News Roundup: New and Noteworthy Information
Investigators have developed a simple test to identify people with asymptomatic carotid stenosis who have an increased risk of stroke, as reported in the August 17 online Neurology. “Two potential markers of high risk are echolucent plaque morphology on carotid ultrasound and embolic signals in the ipsilateral middle cerebral artery on transcranial Doppler ultrasound (TCD),” the authors wrote. To explore the predictive value of a composite score based on these two measures, the investigators recruited 435 participants with asymptomatic carotid stenosis and collected baseline ultrasound images and TCD data. “Plaque morphology assessed using a simple, and clinically applicable, visual rating scale predicts ipsilateral stroke risk in asymptomatic carotid stenosis,” the authors wrote. They also noted that the combination of both markers allows a greater prediction than either measure alone.
Researchers have identified a possible common cause of several forms of amyotrophic lateral sclerosis (ALS), according to a study published in the August 21 online Nature. Although some genetic mutations have been shown to cause certain forms of the disease, the causes of certain types of familial ALS and of the vast majority of sporadic ALS had been unknown. “Here, we show that mutations in the UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS, and ALS/dementia,” the investigators reported. They also performed functional analysis that showed that these mutations lead to impairment in protein degradation. “Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation, and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention,” the authors concluded.
Using computational approaches and drug and genomic information, scientists can predict new uses for existing medicines, according to two studies published online in the August 17 Science Translational Medicine. The practice, known as drug repositioning, was investigated in a study supported by the NIH. The researchers used a computer program that searched through possible drug-disease combinations (from a set of 164 established drug compounds and 100 diseases) to identify drug and disease combinations whose gene expression patterns essentially canceled each other out. In one specific case, topiramate, an anticonvulsant for the treatment of epilepsy, was found to be a potential therapeutic option for inflammatory bowel disease. “The application of established drug compounds to new therapeutic indications … offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval,” the authors wrote. “This computational method provides a systematic approach for repositioning established drugs to treat a wide range of human diseases.”
Women with depression may have an increased risk of subsequent stroke, according to the results of a study published in the August 11 Stroke. A group of researchers followed-up more than 80,000 women (age range, 54 to 79) without a history of stroke from the Nurses’ Health Study to determine if depression was associated with stroke. Depressive symptoms were assessed at multiple time points, and antidepressant medication use and physician-diagnosed depression were recorded biennially. “During six years of follow-up, 1,033 incident strokes were documented,” the authors reported. “For each cycle, participants who reported current depression had an increased risk of stroke (hazard ratio, 1.41), whereas individuals who only had a history of depression were at nonsignificantly elevated risk (hazard ratio, 1.23), compared with women who never reported a diagnosis of depression or antidepressant medication use.”
According to a study published in the August 11 online JAMA, women with sleep-disordered breathing were more likely to develop dementia or cognitive impairment, compared with women without the disorder. “Sleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults,” the authors wrote. “However, it remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults.” To investigate this association and its potential mechanisms, the researchers conducted a prospective sleep and cognition study of 298 women without dementia who underwent polysomnography. “Compared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% versus 44.8%),” they reported. “Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.”
Older patients (ages 80 to 91) with Alzheimer’s disease experience less severe cognitive or brain changes than younger patients (ages 60 to 75) with the disease, according to a study published in the August 10 online Neurology. Researchers compared hippocampal volume and cortical gray matter thickness of 105 patients with Alzheimer’s disease and 125 healthy controls to determine if brain morphometric and cognitive profiles differed according to age. “Several cognitive domains (executive function, immediate memory, and attention/processing speed) were less abnormal in the very old with Alzheimer’s disease than in the young old with Alzheimer’s disease,” the investigators wrote. “Similarly, the very old with Alzheimer’s disease showed less severe cortical thinning than the young old with Alzheimer’s disease.” The authors noted that mild cases of Alzheimer’s disease in older people might go undetected due to these age-related differences in cognitive and morphometric changes.
