Volume 10 Issue 11, November 2014

Epidemiological evidence strongly suggests that circulatory levels of 25-hydroxyvitamin D below 50 nmol/l are associated with cognitive impairment and the development of dementia. A number of biochemical mechanisms could explain these effects; however, interventional studies to date have revealed disappointingly little.

The risks of seizures and antiepileptic drug (AED) teratogenicity must be balanced when treating pregnant women with epilepsy. Two recent articles address these risks for newer AEDs. Lamotrigine and levetiracetam carried low risks of malformations, and topiramate exhibited a dose-dependent risk. Levetiracetam controlled seizures more effectively than lamotrigine and topiramate.

A pandemic influenza vaccine with a specific type of vaccine antigen has been linked to an increased incidence of narcolepsy in children from 2009–2010. However, the recent retraction of an article that reported a putative autoantigen means that the search for the mechanisms behind the vaccine–narcolepsy connection continues.

Finding a peripheral biomarker for early Alzheimer disease (AD) is a major challenge. A recent study has validated a plasma protein signature that is associated with mild cognitive impairment and AD, and could predict conversion; however, longitudinal cohort studies of presymptomatic individuals are needed to confirm the findings.

Functional and structural connectivity measures, assessed by means of functional and diffusion MRI, are emerging as potential intermediate biomarkers for Alzheimer disease and other neurodegenerative disorders. In this article, Pievani et al. evaluate the evidence that connectivity biomarkers are associated downstream with clinical phenotypes and topographic brain imaging markers of neurodegeneration, and upstream with molecular determinants of neurodegeneration and susceptibility genes.

The fifth edition of the American Psyciatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) was published in 2013, and with it came new diagnostic criteria for mild cognitive impairment and dementia. In this Review, members of the working group tasked with writing the DSM-5 criteria for neurocognitive disorders present the new approach to categorization and diagnosis. Three key syndromes are recognized—delirium, mild neurocognitive disorder and major neurocognitive disorder—and each can have distinct aetiological subtypes.

Activation of the immune system during pregnancy can have varied effects on fetal development, and converging evidence highlights maternal immune activation as a risk factor for multiple neurological conditions. In this Review, Knuesel and colleagues discuss the involvement of maternal immune activation in schizophrenia, austim spectrum disorders, epilepsy and other disorders. The authors then discuss how preclinical data indicate a possible link between prenatal exposure to infection and susceptibility to neurodegenerative disease, and they go on to identify fertile ground for further translational research.

Amyotrophic lateral sclerosis (ALS) is a genotypically and phenotypically heterogeneous disease, as reflected in the variability in age and site of onset, extent of extramotor involvement, and survival. Cognitive involvement is also common, and corroborates the connection between ALS and frontotemporal lobar degeneration. In this article, Robberecht and Swinnen review phenotypic heterogeneity in ALS and discuss some of its implications for understanding ALS pathogenesis and development of therapeutic interventions.