Reviews & Analysis

Poststroke dementia is a clinically heterogeneous syndrome with various underlying mechanisms. A better understanding of the pathophysiology of poststroke dementia together with an improved ability to differentiate between various dementia syndromes will be useful for optimizing therapeutic interventions, and for informing patients and carers about treatment options and prognosis.

Primary progressive aphasia (PPA)—a condition characterized by deteriorating language—is a frequent manifestation of neurodegenerative conditions such as frontotemporal lobar degeneration. Evidence exists to link the different PPA variants with specific underlying pathologies and, as Murray Grossman discusses in this article, knowledge of such clinicopathological correlations could aid accurate diagnosis of neurodegenerative disease during a patient's life.

The three secretases that process amyloid precursor protein are central to the generation of amyloid-β, and the accumulation of this peptide in extracellular plaques is one of the hallmarks of Alzheimer disease. In this Review, De Strooper et al. discuss the evidence that suggests that these enzymes are potential therapeutic targets for Alzheimer disease drug treatments.

MRI-based structural imaging has become an integral component of the clinical assessment of patients with suspected Alzheimer disease (AD), and atrophy of medial temporal structures is now considered to be a valid diagnostic marker at the mild cognitive impairment stage. In this article, Frisoni et al. consider the roles of structural MRI markers in the diagnosis of AD and non-AD dementias, and in the tracking of disease progression during clinical trials.

The underlying pathology in Alzheimer disease is thought to precede the onset of cognitive symptoms by many years, and efforts are underway to identify early diagnostic markers and develop disease-modifying treatments for this condition. Nordberg et al. examine how PET imaging is being used to further our understanding of the pathophysiology of Alzheimer disease, and consider future applications of this technique in the clinical setting.

Amyloid-β (Aβ) has become an important therapeutic target in Alzheimer disease, and active and passive Aβ immunotherapies have been shown to reduce cerebral Aβ levels and improve cognition in animal models of this condition. Lemere and Masliah review these preclinical studies and provide an update on the current status of clinical trials of Aβ immunotherapies. They also outline the factors that must be considered in the future development of such treatments.

Severe spinal cord injury (SCI) leads to dysfunction of the spinal neuronal circuits that underlie locomotion and associated reflexes. In this article, Volker Dietz discusses the time course of changes in the spinal circuitry after SCI, and considers how an understanding of these changes might guide the development of countermeasures to prevent neuronal dysfunction in the chronic stage of SCI.

Gene therapies have entered clinical trials for several neurological disorders, most notably Parkinson disease. A study in a nonhuman primate model of Parkinson disease has reported motor deficit improvements following the use of a lentiviral vector to restore extracellular dopamine levels. A clinical trial is now underway to evaluate the effectiveness of this approach in humans.

Ultrasound-based technologies are emerging as promising noninvasive approaches to treat brain disorders. Researchers in Switzerland have shown that chronic pain can be alleviated through thermal ablation of thalamic tissue by high-intensity focused ultrasound.

Genome-wide association studies (GWAS) have uncovered over two dozen candidate Alzheimer disease susceptibility genes; however, the results of these studies showed limited overlap. Two independently performed GWAS involving cohorts from Europe and the US have now identified three additional putative Alzheimer disease genes that show modest but remarkably consistent effects across data sets.

Clinical trials comparing surgical and endovascular interventions for carotid artery stenosis have produced inconclusive and conflicting results. Companion studies now provide data on the long-term efficacy and durability of these therapies for treating carotid artery stenosis. What do these findings tell us about the relative merits of the two techniques?

Prion diseases are fatal and untreatable neurodegenerative brain diseases that can mimic other brain illnesses. Therapies for these conditions are most likely to work in the early stages of the disease, but no simple, early diagnostic tests are currently available. New findings, however, indicate that brain MRI could aid diagnosis.

Practicing clinicians can experience difficulty in differentiating between Parkinson disease and idiopathic normal pressure hydrocephalus. In this article, Morishita and colleagues consider the clinical features that might differentiate Parkinson disease from idiopathic normal pressure hydrocephalus, and highlight the usefulness of the levodopa challenge test in distinguishing between these two conditions.

Movement disorders are frequently encountered in the clinic, but establishing the correct diagnosis can be problematic, especially if the clinical presentation is complex. In this article, Adbo et al. provide a practical guide to pattern recognition in movement disorders and discuss how a clinically classified syndrome might be translated into an etiological diagnosis.

Traditionally, researchers have studied brain function in terms of physiological responses to environmental demands, yet much of the brain's energy is actually devoted to intrinsic neuronal signaling, or 'dark energy'. Zhang and Raichle describe the imaging strategies that are being used to explore intrinsic neuronal activity and examine the relationship between alterations in the functional architecture of intrinsic activity and neurological disease.