Technique moves practical Alzheimer diagnosis one step closer to reality

Researchers at the University of Wisconsin-Madison School of Medicine and Public Health are moving closer to a significant milepost in the battle against Alzheimer’s disease: identifying the first signs of decline in the brain.

After years of frustrating failure to stop late-stage Alzheimer’s, it’s essential to find and treat the mild stages, says Sterling Johnson, professor of geriatrics. “We need to identify Alzheimer’s as early as possible, before the really destructive changes take place. Typically, by the time we diagnose Alzheimer’s disease, patients have already lost much of their brain capacity, and it’s difficult or impossible for them to recover.”

The earlier phases, before large numbers of brain cells have been killed, should be more amenable to treatment, Johnson says. Alzheimer’s disease is the largest single cause of dementia. Early symptoms include memory decline, eventually progressing to widespread cognitive and behavioral changes.

In a study published in the journal Cerebral Cortex in December, Johnson, Ozioma Okonkwo in the Department of Geriatrics, and colleagues reported on measurements of brain blood flow in 327 adults. The researchers used an advanced form of MRI to compare blood flow in people with Alzheimer’s, a preliminary stage called mild cognitive impairment, or those who had no symptoms but had a family history of Alzheimer’s.

Reduced blood flow signifies reduced activity in particular parts of the brain, often due to the atrophy of nerve cells. One affected structure, called the hippocampus, is necessary for making new memories. In mild to moderate cases of Alzheimer’s, 40 percent or more of the hippocampus has disappeared.

As expected, the Alzheimer’s patients had lower blood flow in several brain regions linked to memory. People with mild cognitive impairment had a milder version of the same deficits. And people whose mother (but not father) had Alzheimer’s had clear signs of reduced blood flow, even though they lacked symptoms.

Other techniques that can measure blood flow are more costly and require the use of radiation and injecting a drug tracer during the scan, Johnson says. If this non-invasive MRI technique continues to prove itself, it could be a key to detecting Alzheimer’s disease in its early, and hopefully more treatable, phases.

"In the new paper, we showed that the same areas that show up with more established scanning techniques also are identified with this MRI blood flow technique, in people with Alzheimer’s and mild cognitive impairment," says Johnson. "So this method is valid and reliable, and is now ready to begin deployment in treatment research with people at risk."

Study findings have potential to prevent, reverse serious disabilities affecting children born prematurely

Physician-scientists at Oregon Health & Science University Doernbecher Children’s Hospital are challenging the way pediatric neurologists think about brain injury in the pre-term infant. In a study published online in the Jan. 16 issue of Science Translational Medicine, the OHSU Doernbecher researchers report for the first time that low blood and oxygen flow to the developing brain does not, as previously thought, cause an irreversible loss of brain cells, but rather disrupts the cells’ ability to fully mature. This discovery opens up new avenues for potential therapies to promote regeneration and repair of the premature brain.

“As neurologists, we thought ischemia killed the neurons and that they were irreversibly lost from the brain. But this new data challenges that notion by showing that ischemia, or low blood flow to the brain, can alter the maturation of the neurons without causing the death of these cells. As a result, we can focus greater attention on developing the right interventions, at the right time early in development, to promote neurons to more fully mature and reduce the often serious impact of preterm birth. We now have a much more hopeful scenario,” said Stephen Back, M.D., Ph.D., lead investigator and professor of pediatrics and neurology in the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital.

Researchers at OHSU Doernbecher have conducted a number of studies in preterm fetal sheep to define how disturbances in brain blood flow lead to injury in the developing brain. Their findings have led to important advances in the care of critically ill newborn infants.

For this study, Back and colleagues used pioneering new MRI studies that allow injury to the developing brain to be identified much earlier than previously feasible. They looked at the cerebral cortex, or “thinking” part of the brain, which controls the complex tasks involved with learning, attention and social behaviors that are frequently impaired in children who survive preterm birth. Specifically, they observed how brain injury in the cerebral cortex of fetal sheep evolved over one month and found no evidence that cells were dying or being lost. They did notice, however, that more brain cells were packed into a smaller volume of brain tissue, which led to, upon further examination, the discovery that the brain cells weren’t fully mature.

In a related study published in the same online issue of Science Translational Medicine, investigators at The Hospital for Sick Children and the University of Toronto studied 95 premature infants using MRI and found that impaired growth of the infants was the strongest predictor of the MRI abnormalities, suggesting that interventions to improve infant nutrition and growth may lead to improved cortical development.

“I believe these studies provide hope for the future for preterm babies with brain injury, because our findings suggest that neurons are not being permanently lost from the human cerebral cortex due to ischemia. This raises the possibility that neurodevelopmental enrichment — or perhaps improved early infant nutrition — as suggested by the companion paper, might make a difference in terms of improved cognitive outcome,” Back said.

“Together, these studies challenge the conventional wisdom that preterm birth is associated with a loss of cortical neurons. This finding may change the way neurologists think about diagnosing and treating children born prematurely,” said Jill Morris, Ph.D., a program director at the National Institute’s of Health’s National Institute Neurological Disorders and Stroke.

Research shows brain hub activity different in coma patients

A team of French and British researchers has found that brain region activity for coma patients is markedly different than for healthy people. In their paper published in the Proceedings of the National Academy of Sciences, the group describes the differences found when comparing fMRI scans of people in a coma with healthy volunteers.

To gain a better understanding of what goes on in the brain when a person is in a coma, and perhaps the nature of consciousness, the researchers performed fMRI brain scans on 17 people who had recently become comatose due to medical conditions that led to blockage of oxygen to the brain. They then compared those scans to those taken of 20 healthy volunteers.

In analyzing the results the team found that global comparisons between the two groups revealed very few if any differences. Blood continued to flow to all of the parts of the brain. When focusing on the brain as a network however, they found very large differences.

To look at the brain as a network requires looking at its different parts as regions that communicate with one another, forming hubs. In healthy people, certain regions or hubs are busier than others as evidenced by more blood flow. But for the people in a coma, the team found, the normally busy hubs grew less busy, while other hubs grew busier, indicating a major change in the flow of information.

The researchers suggest that the brain scans reveal that the normally busy hubs in healthy people are centers of consciousness and their reduced role in communications in comatose patients suggests that they are most likely not conscious of their existence. They point to prior research that has suggested that being in a coma is more likely closer to the experience of being under anesthesia than being asleep. They add that the their research indicates that regions of the brain that are responsible for conscience thought likely require more oxygen rich blood, and are thus likely to be more sensitive to oxygen deprivation than other areas of the brain, which might explain why people go into a coma when those regions are harmed.

Pressure switch inside the head

An increase in cerebral pressure may cause dementia and could destroy the brain. Companies have been seeking to find monitoring sensors that can be implanted into the brain, and read from outside the body. A tiny sensor may provide the help needed.

To this day it remains a mystery why the cerebral pressure in certain people suddenly increases. The consequences, however, are better understood: The blood circulation is disrupted and after a while parts of the brain may die off, similar to what occurs in a stroke. This is how dementia takes its insidious path. Experts estimate that up to ten percent of all cases of dementia in Europe can be attributed to rising blood pressure in the brain. Still, making the diagnosis is tough. People with a heightened susceptibility to a rise in intracranial pressure must be treated with intensive medical care today. A probe is inserted that goes from the outside through the skullcap to the brain. The cable keeps the patient connected to the measuring apparatus. Since cerebral pressure fluctuates, it takes extensive measurements in order to reach a definitive diagnosis of this disease. Patients therefore have to stay in hospital typically for several days, and sometimes even weeks.

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Simulations improve predictability of aneurysm development

Using new computer models of blood flow in the vicinity of cerebral aneurysms (dilated sections of blood vessels in the brain), it is now possible to calculate every detail of the patient-specific situation. This has resulted in powerful new techniques for predicting a further weakening or even rupture of the blood vessel’s wall, and for effective intervention. Julia Mikhal was awarded a PhD on this topic by the University of Twente.

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New research funded primarily by the Department of Defense would help emergency care workers and battlefield medics stabilize blood flow in the brains of traumatic injury victims. Rice University and Baylor College of Medicine in Houston developed a nanoparticle-based antioxidant that quickly quenches free radicals that interfere with regulation of the brain’s vascular system.