Fatty aspirin: a new perspective in the prevention of dementia of Alzheimer's type?

Alzheimer's disease (AD) leads to a dramatic decline in cognitive abilities and memory. A more modest disruption of memory often occurs in normal aging and the same circuits that are devastated through degeneration in AD are vulnerable to sub-lethal age-related changes that alter synaptic transmission. There are numerous indications that aberrant plasticity is critically involved in Alzheimer's. Is ageing itself the major risk factor for AD? Is AD an acceleration of normal ageing? We assume that the ability of the brain is to modify its own structural organization and functioning which is liable to become impaired in ageing until it becomes dramatically impaired in Alzheimer's. Moreover, ageing can compromise the conversion of dietary alpha-linolenic acid (ALA) to docosahexaenoic acid (DHA). DHA regulates synaptogenesis and affects the synaptic structure, and synapse density is reduced in ageing. DHA and newly identified DHA-derived messenger, neuroprotecting D1 (NPD1), protect synapses and decrease the number of activated microglia in the hippocampal system. Delaying AD onset by a few years would reduce the number of the cases of dementia in the community. DHA (and NPD1?) and aspirin induce brain-derived neurotrophic factor (BDNF) protein expression and this protein has a crucial role in neuronal survival. The authors--in view of the increased neuroinflammatory reaction frequently observed during normal brain ageing--suggest the long-term use of "fatty aspirin", an association of DHA and/or NPD1 and aspirin (or nitroaspirin), to postpone, or prevent, the structural neurodegeneration of the brain.     

Primary prevention of dementia: from modifiable risk factors to a public brain health agenda?

Introduction

With large numbers of people affected, no treatment in sight and continuing demographic change, the prevention of dementia is becoming a central public health issue.

Methods

We conducted a systematic meta-review including systematic reviews and meta-analyses of longitudinal observational studies on modifiable risk and protective factors for dementia published over the last 5 years.

Results

Compelling evidence on a number of modifiable risk factors, mostly lifestyle factors, is available from longitudinal observational studies to inform primary preventive efforts.

Discussion

Evidence stemming from preventive RCTs is limited. However, multi-domain interventions addressing a variety of risk factors at once seem promising with regard to high-risk individuals (selective preventive approach). However, we argue that it is time to move forward and discuss a public brain health agenda as a universal preventive approach. Based on a risk reduction strategy, the public brain health agenda suggests the following ten key actions: (1) increase physical activity, (2) foster social integration, (3) improve education and foster lifelong learning, (4) provide mentally stimulating workplaces, (5) foster a cognitively active lifestyle, (6) propose a healthy Mediterranean-like diet, (7) reduce alcohol consumption, (8) stop smoking, (9) prevent, diagnose and treat chronic conditions, and (10) reduce anticholinergic medication in the elderly.

     

Is there a primary prevention of schizophrenic psychiasis?

At first, this article comprises the innovative programme of the international "Early Detection and Intervention" research and then shows results of the "Cologne/Bonn Early Recognition - CER" project on schizophrenia, the first longterm prospective study on patients in potentially initial prodromal stages prior to the first psychotic manifestation. At re-examination at an average of 9.6 years later, 79 of 160 patients had subsequently developed a schizophrenic psychosis according to DSM-IV criteria. Prediction values for the complete range of prodromal symptoms, for 5 subsyndromes and for individual symptoms were assessed. Best prediction values with a high positive predictive power (71 - 91 %) and a low rate of false-positive predictions (7.5 - 1.9 %) were achieved for 10 symptoms and symptom complexes mainly out of the group of thought, speech and perception disturbances. As only unsatisfactory prediction values for other prodromal symptom definitions were reported, e.g. the commonly used DSM-III-R definition, empirical evidence for the possibility of diagnosing schizophrenia as early as in the initial prodromal stage, has been found for the first time. In the following, this article considers essential initiatives for the development, performance and evaluation of a promising early intervention programme based on the results found. In Germany, within the project unit "Early Recognition and Intervention" of the competence network "Schizophrenia", such a programme has been initiated. Late prodromal stages are defined by attenuated or transient psychotic symptoms and early prodromal stages by the presence of at least one of the highly predictive prodromal symptoms from the CER-study or decline in psychic functions in combination with other risk factors. Intervention strategies are a multimodal psychological programme for the intervention in early prodromal stages and a combination of psychotherapy with atypical neuroleptic drugs in the late prodromal stages. If such strategies were able to suppress the progress to first psychotic episodes, this prevention could be classified as a primary prevention, not with regard to the prodromal symptoms but to frank/manifest schizophrenia.     

Is dementia a mental illness?

OBJECTIVE: To examine whether dementia is a mental illness. METHOD: An analysis of decisions in the Supreme Court of New South Wales that dementia per se was not a mental illness in terms of the 1958 Mental Health Act. A brief review of the extrusion of other diseases from psychiatry. RESULTS: Concepts in legislation are based on a dichotomy between mental infirmity and mental illness that has changed over time. This change is the result of shifting perceptions about the basis of illness and disease and the causation of mental symptoms. Mental health legislation is aimed as much at social control of feared behaviour as protecting the ill/incompetent. Guardianship legislation offers a more holistic response that better meets the patient's needs and could be extended to supplant mental health legislation. CONCLUSIONS: Dementia's departure from mental illness reflects psychiatry's continuing marginalization within medicine on an outdated mind/body or illness/disease split. This underlines one of the psychiatrist's roles as the vehicle to 'medically' explain abnormal behaviour. This model means that behaviour, once explained in terms of disease as opposed to illness, can be moved from the direct responsibility of psychiatry into other areas of medicine. Paradoxically, this suggests that the future of psychiatry will be in a completely different direction from its current biological focus.     

Is the immobility of advanced dementia a form of lorazepam-responsive catatonia?

Patients with end-stage dementia typically are very immobilized. Could this state actually be a form of lorazepam-responsive catatonia? Catatonia has been documented following cerebrovascular accidents, head injury, HIV encephalitis, brain tumors, and multiple sclerosis. Identified anatomical substrates include frontal lobes, parietal lobes, limbic system, diencephalon, and basal ganglia. Given that Alzheimer's disease, vascular dementia, Lewy body dementia, corticobasal degeneration, frontotemporal dementia, and Parkinsonian dementia often have degeneration in some of the same areas, dramatic awakenings might be possible by giving lorazepam challenges to locked-in dementia patients. If even a small percentage were lorazepam responders, the impact worldwide would be tremendous. Serious consideration should be given to undertaking large-scale clinical trials.     

Towards a Psychiatry of Peoples†

Abstract

This article examines the evolution of psychological and behavioral reactions following the September 2001 terrorist attacks in a nationally representative sample, and describes where people turned for support, information, and counseling. From November 9 to November 28, 2001, we resurveyed 395 (71%) of the original 560 adults 19 years or older within the United States who participated in our national random-digit-dialing telephone survey conducted on September 14 to September 16, 2001, about their terrorism-related psychological distress and behavior. Sixteen percent of adults had persistent distress, reporting one or more substantial distress symptoms in both September and November. Adults with persistent distress reported accomplishing less at work (65%); avoiding public gathering places (24%); and using alcohol, medications, or other drugs to relax, sleep, or feel better because of worries about terrorism (38%). Seventy-five percent talked with family and friends; however, 43% reported sometimes feeling unable to share their terrorism-related thoughts and feelings with others because it made others uncomfortable. Few reported receiving counseling or information about psychological distress from general medical providers (11%). These findings suggest that a significant number of adults across the country were continuing to experience terrorism-related distress and disruption of their daily lives approximately 2 months after September 11; many turned to family and friends for support, but at times many felt uncomfortable doing so, and few used clinicians as a source of information or support. Clinicians and policymakers should consider how the healthcare system and other community organizations might provide a coordinated community-wide response for individuals needing information and counseling following terrorist events.     

Semantic dementia and primary progressive aphasia: a problem of categorization?

The relationship between semantic dementia (SD) and primary progressive aphasia (PPA) has been the subject of debate ever since the syndromes were first described, in converging streams of research from the neuropsychological and neurologic communities. The most salient clinical features of SD are anomia with circumlocution and semantic paraphasia, single-word comprehension deficit, and reduced category fluency. Of critical importance is the fact that patients also show deficits on non-verbal tasks using visual, auditory, and other modalities, suggesting that the key impairment in SD is a breakdown in conceptual knowledge rather than a specific problem with language. The finding of item consistency between the various tests supports this view. The order in which the features appear can be explained by the variable degree of redundancy in access to semantic knowledge from the different perceptual modalities. Atrophy is seen in the anterior and inferior temporal lobe rather than in classic language areas, further distancing SD from aphasic syndromes. Semantic dementia and progressive non-fluent aphasia (PNFA) share some clinical and pathologic characteristics with frontal variant frontotemporal dementia, but there are also clear differences between the three syndromes. We believe that many patients described as having fluent primary progressive aphasia in fact have early SD. Semantic dementia is a well-defined syndrome, distinct from PNFA but related to it within the spectrum of frontotemporal lobar degeneration syndromes.     

Frontotemporal dementia: Pathology of gait?

The main diagnostic criteria of the behavioural variant of frontotemporal degeneration (bvFTD) include neurobehavioral and dysexecutive syndromes, but not specific gait characteristics although strong relationship between gait and prefrontal functions are increasingly recognized. Accordingly, we tested the hypothesis that patients with bvFTD would have more gait changes than older healthy controls and demented patients with Alzheimer's disease (AD). Sixty subjects were included in the study: 19 with bvFTD, 19 with AD and 22 healthy controls. Mean values and coefficients of variation (CV) of stride time while just walking (i.e., single tasking) and while walking with backward counting (i.e., dual tasking) were measured using the SMTEC®‐footswitch system. Stride time, mean value, and CV were significantly increased in both patient groups compared with healthy controls during single task or walking alone (P < 0.001) and during dual tasking (P < 0.001). After adjusting for age, Mini‐mental examination, psychoactive drugs, gender, and history of previous fall, only the patients with bvFTD group was associated with an increase of CV of stride time during single walking (P < 0.001) and dual tasking (P < 0.001). These data suggest that gait instability during single and dual tasking could represent a supportive argument for bvFTD. In clinical practice, such a diagnosis should be at least considered in any demented patient with gait instability. © 2010 Movement Disorder Society     

Treatment of dementia: anything new?

PURPOSE OF REVIEW: The aim of this article is to discuss new data on presently approved drugs for dementia, such as cholinesterase inhibitors and memantine, and concerns regarding the use of antipsychotics for treating neuropsychiatric symptoms, as well as to summarize some relevant studies recently published on emerging therapies with potential disease-modifying effects. RECENT FINDINGS: The main focuses of recent studies of cholinesterase inhibitors and memantine have been on efficacy and safety aspects in extended clinical trials, combined treatments or comparative analysis between agents, and also on potential neuroprotective effects and new indications. Other publications have assessed the evidence of efficacy and the increased risk of cerebrovascular events, rapid cognitive decline, and mortality with the use of antipsychotics in dementia, providing important information in relation to the controversy surrounding its use. Although more studies are warranted, a sizable literature on novel treatment options under investigation is currently available as a result of a better understanding of pathogenesis of dementia. SUMMARY: So far, there is no established method to predict better responders or long-term benefits with currently approved drugs for treatment of dementia. Recent systematic reviews and new research on current treatment, however, provide valuable information for clinicians, and novel drugs under investigation reveal promising new therapeutic strategies.