New research suggests diabetes drug could slow Alzheimer’s progression
A new study published in the journal Neurology is reporting an association between a particular class of drugs used to treat type 2 diabetes and decreased Alzheimer's disease biomarkers. It is unclear exactly how these diabetes drugs could exert neuroprotective effects, but Alzheimer’s experts are calling for large-scale clinical trials to explore these potential treatments in non-diabetic groups.
For some time researchers have observed higher rates of dementia in patients with type 2 diabetes. A UK study earlier this year suggested high blood pressure could be the causal link between diabetes and dementia but it is still unclear what connects the two conditions.
Alongside this association between diabetes and dementia there have increasingly been observations of unusually low rates of neurodegenerative disease in groups of diabetic patients taking some anti-diabetic medications. An Australian observational study last year saw significantly slower rates of cognitive decline in older diabetic patients taking a drug called metformin, compared to rates of decline seen in non-diabetic patients not taking the drug.
This new research looked at a particular class of diabetes drugs called dipeptidyl peptidase 4 inhibitors (DPP-4i), also known as gliptins. Using retrospective data the researchers compared brain scans and cognitive test results from 70 diabetic patients taking DPP-4i against 71 diabetic patients not taking DPP-4i and 141 non-diabetic subjects. The entire cohort had an average age of 76 and all showed early signs of Alzheimer’s disease based on cognitive tests and PET scans.
All subjects were followed for around six years to measure decline over time and cognitive scores were similar in all groups at the start of the study. At the end of the study period, those diabetic patients on DPP-4i drugs showed significantly slower rates of cognitive decline compared to both other groups.
Using a common cognitive test called the Mini-Mental State Exam (MMSE), the researchers saw diabetic patients on DPP-4i drugs show annual scores decline by 0.87 points. In comparison the diabetic patients not on DPP-4i drugs displayed annual declines on the MMSE of 1.65 points, and those without diabetes declined each year by 1.48 points.
Looking at the primary biomarker of Alzheimer’s disease, amyloid protein build-up in the brain, the study found those patients taking DPP-4i drugs had lower average levels than other diabetic patients and non-diabetic patients.
"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," says Phil Hyu Lee, one of the researchers working on the project. "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 big question this new study is not able to answer is whether DPP-4i drugs have direct neuroprotective properties that could be beneficial preventing cognitive decline in non-diabetic subjects. James Connell, a scientist working with Alzheimer’s Research UK says there is urgent need to explore all possible treatment options for dementia.
“Diabetes is an important risk factor for Alzheimer’s disease, but we don’t yet fully understand how the two diseases are linked,” says Connell, who did not work on this new research. “Alzheimer’s Research UK scientists are also exploring other potential diabetes drugs and whether they could have benefit for those with dementia. Ultimately, we’ll need to see the results of these studies and of large-scale clinical trials to fully understand whether this approach could be beneficial.”
The new study was published in the journal Neurology.
Source: American Academy of Neurology
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Diabetic neuropathy (nerve damage eventually leading to amputations) and retinal neuropathy (bleeding in the retina, leading to progressive blindness) are common features of serious diabetes. Capillary abnormalities appear to be the precursor to these problems. Capillaries are where the nutrient/waste exchange occurs in all body tissues. If it is dysfunctional, serious problems arise.
See "Neutrophil Adhesion in Brain Capillaries Reduces Cortical Blood Flow and Impairs Memory Function in Alzheimer's Disease Mouse Models" in Nature Neuroscience, 11 February 2019.