Abstract
Around 6.2 million Americans of 65 years and above are ravaged by Alzheimer’s. Alzheimer’s is characterized by amyloid plaques in the brain. A new study found that people taking certain drugs for type 2 diabetes had less amyloid protein in the brain. Further, people taking these drugs also displayed a slower cognitive decline.
Why its very important to understand Alzheimer’s?
Alzheimer’s is one of the ten leading causes of death in the US. Medically, Alzheimer’s is a progressive neurological disorder, i.e., the nerve cells in the brain start to die, and the brain shrinks.
The area of the brain to get affected earliest is the hippocampus, which is responsible for memory. However, the onset of disease can occur much earlier than the appearance of the first symptoms.
Gradually, neuronal cell death progresses to other areas of the brain. This leads to severe memory impairment and loss of ability to carry out everyday tasks.
To date, there is no cure or treatment for Alzheimer’s. Further progression of the disease ultimately results in death due to severe loss of brain function involving dehydration, malnutrition, or infection.
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How To Detect Alzheimer’s? Biological Markers
Biological markers or biomarkers are characteristics that can be objectively measured as an indicator of a pathological or normal physical process.
For Alzheimer’s, scientists usually look for two proteins as the disease’s biomarkers.
Amyloid Plaques
Amyloid plaques are stacked forms of the beta-amyloid protein fragment. Beta-amyloid is a protein fragment cut from the amyloid protein precursor (APP). Usually, these protein fragments are cleansed from the brain by microglia.
Image Source: Brain Blogger
The image here depicts amyloid plaques formed around nerve cells in the brain.
In Alzheimer’s patients, the beta-amyloid does not get eliminated and starts forming clusters in the brain. In their early cluster stage, the beta-amyloid starts destroying synapses or nerve junctions – leading to memory loss in the individual. Upon forming plaques, the beta-amyloid protein contributes towards brain/nerve cell death.
Tau Tangles
Tau proteins are part of the neuron’s (nerve cell) internal support and transport system.
Image Source: Utah Public Radio
In Alzheimer’s, the tau proteins change their shape and structure to form tangles in the neuronal fibers. These tangles disrupt normal tau protein functioning and become toxic for the cells, thus leading to cell death.
Genetics: The ApoE Gene
The most prevalent genetic risk factor for Alzheimer’s is the ApoE (apolipoprotein E) gene. The 𝜀4 type of this gene is known to confer the highest risk factor and is present among 50% of Alzheimer’s patients.
The ApoE gene present on chromosome 19 makes a protein that helps transport cholesterol and other fat molecules through the bloodstream.
While there are two other types of the ApoE gene (𝜀2 & 𝜀3), only the 𝜀4 variant is associated with increased risk for Alzheimer’s. Having one or both copies of ApoE 𝜀4 in the body increases Alzheimer’s risk. The prevalence of individuals carrying one copy is about 25%, while only 2-3% carry both copies.
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Other Risk Factors
Age
Alzheimer’s is one of the diseases where age, especially old age, plays a significant role. Although Alzheimer’s development is not part of the normal aging process, old age increases the risk.
Mild Cognitive Impairment (MCI)
MCI is characterized by a decline in memory and associated thinking abilities, disrupting an individual’s normal societal or work-environment functioning. Usually, an MCI diagnosis with primary memory deficit leads to Alzheimer’s associated dementia.
Lifestyle and Cardiac Health
Certain factors which pose a risk for cardiac problems also increase Alzheimer’s risk. Some of them are
- Sedentary lifestyle
- Obesity
- High blood pressure and cholesterol
- Smoking
Additionally, people with type 2 diabetes are at a higher risk of Alzheimer’s disease. This may be due to higher blood sugar levels which have been linked to amyloid plaque buildup.
Dipeptidyl Peptidase-4 Inhibitors (DPP-4i)
DPP-4 inhibitors or gliptins are oral diabetes drugs used to block the enzyme dipeptidyl peptidase-4. DPP-4i acts on incretins (a group of hormones that stimulate the release of insulin). In addition, it reduces glucagon (a hormone that increases blood sugar levels), thereby decreasing blood sugar levels.
A previous study exploring the effect of DPP-4i use on dementia among type 2 diabetes patients revealed an increased impact on dementia, albeit not in Alzheimer’s patients.
Studies revealed an increased risk of inflammatory bowel and hypoglycemia when combined with another class of diabetic drug, sulphonylureas (like glipizide and glimepiride), in type 2 diabetic patients.
Know your body’s predisposition to the metabolism of DPP-4i and sulphonylurea drugs with Xcode Life’s pharmacogenomics report, Personalized Medicine.
The Study – DPP-4i Can Decrease Risk Of Alzheimer’s
Scientists at the American Academy of Neurology explored the effect of DPP-4i use in Alzheimer’s patients who may/may not suffer from type 2 diabetes (T2D).
The study involved 282 people with either pre-clinical, early, or probable diagnosis of Alzheimer’s. Individuals were of an average age of 76 and were followed for a six-year period. These people comprised of:
- 70 individuals having T2D being treated with DPP-4i drugs
- 71 individuals having T2D but not on DPP-4i
- 141 individuals not having T2D
Researchers measured the amyloid content in the individuals’ brains using a brain scan.
Study participants were made to take a common thinking and memory test called Mini-Mental State Exam (MSME) every 12 months for 2.5 years to track cognitive decline. The test consisted of questions like counting backward from 100 by sevens or copying a picture on paper. The score ranged from zero to thirty.
Results Of The Study
Between the three subgroups, Alzheimer’s individuals having T2D and on DPP-4i drugs:
- Had lower average amyloid plaque content in their brain
- In terms of cognitive decline (measured using the MSME), they had reduced annual average reduction (by 0.87 points).
Further adjustment of factors that could affect MSME scores, the same Alzheimer’s individuals with T2D and using DPP-4i drugs scored even lower decline by 0.77 points per year.
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Summary
- Among 6.2 million Americans diagnosed with Alzheimer’s, 1 in 3 seniors die.
- Known risk factors for Alzheimer’s include biomarkers (amyloid plaques and tau tangles), genetics (ApoE gene), old age, MCI, and pre-existing cardiac conditions & T2D.
- DPP-4i drugs are usually prescribed as diabetes drugs to lower blood sugar levels.
- The study revealed a reduction in amyloid plaque content and cognitive decline in Alzheimer’s individuals with T2D and treated with DPP-4i drugs.
