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Researchers Agree that Alzheimer’s Test Results Could be Released to Research Participants

A leading group of Alzheimer’s researchers contends that, as biomarkers to detect signals of the disease improve at providing clinically meaningful information, researchers will need guidance on how to constructively disclose test results and track how disclosure impacts both patients and the data collected in research studies. A survey conducted by a group including experts from the Perelman School of Medicine at the University of Pennsylvania found that a majority of Alzheimer’s researchers supported disclosure of results to study participants. The study is published online in Neurology.

“While this is not a call to immediately tell subjects their biomarker results, it does show that the field is moving to a point where experts want to share valid and meaningful results with participants,” said co-senior author Jason Karlawish, MD, professor of Medicine and Medical Ethics and Health Policy. “As we gain more data on the predictive abilities of these measurements, we will need models and methods to effectively reveal results.”

The study surveyed 139 Alzheimer’s clinical trial leaders and coordinators from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in April 2012, just before the U.S. Food and Drug Administration approved the amyloid-binding radiotracer known as Amyvid (florbetapir). 73 percent of respondents supported disclosing amyloid imaging results to study participants with mild cognitive impairment, whereas 58 percent supported giving amyloid imaging results to those with normal cognition.

Six themes emerged from the survey, regarding participant preferences and cognition levels, researchers’ requests to develop standardized counseling procedures, participant education, and standardization of data-gathering, and concerns regarding potential harms and benefits to participants, as well as the ways disclosure could impact study results.

Currently, ADNI has a policy to not disclose results to participants, but the survey showed a growing trend of experts who would favor revising this policy. In addition to finding amyloid imaging results valuable, Alzheimer’s experts also valued other biomarker data collected in ADNI, such as spinal fluid tests, PET imaging, and other psychometric tests, suggesting that if amyloid imaging results were allowed to be disclosed, it would likely lead to disclosure of other test results.

Study: Using AD biomarker research results for clinical care [Neurology] 

Source: EurekAlert!

Imaging in Mental Health and Improving the Diagnostic Process

What are some of the most troubling numbers in mental health? Six to 10 — the number of years it can take to properly diagnose a mental health condition. Dr. Elizabeth Osuch, a Researcher at Lawson Health Research Institute and a Psychiatrist at London Health Sciences Centre and the Department of Psychiatry at Western University, is helping to end misdiagnosis by looking for a ‘biomarker’ in the brain that will help diagnose and treat two commonly misdiagnosed disorders.

Major Depressive Disorder (MDD), otherwise known as Unipolar Disorder, and Bipolar Disorder (BD) are two common disorders. Currently, diagnosis is made by patient observation and verbal history. Mistakes are not uncommon, and patients can find themselves going from doctor to doctor receiving improper diagnoses and prescribed medications to little effect.

Dr. Osuch looked to identify a ‘biomarker’ in the brain which could help optimize the diagnostic process. She examined youth who were diagnosed with either MDD or BD (15 patients in each group) and imaged their brains with an MRI to see if there was a region of the brain which corresponded with the bipolarity index (BI). The BI is a diagnostic tool which encompasses varying degrees of bipolar disorder, identifying symptoms and behavior in order to place a patient on the spectrum.

What she found was the activation of the putamen correlated positively with BD. This is the region of the brain that controls motor skills, and has a strong link to reinforcement and reward. This speaks directly to the symptoms of bipolar disorder. “The identification of the putamen in our positive correlation may indicate a potential trait marker for the symptoms of mania in bipolar disorder,” states Dr. Osuch.

In order to reach this conclusion, the study approached mental health research from a different angle. “The unique aspect of this research is that, instead of dividing the patients by psychiatric diagnoses of bipolar disorder and unipolar depression, we correlated their functional brain images with a measure of bipolarity which spans across a spectrum of diagnoses.” Dr. Osuch explains, “This approach can help to uncover a ‘biomarker’ for bipolarity, independent of the current mood symptoms or mood state of the patient.”

Moving forward Dr. Osuch will repeat the study with more patients, seeking to prove that the activation of the putamen is the start of a trend in large numbers of patients. The hope is that one day there could be a definitive biological marker which could help differentiate the two disorders, leading to a faster diagnosis and optimal care.

In using a co-relative approach, a novel method in the field, Dr. Osuch uncovered results in patients that extend beyond verbal history and observation. These results may go on to change the way mental health is diagnosed, and subsequently treated, worldwide.

Study: Correlation of brain default mode network activation with bipolarity index in youth with mood disorders [Journal of Affective Disorders]

Source: EurekAlert!

New Risk Score Predicts 10-Year Dementia Risk for Type 2 Diabetes Patients

Researchers at Kaiser Permanente and the University Medical Centre Utrecht in the Netherlands have created the first risk score that predicts the 10-year individualized dementia risk for patients with type 2 diabetes, as reported in the inaugural issue of Lancet Diabetes & Endocrinology.

The researchers developed and validated the Diabetes-Specific Dementia Risk Score by examining data from nearly 30,000 patients with type 2 diabetes aged 60 and older over a 10-year period. They found eight factors that were most predictive of dementia — including microvascular disease, diabetic foot and cerebrovascular disease — and assigned each a value related to their association with dementia to create an overall score for patients. The researchers found that individuals in the lowest category of the 20-point risk score had a 5.3 percent chance of developing dementia over the next 10 years, while those in the highest category had a 73 percent chance. Compared with those in the lowest category, those in the highest were 37 times more likely to get dementia, according to the study.

“Patients with type 2 diabetes are twice as likely to develop dementia as those without the disease, but predicting who has the highest future risk is difficult,” said Rachel Whitmer, PhD, an epidemiologistat the Kaiser Permanente Division of Research in Oakland, Calif., who led the study. “While a few dementia risk scores exist, this is the first one that has been developed specifically for individuals with type 2 diabetes and encompasses diabetes-specific characteristics.”

All predictors included in the Diabetes-Specific Dementia Risk Score are easy to obtain and based primarily on medical history, so the risk score can be calculated during a routine medical visit or with electronic health records. No labor-intensive or expensive tests, such as cognitive function or brain imaging, are required.

“This risk score is crucial for the care of patients with diabetes since they are particularly susceptible to dementia. It provides clinicians with an easy and efficient tool to assess their patients’ chances of developing dementia over the next 10 years,” Whitmer said. “Early detection of diabetes patients who are at increased future risk of dementia could help to develop and target preventive treatment.”

According to the Centers for Disease Control and Prevention, more than 25 million children and adults in the United States have diabetes, with type 2 diabetes in particular accounting for more than 90 percent of these cases. In addition to being a risk factor for dementia, diabetes is the leading cause of kidney failure, non-traumatic lower-limb amputations and new cases of blindness among adults in the United States.

“The risk score could be useful in the selection of high-risk patients for early intervention studies and for many applications of personalized medicine,” said Geert Jan Biessels, MD, professor of neurology at the University Medical Centre Utrecht and co-author of the study. “Clinicians can use it to guide their decisions in terms of clinical attention to incipient cognitive impairment which makes people vulnerable to dangerous side effects of diabetes treatment. The risk score will also help us to understand the causes of diabetes associated increased dementia risk, because we can examine those at high risk in early stages of the dementia process.”

Study: Risk score for prediction of 10 year dementia risk in individuals with type 2 diabetes: a cohort study [Lancet]

Source: Kaiser Permanente

Elevated Levels of Copper in Amyloid Plaques Associated with Neurodegeneration in Mouse Models of AD

Metals such as iron, copper, and zinc are important for many biological processes. In recent years, studies have shown that these nutritionally-essential metals are elevated in human Alzheimer’s disease (AD) brains and some animal models of AD. Scientists are now exploring whether these metals are causing the neurodegeneration seen in AD or are indicative of other ongoing pathologic processes.

In a new study, investigators used synchrotron x-ray fluorescence microscopy to image metal ions in the brain, focusing on the amyloid plaques that are the hallmark of AD. They found that, in two AD mouse models that exhibit neurodegeneration, the plaques contained about 25% more copper than an AD mouse model that shows little neurodegeneration. Looking at other metals, they found that none of the mouse models had significant increases in iron and very little increases in zinc. Metal content was not related to the age of the plaque. The study is reported in the current issue of Biomedical Spectroscopy and Imaging.

“Since excess copper should not be ‘free’ in the brain to bind to the plaques, these data suggest that the cellular control of copper is altered in AD, which may lead to toxic reactions between free copper ions and neurons,” comments lead investigator Lisa M. Miller, PhD, a biophysical chemist in the Photon Sciences Directorate at Brookhaven National Laboratory. In previous work, Dr. Miller’s group found very high levels of copper in human AD plaques.

Since elevated iron in the AD brain is well documented in both human brains and AD mouse models, the researchers measured iron content in the cortex of all three mouse models. They found that iron content was doubled in all AD mouse model cortices compared to controls, whether or not the models showed neurodegeneration. Upon further investigation, spectroscopic data revealed that the excess iron was present in the ferric (oxidized) state and consistent with the iron storage protein ferritin. “The increase in iron may be a reflection of changes in metalloprotein content and metal storage within the brain that is not well understood,” says Dr. Miller.

Nevertheless, since iron in ferromagnetic and detectable through MRI, Dr. Miller suggests that in the future iron may be used as a biomarker for AD at early stages of disease, even before plaques are formed.

Source: Elevated copper in the amyloid plaques and iron in the cortex are observed in mouse models of Alzheimer’s disease that exhibit neurodegeneration [Biomedical Spectroscopy and Imaging]

Source: EurekAlert!

Spinal Fluid Biomarkers of AD and Brain Functional Network Integrity on Imaging Studies

Both Aß and tau pathology appear to be associated with default mode network integrity before clinical onset of Alzheimer disease (AD), according to a study by Liang Wang, M.D., and colleagues at Washington University in St. Louis, Missouri.

Accumulation of Aß and tau proteins, the pathologic hallmarks of AD, starts years before clinical onset. Pathophysiological abnormalities in the preclinical phase of AD may be detected using cerebrospinal fluid (CSF) or neuroimaging biomarkers, according to the study background.

A total of 207 older adults with normal cognition participated in the cross-sectional group study. Researchers examined the relationship between default mode network integrity and cerebrospinal fluid biomarkers of Alzheimer disease pathology in cognitively normal older individuals using resting-state functional connectivity magnetic resonance imaging.

According to the study results, decreased cerebrospinal fluid Aß42 and increased cerebrospinal fluid phosphorylated tau181 were independently associated with reduced default mode network integrity, with the most prominent decreases in functional connectivity observed between the posterior cingulate and medial temporal regions (regions of the brain associated with memory). Observed reductions in functional connectivity were unattributable to age or structural atrophy in the posterior cingulate and medial temporal areas.

Study: Cerebrospinal Fluid Aβ42, Phosphorylated Tau181, and Resting-State Functional Connectivity [JAMA Neurology]

Source: EurekAlert!