In the clinical study published online in Neurology, Phil Hyu Lee, MD, PhD, who is affiliated with the Yonsei University College of Medicine in Seoul, South Korea, and colleagues explored whether dipeptidyl peptidase-4 inhibitors (DPP-4i) use is associated with low amyloid burden, resulting in favorable long-term cognitive outcomes in diabetic patients with Alzheimer's disease–related cognitive impairment. The authors hypothesized that because these two diseases were both associated with toxic accumulations of amylin or islet amyloid polypeptide and insulin resistance, there was increased concomitant risk of amyloid beta and neurofibrillary tangle formation.

“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 Dr. Lee, who added, "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 researchers conducted a retrospective analysis of 282 patients with Alzheimer's disease–related cognitive impairment who also had a positive amyloid scan and divided them into three groups: 70 patients with diabetes and who were receiving DPP-4i (ADCI-DPP-4i), 71 patients with diabetes but who were not receiving a DPP-4i, and 141 patients without diabetes and who were not receiving DPP-4i therapy.

After adjusting for known concomitant risk factors, such as age, sex, level of education, and cognitive status, the team used Mini-Mental State Examination (MMSE) scores and examined differences between groups in regional and global amyloid retention. They reported that the ADCI-DPP-4i+ group had lower global amyloid burden, as well as an average annual decline of 0.87 points on their MMSE score, compared with people with diabetes who did not take the drugs. Those not taking the drugs experienced an average annual decline of 1.65 points. People without diabetes scored an average annual decline of 1.48 points.
 
The authors shared that research over a longer period is needed to demonstrate cause and effect because they were not able to observe the potential accumulation of amyloid in the brains of subjects over time. “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 Dr. Lee. “More research is needed to demonstrate whether these drugs may have neuroprotective properties in all people.”

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