Good research has shown that diabetes is linked to heightened risk for brain atrophy, white matter abnormalities, and cognitive impairment. It's a risk factor for dementia, especially if the diabetes is classified as type 2.
Alzheimer’s disease (AD) is the most common form of dementia. Globally, by 2050, 140 million people are expected to have AD. Clinically, AD is explained by proteostatis, which is the process by which the brain accumulates pathological, misfolded proteins. How proteostasis starts is a mystery. However, it is known that certain chronic disorders can accelerate proteostasis.
Diabetes and AD’s pathological mechanisms reinforce one another. Good research has shown that diabetes is linked to heightened risk for brain atrophy, white matter abnormalities, and cognitive impairment. It's a risk factor for dementia, especially if the diabetes is classified as type 2.
AD and T2D use similar amyloidogenesis processes to changes soluble proteins to insoluble fibrillary protein aggregates. In AD, researchers are trying to determine what causes increased soluble amyloid β peptides and their transition to AβOs. In T2D, fibrillary protein aggregates of amylin accumulate in the pancreatic islets. Diabetics' amylin fibrils resemble Aβ fibrils seen in AD. Many researchers believe this is a link between diabetes and AD, and this is why diabetics are at increased risk for AD. In addition, diabetes and AD have other similarities. For example, both are associated with mitochondrial dysfunction.
This is the topic covered in a comprehensive review article published recently in the journal Molecules. Its focus is the potential to use insulin to treat AD.
In addition to covering the similar cellular changes in each disease, this review discusses our inability to find effective preventive interventions and treatments for AD briefly, and then covers experimental use of antidiabetic drugs to date.
Thiazolidinediones increase insulin sensitivity, but early studies found no effect on AD, probably because of poor blood-brain-barrier penetration. Metformin is being studied in AD, and results are expected soon.
Very early research suggested Glucagon-like peptide-1 receptor agonists promoted synaptogenesis and neurogenesis, protected against oxidative injury, reduced AβO and Aβ plaque concentration, and improved memory among other things. These results are very preliminary, and human studies are beginning.
Of the experimental treatments, intranasal insulin is potentially the most promising. This delivery route allows insulin to by-pass the BBB, reach the olfactory bulb, hippocampus, and hypothalamus expediently, and do so with few side effects. In early AD or mild cognitive impairment, 4 phase 2 clinical trials demonstrated improved memory and attention abilities with no concurrent significant adverse effects or systemic hypoglycemia.
Additional studies are underway to determine if insulin might be a safe, effective symptomatic intervention that delays loss of cognition in AD patients.