People who study or treat Alzheimer’s disease and its earliest clinical stage, mild cognitive impairment (MCI), have focused attention on the obvious short-term memory problems. But a new study suggests that people on the road to Alzheimer’s may actually have problems early on in processing semantic or knowledge-based information, which could have much broader implications for how patients function in their lives.
Terry Goldberg, PhD, a professor of psychiatry and behavioral science at the Hofstra North Shore-LIJ School of Medicine and director of neurocognition at the Litwin Zucker Center for Research in Alzheimer's Disease and Memory Disorders at The Feinstein Institute for Medical Research in Manhasset, NY, said that clinicians have observed other types of cognitive problems in MCI patients but no one had ever studied it in a systematic way. Many experts had noted individuals who seemed perplexed by even the simplest task. In this latest study, published in this month's issue of the American Journal of Psychiatry, investigators used a clever series of tests to measure a person’s ability to process semantic information.
Do people with MCI have trouble accessing different types of knowledge? Are there obvious semantic impairments that have not been picked up before? The answer was "yes."
In setting out to test the semantic processing system, Dr. Goldberg and his colleagues needed a task that did not involve a verbal response. That would only confuse things and make it harder to interpret the results. They decided to use size to test a person’s ability to use semantic information to make judgments between two competing sets of facts. “If you ask someone what is bigger, a key or an ant, they would be slower in their response than if you asked them what is bigger, a key or a house,” explained Dr. Goldberg. The greater the difference in size between two objects, the faster a person -- normal or otherwise -- can recognize the difference and react to the question.
Investigators brought in 25 patients with MCI, 27 patients with Alzheimer's and 70 cognitively fit people for testing. They found large differences between the healthy controls and the MCI and Alzheimer's patients. “This finding suggested that semantic processing was corrupted,” said Dr. Goldberg. “MCI and AD (Alzheimer's disease) patients are really affected when they are asked to respond to a task with small size differences."
They then tweaked the task by showing pictures of a small ant and a big house or a big ant and a small house. This time, the MCI and AD patients did not have a problem with the first part of the test -- they were able to choose the house over the ant when asked what was bigger. But if the images were incongruent – the big ant seemed just as big as the small house – they were confused, they answered incorrectly or took longer to arrive at a response.
Patients with MCI were functioning somewhere between the healthy people and those with AD. “When the decision was harder, their reaction time was slower,” he said.
Would this damaged semantic system have an effect on everyday functions? To answer this question, investigators turned to the UCSD Skills Performance Assessment scale, a tool that they have been using in MCI and AD patients that is generally used to identify functional deficits in patients with schizophrenia. The test taps a person’s ability to write a complex check or organize a trip to the zoo on a cold day.
This is actually a good test for figure out whether someone has problems with semantic knowledge. Semantic processing has its seat in the left temporal lobe. “The semantic system is organized in networks that reflect different types of relatedness or association,” the investigators wrote in their study. “Semantic items and knowledge have been acquired remotely, often over many repetitions, and do not reflect recent learning.”
Dr. Goldberg said the finding is critically important because it may be possible to strengthen these semantic processing connections through training. “It tells us that something is slowing down the patient and it is not episodic memory but semantic memory," he said. They will continue to study these patients over time to see if these semantic problems get worse as the disease advances.
In an accompanying editorial, David P. Salmon, PhD, of the Department of Neurosciences at the University of California in San Diego, said that the “semantic memory deficit demonstrated by this study adds confidence to the growing perception that subtle decline in this cognitive domain occurs in patients with amnestic mild cognitive impairment. Because the task places minimal demands on the effortful retrieval process, overt word retrieval, or language production, it also suggests that this deficit reflects an early and gradual loss of integrity of semantic knowledge.”
He added that a “second important aspect of this study is the demonstration that semantic memory decrements in patients with mild cognitive impairment may contribute to a decline in the ability to perform usual activities of daily living.”
Although the physical and mental benefits of exercise and physical activity are well-acknowledged, a new study suggests that exercise can also improve the way the mind functions.
In a new review, researchers investigated the power of exercise to improve cognitive function throughout life.
Hayley Guiney and psychologist Dr. Liana Machado from the University of Otago, New Zealand, have published their review online in the publication Psychonomic Bulletin & Review.
The researchers contend that a certain amount of mental deterioration is expected with advancing age. However, emerging studies suggests aerobic exercise can mitigate the mental decline for particular aspects of cognitive function such as task switching, selective attention and working memory among others.
Studies in older adults reviewed by the authors consistently found that fitter individuals scored better in mental tests than their unfit peers.
In addition, intervention studies found scores in mental tests improved in participants who were assigned to an aerobic exercise regimen compared to those assigned to stretch and tone classes.
Interestingly, these results were not replicated in children or young adults.
Investigators discovered physical fitness or regular exercise aided memory. Both the updating of working memory and the volume of information which could be held was better in fitter individuals or those put on an aerobic exercise regime.
The authors comment that despite physical fitness not affecting all areas of cognitive function in younger people, evidence is mounting that just because they are in their prime developmentally does not mean that they cannot benefit from regular exercise.
In older generations the evidence for improvement in cognitive function is overwhelming as researchers found strong support for exercise attenuating age-related decline for specific tasks.
For example, exercise has been found to positively affect mental tasks relating to activities such as driving, an activity where age is often seen as a limiting factor.
The authors conclude that engagement in exercise can provide a simple means for people to optimize their cognitive function.
They add that more research into the effects of exercise on young adults and children is required. However, they say that “the indications reported thus far — that regular exercise can benefit brains even when they are in their prime developmentally —warrant more rigorous investigation, particularly in the context of society becoming increasingly sedentary.”
While there is no such thing as a perfect panacea for health, the wonders of exercise to relieve stress, improve physical function, and now enhance mental cognition should serve as strong motivation for being engaged in physical activity.
Using a combination of tests is the best way to predict Alzheimer’s in patients who have mild cognitive disorder, according to new research.
The study, conducted at Duke University School of Medicine, focused on three procedures: magnetic resonance imaging (MRI), fluorine 18 fluorodeoxyglucose positron emission tomography (FDG-PET), and cerebrospinal fluid analysis. Researchers added these tests to traditional clinical diagnostic techniques that are already in use, including neuropsychological testing.
Researchers examined the records of 97 older patients who had been diagnosed with mild cognitive impairment. The participants checked in with physicians for a period of up to four years.
The misdiagnosis of the patients’ condition, based on current clinical testing alone, was 41.3 percent. But the misdiagnosis percentage among those who took the three additional tests was 28.4 percent. Of the three tests, FDG-PET was the most effective.
The researchers said the study was important because the misdiagnosis of Alzheimer’s is a serious problem. Study author P. Murali Doraiswamy, MBBS, professor of psychiatry and medicine at Duke and study author, said in a statement that “There are more than 100 conditions that can mimic the disease. In people with mild memory complaints, our accuracy is barely better than chance. Given that the definitive gold standard for diagnosing Alzheimer's is autopsy, we need a better way to look into the brain. “
The researchers said further studies were needed to figure out the cost effectiveness of these procedures.
The findings were published in the journal Radiology.
A mild vitamin B12 deficiency is linked to a higher risk for accelerated cognitive decline in older adults, suggests an observational study by researchers at Tufts University.
Researchers looked at data from 549 men and women enrolled in the Framingham Heart Study. The average age was 75 years old.
Based on their vitamin B12 blood levels, the subjects were divided into five groups. Researchers focused on scores from the Mini-Mental State Examination (MMSE) — a short list of questions often used to screen for dementia.
Being in the two lowest B12 groups was associated with significantly accelerated cognitive decline, based on an analysis of test scores given over a period of eight years.
“Men and women in the second lowest group did not fare any better in terms of cognitive decline than those with the worst vitamin B12 blood levels. Over time, their MMSE scores declined just as rapidly,” said Martha Savaria Morris, Ph.D., an epidemiologist at Tufts University.
“Rapid neuropsychiatric decline is a well-known consequence of severe vitamin B12 deficiency, but our findings suggest that adverse cognitive effects of low vitamin B12 status may affect a much larger proportion of seniors than previously thought.”
The participants in this study were mostly Caucasian women who were at least high school graduates. The authors said future research might include more diverse populations and explore whether vitamin B12 status affects particular cognitive skills, since the current results show only a general picture of decline.
“While we emphasize our study does not show causation, our associations raise the concern that some cognitive decline may be the result of inadequate vitamin B12 in older adults, for whom maintaining normal blood levels can be a challenge,” said Paul Jacques, D.Sc., the study’s senior author and director of the Nutrition Epidemiology Program at Tufts.
The study is published in the Journal of the American Geriatrics Society.
Researchers at Johns Hopkins Medicine in November surgically implanted a pacemaker-like device into the brain of a patient in the early stages of Alzheimer's disease, the first such operation in the United States. The device, which provides deep brain stimulation and has been used in thousands of people with Parkinson's disease, is seen as a possible means of boosting memory and reversing cognitive decline.
The surgery is part of a federally funded, multicenter clinical trial marking a new direction in clinical research designed to slow or halt the ravages of the disease, which slowly robs its mostly elderly victims of a lifetime of memories and the ability to perform the simplest of daily tasks, researchers at Johns Hopkins say. Instead of focusing on drug treatments, many of which have failed in recent clinical trials, the research focuses on the use of the low-voltage electrical charges delivered directly to the brain. There is no cure for Alzheimer's disease.
As part of a preliminary safety study in 2010, the devices were implanted in six Alzheimer's disease patients in Canada. Researchers found that patients with mild forms of the disorder showed sustained increases in glucose metabolism, an indicator of neuronal activity, over a 13-month period. Most Alzheimer's disease patients show decreases in glucose metabolism over the same period.
The first U.S. patient in the new trial underwent surgery at The Johns Hopkins Hospital, and a second patient is scheduled for the same procedure in December. The surgeries at Johns Hopkins are being performed by neurosurgeon William S. Anderson, M.D.
"Recent failures in Alzheimer's disease trials using drugs such as those designed to reduce the buildup of beta amyloid plaques in the brain have sharpened the need for alternative strategies," says Paul B. Rosenberg, M.D., an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, and site director of the trial's Johns Hopkins location. "This is a very different approach, whereby we are trying to enhance the function of the brain mechanically. It's a whole new avenue for potential treatment for a disease becoming all the more common with the aging of the population."
Some 40 patients are expected to receive the deep brain stimulation implant over the next year or so at Johns Hopkins and four other institutions in North America as part of the ADvance Study led by Constantine G. Lyketsos, M.D., M.H.S., a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, and Andres Lozano, M.D., Ph.D., chairman of the neurology department at the University of Toronto. Only patients whose cognitive impairment is mild enough that they can decide on their own to participate will be included in the trial.
Other sites performing the operation, supported by the National Institutes of Health's National Institute on Aging (R01AG042165), are the University of Toronto, the University of Pennsylvania, the University of Florida, and Banner Health System in Phoenix, Ariz. The medical device company, Functional Neuromodulation Ltd., is also supporting the trial.
"We are very excited about the possibilities of this potentially new way to treat Alzheimer's," says Lyketsos, director of the Johns Hopkins Memory and Alzheimer's Treatment Center in Baltimore.
While experimental for Alzheimer's patients, more than 80,000 people with the neurodegenerative disorder Parkinson's disease have undergone the procedure over the past 15 years, with many reporting fewer tremors and requiring lower doses of medication afterward, Lyketsos says. Other researchers are testing deep brain stimulation to control depression and obsessive-compulsive disorder resistant to other therapies.
The surgery involves drilling holes into the skull to implant wires into the fornix on either side of the brain. The fornix is a brain pathway instrumental in bringing information to the hippocampus, the portion of the brain where learning begins and memories are made, and where the earliest symptoms of Alzheimer's appear to arise. The wires are attached to a pacemaker-like device, the "stimulator," which generates tiny electrical impulses into the brain 130 times a second. The patients don't feel the current, Rosenberg says.
For the trial, all of the patients will be implanted with the devices. Half will have their stimulators turned on two weeks after surgery, while the other half will have their stimulators turned on after one year. Neither the patients nor the doctors treating them will know which group gets an early or later start.
"Deep brain stimulation might prove to be a useful mechanism for treating Alzheimer's disease, or it might help us develop less invasive treatments based on the same mechanism," Rosenberg says.
By 2050, the number of people age 65 and older with Alzheimer's disease may triple, experts say, from 5.2 million to a projected 11 million to 16 million, unless effective treatments are found.
New research shows that vitamin D may be a vital component for the cognitive health of women as they age.
Higher vitamin D dietary intake is associated with a lower risk of developing Alzheimer’s disease, according to research conducted by a team led by Cedric Annweiler, M.D., Ph.D., at the Angers University Hospital in France.
At the same time, a team of researchers led by Yelena Slinin, M.D., M.S., at the VA Medical Center in Minneapolis found that low vitamin D levels among older women are associated with higher odds of cognitive impairment and a higher risk of cognitive decline.
Vitamin D is an important, essential vitamin people obtain largely from eating foods like fatty fish, butter and cheese or drinking fortified milk. The body makes Vitamin D when it is exposed to the ultraviolet rays of the sun.
Slinin’s team based its analysis on 6,257 older women who had vitamin D levels measured during the Study of Osteopathic Fractures and whose cognitive function was tested by the Mini-Mental State Examination and/or Trail Making Test Part B.
Very low levels of vitamin D — less than 10 nanograms per milliliter of blood serum — were associated with higher odds of cognitive impairment at baseline.
Low vitamin D levels — less than 20 nanograms per milliliter — among cognitively-impaired women were associated with a higher risk of cognitive decline, as measured by performance on the Mini-Mental State Examination, according to the researchers.
Annweieler’s team’s findings were based on data from 498 women who participated in the Toulouse cohort of the Epidemiology of Osteoporosis study.
Women who developed Alzheimer’s disease had lower baseline vitamin D intakes — an average of 50.3 micrograms per week — than those who developed other dementias (an average of 63.6 micrograms per week) or no dementia at all (an average of 59.0 micrograms per week), these researchers found.
These new studies follow an article published in the Journals of Gerontology Series A earlier this year that found that both men and women who don’t get enough vitamin D — either from diet, supplements, or sun exposure — may be at increased risk of developing mobility limitations and disability.
The two new studies appear in the Journals of Gerontology Series A: Biological Sciences and Medical Sciences.