Inflammation and depression: Is there a causal connection with dementia?

Epidemiological studies show that there is a correlation between chronic depression and the likelihood of dementia in later life. There is evidence that inflammatory changes in the brain are pathological features of both depression and dementia. This suggests that an increase in inflammation-induced apoptosis, together with a reduction in the synthesis of neurotrophic factors caused by a rise in brain glucocorticoids, may play a role in the pathology of these disorders. A reduction in the neuroprotective components of the kynurenine pathway, such as kynurenic acid, and an increase in the neurodegenerative components, 3- hydroxykynurenine and quinolinic acid, contribute to the pathological changes. Such changes are postulated to cause neuronal damage and thereby predispose chronically depressed patients to dementia.     

Are dementia and depression in Parkinson's disease related?

INTRODUCTION: Depression and dementia are common problems in PD. As the depression and dementia of PD share many symptoms such as apathy, anhedonia, anergia, and agitation, it is reasonable to ask if they are related. METHODS: 106 consecutive PD patients, unselected for depression or dementia were evaluated for depression using the Hamilton Depression Scale (Ham-D21). They were also evaluated using a modified neuropsychiatric inventory (NPI). Following the above, 100 consecutive PD patients were evaluated for dementia using Folstein's Mini Mental Status Examination (MMSE). They were also evaluated using the modified NPI. RESULTS: 29 of the first series of patients, 27%, were depressed, score of > or =14 on the Ham-D21. 8 of the second series of consecutive patients, 18%, were demented, score < or =24 on the MMSE. Depressed and demented patients were significantly more likely to suffer from apathy, anhedonia, mood lability, daytime drowsiness, paranoia, and hallucinations. Demented patients were significantly older, had PD longer, were more disabled and more likely to be depressed. COMMENT: The commonality of certain symptoms in demented and depressed patients suggests that dementia and depression in PD may be related and that, in PD depression may be a fore-runner of dementia. Five year follow-up of these patients supports this suggestion.     

Cluster headache and the hypothalamus: causal relationship or epiphenomenon?

Typical clinical features of cluster headache (CH) include circadian/circannual rhythmicity and ipisilateral cranial autonomic features. This presentation has led to the assumption that the hypothalamus plays a pivotal role in this primary headache disorder. Several studies using neuroimaging techniques or measuring hormone levels supported the hypothesis of a hypothalamic involvement in the underlying pathophysiology of CH. Animal studies added further evidence to this hypothesis. Based on previous data, even invasive treatment methods, such as hypothalamic deep brain stimulation, are used for therapy. However, the principal question of whether these alterations are pathognomonic for CH or whether they might be detected in trigeminal pain disorders in general, in terms of an epiphenomenon, is still unsolved. This article summarizes studies on hypothalamic involvement in CH pathophysiology, demonstrates the involvement of the hypothalamus in other diseases and tries to illuminate the role of the hypothalamus based on this synopsis.     

Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent?

The first studies carried out on the mechanisms by which peripheral immune stimuli signal the brain to induce fever, activation of the hypothalamic-pituitary-adrenal axis and sickness behavior emphasized the importance of fenestrated parts of the blood-brain barrier known as circumventricular organs for allowing blood-borne proinflammatory cytokines to act on brain functions. The discovery in the mid-1990s that subdiaphragmatic section of the vagus nerves attenuates the brain effects of systemic cytokines, together with the demonstration of an inducible brain cytokine compartment shifted the attention from circumventricular organs to neural pathways in the transmission of the immune message to the brain. Since then, neuroanatomical studies have confirmed the existence of a fast route of communication from the immune system to the brain via the vagus nerves. This neural pathway is complemented by a humoral pathway that involves cytokines produced at the level of the circumventricular organs and the choroid plexus and at the origin of a second wave of cytokines produced in the brain parenchyma. Depending on their source, these locally produced cytokines can either activate neurons that project to specific brain areas or diffuse by volume transmission into the brain parenchyma to reach their targets. Activation of neurons by cytokines can be direct or indirect, via prostaglandins. The way the neural pathway of transmission interacts with the humoral pathway remains to be elucidated.     

Ischemic stroke and migraine in childhood: coincidence or causal relation?

Although migraine is an accepted cause of cerebral infarction in adults, this association is less well recognized in children. We present two children with migraine and cerebral infarction, which we regard as migrainous stroke, though neither patient fulfills all criteria of the International Headache Society for the diagnosis of migrainous infarction. Review of the literature concerning examples of migraine-associated stroke in childhood suggests that these criteria are too restrictive to comprise the majority of migrainous strokes, especially in this age group.     

The singer or the singing: who sings individually to persons with dementia and what are the effects?

'Live' singing to persons with dementia (PWDs) may be an underused but highly accessible resource for their caregivers, regardless of qualifications. A systematic literature review sought to illuminate who sings to PWDs, and with what objectives and effects, to address the question of whether it is the singer or the singing which is effective. The literature revealed that music therapists seek to address cognitive, behavioral, physiological, and social factors through one-to-one singing, whereas other caregivers are more broadly concerned with quality of life, often through facilitating activities of daily living. All included studies concurred that individual singing to PWDs can be effective in a variety of ways, depending on contexts and goals. PWD's perceptions of situations may influence the effectiveness of singing interventions. Music therapists are urged to empower professional caregivers to sing sensitively to PWDs during caregiving activities.     

Changes in neurogenesis in dementia and Alzheimer mouse models: are they functionally relevant?

Alzheimer’s disease and related dementias are devastating disorders that lead to the progressive decline of cognitive functions. Characteristic features are severe brain atrophy, paralleled by accumulation of beta amyloid and neurofibrillary tangles. With the discovery of neurogenesis in the adult brain, the hopes have risen that these neurodegenerative conditions could be overcome, or at least ameliorated, by the generation of new neurons. The location of the adult neurogenic zones in the hippocampus and the lateral ventricle wall, close to corpus callosum and neocortex, indicates strategic positions for potential repair processes. However, we also need to consider that the generation of new neurons is possibly involved in cognitive functions and could, therefore, be influenced by disease pathology. Moreover, aberrant neurogenic mechanisms could even be a part of the pathological events of neurodegenerative diseases. It is the scope of this review to summarize and analyze the recent data from neurogenesis research with respect to Alzheimer’s disease and its animal models.     

Cannabinoids and the immune system: potential for the treatment of inflammatory diseases?

Since the discovery of the cannabinoid receptors and their endogenous ligands, significant advances have been made in studying the physiological function of the endocannabinoid system. The presence of cannabinoid receptors on cells of the immune system and anecdotal and historical evidence suggesting that cannabis use has potent immuno-modulatory effects, has led to research directed at understanding the function and role of these receptors within the context of immunological cellular function. Studies from chronic cannabis smokers have provided much of the evidence for immunomodulatory effects of cannabis in humans, and animal and in vitro studies of immune cells such as T cells and macrophages have also provided important evidence. Cannabinoids can modulate both the function and secretion of cytokines from immune cells. Therefore, cannabinoids may be considered for treatment of inflammatory disease. This review article will highlight recent research on cannabinoids and how they interact with the immune system and also their potential use as therapeutic agents for a number of inflammatory disorders.     

Frontotemporal dementia and semantic dementia: anatomic variations on the same disease or distinctive entities?

Research into the non-Alzheimer dementias has exploded over the last 2 decades, and frontotemporal lobar degeneration has emerged as the most common cause of dementia in patients below the age of 65. In 1998, an international consortium of investigators focusing on this disease entity met and agreed upon the classification of 3 subtypes of frontotemporal lobar degeneration, using regional atrophy to distinguish them. These are: a frontally predominant form called frontotemporal dementia, a temporally predominant form called semantic dementia, and a left-frontally predominant syndrome, called progressive nonfluent aphasia. With the rise of genetic and neuropathologic findings, however, the usefulness of this subtype classification has been called into question. This paper discusses the major pertinent findings, and the implications of classifying the disease on the basis of atrophy versus genetic or molecular mechanisms.     

Movement disorders in multiple sclerosis: Causal or coincidental association?

Despite the relatively frequent involvement of the basal ganglia and subthalamic nucleus by multiple sclerosis (MS) plaques, movement disorders (MD), other than tremor secondary to cerebellar or brainstem lesions, are uncommon clinical manifestations of MS. MD were present in 12 of 733 patients with MS (1.6%): three patients had parkinsonism, two blepharospasm, five hemifacial spasm, one hemidystonia, and one tourettism. MD in patients with MS are often secondary to demyelinating disease. Also in cases without response to steroid treatment and demyelinating lesions in critical regions, it is not possible to exclude that MD and MS are causally related.     

Naming problems in dementia: Semantic or lexical?

Abstract

The naming behaviour was explored of patients moderately deteriorated with probable Alzheimer's disease (pAD) by analysing responses made on a picture naming and two word-picture matching tasks for the same items. Naming responses were classified into target and non-target and the relationship between non-target responses and their targets were explored. It was found that semantic relatedness influenced these non-target responses but frequency and imageability did not. The pAD participants performed significantly better on the two word-picture matching tasks than the naming task, while there was no difference on these within- and between-category tasks. These findings are explored with reference to a two-stage model of lexical access, which has separate storage of semantic, lexical and phonological information. The participants' difficulties appear to lie largely in retrieving the labels for items they comprehend.     

Methylphenidate effects in the young brain: friend or foe?

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatry disorders in children and adolescents, and methylphenidate (MPH) is a first-line stimulant drug available worldwide for its treatment. Despite the proven therapeutic efficacy, concerns have been raised regarding the possible consequences of chronic MPH exposure during childhood and adolescence. Disturbances in the neurodevelopment at these crucial stages are major concerns given the unknown future life consequences.This review is focused on the long-term adverse effects of MPH to the brain biochemistry. Reports conducted with young and/or adolescent animals and studies with humans are reviewed in the context of long-term consequences after early life-exposure. MPH pharmacokinetics is also reviewed as there are differences among laboratory animals and humans that may be relevant to extrapolate the findings.Studies reveal that exposure to MPH in laboratory animals during young and/or adolescent ages can impact the brain, but the outcomes are dependent on MPH dose, treatment period, and animal’s age. Importantly, the female sex is largely overlooked in both animal and human studies. Unfortunately, human reports that evaluate adults following adolescent or child exposure to MPH are very scarce. In general, human data indicates that MPH is generally safe, although it can promote several brain changes in early ages. Even so, there is a lack of long course patient evaluation to clearly establish whether MPH-induced changes are friendly or foe to the brain and more human studies are needed to assess the adult brain changes that arise from early MPH treatment.