Volume 6 Issue 2, February 2010

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.

Stroke is a frequent cause of neurological morbidity and death in children. Standardized treatment guidelines for childhood stroke can improve patient outcomes when such protocols are implemented early after symptom onset. Medical professionals, however, seem to have a limited awareness of childhood stroke that perpetuates the delay to diagnosis and, hence, intervention.

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.

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.

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.

With the growth of the aged population, the socioeconomic costs of dementia are set to rise sharply. No. disease-modifying drugs currently exist for the main cause of dementia, namely Alzheimer disease. The successful development of such drugs, and disease-modifying therapies for other causes of dementia, will require the ability to make an early diagnosis of the disease and a means to monitor the progression of pathology in vivo, in addition to novel agents. In this Focus issue, leading experts examine pharmacological strategies that are being explored to combat Alzheimer disease and biomarkers that are being developed for this disorder and other causes of dementia.