For this article, I’ve made a selection of interesting publications that came out in August. There were many interesting developments, both in fundamental neuroscience and neurology, and in practical aspects of dealing with brain-related diseases and disorders.

On August 20, the scientific community marked the birthday of Roger Sperry, who received the 1981 Nobel Prize for Medicine and Physiology for his works on “split-brain” patients (i.e. the patients in whom the corpus callosum which connects the two brain hemispheres had been severed). The works of Prof. Sperry helped to establish that two hemispheres of human brain do have different functions and often work independently.

THE BEST

Neuronal activity protects against neurodegeneration

It was well known for some time already that neural activity protects neurons against neurodegenerative diseases. Now a molecular mechanism behind this phenomenon has been discovered. It involves NMDA receptors and activin A. The level of activin A is substantially elevated in active brain. The consequence of this elevation is the reduction of extrasynaptic NMDA receptors. The discovery may help in developing new treatments for such conditions as Alzheimer’s disease and Parkinsonism.

Modafinil is a first scientifically verified nootropics

Modafinil is one of those cognitive enhancers, also known as “smart drugs” or nootropics, that tend to attract lots of attention due to their ability to improve performance of the normal brain. However, it was always debatable how real and significant this effect really is. A systematic review published this month appears to finally confirm that the drug is indeed a nootropic agent capable of producing obvious and measurable effect, at least in a subset of tasks.

Researchers summarised and analysed all data published on the use of modafinil during the years 1990-2014. The drug did not improve the working memory or thought flexibility, but improved planning and decision-making. Very few side effects were reported for the use of drug in non-sleep deprived individuals. The analysis validates modafinil as a first nootropic drug.

Existing drug might be helpful for slowing down Parkinson’s disease progression

In the last month’s review, I was writing about several existing drugs that have a potential to be re-purposed for treating neurodegenerative conditions. Yet another drug re-purposing story emerged this month.

Ursodeoxycholic acid (UDCA), a drug for treating liver diseases, might be able to slow down the progression of Parkinson’s disease. UDCA was shown to have positive effect on dopaminergic neurons that are affected during Parkinson’s. Taking into account that UDCA is already used in clinics for decades and has a good safety records, researchers call for a fast track clinical trial of this drug in patients with Parkinson’s disease.

10-minute test for dementia

Clinical diagnostics of dementia typically relies on the use of complex instrumentation, various cognitive tests and experience of specialized doctors. As a result, the definitive clinical diagnostics of dementia is usually done rather late, when the symptoms are already obvious. However, the successful management of the condition requires it to be diagnosed as early as possible. Without doubt, it would be beneficial to have a simple and effective approach to identify people with early signs of dementia as soon as possible.

This is exactly what the new paper published this month offers. The author developed a simple questionnaire, The Quick Dementia Rating System (QDRS), that consists of several items covering various aspects of developing cognitive impairment, such as memory, orientation, behavior, decision-making, language, mood, attention and others. The QDRS can be administered by nurses or other care providers. This simple system was demonstrated to have the same precision as current gold standards of diagnostics and has a potential to help thousands of patients.

The brain’s ability to get rid of beta-amyloids reduces with age

Alzheimer’s disease, like the majority of chronic neurodegenerative disorders, tends to affect older people. Exactly why younger people usually remain shielded from the disease was not really clear. After all, beta-amyloid, the natural by-product of brain activity and the major culprit in the disease development, is generated in the brain of both young and old people. The answer to this question appears to be in the rate of clearing of beta-amyloid from the brain.

In people aged 30, half of beta-amyloid in the brain is cleared in four hours. In people aged 80 and above, this process takes more than 10 hours. Slow rate of clearing allows beta-amyloid to conglomerate and form the characteristic plaques observed in all Alzheimer’s patients. The discovery may help in the development of future therapeutic interventions aimed at accelerating the beta-amyloid clearing rate.

Physically active elderly people show greater mental flexibility

The benefits of physical activity for the brain were once more emphasized by the research studying mental flexibility in older adults. Brain MRI investigation of 100 adults aged 60 to 80 demonstrated that physically active individuals have higher level of spontaneous brain activity, better perform in cognitive tests and have better white-matter structure. Higher oxygenation level in the brains of active individuals is thought to be behind the differences.

THE WORST

Physical activity cannot prevent dementia in elderly

Although physical activity is linked to better cognitive performance, starting sports later in life does not show much benefits in protecting from age-related dementia.

Researchers subjected over 1600 sedentary adults aged 70 to 89 to either 2-year program of physical activity or health education program. After two years, both groups had very similar results on cognitive tests, and no significant differences in the incidence of dementia or cognitive impairment was detected. Apparently, it takes lifetime of physical activity to fight off neurodegenerative diseases at older age.

Cancer drug may cause memory loss

Targeted therapy is a new promising approach to treat cancer. Unlike usual chemotherapeutic agents, targeted drugs aim at specific biochemical pathways activated in cancer cells. This helps to significantly reduce side effects associated with cancer treatment and increase its efficiency. However, even specifically targeted anticancer compounds might be seriously dangerous.

This idea was highlighted by recent report showing that BET inhibitors, a promising new class of cancer drugs, cause memory loss in mice. Clearly, there is a need to ensure that any clinical drugs developed on the basis of BET inhibitors do not have the same effect on humans. This is particularly important taking into account that some patients with hard-to-treat cancers already receive BET inhibitors as experimental treatment.

Transcranial brain stimulation is not as good as previously thought

Recently, there were media reports that freely available, commercial transcranial direct current stimulation (tDCS) devices improve cognitive performance.

This claim was put to the test on a group of 24 healthy volunteers who received either low intensity current administered to the frontal part of brain or sham treatment with no current applied. Immediately after both treatments, working memory was tested in participants. Surprisingly, tDCS did not improved working memory and, even, worse, statistically significant impairment of working memory was detected. Clearly, there is a need to re-evaluate the use of tDCS devices for commercial purposes.

Poor air quality linked to bad school grades

It is well known that the quality of air we breathe influences our health. A new study shows that it also influences our mental performance: at least, poor air quality can affect the school grades of children.

In the large study performed by researchers from Texas, academic performance of 1,895 fourth and fifth graders was correlated with the level of air pollution around their homes. Children living in the areas with high level of air pollution originating from roads and highways had significantly lower grades. It remains to be investigated how exactly air pollution affects brain functions and whether air toxins impair brain development in children.

Omega-3 does not help in preventing the age-related cognitive decline

Omega-3 supplements are often branded and marketed as protectors of brain health. A new article published this month casts doubts on the validity of this viewpoint.

Researchers followed 4,000 elderly patients over the period of four years providing them with either omega-3, omega-3 in combination with lutein and zeaxanthin, or a placebo. The rate of cognitive decline in all groups over the study period did not differ. Although discouraging, the findings do not completely invalidate the view that omega-3 provides benefits the health of brain. Further research is needed to see how dietary patterns and patient age influence the effects of omega-3.

References

Battleday, R., & Brem, A. (2015). Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: a systematic review European Neuropsychopharmacology DOI: 10.1016/j.euroneuro.2015.07.028

Burzynska, A., Wong, C., Voss, M., Cooke, G., Gothe, N., Fanning, J., McAuley, E., & Kramer, A. (2015). Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults PLOS ONE, 10 (8) DOI: 10.1371/journal.pone.0134819

Clark-Reyna, S., Grineski, S., & Collins, T. (2015). Residential exposure to air toxics is linked to lower grade point averages among school children in El Paso, Texas, USA Population and Environment DOI: 10.1007/s11111-015-0241-8

Galvin, J. (2015). The Quick Dementia Rating System (QDRS): A rapid dementia staging tool Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 1 (2), 249-259 DOI: 10.1016/j.dadm.2015.03.003

Korb, E., Herre, M., Zucker-Scharff, I., Darnell, R., & Allis, C. (2015). BET protein Brd4 activates transcription in neurons and BET inhibitor Jq1 blocks memory in mice Nature Neuroscience DOI: 10.1038/nn.4095

Lau, D., Bengtson, C., Buchthal, B., & Bading, H. (2015). BDNF Reduces Toxic Extrasynaptic NMDA Receptor Signaling via Synaptic NMDA Receptors and Nuclear-Calcium-Induced Transcription of inhba/Activin A Cell Reports, 12 (8), 1353-1366 DOI: 10.1016/j.celrep.2015.07.038

Mortiboys, H., Furmston, R., Bronstad, G., Aasly, J., Elliott, C., & Bandmann, O. (2015). UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2G2019S carriers and in vivo Neurology, 85 (10), 846-852 DOI: 10.1212/WNL.0000000000001905

Patterson, B., Elbert, D., Mawuenyega, K., Kasten, T., Ovod, V., Ma, S., Xiong, C., Chott, R., Yarasheski, K., Sigurdson, W., Zhang, L., Goate, A., Benzinger, T., Morris, J., Holtzman, D., & Bateman, R. (2015). Age and amyloid effects on human central nervous system amyloid-beta kinetics Annals of Neurology, 78 (3), 439-453 DOI: 10.1002/ana.24454

Sink, K., Espeland, M., Castro, C., Church, T., Cohen, R., Dodson, J., Guralnik, J., Hendrie, H., Jennings, J., Katula, J., Lopez, O., McDermott, M., Pahor, M., Reid, K., Rushing, J., Verghese, J., Rapp, S., & Williamson, J. (2015). Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults JAMA, 314 (8) DOI: 10.1001/jama.2015.9617

Steenbergen, L., Sellaro, R., Hommel, B., Lindenberger, U., Kühn, S., & Colzato, L. (2015). “Unfocus” on foc.us: commercial tDCS headset impairs working memory Experimental Brain Research DOI: 10.1007/s00221-015-4391-9

Chew, E., Clemons, T., Agrón, E., Launer, L., Grodstein, F., & Bernstein, P. (2015). Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function JAMA, 314 (8) DOI: 10.1001/jama.2015.9677

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