Both higher overall and abdominal adiposity are associated with an increased risk for restless legs syndrome (RLS), researchers reported in the April 7 Neurology. A total of 65,554 women and 23,119 men without diabetes, arthritis, and pregnancy were included in the analysis. Participants were considered to have RLS if they experienced restless legs five or more times a month and met four diagnostic criteria per the International RLS Study Group. RLS was diagnosed in 6.4% of the women and in 4.1% of the men. Multivariate adjusted odds ratios for RLS were 1.42 for participants with a BMI greater than 30 versus less than 23 and 1.60 for highest versus lowest waist circumference quintiles. “Greater BMI in early adulthood and weight gain were also associated with a higher prevalence of RLS,” stated the investigators.

In utero exposure to valproate is associated with an increased risk of impaired cognitive function at age 3, according to a study in the online April 16 New England Journal of Medicine. Researchers compared neurodevelopmental outcomes at age 3 in 309 children exposed to various antiepileptic drugs. “At three years of age, children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs,” the authors stated. IQ scores for children exposed to valproate were, on average, nine points lower than those exposed to lamotrigine, seven points lower than those exposed to phenytoin, and six points lower than those exposed to carbamazepine. “This finding supports a recommendation that valproate not be used as the first-choice drug in women of childbearing potential,” the investigators concluded.

Older patients with type 2 diabetes and a history of severe hypoglycemic episodes have a greater risk of dementia, per a report in the April 15 JAMA. Researchers collected data on hypoglycemic events that occurred between 1980 and 2002; patients with no prior diagnosis of dementia, mild cognitive impairment, or general memory complaints were followed up through January 15, 2007, for dementia diagnosis. “At least one episode of hypoglycemia was diagnosed in 1,465 patients (8.8%), and dementia was diagnosed in 1,822 patients (11%) during follow-up; 250 patients had both dementia and at least one episode of hypoglycemia (16.95%),” the investigators stated. Compared with patients without hypoglycemia, patients with single or multiple episodes of hypoglycemia had a graded increase in risk, with fully adjusted hazard ratios of 1.26, 1.80, and 1.94 for one, two, and three or more episodes, respectively.

Certain Parkinson’s disease drugs have pathologic syndrome–inducing effects that can be mistaken for primary psychotic disease, according to a report in the April Mayo Clinic Proceedings. Researchers retrospectively reviewed the medical records of 267 patients with Parkinson’s disease. The main outcome measure was compulsive gambling or hypersexuality developing after parkinsonism onset, including the temporal relationship to Parkinson’s disease drug use. Sixty-six patients (10.6%) were taking a dopamine agonist; of these, seven (2.6%) met the main outcome measure. All seven patients were also among a group of 38 patients taking therapeutic doses > 2 mg pramipexole or 6 mg ropinirole daily). “Behaviors were clearly pathologic and disabling in five: 7.6% of all patients taking an agonist and 13.2% of those taking therapeutic doses,” the investigators noted.

Children with prenatal methamphetamine exposure have altered white matter maturation, researchers reported in the April 15 online Neurology. Twenty-nine methamphetamine-exposed children and 37 unexposed children (ages 3 to 4) underwent 12-direction diffusion tensor imaging on a 3-Tesla MRI scanner. Children with prenatal methamphetamine exposure had lower apparent diffusion coefficient in the frontal (right, -2.1%; left, -2.0%) and parietal white matter (right, -3.9%; left, -3.3%). In addition, methamphetamine-exposed children showed a trend for higher fractional anisotropy in left frontal white matter (+ 4.9%). “Since less myelination and higher dendritic or spine density have been reported in animals exposed to methamphetamine, lower diffusion in our children may reflect more compact axons or greater dendritic or spine density associated with prenatal methamphetamine exposure,” investigators commented.

Use of transcranial Doppler (TCD) ultrasonography screening to help prevent stroke in children with sickle cell disease increased sixfold, according to a study in the April 14Neurology. Prior to 1998, the average annual rate of TCD screening in 157 children with sickle cell disease was 1.8 per 100 person-years. From 1998 through 1999, that rate increased to 5.0. From 2000 through 2005, the rate increased to 11.4. Physical proximity to the vascular laboratory was the only independent predictor of screening. “The annualized stroke rate pre-TCD was 0.44 per 100 person-years, compared to 0.19 post TCD,” investigators stated. “Increased availability of TCD screening could improve the utilization of this effective primary stroke prevention strategy.”

Stable isotope labeling of CNS proteins can be used to assess the effects of potential disease-modifying treatments for Alzheimer’s disease and other CNS disorders, as reported in the March 18 online Annals of Neurology. The study was conducted in healthy men, ages 21 to 50. The γ-secretase inhibitor “LY450139 significantly decreased the production of CNS β-amyloid in a dose-dependent fashion, with inhibition of β-amyloid generation of 47%, 52%, and 84% over a 12-hour period with doses of 100, 140, and 280 mg, respectively,” researchers stated. No difference in β-amyloid clearance was observed. “Results from this approach can assist in making decisions about drug dosing and frequency in the design of larger and longer clinical trials for diseases such as Alzheimer’s disease, and may accelerate effective drug validation,” the researchers concluded.

Use of platelet aggregation inhibitors is associated with the presence of cerebral microbleeds, according to findings in the April 13 online Archives of Neurology. In the Rotterdam Scan Study, researchers used MRI to assess the location of possible microbleeds in 1,062 persons ages 60 and older who were free of dementia. “Compared with nonusers of antithrombotic drugs, cerebral microbleeds were more prevalent among users of platelet aggregation inhibitors (adjusted odds ratio [OR], 1.71),” investigators commented. Aspirin users had a higher prevalence of strictly lobular microbleeds (adjusted OR compared with nonusers, 2.70) than those using carbasalate calcium (adjusted OR, 1.16). “This difference was even more pronounced when comparing persons who had used similar dosages of both drugs,” the researchers stated.”

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α could become a novel therapeutic target for patients with Alzheimer’s disease, researchers reported in the March Archives of Neurology. “Using genome-wide complementary DNA microarray analysis, we found that PGC-1α messenger RNA expression was significantly decreased as a function of progression of clinical dementia in the Alzheimer’s disease brain,” the investigators stated. “Most importantly, we found that the reconstitution of exogenous PGC-1α expression in Tg2576 neurons attenuated the hyperglycemic-mediated β-amyloidogenesis through mechanisms involving the promotion of the ‘nonamyloidogenic' α-secretase processing of amyloid precursor protein through the attenuation of the forkheadlike transcription factor 1 (FoxO3a) expression.”

Investigators have identified a common brain-derived neurotrophic factor (BDNF) polymorphism that is a genetic modifier of Rett syndrome severity, according to a report in the April 7 Neurology. The researchers evaluated the association between disease severity and BDNF polymorphism in 125 mutation-positive patients with Rett syndrome from the Australian Rett Syndrome Database and an Israeli cohort. “Those who were heterozygous (Val/Met) had significantly more severe disease than those who were homozygous for the wild-type (Val/Val) BDNF polymorphism (increased severity score, 2.1),” the study authors stated. “In those with p.R168X, a commonly occurring MECP2 mutation in Rett syndrome, there was a six-point increase in severity score for those who were heterozygous for the BDNF polymorphism, both unadjusted and adjusted for age.”

The apolipoprotein E (APOE) ε 4 allele, a risk factor for early- and late-onset Alzheimer’s disease and age-related cognitive impairment, modulates brain function long before any clinical or neurophysiologic expression of neurodegenerative processes is observed, according to findings in the April 8 online edition of Proceedings of the National Academy of Sciences. Investigators assessed structural and functional effects of the APOE polymorphism in 18 healthy APOE ε 4 carriers and 18 matched controls (ages 20 to 35). Blood oxygen level–dependent fMRI was used to study the brain at rest and during an encoding memory paradigm. “Resting fMRI revealed increased ‘default mode network’ … coactivation in ε 4 carriers relative to noncarriers,” researchers stated. “The encoding task produced greater hippocampal activation in ε 4 carriers relative to noncarriers.”

A genetic locus on chromosome 12p14 is associated with an increased risk for stroke, according to data published in the April 15 New England Journal of Medicine. Investigators analyzed genomewide association data from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, which included 19,602 white persons (mean age, 63) in whom 1,544 incident strokes (1,164 of which were ischemic strokes) occurred during an average of 11 years. Markers most strongly associated with stroke were tested in a replication cohort of 2,430 black persons with 215 incident strokes (191 ischemic strokes), 574 black persons with 85 incident strokes (68 ischemic strokes), 652 Dutch persons with ischemic stroke, and 3,613 unaffected participants. “Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke,” the investigators stated.

Statins have no preventative effect for Alzheimer’s disease or dementia when given to at-risk individuals in late life, per results reported in the April 15 Cochrane Database of Systematic Reviews. In the Heart Protection Study (patients 70 and older), no difference in incidence of dementia (31 cases in the simvastatin group and 31 cases in the placebo group) nor on the modified Telephone Interview for Cognitive Status at final follow-up (23.7% in the simvastatin group were cognitively impaired vs 24.2% in the placebo group) was shown. There was no difference between groups in cognition in relation to age at study entry or history of cerebrovascular disease. In the Prospective Study of Pravastatin in the Elderly at Risk (patients aged 70 to 82), cognitive function declined at the same rate in both treatment cohorts.

—Laura Sassano

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