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Objective: Prospective memory (PM) is a cognitive function defined as the ability to perform an intention at an appropriate moment in the future. In the aging population, PM is essential for maintaining independent daily living. Introduced as a simple and quick way to assess PM in clinical settings, the envelope task has to date received very limited empirical and practical interest., Methods: The present study investigated the task's clinical utility in detecting PM impairment in a sample composed of 49 healthy older adults (OA), 41 patients with Alzheimer's disease, and 64 individuals with amnestic and nonamnestic mild cognitive impairment (MCI) of heterogeneous etiology: 17 of idiopathic nature, 20 presenting an idiopathic rapid-eye movement sleep behaviour disorder, and 27 patients diagnosed with idiopathic Parkinson's disease., Results: The envelope task was highly sensitive and specific in discriminating Alzheimer's disease patients from OA. Although it was specific in distinguishing MCI individuals from OA, its sensitivity was modest, especially in patients presenting a nonamnestic MCI subtype., Conclusions: Given its high specificity and simple low-cost administration procedure, the envelope task is a promising instrument for clinicians who seek to rapidly assess PM impairment in their daily practice.

Summary: Aside from motor symptoms, Parkinson's disease is associated with a number of non-motor symptoms arising many years before motor signs. The most prevalent and predictive premotor symptoms include olfactory dysfunction, REM sleep behaviour disorder (RBD) and constipation. Several studies in toxin- or gene-based models have specifically investigated these non-motor signs in a premotor context. Altered olfactory discrimination has been reproduced both in toxin- and in gene-based models, and genetic models may also reproduce the underlying pathophysiological mechanisms. Sleep alterations have also been demonstrated, mostly in toxin-based models, and RBD-like features can be demonstrated in non-human primates. Gastrointestinal dysfunction and associated enteric pathology are reproduced both in toxin and genetic models displaying reduced colonic motility and enteric α-synuclein accumulation. This review describes the main premotor symptoms that are recapitulated both in toxin- and in gene-based models, their relevance to the human disease, and their potential to understand the underlying mechanisms of early symptoms and disease progression. [Copyright &y& Elsevier]

Summary: Imaging allows a window into the pathology of PD during life, and potentially even prior to the appearance of motor manifestations. Functional imaging using dopaminergic tracers with either PET or SPECT can identify dopamine deficiency but may not reliably differentiate between PD and other akinetic-rigid disorders. On the other hand, dopaminergic tracer imaging can identify pre-motor changes in subjects at high risk of developing PD and may be useful as a biomarker to assess disease progression, with caveats. Glucose or cerebral blood flow imaging can provide complementary information on patterns of cerebral activation and thereby be useful for diagnosis and for the assessment of compensatory strategies. Although traditionally considered to be of limited utility for the study of PD and related disorders, novel magnetic resonance imaging techniques are showing increasing promise for diagnosis and potentially as biomarkers. These applications will be reviewed here, as will the potential use of imaging to assess Braak''s hypothesis of caudal to rostral degeneration in vivo. [Copyright &y& Elsevier]

Abstract: Sleep is a coordinated process involving more or less simultaneous changes in sensory, motor, autonomic, hormonal, and cerebral processes. On the other hand, none of the changes occurring with sleep are invariably coupled to sleep. EEG synchrony, heat loss, sleep-related hormone secretion, and even REM-related motoneuron paralysis may occur independent of the parent state. In REM sleep behaviour disorder (RBD) the muscle tone of wakefulness intrudes into REM sleep, allowing the release of dream-enacting behaviours. Status dissociatus (SD) is a condition in which brain and mind are in disarray along the boundaries of sleep and wakefulness. The existence of such dissociated behaviours shows that they have separate neuronal control systems and indicates that the whole organization of sleep is an emergent property of the collective neuronal systems to synchronize. Insults to the brain can drastically alter the circuitries responsible for maintaining the integrity of wakefulness, NREM sleep, and REM sleep. As a consequence, the basic states of existence can become admixed and interchanged with striking disturbances of consciousness, brain electrophysiology, and the behavioural and polygraphic expression of sleep and wakefulness. The evolution of RBD into SD may result from a disarray of (brainstem) structures that orchestrate the whole brain wake–sleep conditions, but with preserved discrete systems and dissociable strategies to still place navigation in wake and sleep. Advances in the fields of genetics, neuroimaging, and behavioural neurology will expand the understanding of the mechanisms underlying the organization of the states of being along with their somatic/behavioural manifestations. [Copyright &y& Elsevier]

Abstract: Agrypnia excitata (AE) is a syndrome characterized by the inability to sleep associated with a generalized motor and autonomic over-activation. AE is caused by a thalamo-limbic system dysfunction and comprises three different conditions: Fatal Familial Insomnia (FFI), Delirium Tremens (DT), and Morvan Syndrome (MS). Oneiric Stupor episodes (OS) are the peculiar motor behaviour of AE. During OS patients perform simple automatic gestures mimicking daily-life activities. This paper is the first description of the different characteristics of OS in two patients with MS and another with FFI, emphasizing the specific clinical features that reliably differentiate OS from REM sleep behaviour disorders. [Copyright &y& Elsevier]

Summary: Positron emission tomography has been widely exploited to study the progression of Parkinson''s disease (PD) and the associated motor impairment. It is however now increasingly appreciated that much of the disability of PD arises from non-motor complications, including cognitive and behavioural problems, sleep disturbances, pain and autonomic dysfunction. Recent studies in which these problems were investigated are reviewed in this paper. Although interesting findings are emerging, much work remains to be done. This will depend upon the ability to investigate non dopaminergic mechanisms as well as extra-striatal release of dopamine and the capacity to assess the impact of behaviourally relevant stimuli on neurotransmitter release and on networks of brain activation. Functional imaging studies, including PET, SPECT and functional MRI may provide valuable insights into the pathophysiology of disorders such as Parkinson''s disease (PD), where structural changes are limited. Until recently, the major focus of such studies has been either on patterns of cerebral blood flow or glucose metabolism at rest or following a variety of activation paradigms, or on studies of the dopamine (DA) system. This article will review non-motor aspects of PD. While there is an enormous volume of imaging literature on the motor aspects of PD or motoric complications, that will not be addressed here. [Copyright &y& Elsevier]

Abstract: Functional imaging can be used to detect preclinical evidence of dopamine deficiency in people deemed to be at increased risk of Parkinson''s disease (PD) based on genetic or environmental risk, or because they have clinical features such as REM sleep behaviour disorder that may be a harbinger of PD. Positron emission tomography (PET) using [11C]dihydrotetrabenazine to label the vesicular monoamine transporter type 2 (VMAT2), a variety of 11C- or 18 F-labeled ligands for the membrane dopamine transporter (DAT), or 6-[18F]fluoro-L-dopa (FD), which assesses uptake and decarboxylation of levodopa as well as vesicular storage of radiolabeled dopamine, can all be used, and all provide comparable, but somewhat different information. DAT binding using either PET or SPECT appears to be the most sensitive marker of dopamine denervation, while FD uptake is subject to compensatory upregulation and its reduction may more closely herald the onset of clinical disease. Alterations in glucose metabolism and in dopamine release also occur in the asymptomatic hemisphere of subjects with unilateral PD. An interesting potential application of PET is the determination of non-dopaminergic abnormalities that correlate with the presence of clinically apparent pre-motor symptoms of PD. [Copyright &y& Elsevier]