Neuropsychological assessment more efficient than MRI for tracking disease progression in memory clinic patients

Progression of disease in memory clinic patients can be tracked efficiently with 45 minutes of neuropsychological testing, new research shows. MRI measures of brain atrophy were shown to be less reliable to pick up changes in the same patients. This finding has important implications for the design of clinical trials of new anti-Alzheimer drugs. If neuropsychological assessment is used as the outcome measure or “gold standard,” fewer patients would be needed to conduct such trials, or the trials may be of shorter duration. Investigators at the University of Amsterdam, The Netherlands, have shown that progression of disease in memory clinic patients can be tracked efficiently with 45 minutes of neuropsychological testing. MRI measures of brain atrophy were shown to be less reliable to pick up changes in the same patients. This finding has important implications for the design of clinical trials of new anti-Alzheimer drugs. If neuropsychological assessment is used as the outcome measure or “gold standard,” fewer patients would be needed to conduct such trials, or the trials may be of shorter duration. The US Food and Drug Administration and its counterparts in other countries, such as the European Medicines Agency, require that pharmaceutical companies test and prove the effectiveness of new drugs through experimental studies. In the case of Alzheimer’s disease, this means amelioration of cognitive and behavioral symptoms or at least slowing down the rate of cognitive and behavioral decline. Until now the outcome measures in this type of research have been cognitive and behavioral rating scales, such as the Alzheimer Disease Assessment Scale (ADAS). If the effect of a new drug cannot be demonstrated with such a scale, the drug will not be approved. The problem with scales like the ADAS is that they are quite crude and cannot pick up subtle changes, especially in early stages of the disease. As an alternative, MRI measures of brain atrophy have been proposed as outcome in clinical trials, because of allegedly better properties to detect subtle changes. This implies that fewer patients are needed in clinical trials of new drugs to show a treatment effect. The Dutch investigators tested this claim at the memory clinic of the Academic Medical Centre, University of Amsterdam, by comparing neuropsychological assessment and MRI measures of brain atrophy in 62 patients with no or early cognitive impairment, but no dementia. At baseline and after two years, neurologists examined the study participants and judged whether or not their cognition was normal. After two years of follow-up, twenty-eight patients were considered to be normal, and 34 had mild cognitive impairment or had progressed to dementia, mostly Alzheimer’s disease. At baseline and at follow-up all patients had a state-of-the-art MRI scan, and memory and other cognitive functions were tested with five standard neuropsychological tests. In the group that the neurologists considered normal at follow-up, cognitive performance was indeed normal at baseline, and it remained so after two years. In the group that was considered impaired, however, cognition was already abnormal at baseline and it declined considerably over the next two years. The MRI measures concerned volumes of the left and right hippocampus, which are extremely important for memory functioning, and are the first to degenerate during the Alzheimer disease process. The volume of the hippocampus decreased less than 1% in the normal group during the follow-up interval, and more than 3% in the impaired group. The pattern of findings was similar for both techniques, but MRI showed less pronounced differences between both groups at baseline than the cognitive tests, and more importantly, less pronounced differences in rate of change. Using figures on rates of change as collected in this study, one may calculate the numbers of patients that would be needed for a hypothetical clinical trial of a new drug. The investigators concluded that only half as many patients would be needed if neuropsychological assessment were used as the gold standard rather than MRI measures of brain atrophy. However, Dr, Edo Richard, one of the neurologists conducting the study, says, “Whichever outcome is selected, evaluation of functioning as it can be noticed by patients will always be needed to confirm the clinical relevance of any treatment effect.” Journal Reference: 1.Ben Schmand, Anne Rienstra, Hyke Tamminga, Edo Richard, Willem A. van Gool, Matthan W.A. Caan, Charles B. Majoie. Responsiveness of Magnetic Resonance Imaging and Neuropsychological Assessment in Memory Clinic Patients. Journal of Alzheimer’s Disease, January 2014 DOI: 10.3233/JAD-131484

Chronic pain research delves into brain: New insight into how brain responds to pain

Source:University of Adelaide Summary:New insights into how the human brain responds to chronic pain could eventually lead to improved treatments for patients, researchers say. Chronic pain is common throughout the world. More than 100 million Americans are believed to be affected by chronic pain. "People living with chronic headache and other forms of chronic pain may experience reduced quality of life, as the pain often prevents them from working, amongst other things. It is therefore imperative that we understand the causes of chronic pain, not just attempt to treat the symptoms with medication," the lead author said.Share This Neuroplasticity is the term used to describe the brain's ability to change structurally and functionally with experience and use. "Neuroplasticity underlies our learning and memory, making it vital during early childhood development and important for continuous learning throughout life," says Dr Ann-Maree Vallence, a Postdoctoral Fellow in the University of Adelaide's Robinson Institute. "The mechanisms responsible for the development of chronic pain are poorly understood. While most research focuses on changes in the spinal cord, this research investigates the role of brain plasticity in the development of chronic pain." Chronic pain is common throughout the world. In Australia, approximately 20% of adults suffer moderate to severe chronic pain. More than 100 million Americans are believed to be affected by chronic pain. Dr Vallence, who is based in the Robinson Institute's Neuromotor Plasticity and Development Group, has conducted a study on patients with chronic tension-type headache (CTTH), a common chronic pain disorder. CTTH is characterized by a dull, constant feeling of pressure or tightening that usually affects both sides of the head, occurring for 15 days or more per month. Other symptoms include poor sleep, irritability, disturbed memory and concentration, and depression and anxiety. "People living with chronic headache and other forms of chronic pain may experience reduced quality of life, as the pain often prevents them from working, amongst other things. It is therefore imperative that we understand the causes of chronic pain, not just attempt to treat the symptoms with medication," Dr Vallence says. In this study, participants undertook a motor training task consisting of moving their thumb as quickly as possible in a specific direction. The change in performance (or learning) on the task was tracked by recording how quickly subjects moved their thumb. A non-invasive brain stimulation technique was also used to obtain a measure of the participants' neuroplasticity. "Typically, when individuals undertake a motor training task such as this, their performance improves over time and this is linked with a neuroplastic change in the brain," Dr Vallence says. "The people with no history of chronic pain got better at the task with training, and we observed an associated neuroplastic change in their brains. However, our chronic headache patients did not get better at the task and there were no associated changes in the brain, suggesting impaired neuroplasticity. "These results provide a novel and important insight into the cause of chronic pain, and could eventually help in the development of a more targeted treatment for CTTH and other chronic pain conditions," she says

Play it again, Sam: How the brain recognizes familiar music

Source:McGill University Summary:Research reveals that the brain’s motor network helps people remember and recognize music that they have performed in the past better than music they have only heard. A recent study sheds new light on how humans perceive and produce sounds, and may pave the way for investigations into whether motor learning could improve or protect memory or cognitive impairment in aging populations.Share This For the study, researchers recruited twenty skilled pianists from Lyon, France. The group was asked to learn simple melodies by either hearing them several times or performing them several times on a piano. Pianists then heard all of the melodies they had learned, some of which contained wrong notes, while their brain electric signals were measured using electroencephalography (EEG). Credit: Palmer, Mathias McGill University[Click to enlarge image] For the study, researchers recruited twenty skilled pianists from Lyon, France. The group was asked to learn simple melodies by either hearing them several times or performing them several times on a piano. Pianists then heard all of the melodies they had learned, some of which contained wrong notes, while their brain electric signals were measured using electroencephalography (EEG).Credit: Palmer, Mathias McGill University Research from McGill University reveals that the brain's motor network helps people remember and recognize music that they have performed in the past better than music they have only heard. A recent study by Prof. Caroline Palmer of the Department of Psychology sheds new light on how humans perceive and produce sounds, and may pave the way for investigations into whether motor learning could improve or protect memory or cognitive impairment in aging populations. The research is published in the journal Cerebral Cortex. "The memory benefit that comes from performing a melody rather than just listening to it, or saying a word out loud rather than just hearing or reading it, is known as the 'production effect' on memory," says Prof. Palmer, a Canada Research Chair in Cognitive Neuroscience of Performance. "Scientists have debated whether the production effect is due to motor memories, such as knowing the feel of a particular sequence of finger movements on piano keys, or simply due to strengthened auditory memories, such as knowing how the melody tones should sound. Our paper provides new evidence that motor memories play a role in improving listeners' recognition of tones they have previously performed." For the study, researchers recruited twenty skilled pianists from Lyon, France. The group was asked to learn simple melodies by either hearing them several times or performing them several times on a piano. Pianists then heard all of the melodies they had learned, some of which contained wrong notes, while their brain electric signals were measured using electroencephalography (EEG). "We found that pianists were better at recognizing pitch changes in melodies they had performed earlier," said the study's first author, Brian Mathias, a McGill PhD student who conducted the work at the Lyon Neuroscience Research Centre in France with additional collaborators Drs. Barbara Tillmann and Fabien Perrin. The team found that EEG measurements revealed larger changes in brain waves and increased motor activity for previously performed melodies than for heard melodies about 200 milliseconds after the wrong notes. This reveals that the brain quickly compares incoming auditory information with motor information stored in memory, allowing us to recognize whether a sound is familiar. "This paper helps us understand 'experiential learning', or 'learning by doing', and offers pedagogical and clinical implications," said Mathias, "The role of the motor system in recognizing music, and perhaps also speech, could inform education theory by providing strategies for memory enhancement for students and teachers." This study was conducted within the framework of the European Erasmus Mundus Auditory Cognitive Neuroscience exchange program, in which North American researchers complete a research project in collaboration with a European laboratory for 6-12 months.