative of decreasing brain health. All changes were found after adjusting for APO E4 status, age, gender, cognitive diagnosis, and total intracranial volume.

This study does not explain why type 2 diabetes is linked to these brain changes; it only shows a link. It also does not distinguish between correlation and causation. Type 2 diabetes has previously been connected to Alzheimer’s disease, which has been termed by some in the scientific community as “type 3 diabetes.” Furthermore, type 2 diabetes has been recognized as a risk factor for development of Alzheimer’s disease.

Lead author Srikanth has posited several explanations for the connection between type 2 diabetes and Alzheimer’s disease. Chronic hyperglycemia can cause damage in the brain. Glycation of proteins is increased in type 2 diabetes, which may lead to tau-protein congregation. Chronic inflammation may also have a causative role. Systemic low-grade inflammation is a feature of diabetes and other diseases.

Another possible link is obesity. Obesity, which is a leading risk factor for type 2 diabetes, has been linked to increased tau-protein pathology. Autopsies performed as part of a recent study published in Molecular Psychiatry showed that the brains of patients who had been overweight at the age of 50 demonstrated more of the tangles than the brains of patients who were not overweight or obese.

The results of this study contribute to the existing body of evidence that suggests controlling or preventing type 2 diabetes can reduce the risk or severity of Alzheimer’s disease. More studies are needed to flesh out the exact mechanisms of tau pathology and other neurodegenerative markers, and the features of type 2 diabetes that contribute to them.

Practice Pearls:

  • Type 2 diabetes is a risk factor for Alzheimer’s disease.
  • Although the exact mechanisms are unknown, type 2 diabetes has been correlated with increased tau pathology and decreased cortical thickness.
  • Controlling or preventing type 2 diabetes, as well as risk factors for type 2 diabetes such as obesity, may reduce development of dementia later in life.

Moran C, Beare R, Phan TG, et al. “Type 2 diabetes mellitus and biomarkers of neurodegeneration.” Neurology. 2015. http://www.ncbi.nlm.nih.gov/pubmed/26333802.