Alzheimers disease and its promising links with diabetes

In the excellent book, The Innovators Prescription, the authors predict that precision medicine will replace intuitive medicine, and diseases will be defined by their underlying metabolic mechanisms, and not by the organs they affect, or the symptoms they produce. Clayton Christensen and colleagues argue that this precise definition of diseases will lead to more effective treatments. But they also show that precision medicine will show that many different diseases actually share the same underlying metabolic derangements. Many disparate diseases will therefore turn out to be just mere manifestations of the same metabolic disease.

Precision Medicine Conference at Harvard. Isaac Kohane on Flikr. https://www.flickr.com/photos/52786697@N00/16892093678
Precision Medicine Conference at Harvard. Isaac Kohane on Flikr. https://www.flickr.com/photos/52786697@N00/16892093678

A clear indication that precision medicine will blur the boundaries between diseases is the recent suggestion that the anti-diabetes drug Liraglutide may help to treat Alzheimer’s disease (AD). Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist which is effective in type 2 diabetes, a condition which is worlds apart from Alzheimer’s disease. So far removed from each other, it would be easy to dismiss any links as tenuous. But the headlines were emphatic: Drug used to treat diabetes could cure Alzheimer’s, and Diabetes drug could influence brain activity in Alzheimer’s. 

diabetes-1326964_1280

It is however no hype: there is evidence that Liraglutide may benefit people with Alzheimer’s disease. Trials in animal have shown that Liraglutide promotes neuronal survival, learning and memory, and reduces neuroinflammation and amyloid plaque formation. One such study is titled Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice. Beyond animals, small human trials have shown that Liraglutide improves brain glucose metabolism in Alzheimer’s disease.

beta-amyloid-plaques. vestque on Flikr. https://www.flickr.com/photos/35049835@N00/16867428955
beta-amyloid-plaques. vestque on Flikr. https://www.flickr.com/photos/35049835@N00/16867428955

Why should Liraglutide work so well in both diabetes and Alzheimer’s, diseases with apparently different pathologies? The answer lies in insulin resistance, the underlying mechanism of type 2 of diabetes; there is now evidence that insulin resistance contributes to dementia. If this is the case, Liraglutide, by improving glucose metabolism, could potentially treat both diabetes and Alzheimer’s disease.

Sugar Cubes. David Pace on Flikr. https://www.flickr.com/photos/63723146@N08/7164573186
Sugar Cubes. David Pace on Flikr. https://www.flickr.com/photos/63723146@N08/7164573186

To explore this potential further, there is now a large multicentre trial exploring the real benefit of Liraglutide in Alzheimer’s disease. Titled Evaluating Liraglutide in Alzheimer’s Disease or ELAD, it is recruiting people with mild disease, aged between 50-85 years old, and who do not have diabetes. As they say, watch this space!

Brain Aging. Kalvicio de las Nieves on Flikr. https://www.flickr.com/photos/118316968@N08/19444505382
Brain Aging. Kalvicio de las Nieves on Flikr. https://www.flickr.com/photos/118316968@N08/19444505382

Going back to the subject of precision medicine, why not visit my other blog, The Doctors Bookshelf where I will soon be reviewing The Innovators Prescription

9 thoughts on “Alzheimers disease and its promising links with diabetes

  1. So strong is the link between Type 2 DM and Alzheimer’s disease that there are those that consider Alzheimer’s Type 3 DM. Interesting article. Thank you Ibrahim!

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  2. “type 2 diabetes, a condition which is worlds apart from Alzheimer’s disease.” – in fact, there is a vast amount of evidence that these two disorders are metabolically linked (mitochondrial dysfunction!). My PhD is based on looking further into the mechanisms underlying the observation that diabetic patients are at a two-fold increased risk of developing dementia, specially Alzheimer’s disease. it’s great to see an article like yours as it frustrates me that not enough attention is given to cognitive impairment as a complication of diabetes (in addition to blindness, kidney failure, peripheral neuropathy etc..)!

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  3. If there is a correlation between insulin-resistance and Alzheimer’s, would it be more beneficial and cost efficient to directly treat the insulin-resistance with dietary changes (ketogenic diet) instead of treating it with Liraglutide?

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