In November there were plenty of reasons to be thankful. Although there was some bad news, last month was full of promising findings, including new therapies for neurological disorders and even for drug addiction. Here are the best and worst news I came across.
THE BEST
Targeting angiogenesis in Parkinson’s disease
Movement and balance disorders are a well-known consequence of Parkinson’s disease (PD). Hypothesizing that these features could be related to the formation of new blood vessels, a study published in Neurology assessed the presence of biomarkers of new blood vessel formation (angiogenesis) in the cerebrospinal fluid of patients with PD, and compared it with blood-brain barrier permeability, white matter lesions, and cerebral microbleeds. This study initially used samples from 100 PD patients and was followed by two additional validation groups of 87 patients with PD with dementia 93 patients with PD with and without dementia.
The findings showed that there is indeed a connection between the presence of markers of angiogenesis in the brain and the motor and balance impairments of PD patients. Increased angiogenesis was also linked to an increased permeability of the blood-brain barrier, to white matter lesions, and to cerebral microbleeds. These results indicate that medication for angiogenesis may be an additional and promising therapy for PD patients in the future.
A therapeutic target for Down Syndrome-associated dementia
Individuals with Down Syndrome carry an extra chromosome 21. Since this is where the amyloid-beta precursor protein gene is located, they are at higher risk of developing early onset dementia with features very similar to Alzheimer’s disease.
In a study published in the Annals of Neurology, it was shown that GSAP, a key enzyme in the generation of amyloid plaques, is increased in the brain of Down Syndrome patients. Some of the mechanisms that regulate its production were also reported, namely, an abnormal action of a transcription factor named GATA1. It was shown that GATA1 can regulate the activity of GSAP and that this pathway is linked to the excessive production of amyloid-beta. Silencing GATA1 gene expression led to a decrease in GSAP and amyloid-beta levels. These results thus revealed a therapeutic target for dementia associated with Down Syndrome.
Stroke patients may recover speech using the right hemisphere
Around 70% of people with left brain hemisphere strokes have speech impairments. Whether speech can be recovered on the right side of the brain has been a long lasting doubt. There are reports stating that the right hemisphere can interfere with recovery, but a new study published in the journal Brain claims the opposite.
The authors studied brain structure and grey matter volume while trying to understand how speech may be recovered after a stroke. Their data showed that patients who recovered their speech had an increased grey matter volume in the back of their right hemisphere, an area corresponding to one of the two left hemisphere speech areas. The quality of their speech abilities correlated with the increase in grey matter. This finding may contribute for better rehabilitation approaches for stroke patients.
Physical activity for a healthy brain
Memory deteriorates with age, but the rate of memory decline is highly variable. One of the factors that can have an impact on the rate of memory decline is physical activity. A new study published in the Journal of the International Neuropsychological Society examined the connection between physical activity, memory and cognition both in young and old adults.
Data showed that, as expected, older adults (ages 55-82 years) had a poorer performance in cognitive and memory tasks. Although physical activity was not associated with cognitive performance in younger adults, it was positively correlated with memory accuracy in older individuals. Long-term memory, the type of memory that is most affected by aging and neurodegenerative dementias, was better in physically active older adults. This once again highlights the importance of an active lifestyle on the brain’s health.
A new therapy for cocaine addiction
Cocaine addiction affects millions of people throughout the world, and an effective treatment is still lacking. A step forward may have been taken with the results of a pilot clinical study published in European Neuropsychopharmacology.
The study indicated that cocaine use can be reduced by treatment with repetitive Transcranial Magnetic Stimulation (rTMS). These magnetic pulses to the brain were shown to reduce craving and substance use in cocaine-addicted patients. Furthermore, data showed that rTMS also reduced relapse – 69% of patients receiving rTMS showed no relapse to cocaine use, whereas only 19% in the control group showed a similar positive outcome. Although a larger trial is still needed, these results suggest that rTMS may become an effective and much needed medical treatment for patients with cocaine use disorder.
THE WORST
Altered neurochemistry in PTSD
Experiencing traumatic events can cause serious anxiety problems, namely post-traumatic stress disorder (PTSD). Given that the neurotransmitter serotonin and the neuropeptide substance P have been independently implicated in stress and anxiety, and that their interaction is considered to be important in anxiety conditions, a study published in Molecular Psychiatry addressed the contribution of serotonin and substance P to PTSD, both individually and in interaction.
It was found that an abnormal interaction between the two neurochemical systems in the brain can contribute to the development of PTSD. The magnitude of symptoms was mainly determined by the degree of neurochemical imbalance between the two systems, rather than by changes in a single system. PTSD treatment often targets serotonin, not always with success. These results show that the current approaches may not be the most effective. Hopefully, these findings may contribute to a better treatment design.
Contact sports as a risk factor for neurodegeneration
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury. When severe, this condition can affect mood, behavior and cognition. In a study published in Acta Neuropathologica, the association between the development of CTE and the practice of contact sports was investigated.
This study showed that individuals who had participated in amateur contact sports in their youth, including football, boxing, wrestling, rugby, basketball or baseball, were at a higher risk developing CTE. The numbers were impressive: from the 66 males that had participated in contact sports in their youth, 32% had CTE, showing that contact sports are a serious risk factor for CTE pathology. This study highlights the need for effective protective equipment when engaging in these sports.
Fatty acid availability in the brain contributes to bipolar disorder
Polyunsaturated fatty acids, such as omega-3 and omega-6, have a widely recognized importance in the brain. They have been linked to depression and bipolar disorder (BD). A new study published in Bipolar Disorders aimed at clarifying their role in BD development. The levels of PUFAs was measured in people with symptomatic bipolar disorder and compared with healthy controls. Free fatty acids are able to cross the blood-brain barrier, whereas fatty acids coupled to proteins are not.
Results showed that patients with bipolar disorder had a lower ratio of a free-circulating omega-3 fatty acid than controls. This suggests that bipolar subjects have a lower availability of omega-3 in the brain. Interestingly, there were no differences in self-reported fatty acid consumption between bipolar and healthy subjects, suggesting that a dietary intervention may not be necessarily effective.
High-fat diet and cognitive impairment
A high-fat diet has a clear negative impact on our overall health, including our brain. The extent of the impact of a high-fat diet on our brain has just become clearer with a study published in the journal Brain, Behavior, and Immunity.
This work, carried out in mice, showed that fat can prompt immune cells in our brain to become sedentary and start consuming the connections between our neurons. Too much fat in the body leads to chronic inflammation, inducing an autoimmune response by microglial cells in the brain, which start degrading synapses. The consequences can be tremendous, including cognitive impairment. The silver lining was that returning to a low-fat diet was able to reverse these effects in a small amount of time.
Congenital heart defects increase the risk of stroke
Research published in the journal Circulation has shown that adults who were born with congenital heart defects have higher risk of stroke. The study showed that adults with congenital heart defects had a 9 to 12-fold higher risk of ischemic stroke and a 5 to 6-fold higher risk of hemorrhagic stroke before the age of 55; between the ages 55 and 64, the risk of ischemic stroke was 2 to 4 times higher and the risk of hemorrhagic was 2 to 3 times higher. It was also determined that 8.9% of men and 6.8% of women with congenital heart defects experienced at least one stroke before age 65.
Although a connection between heart failure and stroke was already recognized in patients with heart defects, this study now shows the full extent of this link.
References
Bieniek KF, Ross OA, Cormier KA, Walton RL, Soto-Ortolaza A, Johnston AE, DeSaro P, Boylan KB, Graff-Radford NR, Wszolek ZK, Rademakers R, Boeve BF, McKee AC, & Dickson DW (2015). Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank. Acta neuropathologica, 130 (6), 877-89 PMID: 26518018
Chu J, Wisniewski T, & Praticò D (2015). GATA1-mediated transcriptional regulation of the ?-secretase activating protein increases A? formation in Down syndrome. Annals of neurology PMID: 26448035
Frick A, Åhs F, Palmquist ÅM, Pissiota A, Wallenquist U, Fernandez M, Jonasson M, Appel L, Frans Ö, Lubberink M, Furmark T, von Knorring L, & Fredrikson M (2015). Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study. Molecular psychiatry PMID: 26619809
Hao S, Dey A, Yu X, & Stranahan AM (2016). Dietary obesity reversibly induces synaptic stripping by microglia and impairs hippocampal plasticity. Brain, behavior, and immunity, 51, 230-9 PMID: 26336035
Hayes SM, Alosco ML, Hayes JP, Cadden M, Peterson KM, Allsup K, Forman DE, Sperling RA, & Verfaellie M (2015). Physical Activity Is Positively Associated with Episodic Memory in Aging. Journal of the International Neuropsychological Society : JINS, 21 (10), 780-90 PMID: 26581790
Janelidze S, Lindqvist D, Francardo V, Hall S, Zetterberg H, Blennow K, Adler CH, Beach TG, Serrano GE, van Westen D, Londos E, Cenci MA, & Hansson O (2015). Increased CSF biomarkers of angiogenesis in Parkinson disease. Neurology, 85 (21), 1834-42 PMID: 26511451
Lanz J, Brophy JM, Therrien J, Kaouache M, Guo L, & Marelli AJ (2015). Stroke in Adults With Congenital Heart Disease: Incidence, Cumulative Risk and Predictors. Circulation PMID: 26597113
Saunders EF, Reider A, Singh G, Gelenberg AJ, & Rapoport SI (2015). Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment. Bipolar disorders, 17 (7), 729-42 PMID: 26424416
Terraneo A, Leggio L, Saladini M, Ermani M, Bonci A, & Gallimberti L (2015). Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology PMID: 26655188
Xing S, Lacey EH, Skipper-Kallal LM, Jiang X, Harris-Love ML, Zeng J, & Turkeltaub PE (2015). Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke. Brain : a journal of neurology PMID: 26521078
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