Brain Imaging: UK Biobank Epidemiology Study

I wanted to alert Brain Posts readers to a very important ongoing study out of the United Kingdom.

The UK Biobank prospective epidemiological study is a study designed to identify imaging markers for a wide variety of diseases. Additionally, a goal of the study is to better understand disease mechanisms.

Here is what is being collected on 100,000 healthy participants who will be tracked over decades:

• Brain structural and functional imaging (fMRI)
• Brain diffusion tensor imaging (DTI)
• Neuropsychological testing, i.e. cognition
• Body and cardiac imaging
• Genetics
• Lifestyle information
• Biomarker phenotyping
• Health records

This ambitious study reminds me of the Framingham study in the U.S. that helped identify a group of risk factors for cardiac and vascular disease.

Some early results from the UK Biobank study of early 5,000 subjects has been published in Nature Neuroscience.

The manuscript shows that the UK Biobank will be a powerful resource in replicating other studies. They reported a initial attempt to replicate an Austrian Stroke Prevention study (ASPS) finding. The UK Biobank data analysis demonstrated changes in brain gray matter on T2* imaging linked to older age, smoking and increased BMI. This finding is felt to demonstrate increased brain iron accumulation with aging and degeneration.

The UK Biobank data results were "highly concordant with the ASPS".

I highly recommend reviewing this early manuscript in the UK Biobank Epidemiological Study.  Readers can access the free full-text manuscript by clicking on the PMID link in the citation below. It features a review of the methodology of the study. Numerous important research findings will emerge from this study in the years and decades to come.

The Brits are to be congratulated on such an important and costly effort.

Image of brain is an iPad screen shot from the iPad app 3D Brain.

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Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Andersson JL, Griffanti L, Douaud G, Okell TW, Weale P, Dragonu I, Garratt S, Hudson S, Collins R, Jenkinson M, Matthews PM, & Smith SM (2016). Multimodal population brain imaging in the UK Biobank prospective epidemiological study. Nature neuroscience PMID: 27643430

Alzheimer's Disease: The Promise of Diabetes Drugs

Current pharmacologic interventions in Alzheimer's disease (AD) have limited effectiveness.

Most of the current AD drugs available promise to slow the rate of progression but fail to reverse or prevent the disease.

Novel strategies for AD drug treatment are desperately needed and one promising class of agents are the newer drugs for treatment of diabetes. 

How might a diabetes treatment drug potentially treat a brain disease like AD?

A recent review article in World Journal of Diabetes summarizes what is known about the neuroprotective effect of the anti-diabetic drug liraglutide (trade name Saxenda in the U.S.). This review article is extensive but I will try to summarize the key points.

1. Long-acting glucagon-like peptide-1 (GLP-1) is a naturally occuring peptide known to promote insulinotropic activity and glucose homeostasis
2. GLP-1 is primarily excreted in the gut but receptors for the compound are found throughout the body including the brain.
3. GLP-1 is a key component of the gut-brain axis and along with the vagal nerve helps regulate energy metabolism, insulin secretion, appetite and weight control.
4. Liraglutide is a recently approved GLP-1 receptor agonist with an effect similar to naturally occuring GLP-1.
5. Liraglutide along with regulating glucose in type 2 diabetes has brain anti-inflammatory, anti-oxidant, microglia inhibition and neuroprotective actions.
6. Higher doses of liraglutide promote weight loss and the drug has recently been approved for weight loss in the U.S.
7. Preclinical trials suggest liraglutide may improve cognitive function in AD and may have beneficial effects on AD biomarkers such as beta amyloid brain levels.
8. Future research combining liraglutide with dipeptidyl peptidase-4 (DPP-4) inhibitors may lead to a "therapeutic dream team" combination for both diabetes and neurodegenerative diseases including AD
9. Basic research suggests brain insulin resistance is a key mechanism in AD and other central neurodegenerative disorders. Brain insulin resistance may be reduced or eliminated by the use of centrally acting anti-diabetic drugs like liraglutide.
10. Preclinical studies also find evidence that liraglutide "modulates synaptic plasticity by enhancing long-term potentiation" and improves learning an memory in rat models of AD.

This review makes some quite remarkable predictions about the potential for GLP-1 drugs in brain disorders including AD. Whether these predictions will be true is yet to be seen.

Certainly we can expect to see more research using anti-diabetic drugs in AD and other brain diseases.

Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.

Photo of great egret is from the author's files.

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Candeias EM, Sebastião IC, Cardoso SM, Correia SC, Carvalho CI, Plácido AI, Santos MS, Oliveira CR, Moreira PI, & Duarte AI (2015). Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide. World journal of diabetes, 6 (6), 807-27 PMID: 26131323

Brain Posts Hits 3 Million Pageviews

Dear Brain Posts Reader:

This week has been a fireworks experience for me as Brain Posts passed the 3 million pageview mark.

I started the blog in 2009 and have posted 676 posts over the last six years.

I started the blog primarily as a note-taking forum for my scientific reading. I select neuroscience research I feel is noteworthy and important from PubMed. Selecting a single study for more detailed notes has been a helpful focus and memory tool.

Over 400,000 Brain Posts pageviews have come via the research blogging aggregation website ResearchBlogging.org. They have a very helpful tool for adding citations to scientific blogs. I highly recommend adding their website to your RSS feed and following them on Twitter  @ResearchBlogs

I want say thanks to everyone who has been accessing Brain Posts. Readers from the U.S. are the top readers of the site. But I want to also thank readers from around the world including those from the United Kingdom, Canada, Australia, Germany and India who rank in the top 5 international Brain Posts pageviews. Thanks also to the growing number of readers from Russia and Ukraine in the last year

Brain Posts will remain a commercial free, non-profit site that does not accept sponsored or guest posts. 

I try to limit self promotion on Brain Posts, so you won't see another post like this until 4 million pageviews. Follow me on Twitter @WRY999 for real-time updates to the blog and other links I find informative. You can also subscribe to Brain Posts by using the subscribe by email button on the upper right.

Feel free to contact me directly with comments and recommendations at my email address WRY888 [at] gmail.com

Best wishes: Bill