New and Noteworthy Information—August 2015
Cognitive impairment may manifest in the preclinical phase of Alzheimer’s disease substantially earlier than previously established, according to a study published online ahead of print June 24 in Neurology. A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants ages 65 and older. In all, 442 participants developed clinical Alzheimer’s disease over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of Alzheimer’s disease. The magnitude of association between composite cognitive test score and development of Alzheimer’s disease dementia increased from an odds ratio of 3.39 at 13.0 to 17.9 years to an odds ratio of 9.84 at 0.1 to 0.9 years, per standard deviation increment.
Shared biological processes contribute to the risk of migraine and coronary artery disease, but this commonality is restricted to migraine without aura, according to a study published online ahead of print July 2 in Neurology Genetics. Researchers analyzed two large genome-wide association studies of migraine and heart disease. The migraine study involved 19,981 people with migraine and 56,667 people without migraine. Also included were 21,076 people with heart disease and 63,014 people without heart disease. Investigators found a significant overlap of genetic risk loci for migraine and coronary artery disease. When stratified by migraine subtype, this overlap was limited to migraine without aura. The overlap was protective, in that patients with migraine had a lower load of coronary artery disease risk alleles than controls did.
Women with stimulant dependence have significant changes in gray matter volume after prolonged abstinence, but men do not, according to a study published online ahead of print July 14 in Radiology. For this prospective, parallel-group study, 127 age- and sex-matched participants underwent T1-weighted spoiled gradient-echo inversion recovery MRI of the brain at 3 T. Compared with female control subjects, women with stimulant dependence had significantly lower gray matter volume in various brain regions. There were no significant differences in gray matter volume between male control subjects and men with stimulant dependence. Dependence symptom count negatively correlated with gray matter volume in the nucleus accumbens in women. Behavioral approach and impulsivity correlated negatively with frontal and temporal gray matter volume changes in women with stimulant dependence.
The FDA has approved Fycompa (perampanel) CIII for adjunctive therapy in the treatment of primary generalized tonic-clonic seizures. The approval is based on a phase III, randomized, double-blind, placebo-controlled clinical trial of 162 patients taking one to three antiepileptic drugs. Patients treated with Fycompa achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency. In addition, 64% of patients treated with Fycompa had a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo. The most frequently reported adverse events in patients treated with Fycompa were dizziness, fatigue, headache, somnolence, and irritability. The adverse event profile was similar to that in the controlled phase III partial-onset seizure trials of the drug. Eisai, headquartered in Woodcliff Lake, New Jersey, manufactures Fycompa.
Imaging biomarkers, including white matter disruption, may help explain some of the heterogeneity in postinjury outcome among children with traumatic brain injury (TBI), according to a study published July 15 in Journal of Neuroscience. Researchers used high angular resolution diffusion-weighted imaging to evaluate the structural integrity of the corpus callosum following brain injury in a sample of 32 children with moderate-to-severe TBI at one to five months post injury, and in healthy control children. A subset of children with TBI had markedly impaired functioning and structural integrity in the corpus callosum. These impairments were associated with poor neurocognitive functioning. The children with impaired functioning also had significantly slower interhemispheric transfer times than the control group did, as measured using event-related potentials.
Longitudinal CSF biomarker patterns consistent with Alzheimer’s disease are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline, according to a study published online ahead of print July 6 in JAMA Neurology. Cognitively normal middle-aged participants enrolled in the Adult Children Study at Washington University underwent serial CSF collection and longitudinal clinical assessment at three-year intervals. A subset of patients underwent longitudinal amyloid PET imaging with Pittsburgh compound B (PiB) in the same period. The researchers found no consistent longitudinal patterns in Aβ40. Longitudinal reductions in Aβ42 were observed in some individuals as early as middle age, and low Aβ42 levels were associated with the development of cortical PiB-positive amyloid plaques. The patterns were more apparent in at-risk carriers of the ε4 allele.
