Alzheimer’s Drugs Linked to a Reduced Risk of Heart Attacks

The European Heart Journal, an online publication, looked at a study from Sweden involving Alzheimer’s medication and heart attacks.  The research, which had a testing base of 7,000 people with Alzheimer’s disease, showed that drugs typically administered in the early stages of Alzheimer’s reduced patient risk of heart attack and death by any means.

The study looked at cholinesterase inhibitors (ChEIs), including donepezil, rivastigmine, and galantamine, which aid in the treatment of moderate Alzheimer’s disease.  Scientists became interested in the possible effect of this drug on the heart because it is targeted at reducing the chronic inflammation seen in Alzheimer’s patients, and a side effect of ChEls is the calming of the vagus nerve, which is responsible for controlling the heartbeat.  At Umea University in Sweden, Professor Peter Nordstrom and his colleagues followed 7,073 people with Alzheimer’s disease who appeared on the Swedish Dementia Registry for an average of two years. They found that those individuals who were on ChEIs had a 36 percent reduced risk of death in general, a 38 percent reduced risk of a myocardial infarction (heart-attack), and a 26 percent reduction in the risk of any cardiovascular-related death, such as stroke, compared to those not on the ChEIs. Professor Nordstrom remarked the results if translated into absolute figures representing the data of one year for a group of 100,000 individuals with Alzheimer’s disease on ChEls; there would be 180 fewer heart attacks (295 compared to 475), and 1,125 fewer deaths overall (2000 cases versus 3,125).  It was also recorded that patients who took the highest levels possible of ChEIs while remaining safe had a 65% lower risk of heart attack and a 46 % lower risk of death than those who did not take the anti-inflammatory.  As a control, scientists tested other types of medication commonly administered to Alzheimer’s and dementia patients, and the research found no change or significant results. The study holds scientific uncertainty, for while it yields promising data, the scientists cannot say that ChEls are responsible for the lowering the risks, only that is in some way related to said reduction.  However, the strong results hold promise, and Professor Nordstrom said that further experimentation and trials involving the anti-inflammatory drug could bring forth more information regarding its role in the reduction of risk of myocardial infarction and death.

1) P. Nordstrom, D. Religa, A. Wimo, B. Winblad, M. Eriksdotter. The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer’s disease. European Heart Journal, 2013; DOI: 10.1093/eurheartj/eht182

2) European Society of Cardiology (ESC) (2013, June 5). Alzheimer’s disease drugs linked to reduced risk of heart attacks. ScienceDaily. Retrieved June 7, 2013, from http://www.sciencedaily.com/releases/2013/06/130605090257.htm

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

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The Parkin Protein and Disease Mutations

From the MRC Laboratory of Molecular Biology in the United Kingdom comes research that has determined the crystal structure of Parkin, a protein linked to Parkinson’s disease.  Results published in The EMBO Journal better define the positioning of many mutations that are linked to hereditary Parkinson’s disease.

Parkinson’s disease is a progressive neurodegenerative disease that occurs mostly in older individuals sporadically, or not hereditarily.  However, around 15% of patients develop symptoms early in life due to inherited mutations in a limited number of disease genes. These mutations are especially detrimental, causing more damage to nerve cells than non-mutated forms of Parkin.  Scientists believe this occurs because previous research has suggested the Parkin protein regulates energy production within cells.  For familial cases of inherited disease genes, around 50% are caused by mutations in the PARKIN gene that encodes a protein within the RBR ubiquitin ligase enzyme family. These mutated enzymes couple other proteins together within the cell to create a molecule called ubiquitin.  But since the enzymes catalyzing these reactions are mutated forms of the PARKIN gene, the critical ubiquitin proteins can be unstable or altered in their function.

EMBO investigator David Komander and his co-worker Tobias Wauer crystallized a form of human Parkin and used X-ray diffraction patterns to determine the way in which the protein chain folds into a three-dimensional structure. The experiments revealed the existence of an in-built control mechanism for Parkin activity, one that is lost in the presence of the mutations which cause Parkinson’s disease. Komander and Wauer pinpointed amino acids of Parkin that had key functions of ubiquitin ligase enzyme activity, and found that the proteins they create are sensitive to blocking by reagents that had already been categorized by their laboratory.  This means that after identifying building blocks of Parkin, the scientists blocked their ability to form larger, mutated, ubiquitin molecules.  The crystal structure of Parkin goes on to reveal secrets regarding the molecule, which scientists are hopeful may one day be used as a way to treat or slow the progression of Parkinson’s. There is reason to believe that other studies on crystal structure could lead scientists to find compounds that are capable of altering Parkin’s activity.

1) Tobias Wauer, David Komander. Structure of the human Parkin ligase domain in an autoinhibited state. The EMBO Journal, 2013; DOI: 10.1038/emboj.2013.125

2) EMBO – ecellence in life sciences (2013, May 31). How disease mutations affect the Parkin

protein. ScienceDaily. Retrieved June 3, 2013, from http://www.sciencedaily.com/releases/2013/05/

By: Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

Brain Function Affected by Change in Gut Bacteria

At ULCA, researchers conducted a study that tested women who regularly consumed yogurt containing beneficial bacteria called probiotics, to see if they had any alteration in brain function compared to women who did not consume the probiotics in yogurt. The study showed that the women who regularly ate yogurt had an alteration in both a resting state and emotional recognition brain function.

Researchers speculated that by changing the bacteria’s environment in the gut, brain functionality could be augmented. The study was small, consisting of only 36 healthy women of ages 18-55. The women were divided into three groups: one group was given yogurt with probiotics twice a day for four weeks, one group was given a look-alike yogurt with no probiotics, and the third group did not have any yogurt. Comparing MRI scans taken before and after the study, researchers found that women who consumed the probiotic yogurt saw a decrease in insula, which processes and integrates body sensations, as well as in the somatosensory cortex during emotional-recognition testing. These women also saw a decrease in widespread engagement of the brain to deal with emotion, cognition, and sensory-related tasks.  The women who did not eat the probiotic yogurt had increased levels of brain network activity, spread out across more area. Furthermore, during the resting brain scan, women consuming probiotics had a higher connectivity of the brainstem to cognition, while the women not eating any yogurt saw increase of emotional and sensational connection to the brainstem.  The women eating the look-alike yogurt fit between the two extremes.  Researchers were astounded to find the various effects on the brain due to consumption of probiotics, such as the change in sensations as well as processes of emotional responses. The linkage of signals between the intestines and the brain will lead scientists to explore new routes of research.  These innovative news possibilities include changes in diet to test for varying levels of brain response and functionality.

Sources:

1) Kirsten Tillisch, Jennifer Labus, Lisa Kilpatrick, Zhiguo Jiang, Jean Stains, Bahar Ebrat, Denis Guyonnet, Sophie Legrain-Raspaud, Beatrice Trotin, Bruce Naliboff, Emeran A. Mayer. Consumption of Fermented Milk Product with Probiotic Modulates Brain Activity. Gastroenterology, 2013; DOI: 10.1053/j.gastro.2013.02.043

2) University of California, Los Angeles (UCLA), Health Sciences (2013, May 28).

Changing gut bacteria through diet affects brain function. ScienceDaily. Retrieved May 29, 2013, from http://www.sciencedaily.com/releases/2013/05/130528180900.htm

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.