Diabetes Drug Tied to Slower Cognitive Decline in Alzheimer’s – Everyday Health

A class of type 2 diabetes drugs is associated with reduced brain plaque and better cognitive scores in people with Alzheimers disease, a new study suggests. The findings appear in theAugust 2021 issue ofNeurology.

The drugs called dipeptidyl peptidase4, or DPP-4, inhibitors are prescribed to people with type 2 diabetes to help lower blood sugar. Examples of DPP-4 inhibitors that are approved by the Food and Drug Administration are Januvia (sitagliptin), Onglyza (saxagliptin), Tradjenta (linagliptin), and Nesina (alogliptin).

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 senior study author Philhyu Lee, MD, PhD, of Yonsei University College of Medicine in Seoul, South Korea, in a statement.

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, Dr. Lee said in the statement.

At the start of the study, researchers gave 282 participants with Alzheimers disease brain scans to measure the accumulation of amyloid plaque, or abnormal protein deposits in the brain that are associated with memory decline. They also administered cognitive tests and repeated assessments roughly every 12 months over a median follow-up period of 2.5 years. The study included three cohorts: 70 people with diabetes treated with DPP-4 inhibitors; 71 people with diabetes who didnt take DPP-4 inhibitors; and 141 people without diabetes.

Brain scans showed that people on DPP-4 inhibitors had a lower amyloid burden than either of the other two groups in the study after researchers adjusted for age, sex, education, cognitive status, and a mutation of the APOE-4 gene associated with Alzheimers disease.

Individuals with diabetes also experienced smaller declines in global cognition and memory recall when they took DDP-4 inhibitors than when they didnt use these drugs.

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Activities on the cognitive test repeated during the study included tasks like counting backwards from 100 by sevens or copying a picture. Scores on the test, called the Mini-Mental State Examination (MMSE), ranged from 0 to 30, with higher scores indicating better cognitive function. The average annual decline in scores was 0.87 points for people with diabetes on DPP-4 inhibitors, 1.65 points for people with diabetes not on these drugs, and 1.48 points for people without diabetes.

Id suspect that by lowering amyloid there might be some effect on reducing memory decline, says Glen Finney, MD, the director of the memory and cognition program and a neurology professor at the Geisinger Commonwealth School of Medicine in Scranton, Pennsylvania.

A bigger study would help to see if that were the case, adds Dr. Finney, who wasnt involved in the study.

Beyond its small size, the study was limited because researchers lacked data on baseline blood sugar levels, which would be needed to help determine what role the changes in blood sugar over time might play in the results.

The study also didnt use brain scans to look for changes in amyloid accumulation over time. In addition, the MMSE tests administered multiple times, while considered an accurate way to track changes in cognitive function, dont offer the same precision as more comprehensive cognitive assessments such as neuropsychological testing, Lee and colleagues note in their study.

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Yet previous studies have also linked diabetes medications to better outcomes for people with Alzheimers disease, says Finney.

Over the decades thereve been hints in research that at least some Alzheimers disease cases relate to glucose and diabetes, and may be helped by treatments that are used for diabetes, Finney says. This is another example of a treatment, DPP-4 inhibitors, that is showing some signal of that.

One study published in August 2020 in Alzheimers & Dementia, for example, looked at memory test results for 1,192 people with type 2 diabetes who didnt have cognitive impairment and for 807 people with type 2 diabetes who had Alzheimers disease. This study found that DPP-4 inhibitors were linked with a slower deterioration in memory among those with Alzheimers disease. It also found that Glucophage (metformin), another type of medicine to lower blood sugar, was associated with slower memory decline among carriers of an APOE-4 gene mutation linked to Alzheimers disease.

An earlier study, published in June 2018 in the Annals of Translational Medicine, reviewed preclinical lab work and human studies to date on the effect of DPP-4 inhibitors on cognition and found that DPP-4 inhibitors were protective against further memory decline in people with diabetes who had mild cognitive impairment.

DPP-4 inhibitors are used to improve the regulation of blood sugar, which preclinical studies suggest may be associated with increased amyloid accumulation in the brain, says Jill Morris, PhD, assistant professor of neurology at the University of Kansas Medical Center in Kansas City, who wasnt involved in the latest study.

Bringing blood sugar levels back to normal could potentially normalize amyloid processing, Dr. Morris says.

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Randomized clinical trials are needed to answer this question and to determine if DPP-4 inhibitors can directly cause slower cognitive decline, Morris adds. Thats because DPP-4 inhibitors are often prescribed for people whose blood sugar is not ideally managed and who dont respond to other diabetes medicines. As a result, people on DPP-4 inhibitors may have higher blood sugar levels when they initiate treatment than patients who dont use these drugs this was the case for the patients in the latest study.

Randomized clinical trials are needed to evaluate the effectiveness of DPP-4 inhibitors to slow cognitive decline in individuals both with and without diabetes, Morris says.

While all people with type 2 diabetes should still take medications as needed to lower their blood sugar, including DPP-4 inhibitors if theyre prescribed, people shouldnt be on this medication just because they think it might help prevent dementia, Finney says.

It is too early to make any decisions on taking DPP-4 inhibitors solely for hope of slowing Alzheimers disease, but if you have a good reason otherwise to be on a DPP-4 inhibitor, then we can hope you may get an added benefit, Finney says. But whether or not to use a DPP-4 inhibitor should be based on what is best for your diabetes control.

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Diabetes Drug Tied to Slower Cognitive Decline in Alzheimer's - Everyday Health