Alzheimer's disease: the amyloid-beta peptide accumulates to amyloid fibrils that build up dense amyloid plaques.
Credit: selvanegra/Getty Images

People taking dipeptidyl peptidase-4 inhibitors (DPP-4i) to lower blood sugar for type 2 diabetes had less amyloid in the brain, a biomarker of Alzheimer’s disease (AD), when compared to both people with type 2 diabetes not taking the drugs and people without diabetes. This study, from Yonsei University College of Medicine in Seoul, also found people taking these drugs showed slower cognitive decline than people in the other two groups.

The new study was published this week in the online issue of Neurology, the medical journal of the American Academy of Neurology.

In people with type 2 diabetes, the body no longer efficiently uses insulin to control blood sugar. DPP-4is, also known as gliptins, can be prescribed when other diabetes drugs do not work. They help control blood sugar when combined with diet and exercise.

“People with diabetes have been shown to have a higher risk of Alzheimer’s disease, possibly due to high blood sugar levels, which have been linked to the buildup of amyloid beta in the brain,” said study author Phil Hyu Lee, M.D., Ph.D. “Not only did our study show that people taking dipeptidyl peptidase-4 inhibitors to lower blood sugar levels had less amyloid in their brains overall, it also showed lower levels in areas of the brain involved in Alzheimer’s disease.”

The study involved 282 people with an average age of 76 who were followed up to six years. All had been diagnosed with either pre-clinical, early, or probable Alzheimer’s disease. Of the group, 70 people had diabetes and were being treated with DDP-4is, 71 had diabetes but were not being treated with the drugs and 141 did not have diabetes. Those without diabetes were matched to those with diabetes for age, sex, and education levels. All had similar scores on cognitive tests at the start of the study.

Participants had brain scans, using 18F-florbetaben amyloid PET, to measure the amount of amyloid in the brain.

Researchers found that people with diabetes who took DPP-4is had lower average amounts of amyloid plaques in the brain compared those who did not take the drugs and compared to people who did not have diabetes.

All participants took a common thinking and memory test called the Mini-Mental State Exam (MMSE) on average, every 12 months for 2.5 years. Questions include asking a person to count backward from 100 by sevens or copying a picture on a piece of paper. Scores on the test range from zero to 30.

Researchers found that people with diabetes who took DPP-4is had an average annual decline of 0.87 points on their MMSE score, while people with diabetes who did not take the drugs had an average annual decline of 1.65 points. People without diabetes scored an average annual decline of 1.48 points.

When researchers adjusted for other factors that could affect test scores, they found that the scores of the people taking the drug declined by 0.77 points per year more slowly than the people who did not take the drug.

“Our results showing less amyloid in the brains of people taking these medications and less cognitive decline, when compared to people without diabetes raises the possibility that these medications may also be beneficial for people without diabetes who have thinking and memory problems,” said Lee. “More research is needed to demonstrate whether these drugs may have neuroprotective properties in all people.”

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