Posts tagged neuroscience
Articles and news from the latest research reports.
Brain inflammation a recipe for chronic fatigue
Patients with chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis, experience severe and often disabling exhaustion. Other symptoms include cognitive dysfunction, pain and depression. Although brain inflammation is thought to be involved in the development of these symptoms, direct evidence of this relationship has proved elusive.
Yasuyoshi Watanabe, Yasuhito Nakatomi, Kei Mizuno and colleagues from the RIKEN Center for Life Science Technologies and other institutes in Japan have now shown using a noninvasive brain imaging technique that the neuropsychological symptoms of patients with CFS are closely associated with widespread inflammation in the brain.
Positron emission tomography (PET) is a brain imaging technique that uses radioactive tracers attached to particular cell types or molecules to noninvasively track changes in the brain in disease states. To examine the effect of CFS, the researchers used a radioactive tracer that labels activated glial cells, which tend to be associated with neuroinflammation. They performed PET imaging studies on nine CFS sufferers and ten healthy individuals to identify the extent to which brain inflammation plays a role in CFS. They found that the levels of tracer binding were much higher in multiple brain regions in the CFS patients compared with the same brain regions in the healthy participants.
The investigation also found correlations between tracer binding in various brain regions and the severity of symptoms in the CFS patients. The researchers found that inflammation in the thalamus—a region of the brain responsible for relaying motor and sensory information to and from the cerebral cortex—correlated with the severity of both cognitive impairment and pain in the CFS patients. They also identified a correlation between inflammation in the amygdala—a part of the brain linked to emotional memory—and the severity of cognitive impairment. The severity of depression in CFS patients, on the other hand, was linked to the extent of inflammation in the hippocampus, which is a part of the brain known to be associated with depression.
The findings suggest that inflammation in the brain plays a key role in CFS in humans. Drugs that fight inflammation in the brain may therefore offer promising therapies to prevent or treat CFS and its related symptoms of pain, depression and cognitive dysfunction.
“Because CFS is diagnosed based on subjective symptoms such as fatigue, pain, sleep problems and cognitive impairment,” says Mizuno, “neuroinflammation as observed by PET imaging could be helpful as a more objective biomarker for diagnosis of the disorder.”
Investigators Discover How Key Protein Enhances Memory and Learning
Case Western Reserve researchers have discovered that a protein previously implicated in disease plays such a positive role in learning and memory that it may someday contribute to cures of cognitive impairments. The findings regarding the potential virtues of fatty acid binding protein 5 (FABP5) — usually associated with cancer and psoriasis — appear in the May 2 edition of The Journal of Biological Chemistry.
“Overall, our data show that FABP5 enhances cognitive function and that FABP5 deficiency impairs learning and memory functions in the brain hippocampus region,” said senior author Noa Noy, PhD, a professor of pharmacology at the School of Medicine. “We believe if we could find a way to upregulate the expression of FABP5 in the brain, we might have a therapeutic handle on cognitive dysfunction or memory impairment in some human diseases.”
FABP5 resides in many tissues and is especially highly expressed in the brain. Noy and her Case Western Reserve School of Medicine and National Institute on Alcohol Abuse and Alcoholism colleagues particularly wanted to understand how this protein functioned in neurons. They performed imaging studies comparing the activation of a key transcription factor in the brain tissue of normal mice and in FABP5-deficient mice. (Transcription factor is a protein the controls the flow of genetic information). The investigations revealed that FABP5 performs two different functions in neurons. First, it facilitates the degradation of endocannabinoids, which are neurological modulators controlling appetite, pain sensation, mood and memory. Second, FABP5 regulates gene expression, a process that essentially gives cells their marching orders on structure, appearance and function.
“FABP5 improves learning and memory both because it delivers endocannabinoids to cellular machinery that breaks them down and because it shuttles compounds to a transcription factor that increases the expression of cognition-associated genes,” Noy said.
Even though endocannabinoids affect essential physiological processes from appetite to memory, the “cannabinoid” part of the word signifies that these natural biological compounds act similarly to drugs such as marijuana and hashish. Too much endocannabinoid can lead to impaired learning and memory.
In simple terms, FABP5 transports endocannabinoids for processing. FABP5 functions like a bus and carries the brain’s endocannabinoids and their biological products to two stations within the neuron cell. FABP5 captures endocannabinoids entering the neuron and delivers them to an enzyme that degrades them (station 1). Then, that degraded product is picked up by the same protein (FABP5) and shuttled to the cell nucleus — specifically, to a transcription factor within it (station 2). Binding of the degraded product activates the transcription factor and allows it to induce expression of multiple genes. The genes that are induced in this case tell the cells to take steps that promote learning and memory.
Noy and associates also compared memory and learning in FABP5-deficient mice and in normal ones. In one test, both sets of mice repeatedly swam in mazes that had a platform in one established location where they could climb out of the water. During subsequent swims, the wild-type mice reached the platform quickly because they had learned — and remembered — its location. Their FABP5-deficient counterparts took much longer, typically finding the platform’s location by chance.
“In addition to regulating cell growth as in skin and in cancer cells, for example, FABP5 also plays a key role in neurons of the brain,” Noy said. “FABP5 controls the biological actions of small compounds that affect memory and learning and that activate a transcription factor, which regulates neuronal function.”
(Source: casemed.case.edu)
Study explores genetics behind Alzheimer’s resiliency
Autopsies have revealed that some individuals develop the cellular changes indicative of Alzheimer’s disease without ever showing clinical symptoms in their lifetime.
Vanderbilt University Medical Center memory researchers have discovered a potential genetic variant in these asymptomatic individuals that may make brains more resilient against Alzheimer’s.
“Most Alzheimer’s research is searching for genes that predict the disease, but we’re taking a different approach. We’re looking for genes that predict who among those with Alzheimer’s pathology will actually show clinical symptoms of the disease,” said principal investigator Timothy Hohman, Ph.D., a post-doctoral research fellow in the Center for Human Genetics Research and the Vanderbilt Memory and Alzheimer’s Center.
The article, “Genetic modification of the relationship between phosphorylated tau and neurodegeneration,” was published online recently in the journal Alzheimer’s and Dementia.
The researchers used a marker of Alzheimer’s disease found in cerebrospinal fluid called phosphorylated tau. In brain cells, tau is a protein that stabilizes the highways of cellular transport in neurons. In Alzheimer’s disease tau forms “tangles” that disrupt cellular messages.
Analyzing a sample of 700 subjects from the Alzheimer’s Disease Neuroimaging Initiative, Hohman and colleagues looked for genetic variants that modify the relationship between phosphorylated tau and lateral ventricle dilation — a measure of disease progression visible with magnetic resonance imaging (MRI). One genetic mutation (rs4728029) was found to relate to both ventricle dilation and cognition and is a marker of neuroinflammation.
“This gene marker appears to be related to an inflammatory response in the presence of phosphorylated tau,” Hohman said.
“It appears that certain individuals with a genetic predisposition toward a ‘bad’ neuroinflammatory response have neurodegeneration. But those with a genetic predisposition toward no inflammatory response, or a reduced one, are able to endure the pathology without marked neurodegeneration.”
Hohman hopes to expand the study to include a larger sample and investigate gene and protein expression using data from a large autopsy study of Alzheimer’s disease.
“The work highlights the possible mechanism behind asymptomatic Alzheimer’s disease, and with that mechanism we may be able to approach intervention from a new perspective. Future interventions may be able to activate these innate response systems that protect against developing Alzheimer’s symptoms,” Hohman said.
(Source: news.vanderbilt.edu)
Out of shape? Your memory may suffer
Here’s another reason to drop that doughnut and hit the treadmill: A new study suggests aerobic fitness affects long-term memory.
Michigan State University researchers tested 75 college students during a two-day period and found those who were less fit had a harder time retaining information.
“The findings show that lower-fit individuals lose more memory across time,” said Kimberly Fenn, study co-author and assistant professor of psychology.
The study, which appears online in the research journal Cognitive, Affective & Behavioral Neuroscience, is one of the first to investigate young, supposedly healthy adults. Previous research on fitness and memory has focused largely on children, whose brains are still developing, and the elderly, whose memories are declining.
Participants studied related word pairs such as “camp” and “trail.” The next day, they were tested on the word pairs to evaluate long-term memory retention. Long-term memory is anything remembered more than about 30 seconds ago.
Aerobic fitness was gauged by oxygen consumption derived from a treadmill test and factored with the participants’ weight, percent body fat, age and sex.
The findings speak to the increasingly sedentary lifestyles found in the United States and other Western cultures. A surprising number of the college students in the study were significantly out of shape and did much worse at retaining information than those who were extremely fit, Fenn said.
Her co-authors included kinesiology researchers Matthew Pontifex and Karin Pfeiffer.
Scientists reveal circuitry of fundamental motor circuit
Scientists at the Salk Institute have discovered the developmental source for a key type of neuron that allows animals to walk, a finding that could help pave the way for new therapies for spinal cord injuries or other motor impairments related to disease.
The spinal cord contains a network of neurons that are able to operate largely in an autonomous manner, thus allowing animals to carry out simple rhythmic walking movements with minimal attention—giving us the ability, for example, to walk while talking on the phone. These circuits control properties such as stepping with each foot or pacing the tempo of walking or running.
The researchers, led by Salk professor Martyn Goulding, identified for the first time which neurons in the spinal cord were responsible for controlling a key output of this locomotion circuit, namely the ability to synchronously activate and deactivate opposing muscles to create a smooth bending motion (dubbed flexor-extensor alternation). The findings were published April 2 in Neuron.
Motor circuits in the spinal cord are assembled from six major types of interneurons—cells that interface between nerves descending from the brain and nerves that activate or inhibit muscles. Goulding and his team had previously implicated one class of interneuron, the V1 interneurons, as being a likely key component of the flexor-extensor circuitry. However when V1 interneurons were removed, the team saw that flexor-extensor activity was still intact, leading them to suspect another type of cell was also involved in coordinating this aspect of movement.
To determine what other interneurons were at play in the flexor-extensor circuit, the team looked for other cells in the spinal cord with properties that were similar to those of the V1 neurons. In doing this they began to focus on another class of neuron, whose function was not known, V2b interneurons. Using a specialized experimental setup that allows one to monitor locomotion in the spinal cord itself, the team saw a synchronous pattern of flexor and extensor activity when V2b interneurons were inactivated along with the V1 interneurons.
The team also showed that this synchronicity led to newborn mice displaying a tetanus-like reaction when the two types of interneurons were inactivated: the limbs froze in one position because they no longer had the push-pull balance of excitation and inhibition that is needed to move.
These findings further confirm the hypothesis put forward over 120 years ago by the Nobel Prize-winning neuroscientist, Charles Sherrington, that flexor-extensor alternation is essential for locomotion in all animals that have limbs. He proposed that specialized cells in the spinal cord called switching cells performed this function. After 120 years, Goulding and researchers have now uncovered the identity of these switching cells.
"Our whole motor system is built around flexor-extension; this is the cornerstone component of movement," says Goulding, holder of Salk’s Frederick W. and Joanna J. Mitchell Chair. "If you really want to understand how animals move you need to understand the contribution of these switching cells."
With a more thorough understanding of the basic science around how this flexor-extensor circuit works, scientists will be in a better position to, for example, create a system that can reactivate the spinal cord or mimic signals sent from the brain to the spinal cord.
Individual Brain Activity Predicts Tendency to Succumb to Daily Temptations
Activity in areas of the brain related to reward and self-control may offer neural markers that predict whether people are likely to resist or give in to temptations, like food, in daily life, according to research in Psychological Science, a journal of the Association for Psychological Science.
“Most people have difficulty resisting temptation at least occasionally, even if what tempts them differs,” say psychological scientists Rich Lopez and Todd Heatherton of Dartmouth College, authors on the study. “The overarching motivation of our work is to understand why some people are more likely to experience this self-regulation failure than others.”
The research findings reveal that activity in reward areas of the brain in response to pictures of appetizing food predicts whether people tend to give in to food cravings and desires in real life, whereas activity in prefrontal areas during taxing self-control tasks predicts their ability to resist tempting food.
Lopez and colleagues used functional MRI (fMRI) to explore the interplay between activity in prefrontal brain regions associated with self-control (e.g., inferior frontal gyrus) and subcortical areas involved in affect and reward (e.g., nucleus accumbens), and to see whether the interplay between these regions predicts how successful (or unsuccessful) people are in controlling their desires to eat on a daily basis.
The researchers recruited 31 female participants to take part in an initial fMRI scanning session that included two important tasks.
For the first task, the participants were presented with various images, including some of high-calorie foods, like dessert items, fast-food items, and snacks. The participants were simply asked to indicate whether each image was set indoors or outdoors — the researchers were specifically interested in measuring activity in the nucleus accumbens in response to the food-related images.
For the second task, the participants were asked to press or not press a button based on the specific cues provided with each image, a task designed to gauge self-control ability. During this task, the researchers measured activity in the inferior frontal gyrus (IFG).
The fMRI scanning session was followed by 1 week of so-called “experience sampling,” in which participants were signaled several times a day on a smartphone and asked to report their food desires and eating behaviors. Any time participants reported a food desire, they were then asked about the strength of the desire and their resistance to it. If they ultimately gave in to the craving, they were asked to say how much they had eaten.
As expected, participants who had relatively higher activity in the nucleus accumbens in response to the food images tended to experience more intense food desires. More importantly, they were also more likely to give in to their food cravings and eat the desired food.
The researchers were surprised by how robust this association was:
“Reward-related brain activity, which can be considered an implicit measure, predicted who gave in to temptations to eat, as well as who ate more, above and beyond the desire strength reported by participants in the moment,” say Lopez and Heatherton. “This could help to explain a previous finding from our lab that people who show this kind of brain activity the most are also the most likely to gain weight over six months.”
But brain activity also predicted who was more likely to be able to resist temptation: Participants who showed relatively higher IFG activity on the self-control task acted on their cravings less often.
When the researchers grouped the participants according to their IFG activity, the data revealed that participants who had high IFG activity were more successful at controlling how much they ate in particularly tempting situations than those who had low IFG activity. In fact, participants with low IFG activity were about 8.2 times more likely to give in to a food desire than those who had high IFG activity.
“Taken together, the results from the present study provide initial evidence for neural markers of everyday eating behaviors that can identify individuals who are more likely than others to give in to temptations to eat,” the researchers write.
Lopez, Heatherton, and colleagues are currently conducting studies focused on groups of people who are especially prone to self-regulation failure: chronic dieters.
They’re investigating, for example, how dieters’ brains respond to food cues after they’ve exhausted their self-control resources. The researchers hypothesize that depleting self-control may heighten reward-related brain activity, effectively “turning up the volume on temptations,” and predicting behaviors like overeating in daily life.
“Failures of self-control contribute to nearly half of all death in the United States each year,” the researchers note. “Our findings and future research may ultimately help people learn ways to resist their temptations.”
Researchers find brain reserve and cognitive reserve have long-term protective effect against cognitive decline in MS
Multiple sclerosis researchers have found that brain reserve and cognitive reserve confer a long-term protective effect against cognitive decline.
“Our research aims to answer these questions,” explained Dr. DeLuca. “Why do some people with MS experience disabling symptoms of cognitive decline, while others maintain their cognitive abilities despite neuroimaging evidence of significant disease progression? Can the theories of brain reserve and cognitive reserve explain this dichotomy? Can we identify predictors of cognitive decline?”
In this study, memory, cognitive efficiency, vocabulary (a measure of intellectual enrichment/cognitive reserve), brain volume (a measure of brain reserve), and disease progression on MRI, were evaluated in 40 patients with MS at baseline and at 4.5-year followup. After controlling for disease progression, scientists looked at the impact of brain volume and intellectual enrichment on cognitive decline.
Results supported the protective effects of brain reserve and cognitive reserve,” noted Dr. Sumowski. “Patients with greater intellectual enrichment experienced lesser degrees of cognitive decline. Those with greater brain reserve showed a protective effect for cognitive efficiency. This study not only confirms these protective effects of brain and cognitive reserve, it shows that these beneficial effects persist for years.”
(Source: kesslerfoundation.org)
The human body produces chemical cues that communicate gender to members of the opposite sex, according to researchers who report their findings in the Cell Press journal Current Biology on May 1. Whiffs of the active steroid ingredients (androstadienone in males and estratetraenol in females) influence our perceptions of movement as being either more masculine or more feminine. The effect, which occurs completely without awareness, depends on both our biological sex and our sexual orientations.
"Our findings argue for the existence of human sex pheromones," says Wen Zhou of the Chinese Academy of Sciences. "They show that the nose can sniff out gender from body secretions even when we don’t think we smell anything on the conscious level."
Earlier studies showed that androstadienone, found in male semen and armpits, can promote positive mood in females as opposed to males. Estratetraenol, first identified in female urine, has similar effects on males. But it wasn’t clear whether those chemicals were truly acting as sexual cues.
In the new study, Zhou and her colleagues asked males and females, both heterosexual and homosexual, to watch what are known as point-light walkers (PLWs) move in place on a screen. PLWs consist of 15 dots representing the 12 major joints in the human body, plus the pelvis, thorax, and head. The task was to decide whether those digitally morphed gaits were more masculine or feminine.
Individuals completed that task over a series of days while being exposed to androstadienone, estratetraenol, or a control solution, all of which smelled like cloves. The results revealed that smelling androstadienone systematically biased heterosexual females, but not males, toward perceiving walkers as more masculine. By contrast, the researchers report, smelling estratetraenol systematically biased heterosexual males, but not females, toward perceiving walkers as more feminine.
Interestingly, the researchers found that homosexual males responded to gender pheromones more like heterosexual females did. Bisexual or homosexual female responses to the same scents fell somewhere in between those of heterosexual males and females.
"When the visual gender cues were extremely ambiguous, smelling androstadienone versus estratetraenol produced about an eight percent change in gender perception," Zhou says, a statistically very significant effect.
"The results provide the first direct evidence that the two human steroids communicate opposite gender information that is differentially effective to the two sex groups based on their sexual orientation," the researchers write. "Moreover, they demonstrate that human visual gender perception draws on subconscious chemosensory biological cues, an effect that has been hitherto unsuspected."
Studies Identify Spinal Cord Neurons that Control Skilled Limb Movement
Researchers have identified two types of neurons that enable the spinal cord to control skilled forelimb movement. The first is a group of excitatory interneurons that are needed to make accurate and precise movements; the second is a group of inhibitory interneurons necessary for achieving smooth movement of the limbs. The findings are important steps toward understanding normal human motor function and potentially treating movement disorders that arise from injury or disease.
“We take for granted many motor behaviors, such as catching a ball or flipping a coin, that in fact require considerable planning and precision,” said Columbia University Medical Center’s (CUMC’s) Thomas M. Jessell, PhD, a senior author of both studies, which were published separately in recent issues of Nature (1, 2). “While such motor acts seem effortless, they depend on intricate and carefully orchestrated communication between neural networks that connect the brain to the spinal cord and muscles.”
To move one’s hand to a desired target, the brain sends the spinal cord signals, which activate the motor neurons that control limb muscles. During subsequent movements, information from the limb is conveyed back to the brain and spinal cord, providing a feedback system that can support the control and adjustment of motor output.
“But feedback from muscles is not quick enough to permit the most rapid real-time adjustments of fine motor control,” said Dr. Jessell, “suggesting that there may be other, faster, systems at play.” Dr. Jessell is the Claire Tow Professor of Motor Neuron Disorders in the Departments of Neuroscience and of Biochemistry and Molecular Biophysics, co-director of the Mortimer B. Zuckerman Mind Brain Behavior Institute, co-director of the Kavli Institute for Brain Science, and a Howard Hughes Medical Institute investigator, all at Columbia.
Researchers had suspected that one rapid form of feedback might derive from a group of interneurons in the cervical spinal cord called propriospinal neurons (PNs). Like many other neurons, PNs send signals to motor neurons that innervate arm muscles and trigger movement. But this subset of neurons also has a distinct output branch that projects away from motor neurons towards the cerebellum. Through this dual-branched anatomy, these neurons have the potential to carry internal copies of motor output signals up to the brain.
However, the nature of this internal feedback pathway and whether it has any impact on movement have not been clear. “If PNs were indeed sending copies of outgoing motor commands to the brain, they could provide a conveniently rapid means of adjusting ongoing movements when things go awry,” said Eiman Azim, PhD, a postdoctoral fellow in Dr. Jessell’s lab and lead author of the first paper. “But without a way to selectively target the copy function of PNs, there was no way to test this theory.”
The CUMC team, in collaboration with Bror Alstermark, PhD, a professor in integrative medical biology at Umeå University in Sweden, overcame this technical barrier by developing a genetic method for accessing and eliminating PNs in mice, abolishing both motor-directed and copy signals sent by the neurons. When the researchers quantified the limb movements of the PN-deprived mice in three dimensions as they reached for food pellets, they found that the mice’s ability to reach for the target accurately was badly compromised. “Basically, their movements were uncoordinated,” said Dr. Azim. “The PN-deprived mice consistently over- or under-reached.”
But with both PN output signals gone, the precise role of the PN copy signal remained unclear. The researchers then turned to optogenetics—the use of light to control neuronal activity. They selectively activated the copy axonal branch alone, decalibrating this copy signal from the version sent to motor neurons. With the copy signal altered, the animals’ ability to reach was severely compromised, indicating that the PN copy pathway is capable of influencing the outcome of goal-directed reaching movements.
The PN copy signal also works blazingly fast. It takes just 4 to 5 milliseconds for motor neuron activity to be altered after transmission of a PN copy signal. “These reaching movements typically take 200 to 300 milliseconds, so the PN copy signal pathway appears well equipped to correct arm movements,” said Dr. Azim. The researchers think that this copy signal represents just one of many similar internal feedback pathways that the spinal cord and brain use to validate and correct movements throughout the body.
Are these findings relevant to human motor performance? Many of the pathways and circuits that influence reach and grasp in monkeys and humans are conserved in mice. “We need to learn more about these pathways before we can evaluate how their dysfunction contributes to deficits seen after spinal cord injury and neurodegenerative disease,” said Dr. Azim.
In the second Nature study, CUMC researchers examined how spinal circuits regulate sensory feedback from muscles to control movement. The simplest form of this feedback system involves a reflex pathway (such as the knee-jerk reflex), in which sensory endings in muscles convey signals to the motor system through direct monosynaptic connections with motor neurons. Signals from motor neurons, in turn, cause muscles to contract, completing the reflex cycle.
Researchers have long wondered how the strength of this sensory signal might be regulated. Studies had shown that spinal interneurons—in particular those that release the neurotransmitter GABA, inhibiting neuronal activity—play a key role in this process. But most GABA-releasing interneurons exert their effects postsynaptically, by blocking the excitation of neurons on the receiving end of a synapse (the gap across which two neurons communicate).
“We knew that such neurons are unlikely to be responsible for fine-tuning the sensory signal,” said lead author Andrew J. P. Fink, PhD, a former graduate student in Dr. Jessell’s lab. “Postsynaptic inhibition affects the entire neuron, and motor neurons receive many different inputs. So a mechanism that shut down the motor neuron to all of its inputs would lack refinement.”
Researchers have long speculated that one subset of GABAergic interneurons might regulate movement by controlling the strength of sensory feedback signals from muscles. “These particular neurons are known to work presynaptically, by forming direct connections with the terminals of sensory neurons and suppressing the release of sensory neurotransmitter,” said Dr. Fink. For technical reasons, the function of these interneurons, if any, in motor behavior has remained elusive.
Dr. Fink and his colleagues identified a way to access this subset of interneurons genetically in mice and then devised approaches to manipulate their function in a selective manner. In one experiment, they activated presynaptic inhibitory interneurons optogenetically, decreasing the strength of sensory-motor transmission. They also ablated these interneurons by making them selectively sensitive to a lethal toxin, abolishing their control over sensory feedback strength. Without sensory feedback regulation, forelimb movements were dominated by severe oscillatory tremors, drastically diminishing motor accuracy.
This finding, along with parallel modeling studies, indicates that presynaptic inhibitory neurons normally adjust the “gain” of sensory feedback at synapses with motor neurons and are therefore crucial for the smooth execution of movement. Understanding how these basic microcircuits regulate sensory input and motor output may, in the long run, provide insight into ways to combat the movement instability and tremor seen in many neurological disorders.
“These two studies shed new light on how discrete classes of spinal interneurons empower the nervous system to direct motor behaviors in ways that match the particular task at hand,” said Dr. Jessell.
Atypical Form of Alzheimer’s Disease May be Present in a More Widespread Number of Patients
Neuroscientists at Mayo Clinic in Florida have defined a subtype of Alzheimer’s disease (AD) that they say is neither well recognized nor treated appropriately.
The variant, called hippocampal sparing AD, made up 11 percent of the 1,821 AD-confirmed brains examined by Mayo Clinic researchers — suggesting this subtype is relatively widespread in the general population. The Alzheimer’s Association estimates that 5.2 million Americans are living with AD. And with nearly half of hippocampal sparing AD patients being misdiagnosed, this could mean that well over 600,000 Americans make up this AD variant, researchers say.
In an oral presentation at the annual meeting of the American Academy of Neurology in Philadelphia, scientists say hippocampal sparing AD often produces symptoms that are substantially different from the most commonly known form of AD, which affects the hippocampus, the center of memory.
The patients, mostly male, are afflicted at a much younger age, and their symptoms can be bizarre — behavioral problems such as frequent and sometimes profane angry outbursts, feelings that their limbs do not belong to them and are controlled by an “alien” unidentifiable force, or visual disturbances in the absence of eye problems, researchers say.
They also decline at a much faster rate than do patients with the most common form of AD.
“Many of these patients, however, have memories that are near normal, so clinicians often misdiagnose them with a variety of conditions that do not match the underlying neuropathology,” says the study’s lead author, Melissa Murray, Ph.D., an assistant professor of neuroscience at Mayo Clinic in Florida.
Many of these patients are diagnosed with frontotemporal dementia, a disorder characterized by changes in personality and social behavior, or corticobasal syndrome, characterized by movement disorders and cognitive dysfunction. Language dysfunction is also more common in hippocampal sparing AD, although patients do not have vocal or hearing deficits.
“What is tragic is that these patients are commonly misdiagnosed and we have new evidence that suggests drugs now on the market for AD could work best in these hippocampal sparing patients — possibly better than they work in the common form of the disease,” Dr. Murray says.
The researchers benefit greatly from one of the largest brain banks in the country — more than 6,500 brain donations — as well as a collaborative environment between neuroscience research and neurology at Mayo Clinic, she says.
Both hallmark proteins of AD — amyloid beta (Aβ), which forms Aβ plaques, and tau, which produces tangles — are found across all subtypes of AD, including hippocampal sparing AD. The researchers developed a mathematical algorithm to classify AD subtypes using tangle counts. “What is fascinating is that all the AD patient subtypes had the same amount of amyloid, but for some reason tau tangles were found in strategic cortical regions disproportionate to the hippocampus.”
In these patients, tau preferentially damages and eventually destroys neurons in parts of the brain involved in behavior, motor awareness and recognition, as well as use of speech and vision, Dr. Murray says.
She says she hopes this research, the second high-profile Mayo study to highlight hippocampal sparing AD, will “open the minds” of clinicians who are trying to diagnose dementia, helping them understand that loss of memory is not present in every AD patient.
“Our studies support the notion that dementia related to AD does not necessarily equate to a loss of memory, and points to the need for more research in amyloid and tau imaging biomarkers to help clinicians accurately diagnose AD — regardless of subtype,” Dr. Murray says.
(Source: newsnetwork.mayoclinic.org)