Dehydroepiandrosterone (DHEA) showed no effect on Alzheimer’s disease in patients who took the supplement for six months, according to a report in the April 8 Neurology. Investigators gave 58 patients with Alzheimer’s disease either 100 mg/day of DHEA or a placebo. Patients were tested for cognitive functioning at baseline, three, and six months and were rated by physicians and caregivers on any changes in the severity of the disease. They found that DHEA did not significantly improve cognitive performance or ratings of disease severity. Investigators hypothesized that the small size of the study and the high dropout rate may have limited the findings and suggested larger trials to test the results.

Amyloid precursor protein (APP), long associated with Alzheimer’s disease, seals off mitochondria in affected neurons, leading to a buildup of toxins that causes cells to die, according to a report in the April 14 Journal of Cell Biology. Researchers observed that the end of the protein remaining outside the mitochondrion contains the toxin A-Beta, which is cleaved from the rest of the protein and accumulates in the cell. Because researchers believed that mitochondria were not on APP’s itinerary, they had focused on the protein’s effects on other organelles and were surprised by the mitochondrial failure. It remains unclear whether APP gets caught in mitochondria’s protein entryways because of its negative charge or improper protein folding. Investigators feel that further research into this question may eventually yield medications to correct the problem.

Age-related changes in the brain, specifically the appearance of white-matter lesions, significantly affect cognitive function in old age, according to a report in the March Psychology and Aging. Investigators followed up a cognitive test administered to 11-year-old Scottish students in 1932. Eighty-three of the participants, now approximately age 78, underwent MRI to assess the extent of white-matter lesions and took four cognitive tests to determine general cognitive ability. The researchers found that the amount of white-matter abnormalities made a significant contribution to cognitive ability differences in old age, independent of prior ability; they also noted that hypertension accounted for a small but significant variance both in lesions and in general cognitive scores in old age. Investigators believe that “avoiding risk factors for [white-matter abnormalities] or preventing their accumulation may ameliorate age-related cognitive decrements.”

Apolipoprotein E (APOE) genotype is a risk factor for diabetic neuropathy severity equal to 15 extra years of age or diabetes duration, according to a report in the March 25 Neurology. Patients with APOE e3 and e4 genotypes scored 3 points higher on the Neuropathy Impairment Score in the Lower Limbs than did patients with other genotypes. The study took into account the patient’s age, duration of diabetes, most recent and highest recorded hemoglobin, most recent and highest recorded triglycerides, and the presence of the APOE gene. Researchers believe the solution to the problem may lie in biomarkers that identify the risk for diabetic peripheral neuropathy.

Creatine therapy for amyotrophic lateral sclerosis (ALS) has no effect on disease progression, concluded researchers in an April Annals of Neurology study. The investigators recruited 175 patients with ALS to receive either 10 g of creatine daily or placebo. During the 10-month study, 30 of the 87 patients in the creatine group died, compared with 28 of 88 patients in the control group; there was also no indication that creatine slowed the rate at which muscle strength declined. While some researchers hope that the drug will show modest benefits for patients in two upcoming trials of creatine, others feel that “the trial effectively rules out the value in ongoing use of creatine, at least at that dose,” and higher doses, “if effective at all, would be of marginal benefit.”

Following regulatory clearance granted by the Food and Drug Administration (FDA) under its Humanitarian Device Exemption, Medtronic’s Activa® Therapy deep brain stimulation is now available to patients with chronic, intractable primary dystonia. Medtronic estimates that about 10% of dystonia patients, or roughly 4,000 adults and children 7 or older, are candidates for the treatment, which delivers controlled electrical pulses to targeted brain areas involved in movement control. Activa Therapy is currently also FDA-approved for the treatment of advanced Parkinson’s disease and essential tremor.

Caffeinol, an experimental caffeine and alcohol cocktail with the potency of two cups of coffee and a shot of alcohol, could prevent severe brain damage in stroke victims, according to a study in the April 10 advance online edition of Stroke. When the drug was injected into rats within three hours of an artificially stimulated stroke, brain damage was decreased by up to 80%. The safety of caffeinol has now also been demonstrated in a small pilot study involving patients with ischemic strokes. The researchers are unclear about how caffeinol protects the brain after stroke, but they speculate that the combination might interfere with the biochemical reactions triggered in cells by stroke.

The majority of people with migraine headaches may not be receiving the most effective treatments, reported a study in the April Headache. Researchers noted that while the number of patient visits for migraine have increased, less than 20% of the patients were seen by a neurologist. The majority of patients were seen by their primary care physician, despite reports that patients express more satisfaction and have better treatment outcomes when treated by a specialist. In the primary care setting, migraines have often been treated with analgesics and habit-forming drugs, although studies show that patients taking more effective medications, such as sumatriptan or anti-epileptic drugs, missed fewer days of work and had fewer days in which their normal activities were altered by a headache.

People with chronic daily headache are more than twice as likely to be chronic snorers than people with occasional headaches, reported a study in the April 22 Neurology. The results stayed the same even after adjusting for factors that can affect breathing during sleep. Researchers examined 206 individuals who have experienced chronic daily headache for five years or less and 507 individuals with occasional headache. The participants were asked how often they snored, and investigators classified their headache types. Researchers believe that more study is needed to determine the link between snoring and chronic daily headache. “The headaches could be causing the snoring, or the snoring could be causing the headaches, or both,” said Ann Scher, PhD, of the National Institute on Aging in Bethesda, Maryland.

Neprilysin, a molecule that naturally degrades beta-amyloid, appears to reduce the levels of the protein by nearly 50% when delivered by gene therapy, researchers stated in the March 15 Journal of Neuroscience. Investigators discovered this potential treatment for Alzheimer’s disease after transferring neprilysin to neurons of mice producing beta-amyloid. They found that not only did the treatment lower levels of beta-amyloid by half but it also eliminated the degeneration that was caused by buildups of the protein. The researchers believe that what is “significant about this is that neprilysin isn’t a drug but a molecule that controls levels of beta-amyloid naturally,” suggesting that “understanding the basic mechanisms of protein interaction can lead to new disease treatments.”

Reducing the amount of iron in brain cells, either by genetic or pharmacological means, can slow the progression of Parkinson’s disease, reported an article in the March 27 Neuron. Researchers injected mouse embryos with a gene that encodes the iron-binding protein ferritin; the gene was engineered so that only cells in the substantia nigra and related regions would produce ferritin. They found that fewer neurons broke down in the mice than in the untreated animals. The investigators also tested the effect of the drug clioquinol, which binds iron and zinc. The mice given clioquinol lost fewer brain cells than those that did not receive the drug. Ferritin treatments and clioquinol also preserved the mice’s motor skills.

Exposure to nicotine in the developing rat fetus enhances GABAa receptor function, making newborns more susceptible to apnea. Researchers gave pregnant rats either a saline solution or a nicotine dose similar to that of a person smoking two packs of cigarettes per day. After removing and preserving the brain stem and spinal cord of the newborn rats, the investigators bathed the brain stem and spinal cord in drugs used to stimulate GABAa receptors. They found that the same drug doses that caused marginal slowing in the brains that were not exposed to nicotine caused apnea in nocotine-exposed brains. Researchers suggest that prenatal nicotine exposure increases a human infant’s risk of frequent and possibly fatal apnea. Study findings were presented at the Experimental Biology 2003 meeting in San Diego.

NR