Posts Tagged Risk Factor

Alzheimer’s More Aggressive in Younger Elderly


Alzheimers More Aggressive in Younger Elderly New research shows that Alzheimer’s disease hits people in their 60s and 70s harder than people who are 80 years and older.

Researchers at the University of California, San Diego School of Medicine note that the greatest risk factor for Alzheimer’s is age. In fact, by the age of 85, the likelihood of developing the dreaded neurological disorder is roughly 50 percent, they say.

But in their study, they found that the “younger elderly” — those in their 60s and 70s — showed higher rates of cognitive decline and faster rates of tissue loss in brain regions that are vulnerable during the early stages of Alzheimer’s, according to Dominic Holland, Ph.D., a researcher in the Department of Neurosciences at UC San Diego and the study’s first author.

“Additionally cerebrospinal fluid biomarker levels indicate a greater disease burden in younger than in older individuals,” he said.

Holland and his colleagues, using imaging and biomarker data from participants in the Alzheimer’s Disease Neuroimaging Initiative, examined 723 people, ages 65 to 90 years, who were categorized as either cognitively normal, with mild cognitive impairment (an intermediate stage between normal, age-related cognitive decline and dementia) or suffering from full-blown Alzheimer’s disease (AD).

The findings have implications for diagnosing the disease — which currently afflicts an estimated 5.6 million Americans, a number expected to triple by 2050 — and efforts to find new treatments, the researchers said.

At present, there is no cure for Alzheimer’s and existing therapies do not slow or stop the disease’s progression.

A key feature in the diagnosis of Alzheimer’s is its “relentless progressive course,” Holland said.

“Patients typically show marked deterioration year after year. If older patients are not showing the same deterioration from one year to the next, doctors may be hesitant to diagnose AD, and thus these patients may not receive appropriate care, which can be very important for their quality of life.”

Holland said it’s not clear why the disease is more aggressive among the younger elderly.

“It may be that patients who show onset of dementia at an older age, and are declining slowly, have been declining at that rate for a long time,” added co-author Linda McEvoy, Ph.D., associate professor of radiology. “But because of cognitive reserve or other still-unknown factors that provide ‘resistance’ against brain damage, clinical symptoms do not manifest till later age.”

Another possibility is that older patients may be suffering from mixed dementia — a combination of Alzheimer’s and other neurological conditions, Holland said. These patients might withstand the effects of Alzheimer’s until other adverse factors, such as brain lesions caused by cerebrovascular disease, take hold. At that time, Alzheimer’s can only be definitively diagnosed by an autopsy, he said.

Clinical trials to find new treatments for the disease may be affected by the differing rates of progression, researchers said.

“Our results show that if clinical trials of candidate therapies predominately enroll older elderly, who show slower rates of change over time, the ability of a therapy to successfully slow disease progression may not be recognized, leading to failure of the clinical trial,” said Holland. “It’s critical to take into account age as a factor when enrolling subjects for AD clinical trials.”

While the obvious downside of the findings is that younger patients with Alzheimer’s lose more of their productive years, “the good news in all of this is that our results indicate those who survive into the later years before showing symptoms of AD will experience a less aggressive form of the disease,” Holland concluded.

The research appears online in the journal PLOS One.

Source: University of California, San Diego

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Increased Dopamine Can Reduce Impulsivity


Increased Dopamine Can Reduce ImpulsivityResearchers have discovered that elevating the level of the neurotransmitter dopamine in the frontal lobe of the brain can significantly decrease impulsivity in healthy adults.

The finding is important as impulsiveness is a risk factor for substance abuse.

“Impulsivity is a risk factor for addiction to many substances, and it has been suggested that people with lower dopamine levels in the frontal cortex tend to be more impulsive,” said lead author Andrew Kayser, Ph.D.

Researchers from the Ernest Gallo Clinic and Research Center at the University of California, San Francisco performed a double-blinded placebo study. The study has been published in the Journal of Neuroscience.

In the research, 23 adult research participants were given either tolcapone, a medication approved by the Food and Drug Administration (FDA) that inhibits a dopamine-degrading enzyme, or a placebo.

Investigators then gave the participants a task that measured impulsivity, asking them to make a hypothetical choice between receiving a smaller amount of money immediately (“smaller sooner”) or a larger amount at a later time (“larger later”).

Each participant was tested twice, once with tolcapone and once with placebo.

More impulse (at baseline) participants were more likely to choose the less impulsive “larger later” option after taking tolcapone than they were after taking the placebo.

Magnetic resonance imaging conducted while the participants were taking the test confirmed that regions of the frontal cortex associated with decision-making were more active in the presence of tolcapone than in the presence of placebo.

“To our knowledge, this is the first study to use tolcapone to look for an effect on impulsivity,” said Kayser.

The study is a proof-in-concept investigation and was not designed to investigate the reasons that reduced dopamine is linked with impulsivity.

However, explained Kayser, scientists believe that impulsivity is associated with an imbalance in dopamine between the frontal cortex, which governs executive functions such as cognitive control and self-regulation, and the striatum, which is thought to be involved in the planning and modification of more habitual behaviors.

“Most, if not all, drugs of abuse, such as cocaine and amphetamine, directly or indirectly involve the dopamine system,” said Kayser.

“They tend to increase dopamine in the striatum, which in turn may reward impulsive behavior. In a very simplistic fashion, the striatum is saying ‘go,’ and the frontal cortex is saying ‘stop.’ If you take cocaine, you’re increasing the ‘go’ signal, and the ‘stop’ signal is not adequate to counteract it.”

Kayser and his research team plan a follow-up study of the effects of tolcapone on drinking behavior.

“Once we determine whether drinkers can safely tolerate this medication, we will see if it has any effect on how much they drink while they’re taking it,” said Kayser.

Currently, Tolcapone is approved as a medication for Parkinson’s disease — a disease in which a chronic deficit of dopamine inhibits movement.

Source: University of California – San Francisco

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First Marijuana Use Linked to Psychosis in Vulnerable People


Among individuals with psychosis who are also heavy marijuana users, the age they first used marijuana is strongly linked to the age of their first bout of psychosis, according to a study of 57 patients.

Although marijuana use by itself is neither sufficient nor needed to trigger schizophrenia, “if cannabis use precipitates the onset of psychosis, efforts should be focused on designing interventions to discourage cannabis use in vulnerable individuals,” Dr. Juan A. Galvez-Buccollini and his associates said.

This caution pertains to someone with a first-degree relative with psychosis, which is “the highest risk factor for schizophrenia,” said Dr. Lynn E. Delisi, senior investigator for the study, a psychiatrist at the Boston VA Medical Center in Brockton, Mass., and professor of psychiatry at Harvard Medical School, Boston.

If someone had a first-degree relative, “I would caution them about the consequences of cannabis use and the association with schizophrenia,” she said.

Findings from previous research has shown that marijuana use is associated with an earlier age of psychosis onset in people abusing multiple substances, but studies have not looked at a possible link between the onset of cannabis use itself and resulting psychosis.

Because of this, Dr. Galvez-Buccollini, a psychiatry researcher at VA Boston Healthcare System and Harvard, and his colleagues interviewed 57 patients with a current diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychosis not otherwise specified, who also had a history of heavy cannabis use before the onset of psychosis. They defined heavy cannabis use as 50 or more uses during a one year period.

Average age of the subjects was 25 years with a range of 18-39 years. Of the total, 83 percent were men, and 88 percent were not married. The average age of psychosis onset was 22 years, and the average age for first psychosis-related hospitalization was 23.

Schizophrenia was the most common psychosis (42 percent), followed by schizoaffective disorder (32 percent). The average age of first marijuana use was 15, preceding psychosis onset by an average of 7 years.

During the study period, the prevalence of daily cannabis was 59 percent with another 30 percent reporting use 2-5 days per week, and the remaining 11 percent reporting weekly use. Alcohol abuse was 16 percent and alcohol dependence was 8 percent.

The researchers found a statistically significant link between the age when cannabis use first started and the age when psychosis was first diagnosed. This association was consistent after researchers excluded patients with any diagnosis of alcohol abuse or dependency during their lifetime.

The analysis also showed a strong link between the time a patient first smoked marijuana and their age of first psychosis hospitalization.

Marijuana affects dopamine receptors and can have other neurochemical effects.

“There are two components of cannabis, one that potentiates and another that antagonizes psychotic symptoms,” said Delisi. The balance between these two effects can differ among various strains of cannabis, she added.

Source: Schizophrenia Research

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Mindfulness Practice Helps Seniors Combat Loneliness


Mindfulness Practice Helps Elders Combat LonelinessLoneliness can be a major risk factor for health conditions such as depression, cardiovascular disease and Alzheimer’s. It is especially problematic among seniors, for whom seclusion and isolation may even lead to death.

Experts say that modern strategies to reduce loneliness in the elderly population — by participation in social networking programs in community centers — have not been successful. But a new study finds that a new/old approach may provide an innovative solution.

In the investigation, J. David Creswell, Ph.D., from Carnegie Mellon University looked at the use of mindfulness meditation to reduce loneliness in older adults.

In the review, researchers found that mindfulness meditation — a 2,500-year-old practice dating back to Buddha that focuses on creating an attentive awareness of the present moment — not only reduced loneliness but also lowered inflammation levels.

Inflammation is believed to promote the development and progression of many diseases.

These findings, published in Brain, Behavior & Immunity, provide valuable insights into how mindfulness meditation training can be used as a novel approach for reducing loneliness and the risk of disease in older adults.

“We always tell people to quit smoking for health reasons, but rarely do we think about loneliness in the same way,” said Creswell.

“We know that loneliness is a major risk factor for health problems and mortality in older adults. This research suggests that mindfulness meditation training is a promising intervention for improving the health of older adults.”

For the study, the research team recruited 40 healthy adults aged 55-85 who indicated an interest in learning mindfulness meditation techniques. Each person was assessed at the beginning and end of the study using an established loneliness scale. Blood samples also were collected.

The participants were randomly assigned to receive either the eight-week Mindfulness-Based Stress Reduction (MBSR) program or no treatment.

The MBSR program consisted of weekly two-hour meetings in which participants learned body awareness techniques — noticing sensations and working on breathing — and worked their way toward understanding how to mindfully attend to their emotions and daily life practices.

They also were asked to practice mindfulness meditation exercises for 30 minutes each day at home and attended a daylong retreat.

Investigators determined that eight weeks of the mindfulness meditation training decreased the participants’ loneliness.

They also discovered that participants reduced genetic blood inflammatory responses as well as a measure of C-Reactive Protein (CRP).

These findings suggest that mindfulness meditation training may reduce older adults’ inflammatory disease risk.

“Reductions in the expression of inflammation-related genes were particularly significant because inflammation contributes to a wide variety of the health threats including cancer, cardiovascular diseases and neurodegenerative diseases,” said study collaborator Steven Cole.

While the health effects of the observed gene expression changes were not directly measured in the study, Cole noted that “these results provide some of the first indications that immune cell gene expression profiles can be modulated by a psychological intervention.”

Creswell added that while this research suggests a promising new approach for treating loneliness and inflammatory disease risk in older adults, more work needs to be done.

“If you’re interested in using mindfulness meditation, find an instructor in your city,” he said. “It’s important to train your mind like you train your biceps in the gym.”

Source: Carnegie Mellon University

Elderly woman meditating photo by shutterstock.

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Mice Study Shows Overactive Immune System Contributes to Autism


Mice Study Shows Overactive Immune System Contributes to Autism  A new study suggests that changes in an overactive immune system can contribute to autism-like behaviors in mice.

The study from the California Institute of Technology (Caltech) also found that, in some cases, this activation can be related to what a developing fetus experiences in the womb.

“We have long suspected that the immune system plays a role in the development of autism spectrum disorder,” said Dr. Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences at Caltech, who led the work.

“In our studies of a mouse model based on an environmental risk factor for autism, we find that the immune system of the mother is a key factor in the eventual abnormal behaviors in the offspring.”

The first step was establishing a mouse model that tied the autism-related behaviors to immune changes, he said.

Several large studies — including one that involved tracking the medical history of every person born in Denmark between 1980 and 2005 — found a correlation between viral infection during the first trimester of a mother’s pregnancy and a higher risk for autism in her child. As part of the new study, researchers injected pregnant mouse mothers with a viral mimic that triggered the same type of immune response a viral infection would.

“In mice, this single insult to the mother translates into autism-related behavioral abnormalities and neuropathologies in the offspring,” said Elaine Hsiao, a graduate student in Patterson’s lab and lead author of the paper.

The team found that the offspring exhibit the core behavioral symptoms associated with autism spectrum disorder, including repetitive or stereotyped behaviors, decreased social interactions, and impaired communication.

In mice, this translates to such behaviors as compulsively burying marbles placed in their cage, excessively self-grooming, choosing to spend time alone or with a toy rather than interacting with a new mouse, or vocalizing ultrasonically less often or in an altered way compared to typical mice.

Next, the researchers studied the immune system of the offspring of mothers that had been infected and found that they displayed a number of immune changes.

Some of those changes parallel those seen in people with autism, including decreased levels of regulatory T cells, which play a role in suppressing the immune response, the researchers said.

Taken together, the observed alterations add up to an immune system in overdrive, which promotes inflammation.

“Remarkably, we saw these immune abnormalities in both young and adult offspring of immune-activated mothers,” Hsiao said. “This tells us that a prenatal challenge can result in long-term consequences for health and development.”

The researchers were then able to test whether the offspring’s immune problems contribute to their autism-related behaviors. In a test of this hypothesis, the researchers gave the affected mice a bone-marrow transplant from typical mice.

The normal stem cells in the transplanted bone marrow not only replenished the immune system of the mice, but altered their autism-like behavior, the researchers report.

The researchers note that because the work was conducted in mice, the results cannot be readily extrapolated to humans, and they do not suggest that bone-marrow transplants should be considered as a treatment for autism.

They also have yet to establish whether it was the infusion of stem cells or the bone-marrow transplant procedure itself — complete with irradiation — that corrected the behaviors.

However, the results do suggest that immune irregularities in children could be an important target for innovative immune manipulations in addressing the behaviors associated with autism, said Patterson. By correcting these immune problems, it might be possible to ameliorate some of the classic developmental delays seen in autism, he noted.

The results appear in a paper in the Proceedings of the National Academy of Sciences (PNAS).

Source: California Institute of Technology

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