Author Interviews, Cognitive Issues, NEJM / 11.02.2016

MedicalResearch.com Interview with: Claudia L. Satizabal, PhD Instructor in Neurology Boston University School of Medicine The Framingham Heart Study Boston, MA 02118-2526 MedicalResearch: What is the background for this study? What are the main findings?   Dr. Satizabal: Our societies are expected to face an increasing burden of dementia in the next decades due to increasing life expectancies and the aging of a big proportion of the population, the so called “baby boomers”. However, some studies conducted in high-income countries have suggested a decline in the total number of cases (prevalence) as well as new cases (incidence) of dementia at any given age. Yet the findings of these studies were not seen as definitive, either because results were of borderline significance or because they were based on survey data, and stronger evidence was lacking. We used information collected since 1975 in the Framingham Heart Study to estimate the trends in dementia incidence. One of the strengths of this study is that investigators have been careful to use the same diagnostic criteria for over the past 30 decades, which allows us to provide more robust evidence of dementia trends over time. We found that there has been a progressive decline in the incidence of dementia at any given age over the past 30 decades. Compared to the late 1970s, we observed a decline of 22% in the late 1980s, 38% in the 1990s and 44% in the 2000s. This beneficial trend was only seen among persons with at least a high school diploma. We also explored trends in vascular risk factors such as blood pressure, smoking, diabetes, and others; however, these trends did not completely explain the decline in dementia incidence. One interesting finding was that the risk of dementia associated with cardiovascular diseases, such as stroke or atrial fibrillation, decreased dramatically over the course of time from the late 1970s to the 2000s. (more…)
Aging, Author Interviews, Cognitive Issues, JAMA, Mayo Clinic, Weight Research / 01.02.2016

MedicalResearch.com Interview with: Rosebud O. Roberts, M.B., Ch.B. Mayo Clinic Rochester, Minn.  Medical Research: What is the background for this study? Dr. Roberts: Decline in weight has been observed 10-20 years prior to onset of dementia. We wanted to study whether this decline also occurs for mild cognitive impairment (an intermediate stage in the progression from normal cognition to dementia). Medical Research: What are the main findings? Dr. Roberts: The main finding was that there was indeed a decline in weight (from the maximum weight in midlife to weight assessed in late life) was associated with a increased risk of mild cognitive impairment. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Memory / 26.01.2016

MedicalResearch.com Interview with: Dr. Brian K. Lebowitz, PhD ABPP-CN DIRECTOR OF NEUROPSYCHOLOGY TRAINING Clinical Neuropsychologist Clinical Assistant Professor, Neurology Stony Brook University Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Lebowitz: As a lifespan neuropsychologist, my clinical work involves evaluating cognitive concerns in both children and adults.  We know that children with learning disorders, such as dyslexia, often demonstrate difficulties on neuropsychological tests that are seemingly unrelated to reading.  For example, children with dyslexia may have difficulty with auditory processing and short-term memory.  We also know that, for many individuals, learning disorders remain present throughout the lifespan.  Despite awareness of the relationship between reading disorder and other areas of cognitive weakness, many clinicians who work with older adults do not routinely ask about academic/neurodevelopmental history.  Further, little research has assessed the potential impact of lifelong learning disorder on later life neuropsychological test performance. Our study attempted to assess whether or not a history of possible reading disorder increased the likelihood that an individual's performance would fall at a level suggestive of possible Mild Cognitive Impairment MCI), a diagnosis associated with increased risk for Alzheimer’s disease.  Individuals with MCI continue to function normally in everyday life but experience subjective memory problems and identified weaknesses on neuropsychological tests.  Our study found a strong relationship between poor reading ability and low memory test scores on two tests commonly used to evaluate memory complaints in older adults.  Depending on the test, individuals with a suspected reading disorder were two to three-and-one-half times more likely than their peers to score at a level indicative of Mild Cognitive Impairment. (more…)
Author Interviews, Cognitive Issues, Weight Research / 16.12.2015

MedicalResearch.com Interview with: Dr Anne Martin PhD Research Associate/Research Fellow Physical Activity for Health Research Centre (PAHRC) Institute for Sport, PE & Health Sciences University of Edinburgh TeleScot Research Group Usher Institute for Population Health Sciences and Informatics Edinburgh Medical Research: What is the background for this study? What are the main findings? Dr. Martin: Impairments in cognitive development during childhood can have detrimental effects on health behaviour, educational attainment, and socio-economic status later in life. Epidemiological evidence indicates an association between childhood obesity and cognition and educational attainment. Knowledge of when obesity related deficits in cognition and attainment emerge, and how large the deficits are at various ages, may be useful to support arguments for school-based obesity prevention initiatives and in translating evidence on this topic into policy aimed at preventing obesity. In this study we explored whether the adverse association between obesity and cognition emerges in early childhood. Measures of cognitive abilities included visuo-spatial skills, expressive language skills and reasoning skills. Our findings indicated that obesity in the pre-school years may be weakly associated with some poorer cognitive outcomes at age 5 years in boys, independently of socioeconomic status. Stronger relationships between obesity and cognition or educational attainment may emerge later in childhood. Evidence from an English cohort study suggested an adverse association between obesity in teenage girls and lower academic attainment in Mathmatics, Science and English. (more…)
Author Interviews, Cognitive Issues, Exercise - Fitness, JAMA, Lifestyle & Health / 02.12.2015

MedicalResearch.com Interview with: Tina Hoang MSPH Staff Research Associate Northern California Institute for Research and Education, Veterans Affairs Medical Center Dr. Kristine Yaffe MD Professor of Psychiatry, Neurology, and Epidemiology University of California San Francisco, CA  94121 Medical Research: What is the background for this study? What are the main findings? Response: We assessed physical activity and TV watching in young adults over 25 years to see if there was an association with cognitive function in middle age.  Most previous studies have only considered this association in older adults. We found that both low physical activity and high TV watching over time were associated with worse cognitive function. (more…)
Author Interviews, Cognitive Issues / 24.11.2015

MedicalResearch.com Interview with: Catherine Mewborn, B.A. Neuropsychology and Memory Assessment Laboratory Department of Psychology University of Georgia Medical Research: What is the background for this study? Response: Vision and cognitive functioning both tend to decline as individuals age. Processing speed, or the speed at which an individual can process information, is particularly vulnerable to age-related declines. In previous studies, cognition has typically been measured using traditional paper-and-pencil tests; however, these tests can be quite complex and recruit many different abilities. We wanted to use a simpler test to assess processing speed in the hopes of tapping into the more basic abilities that underlie performance on more complex cognitive tasks. For this study, we chose a measure of visual processing speed called critical flicker fusion, or CFF. We tested how well CFF could predict cognition in both younger and older adults. Medical Research: What are the main findings? Response: As expected, younger adults had better visual processing speed than older adults. Interestingly, in both age groups, CFF significantly predicted performance on a test of executive functioning, which assess abilities such as problem-solving and shifting attention between different tasks. (more…)
AHA Journals, Author Interviews, Cognitive Issues, Stroke / 19.11.2015

MedicalResearch.com Interview with: Dr. Thomas Bak Centre for Cognitive Aging and Cognitive Epidemiology and Centre for Clinical Brain Sciences, University of Edinburgh and Dr. Suvarna Alladi Nizam's Institute of Medical Sciences, Hyderabad, India Medical Research: What is the background for this study? What are the main findings? Response: In a previous study published in 2013 (attached) we have reported that bilingual patients develop dementia around 4 years later than monolingual ones - a phenomenon, which we tried to explain in a commentary in 2014 (also attached); the mechanism we have postulated as a possible explanation is so called "cognitive reserve": the ability of the brain, boosted by a range of different mental activities, to cope better with potential damage. One manifestation of it has been now described in several studies: bilingual patients seem to develop dementia later than monolingual ones. But if the cognitive reserve helps in coping with brain damage, it should also help with the recovery after stroke. This was exactly what we set out to examine and exactly what we found. Bilingual patients showed a complete recovery of cognitive functions after stroke over twice as often as monolingual ones (40/5% vs. 19.6%). (more…)
Author Interviews, Cancer Research, Cognitive Issues, Journal Clinical Oncology, Memory / 03.11.2015

MedicalResearch.com Interview with: Dr Janette Vardy  BMed (Hons), PhD, FRACP A.Prof of Cancer Medicine University of Sydney Medical Oncologist ,Concord Cancer Centre Concord Repatriation & General Hospital Concord, Australia  Medical Research: What is the background for this study? Dr. Vardy: Many patients complain that their memory and concentration is not as good after chemotherapy.  Most of the studies have been in younger women with breast cancer, and are often limited by small sample sizes and short term follow up.    This is the largest longitudinal cohort study assessing impacts of cancer and its treatment on cognitive function. We evaluated changes in cognitive function in 289 men and women with localized colorectal cancer (CRC), comparing those who received chemotherapy to those who did not require chemotherapy, 73 with metastatic disease, and a group of 72 healthy controls.?The localized CRC patients were assessed at baseline (soon after diagnosis and prior to any chemotherapy), 6, 12 and 24 months.  The healthy controls and metastatic group were assessed at baseline, 6 and 12 months.  We also examined underlying mechanisms. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Cognitive Issues / 03.11.2015

MedicalResearch.com Interview with: Kelly N. H. Nudelman, Ph.D. Department of Radiology and Imaging Sciences Indiana University-Purdue University Indianapolis (IUPUI) Indianapolis, IN 46202 Medical Research: What is the background for this study? Dr. Nudelman: Varying levels of cognitive problems and related changes in brain structure and function have been reported in breast cancer patients treated with chemotherapy. Pain has also been associated with altered brain structure and function. However, the association of chemotherapy-induced peripheral neuropathy (CIPN), a side-effect of chemotherapy treatment characterized by nerve damage primarily in the extremities, has not been specifically investigated for association with cognitive symptoms in breast cancer. We used data from a prospective, longitudinal breast cancer cohort to investigate the relationship of CIPN and neuroimaging measures of cognitive dysfunction.  Medical Research: What are the main findings? Dr. Nudelman: We found that increased chemotherapy-induced peripheral neuropathy symptoms were associated with resting brain blood flow increase in regions known to be involved in pain processing. We also found that decreased frontal lobe gray matter density was correlated with these changes, suggesting a link between chemotherapy-induced peripheral neuropathy and cognitive dysfunction. (more…)
Annals Internal Medicine, Author Interviews, Cognitive Issues, Cost of Health Care, End of Life Care / 28.10.2015

MedicalResearch.com Interview with: Amy S. Kelley, MD, MSHS Department of Geriatrics and Palliative Medicine Icahn School of Medicine at Mount Sinai New York, NY Medical Research: Why is it so important to understand the financial burdens families may face in providing end-of-life care for a loved one and why do you think the burdens may be greater for dementia than for other medical conditions? Dr. Kelley: Understanding the financial risks that older adults face in the last years of life is important for individuals and families, in order to plan and save, if possible. It is also important for our policy makers, in particular, to know about these costs so that this information can help shape health and social policy that will best serve our society. Households of those with dementia face the greatest burden of costs, on average, particularly with regard to out-of-pocket expenses and the costs of caregiving.  Many costs related to daily care for patients with dementia are not covered by health insurance, and these care needs, including everything from supervision, to bathing and feeding, may span several years. (more…)
Author Interviews, Cognitive Issues, Pediatrics, PLoS / 27.09.2015

Sophie von Stumm BSc MSc PhD Department of Psychology Goldsmiths University of London London, United KingdomMedicalResearch.com Interview with: Sophie von Stumm BSc MSc PhD Department of Psychology Goldsmiths University of London London, United Kingdom Medical Research: What is the background for this study? Dr. von Stumm: At the Hungry Mind Lab (www.hungrymindlab.com), which I direct, we study individual differences in lifespan cognitive development. In particular, I am interested in factors that influence change in cognitive ability and knowledge. One such factor is breastfeeding, which some previous studies suggested to be associated children's intelligence and IQ gains while others failed to find a relationship. Medical Research: What are the main findings? Dr. von Stumm: For this study, which was published last week in PloS One (link:http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138676), data were analyzed from more than 11,000 children born in the UK between 1994 and 1996. The children had been repeatedly assessed on IQ: the first time they were tested on intelligence at age 2, and then again repeatedly throughout childhood, overall 9 times, until the age of 16 years. We found that having been breastfed versus not having been breastfed was not meaningfully associated with children's IQ differences at age 2 and also not with differences in children's IQ gains until age 16. That is not to say that breastfeeding may not have other benefits for children's development but our study strongly suggests that breastfeeding is not important for children's IQ.   (more…)
Author Interviews, Cognitive Issues, Exercise - Fitness, Nutrition / 21.09.2015

Beetroot juice WikipediaMedicalResearch.com Interview with: Chris Thompson BSc MSc ANutr AFHEA University of Exeter St. Luke's Campus Exeter Devon Medical Research: What is the background for this study? Response: Dietary nitrate has been shown to favourably alter the contractility of type II muscle fibres and enhance blood flow to working muscles that are predominantly type II. Dietary nitrate may also improve perfusion to areas of the brain responsible for cognitive function. It is therefore possible that through these mechanisms, nitrate-rich beetroot juice supplementation may improve both physical and cognitive performance during exercise which reflects the high intensity intermittent nature of team sport play. Medical Research: What are the main findings? Response: Participants were able to complete greater total work during an intermittent sprint test following nitrate-rich beetroot juice supplementation. We also found that dietary nitrate enabled a reduction in response time to decision making during the cognitive tasks performed throughout the exercise test. (more…)
AHA Journals, Author Interviews, Blood Pressure - Hypertension, Cognitive Issues, Mental Health Research / 16.09.2015

Daniela Carnevale, PhD, Researcher Laboratory of Giuseppe Lembo, MD, PhD Dept. of Molecular Medicine "Sapienza" University of Rome & Dept. of Angiocardioneurology and Translational Medicine IRCCS Neuromed - Technology Park Località CamerelleMedicalResearch.com Interview with: Daniela Carnevale, PhD, Researcher Laboratory of Giuseppe Lembo, MD, PhD Dept. of Molecular Medicine "Sapienza" University of Rome & Dept. of Angiocardioneurology and Translational Medicine IRCCS Neuromed - Technology Park Località Camerelle Medical Research: What is the background for this study? Dr. Carnevale: Nowadays, one of the most demanding challenge in medicine is preserving cognitive functions during aging. It is well known that cardiovascular risk factors have a profound impact on the possibility of developing dementia with aging. However, we have no means to investigate this aspect in patients with cardiovascular diseases. Indeed, although we have clear clinical paradigms to explore target organ damage of vascular diseases like hypertension, we are less prepared to afford the brain damage that may result from chronic vascular diseases and impact on cognitive functions. Thus, we aimed at finding a diagnostic paradigm to assess brain damage that could predict for future development of dementia. Since it is becoming increasingly clear that hypertension may determine cognitive decline, even before manifest neurodegeneration, we elaborated a paradigm of analysis that are essentially focused on brain imaging and cognitive assessment. In particular, we used diffusion tensor imaging (DTI) on magnetic resonance that allows to reconstruct white matter connections that correlate with selective cognitive functions, and specifics tests for the evaluation of subtle alterations of cognitive functions. (more…)
Author Interviews, Cognitive Issues, JAMA, Vitamin D / 15.09.2015

Joshua W. Miller, PhD Professor and Chair Dept. of Nutritional Sciences Rutgers The State University of New Jersey New Brunswick, NJ 08901 MedicalResearch.com Interview with: Joshua W. Miller, PhD Professor and Chair Dept. of Nutritional Sciences Rutgers The State University of New Jersey New Brunswick, NJ 08901  Medical Research: What is the background for this study? What are the main findings? Response: In recent years, there has been a growing scientific literature on the associations between low vitamin D status in older adults and risk of Alzheimer's disease/dementia, cognitive impairment and decline, and brain atrophy.  The vast majority of these studies have been conducted in predominantly white populations.  The relatively unique aspect of our study was that over half of the cohort consisted of African Americans and Hispanics.  What we found in our cohort (mean age ~75y, n=382 at baseline) was that participants with vitamin D deficiency (serum 25-hydroxyvitamin D <12 ng/ml) or vitamin D insufficiency (serum 25-hydroxyvitamin D between 12 ng/ml and <20 ng/ml) on average experienced faster rates of cognitive decline in episodic memory and executive function than participants with adequate vitamin D status.  Importantly, the association between vitamin D status and the rate of decline in cognitive function was independent of race/ethnicity.  However, the prevalence of low vitamin D status in the study participants was significantly higher in the African American and Hispanic participants compared with the White participants.  This is most likely due to the fact that darker skin pigmentation reduces the ability of sunlight to induce vitamin D synthesis in the skin.  It may also reflect differences in dietary intake of vitamin D and supplement use between the different race/ethnicity groups, though we did not assess this in our study.  Thus, though the rate of cognitive decline in African Americans and Hispanics does not seem to be more or less affected by low vitamin D status than in Whites, because African Americans and Hispanics have a higher prevalence of low vitamin D status, as subpopulations they may be more prone to rapid cognitive decline in old age.  Further studies addressing this possibility are needed. (more…)
Author Interviews, Blood Pressure - Hypertension, Cognitive Issues, Geriatrics / 05.09.2015

Christine McGarrigle PhD Research Director The Irish Longitudinal Study on Ageing (TILDA) Lincoln Gate Trinity College Dublin Dublin MedicalResearch.com Interview with: Christine McGarrigle PhD Research Director The Irish Longitudinal Study on Ageing (TILDA) Lincoln Gate Trinity College Dublin Dublin   Medical Research: What is the background for this study? What are the main findings? Dr. McGarrigle: Mild cognitive impairment (MCI) is the intermediate state between healthy ageing and dementia and is a stage at which intervention could be effective in reducing conversion to dementia. Neurocardiovascular instability is an age-related dysregulation of the blood pressure systems manifesting as exaggerated blood pressure variability and orthostatic hypotension (OH). Previous evidence has shown that autonomic dysfunction, blood pressure variation and hypotension are associated with mild cognitive impairment. Our study found that systolic blood pressure variation was associated with cognitive decline. Mild cognitive impairment participants were more likely to have had OH and more prolonged OH compared to cognitively normal controls. Mild cognitive impairment participants with impaired orthostatic blood pressure responses were twice more likely to convert to dementia than mild cognitive impairment participants without the impaired response over a three year follow-up period. (more…)
Author Interviews, Blood Pressure - Hypertension, Cognitive Issues, Geriatrics, JAMA / 25.08.2015

MedicalResearch.com Interview with: Justine Moonen and Jessica Foster-Dingley On behalf of the principal investigators: Roos van der Mast, Ton de Craen, Wouter de Ruijter and Jeroen van der Grond Department of Psychiatry, Leiden University Medical Center Leiden, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Mid-life high blood pressure is a well-known risk factor for cerebrovascular pathology and, consequently, cognitive decline in old age. However, the effect of late-life blood pressure on cognition is less clear. It has been suggested that at old age not a higher, but a lower blood pressure increases the risk of cognitive decline as well as neuropsychiatric symptoms. Older persons are at risk for impaired regulation of their cerebral blood flow, and stringently lowering their blood pressure may compromise cerebral blood flow, and thereby cognitive function. Therefore, we hypothesized that increasing blood pressure by discontinuation of antihypertensive treatment would improve cognitive and psychological functioning. We performed a community-based randomized controlled trial in a total of 385 participants aged ≥75 years with mild cognitive deficits and without serious cardiovascular disease, and who were all receiving antihypertensive treatment. Persons were randomized to continuation or discontinuation of antihypertensive treatment. Contradictory to our expectation, we found that discontinuation of antihypertensive treatment in older persons did not improve cognitive functioning at 16-week follow-up. (more…)
Author Interviews, Cognitive Issues, UCSF / 22.08.2015

Jin-Tai Yu MD, PhD Memory and Aging Center, Department of Neurology University of California San Francisco San Francisco, CA 94158 MedicalResearch.com Interview with: Jin-Tai Yu MD, PhD Memory and Aging Center, Department of Neurology University of California San Francisco San Francisco, CA 94158 Medical Research: What is the background for this study? What are the main findings? Response: The number of dementia cases in the whole world was estimated to be 35.6 million in 2010 and this number was expected to almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050. The global prevalence of dementia was 5-7% and Alzheimer’s disease accounts for roughly 60%. This data means that we are facing an increasing number of global populations of this specific neurodegenerative disease and also the heavy burden brought by it. Data from the website of global clinical trials (http://clinicalTrials.gov) showed that a total of 1,732 clinical trials for Alzheimer’s disease were under way. However, the previous results are not so optimistic, possibly due to the complex etiological mechanisms. In one word, we had currently no effective drugs for this disease. Figuring out how to effectively prevent its occurrence is increasingly attracting people’s attentions.Therefore, we have done the most extensive and comprehensive systematic review and meta-analysis to date, which employs a full-scale search of observational studies to calculate effect sizes and grade the evidence strength of various modifiable risk factors for this disease. We hope these results will be informative and instructive. (more…)
Aging, Author Interviews, Cognitive Issues, Exercise - Fitness / 22.08.2015

Rikke Hodal Meincke PhD student Center for Healthy Aging and the Department of Public Health University of CopenhagenMedicalResearch.com Interview with: Rikke Hodal Meincke PhD student Center for Healthy Aging and the Department of Public Health University of Copenhagen Medical Research: What is the background for this study? Response: A sufficient level of physical capability is a precondition for maintaining independence and quality of life. Physical capability can be assessed objectively by tests of physical performance, for instance handgrip strength, chair-rising and postural balance. Physical performance is associated with mortality and disability in late life, so gaining insights into the variance in physical performance is important to promote sustained physical capability and prevent disability. Research has previously found physical activity, health status and socioeconomic position to be associated with physical performance. In addition, early life factors, such as childhood SEP, have been found to be associated with measures of physical performance later in life. The objective of our study was to examine the association between intelligence in early adulthood and midlife physical performance in Danish men. If an association between intelligence in early life and midlife physical performance exists it may indicate that cognitive abilities and physical performance share some of the same neurodevelopmental processes, but may also indicate that intelligence has an independent effect on later physical performance through various pathways. Medical Research: What are the main findings? Response: In our study of more than 2800 Danish men, we found positive associations between intelligence in early adulthood and five objective measures of physical performance in midlife independent of other early life factors. A one standard deviation increase in intelligence score resulted in 1.1 more chair-rises in 30 seconds, a 1 cm higher jump, a 3.7% smaller balance area, a 0.7 kg increase in handgrip-strength, and a 0.5 kg increase in lower back force. (more…)
Author Interviews, Cognitive Issues, Geriatrics, UCSF, Weight Research / 13.08.2015

Meera Sheffrin MD Geriatrics Fellow Division of Geriatrics | Department of Medicine San Francisco VA Medical Center University of California, San Francisco MedicalResearch.com Interview with: Meera Sheffrin MD Geriatrics Fellow Division of Geriatrics | Department of Medicine San Francisco VA Medical Center University of California, San Francisco Medical Research: What is the background for this study? What are the main findings? Dr. Sheffrin: The main drug treatments for dementia are a class of medications called cholinesterase inhibitors. They have only modest effects on cognition and function in most patients, but since they are one of the few available treatments for dementia and thus very commonly prescribed. However,they are known to cause GI side effects (nausea, vomiting, diarrhea, and anorexia) in many patients when first started. It is plausible they could also caust weight loss, espeically considering they cause nausea and anorexia. However, the data on weight loss from randomized controlled trials is very limited and inconclusive, so we did a very large observational study in a real-world of the VA national healthcare system who were newly started on these medications, to see if they were associated with weight loss. We found that patient with dementia started on cholinesterase inhibitors had a substantially higher risk of clinically significant weight loss over a 12-month period compared to matched controls. 1,188 patients started on cholinesterase inhibitors were matched to 2,189 similar patients who were started on other new chronic medications. The primary outcome was time to a 10-pound weight loss over a 12-month period, as this represents a degree of loss that would be clinically meaningful – not only noticed by a clinician but would perhaps prompt further action in considering the causes of the weight loss and medical work-up. We found that starting cholinesterase inhibitors was associated with a 24% greater risk of developing weight loss. Overall, 29% of patients started on cholinesterase inhibitors experienced a weight loss of 10 pounds or more, compared with 23% of the control group. This corresponds to a number needed to harm of 21 over 1 year; meaning only 21 patients need to be treated with a cholinesterase inhibitor over the course of a year for one patient to experience a 10 pound weight loss. (more…)
Author Interviews, Cancer Research, Cognitive Issues, Radiation Therapy / 13.07.2015

MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UKMedicalResearch.com Interview with: MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UK Medical Research: What is the background for this study? Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months. The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions. Medical Research: What are the main findings? Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors. For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response. For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking. Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted. (more…)
Author Interviews, Cognitive Issues, Diabetes, JCEM / 11.07.2015

MedicalResearch.com Interview with: Wei-Che Chiu, MD, PhD National Taiwan University College of Public Health, Cathay General Hospital and Fu Jen Catholic University Taipei, Taiwan Medical Research: What is the background for this study? Response: Diabetes mellitus is a common risk factor for dementia and accounts for 6–8% of all cases of dementia in older populations. Cognitive impairment is associated with the presence of diabetic complications and diabetic severity, but the effects of diabetic severity on dementia are unclear. Our study was to investigate the association between the severity and progress of diabetes and the risk of dementia. Medical Research: What are the main findings? Response: The diabetic severity and progression reflected the risk of dementia, and the early progress in diabetic severity could predict the risk of dementia in new-onset diabetic patients. (more…)
Author Interviews, Beth Israel Deaconess, Cognitive Issues, Diabetes, Neurology / 11.07.2015

Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MAMedicalResearch.com Interview with: Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MA MedicalResearch: What is the background for this study? Dr. Novak: Diabetes mellitus (DM) is a major contributor to morbidity and mortality. Type 2 diabetes mellitus affects more than 44 million people in the U.S., and its numbers are growing rapidly, affecting up to 27% of older adults. Diabetes mellitus accelerates brain aging by about 5 years1, manifests as a widespread generalized atrophy2, and promotes earlier onset of vascular dementia and Alzheimer’s disease (AD).3,4 Diabetes mellitus -related atrophy manifests as worse cognitive function, memory, and gait, especially during a dual task, 5,6 and even a tight glycemic control did not improve cognitive function in participants of the large clinical trials 7. MedicalResearch: What are the main findings? Dr. Novak: Sixty-five participants (aged 66± 9.2 years) 35 with T2DM and 30 non-diabetic controls participated in this study. After 2 years of follow-up, participants with T2 Diabetes mellitus had diminished vascular reactivity in the brain (an ability to increase blood flow in responses to a task or metabolic demands) and performed worse on multiple cognitive tasks (in particular verbal learning and memory). In T2DM group, lower cerebral vasoreactivity correlated with worse performance on daily living activities. Specifically, the lower vasodilatation (ability to increase blood flow) was associated with worse mental functions. In addition, those with higher markers of inflammation had greater decline in vascular function in the brain. (more…)
Author Interviews, Cognitive Issues, FASEB / 05.07.2015

Milan Fiala, M.D. Research Professor, UCLA Department of Surgery Los Angeles, CAMedicalResearch.com Interview with: Milan Fiala, M.D. Research Professor, UCLA Department of Surgery Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Fiala: Omega-3 fatty acid supplementation is well-known to public for its health benefits in cardiovascular diseases and putative benefits against “Minor Cognitive Impairment” reported in other studies . This study shows that omega-3 protected against oxidation and resveratrol improves the immune system against amyloid-beta in the brain,  probably by increasing its clearance from the brain by the immune system. Overall the patients taking the drink seemed to preserve their memory better for up to 2 years than expected based on previous studies. However, our study was small and not controlled by a placebo, which may present a bias.   (more…)
Author Interviews, Cognitive Issues / 12.06.2015

Dr. Li-Huei Tsai Ph.D. Professor and Director - Picower Institute For Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge, MA MedicalResearch.com Interview with: Dr. Li-Huei Tsai Ph.D. Professor and Director - Picower Institute For Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Medical Research: What is the background for this study? What are the main findings? Dr. Tsai: For a while now, we have been interested in observations made by many labs, including our own, that the accumulation of DNA lesions is a hallmark of the aging brain, and that mutations in DNA repair factors manifest in congenital and neurodegenerative disorders. However, the precise contribution of unrepaired DNA lesions to the development of neurological disorders remains poorly understood. A major confounding factor is that the sources that generate DNA lesions in the brain are not well characterized, and it is not known whether damage accumulates non-specifically throughout the genome, or whether there are certain regions that are more prone to accumulate DNA damage. In this regard, our study reports three major findings: (1) Physiological neuronal activity itself results in the formation of DNA breaks; (2) Neuronal activity-induced DNA breaks form at highly specific locations, including within the promoters of a subset of immediate early genes, including Fos, Npas4, and Egr1. These genes are also rapidly expressed in response to neuronal stimulation, and play crucial roles in experience-driven changes to synapses, and learning and memory; (3) Neuronal activity-induced breaks are generated by a topoisomerase, Topo IIβ, and Topo IIβ-generated DNA breaks facilitate the rapid expression of these immediate early genes following neuronal stimulation. (more…)
Author Interviews, Cognitive Issues, Endocrinology, OBGYNE / 03.06.2015

Dr.Carey Gleason Ph.D School of Medicine and Public Health, University of Wisconsin Geriatric Research, Education and Clinical Center William S. Middleton Memorial Veterans Hospital Wisconsin Alzheimer's Disease Research Center, Madison, WisconsinMedicalResearch.com Interview with: Dr.Carey Gleason Ph.D School of Medicine and Public Health, University of Wisconsin Geriatric Research, Education and Clinical Center William S. Middleton Memorial Veterans Hospital Wisconsin Alzheimer's Disease Research Center, Madison, Wisconsin Dr. Gleason: In this response I refer to hormone therapy (HT), which was formally called hormone "replacement" therapy. In particular, we examined menopausal HT, i.e., the use of HT during the menopausal transition to address menopausal symptoms. Medical Research: What is the background for this study? What are the main findings? Dr. Gleason: The WHI Memory Study (WHIMS) suggested that HT was associated with cognitive harm for women age 65 and older. In contrast, we found that the cognitive performance of women randomized to receive menopausal hormone therapy did not differ from that of women randomized to receive the placebo. On a measure of mood states, women treated with conjugated equine estrogens showed improvements compared to those on placebo. (more…)
Author Interviews, Cognitive Issues, Infections, PLoS / 24.05.2015

Dr. Michael Eriksen Benrós Mental Health Centre Copenhagen University of Copenhagen Faculty of Health Sciences Copenhagen NV, Denmark, National Centre for Register-based Research Aarhus University DenmarkMedicalResearch.com Interview with: Dr. Michael Eriksen Benrós Mental Health Centre Copenhagen University of Copenhagen Faculty of Health Sciences Copenhagen NV, Denmark, National Centre for Register-based Research Aarhus University Denmark Medical Research: What is the background for this study? Response: It is increasingly recognized that infections and immune responses can affect the brain and activate immunocompetent cells within the brain, influencing on neuronal signal transduction and possibly cognition. Impaired cognition has been observed in association with several infections and with elevated levels of CRP in smaller studies. Furthermore, experimental activation of inflammatory reactions in healthy volunteers has been shown to induce short-term reduced cognitive performance. Moreover, particularly patients with infection in the brain or sepsis have been shown to have affected cognition in long time periods after the infection has been cleared, thus infections might also have a longer lasting effect on cognition. However, large-scale longitudinal studies had been lacking on the association between infections and cognitive ability in the general population. Medical Research: What are the main findings? Response: Our study is the first large-scale study utilizing the extensive Danish registers to follow 190,000 males that had their IQ assessed at conscription, out of which 35% had a previous hospital contact with infection before the IQ testing was conducted. Our research shows a correlation between severe infections with a hospital contact and subsequent impaired cognition corresponding to an IQ score of 1.76 lower than the average. People with five or more hospital contacts with infections had an IQ score of 9.44 lower than the average. The study thus shows a clear dose-response relationship between the number of infections. Furthermore the effect on cognitive ability increased with the temporal proximity of the last infection and with the severity of the infection. Infections in the brain affected the cognitive ability the most, but many other types of infections severe enough to require a hospital contact where also associated with impairment of the cognitive ability. (more…)
Author Interviews, Breast Cancer, Cancer Research, Cognitive Issues, JNCI / 19.04.2015

Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of MunichMedicalResearch.com Interview with: Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of Munich MedicalResearch: What is the background for this study? What are the main findings? Dr. Hermelink: Many breast cancer patients report problems of cognitive functioning that interfere considerably with their professional and private lives. In the last two decades, a number of studies have confirmed that subgroups of breast cancer patients show at least subtle cognitive impairment. Initially, the condition has entirely been attributed to chemotherapy effects and has therefore colloquially been named “chemobrain”. Meanwhile, however, cognitive impairment has also been found in patients who were managed without chemotherapy and, surprisingly, even in patients who had not yet received any systemic treatment at all. Several hypotheses on the causation of cognitive impairment that occurs already pretreatment have been put forward; for instance, biological effects of the cancer itself might affect cognitive functioning, or there might be shared genetic vulnerability for cancer and cognitive impairment. None of these hypotheses have been empirically confirmed; thus, pretreatment cognitive impairment is as yet unexplained. Our study was designed to investigate the effects of cancer-related post-traumatic stress on cognitive function in breast cancer patients before the start of treatment. Stress has a substantial influence on cognitive functioning, and post-traumatic stress disorder (PTSD) is associated with impairment of cognitive function. While the incidence of full diagnosis of stress disorder is low among breast cancer patients, many of these patients show symptoms of PTSD, with a peak shortly after diagnosis. We did not find an elevated risk of overall cognitive impairment in pretreatment breast cancer patients compared with matched non-cancer controls; however, the cancer patients scored worse than the controls on a small fraction of the cognitive indices that were used. Performance on these indices was indeed robustly associated with PTSD symptoms. Our results therefore indicate that pretreatment cognitive impairment in breast cancer patients may be largely caused by the stress of being diagnosed with cancer. (more…)
Author Interviews, Cognitive Issues, Nutrition / 16.04.2015

Dr. Fredrik Jernerén PhD Postdoctoral Research Fellow Department of Pharmacology University of Oxford Oxford, United KingdomMedicalResearch.com Interview with: Dr. Fredrik Jernerén PhD Postdoctoral Research Fellow Department of Pharmacology University of Oxford Oxford, United Kingdom Medical Research: What is the background for this study? What are the main findings? Dr. Jernerén: Development of dementia and Alzheimer’s disease is associated with an accelerated rate of brain shrinkage. Identifying ways to reduce the brain atrophy rate at an early stage may offer new strategies to prevent or delay the onset of dementia. In this study on elderly subjects diagnosed with Mild cognitive impairment (MCI), who are at increased risk of developing dementia, we investigated whether the effect of B vitamin supplementation on reducing the brain atrophy rate was influenced by circulating levels of omega-3 fatty acids. We have found that this indeed was the case. The higher the baseline concentration of the combined omega-3 fatty acids (DHA+EPA), the greater the protective effect of the B vitamin treatment. In subjects with high omega-3 concentrations who at the same time had elevated homocysteine levels (indicating a lack of B vitamins), B vitamin treatment reduced the brain atrophy rate by about 70% compared with the placebo group.  (more…)