Subcortical dementia and the frontal lobe syndrome

Subcortical dementia is a clinical syndrome incorporating disorders of cognitive and affective sphere, which is caused by organic damage to subcortical structures. The syndrome is usually connected with Progressive Supranuclear Palsy, Huntington Disease, Parkinson's Disease. Subcortical dementia is mainly characterized by: slowing down of psychic functions and impairment of their precision, disorders in the ability to use achieved knowledge and personality changes. Most authors stress the fact that similar cognitive and emotional personality defects are observed in cases of frontal cortex damage. Recent research points to the existence of functional subcortical-prefrontal circuits which regulate human behaviour. There is a link between subcortical dementia and functional or structural break of one or more cortical-subcortical connections. Attention is also called to disorders in certain neurotransmitting systems (dopaminergic, acetylcholinergic) as well as to brain hypometabolism in basal ganglia, thalamus and prefrontal cortex.     

Ethics and research: ethical considerations in clinical research

Two subjects are discussed: the use of placebo controls in clinical trials and informed consent. Particularly in trials of drugs for disorders for which there exist effective treatments, the use of placebo is still controversial, although anyhow in violation of the Declaration of Helsinki. Informed consent aims at giving a subject all the necessary information to allow him to decide, with full knowledge, whether to accept a particular treatment or experimental protocol. Its importance would seem, albeit essential, to be rather illusory.     

Posatirelin in the treatment of vascular dementia: a double-blind multicentre study vs placebo

INTRODUCTION: The usefulness of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having modulatory activity on the monoaminergic and cholinergic systems and neurotrophic effects, was evaluated in vascular dementia. PATIENTS AND METHODS: A multicentre, parallel groups, double-blind clinical study vs placebo was carried out with patients suffering from probable vascular dementia according to the NINDS-AIREN criteria. The study consisted of a two-week run-in of a once daily, orally administered, placebo phase, followed by 12 weeks of intramuscular treatment with posatirelin 10 mg/ml or placebo given once a day and a follow-up after one month's withdrawal. Efficacy was assessed using the Gottfries-Br?ne-Steen (GBS) Rating Scale for dementia, the Randt Memory Test and the Toulouse-Piéron Attention Test. Data were evaluated using analysis of variance and covariance. RESULTS: As regards GBS scores, patients treated with posatirelin showed a significant improvement in intellectual performance, in orientation, motivation and memory as compared to controls. The improvement of memory performance was also confirmed by the acquisition score and memory index of the Randt Memory Test. At the end of the follow-up period the differences between treatments were still maintained. Tolerability was good. CONCLUSIONS: The significant improvement observed in cognitive functions, attention and motivation of demented patients treated with posatirelin suggests the potential usefulness of this drug in vascular dementia. Furthermore, the presence of a long-lasting effect after drug withdrawal suggests the possibility of administering the drug cyclically.     

Methodological considerations in treatment outcome research on obesity.

Identifies methodological problems in treatment research on obesity. The importance of multiple measurement of outcome, including appropriate assessment of weight, activity, and relevant physical, emotional, and social indices of adjustment, is emphasized. Traditional evaluation criteria need to be broadened to encompass factors such as cost effectiveness of treatment. The relative merits of alternative single-S and between-groups experimental designs are discussed, the latter including the treatment package, constructive, dismantling, and comparative research strategies. Ways of controlling for non-specific treatment influences are reviewed, and the contribution of client and therapist variables to outcome are mentioned. The reasons for conspicuous lack of long-term follow-ups are analyzed, and recommendations for reducing S attrition during treatment and follow-up are advanced. (80 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological aspects of vascular dementia

Vascular dementia (VaD) is the second most common cause of dementia in the elderly. Neuropsychologically, VaD has been characterized traditionally as having a "patchy" pattern of cognitive deficits. Newly developed diagnostic criteria for VaD suggest that this "patchy" pattern is associated with one type of VaD-multiple cortical infarctions, and that several additional subtypes of VaD exist, each featuring a characteristic pattern of neuropsychological deficits. Strategic infarct dementias have unique features that reflect the specific brain region affected. Lacunar state and Binswanger's disease produce subcortical dementia with disproportionate executive dysfunction. The profile of neuropsychological disturbances observed in VaD patients provides important insight into the localization and pathophysiology of the underlying cerebrovascular disease.     

Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia

OBJECTIVE: To compare the evolution of Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia by cognitive domain. SETTING: The University of Western Ontario Dementia Study, which is a registry of cases of dementia seen for secondary and tertiary assessment in a university memory disorders clinica with extensive follow-up data and histopathological confirmation of clinical diagnoses. PATIENTS: One hundred twenty-nine patients with definite or probable AD, 12 patients with definite or probable VaD, and 36 patients with definite or probable mixed dementia. METHODS: Patients were grouped as having an early, moderate, or advanced stage of disease according to the extended scale for dementia (ESD). The ESD was subdivided into cognitive domains, and the domain scores were compared for each stage of disease by diagnostic category with the use of a 2-way analysis of variance with repeated measures. RESULTS: As expected, the scores in all domains decreased significantly with increasing severity. There was a significant difference in the decline in memory among the diagnostic groups (P = .02) that was mostly attributable to the difference between AD and mixed dementia (P = .03), with the difference between AD and VaD only approaching significance (P = .06). There was a similar finding for praxis. The interaction between diagnosis (AD and VaD) and severity was significant only for memory (P = .02), showing a less severe memory deficit at onset but a proportionately more rapid progression in VaD and arithmetic ability (AD and mixed dementia [P = .03]). CONCLUSIONS: Alzheimer disease, VaD, and mixed dementia evolve similarly as assessed using cognitive domains obtained by subdivision of the ESD in a patient population derived from a memory clinic and by analyzing VaD as a single entity. Only memory impairment evolves differently between AD and VaD, with this depending on the severity. Memory is more severely impaired in the early stage of AD; however, with increasing severity of dementia, memory impairment in VaD accelerates and catches up with AD at the level of moderate impairment. The differences between AD and mixed dementia are greater than those between mixed dementia and VaD, suggesting an important role for the ischemic component of mixed dementia. Simple neuropsychological tools (eg, the ESD) may be incapable of distinguishing between AD and VaD, and more focused instruments may be required. Inherent bias in case selection may prevent extrapolation of these results to VaD in general, but the neuropsychological criteria for VaD may need to vary, depending on the severity.     

Nitric oxide and regulation of vascular tone: pharmacological and physiological considerations

The endothelial cells of the vascular system are responsible for many biological activities that maintain vascular homeostasis. Responding to a variety of chemical and physical stimuli, the endothelium elaborates a host of vasoactive agents. One of these agents, endothelium-derived relaxing factor, now accepted as nitric oxide, influences both cellular constituents of the blood and vascular smooth muscle. A principal intracellular target for nitric oxide is guanylate cyclase, which, when activated, increases the intracellular concentration of cyclic guanosine monophosphate, which in turn activates protein kinase G. Acting by this pathway, nitric oxide induces relaxation of vascular smooth muscle and inhibits platelet activation and aggregation. Derangements in endothelial production of nitric oxide are implicated as both cause and consequence of vascular diseases, including hypertension, atherosclerosis, and coronary artery disease.     

Empathy research: Some methodological considerations.

Calls for a systematic inquiry into the construct of empathy and suggests that improved definitional and methodological consideration in research will lead to more persuasive findings about the alleged relations between empathy and client outcomes. A category system is proposed for analyzing methodological deficiencies. The system is applied to 4 different measures of empathy and 3 studies having different findings but purportedly similar designs. Renewed attention to the construct of empathy is advocated. (93 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acetylcholine in human CSF: methodological considerations and levels in dementia of Alzheimer type

Four different methods to measure acetylcholine (ACh) and choline (Ch) concentration, i.e. thermospray/mass spectroscopy (TS/MS), high pressure liquid chromatography/mass spectroscopy (HPLC/MS), high pressure liquid chromatography/electrochemical detection (HPLC/ECD) and gas chromatography/mass spectroscopy (GC/MS), both latter methods coupled to a solid phase extraction system were compared for their applicability to human lumbar cerebrospinal fluid (CSF). Furthermore, samples from 15 control persons and 11 patients with dementia of Alzheimer-type (DAT) were compared to search for an ACh deficit in the CSF in DAT. GC/MS was the most sensitive, but most laborious method, and HPLC/ECD was acceptably sensitive, reliable and more specific. TS/MS was not specific enough for CSF extracts and HPLC/MS was more specific, but far less sensitive. Thus, only GC/MS and HPLC/ECD were qualified to detect ACh in human CSF extracts. Comparison of GC/MS and HPLC/ECD revealed highly correlated levels of ACh (r = 0.999). Using HPLC/ECD, ACh concentrations were greatly reduced in the DAT group (3.75 +/- 1.40 pmol/ml CSF) as compared to the controls (6.14 +/- 1.39 pmol/ml CSF), but the difference between controls and DAT patients was not statistically significant due to the number of samples below detection limit (8 out of 11 samples in DAT, 7 out of 15 in controls). Ch concentrations were not statistically significant between the two groups. The data show that methodological limitations preclude a widespread clinical application of determining ACh in the human CSF. Despite of reductions of ACh in the CSF in DAT, the determination of Ach in the CSF is not suitable for diagnostic purposes.     

Stroke, disability, and dementia: results of a population survey

The arcuate nucleus of the hypothalamus, a highly sexually dimorphic brain region, has been called the bed nucleus for endogenous opioids. The potential contribution of opioids in this nucleus to modulate control of ventilation in male and female rats has not been investigated. The purpose of the present study is to determine the effect of microinjecting naloxone, an opioid receptor antagonist, into the arcuate nucleus of awake male and female rats on ventilation, oxygen consumption, heart rate, and blood pressure. Results of this study demonstrate that naloxone at doses of 1.5 and 3.0 nmol relative to vehicle caused a depression of ventilation due to a decrease of both frequency of breathing and tidal volume in male rats and a decreased response to a hypercapnic challenge in female rats. Although there were gender differences noted in oxygen consumption, heart rate, blood pressure, and ventilatory response to a hypoxic challenge, only oxygen consumption was significantly affected by naloxone. Potential mechanisms whereby naloxone may act to depressing ventilation are discussed.     

Medical treatment patterns of ASCRS members for primary open-angle glaucoma--1998 survey

Tanycytes present in the mediobasal hypothalamus are able to support axonal regeneration and neuron survival. Pilot experiments of transplantation of these cells into various lesioned areas of the central nervous system (CNS) were thus performed to determine whether these cells could support the regeneration of the lesioned axons. These pilot experiments, however, demonstrated that the grafted tanycytes failed to survive in the lesioned sites. The present study was designed to determine which of the compounds released at the lesion would be toxic for tanycytes. Tanycyte cultures obtained from the median eminence of 10-day-old rats and astrocyte cultures obtained from the cortex of 10-day-old rats or E-14 embryos were incubated with two types of toxic molecules, including excitatory amino acids (EAA) and hydrogen peroxide (H2O2). The effect of these substances on cell death was estimated by measuring the lactate deshydrogenase (LDH) released and the surface occupied by immunostained glial structures after each treatment. The results indicated that the viability of both the tanycytes and the astrocytes was not affected by incubation for 24 h with 1 mM glutamate or 1 mM kainate. In contrast, increasing concentrations of H2O2 induced concentration-dependent cell death of tanycytes and immature astrocytes, without affecting the mature astrocytes. The use of antioxidant molecules such as catalase, tempol, or vitamin C effectively protected cultured tanycytes from H2O2 toxicity. These data indicate that (1) both mature astrocytes and tanycytes are resistant to EAA and (2) contrary to mature astrocytes, immature astrocytes and tanycytes are sensitive to the free radicals generated by H2O2. This suggest that oxidative stress is at least partly responsible for the death of tanycytes grafted into the lesioned CNS.     

Perioperative considerations of vascular access for dialysis

Perioperative nurses can be advocates for dialysis patients by being knowledgeable about various access routes, advantages and disadvantages of each, and associated nursing care. The longevity of vascular access devices depends on avoiding infection and blood clot formation. Perioperative nurses need to assess the knowledge level of the dialysis patient before surgical intervention in any situation.     

Assisted suicide in dementia. Ethical considerations between paternalism and autonomy

This article discusses the problem of euthanasia presenting the case of an 82-year-old man with progressive dementia. Difficulties encountered during daily clinical work are described and analysed, in order to clarify decisions on ethical, legal and professional medical grounds. General decisions concerning life-sustaining measures may be qualitatively improved if the situation of the individual is constantly assessed and considered within the treatment process.     

Arylsulphatase A pseudodeficiency in vascular dementia and Alzheimer's disease

The carrier rates of a genetic marker for arylsulphatase A pseudodeficiency (ASA-PD) were determined in three series of patients with vascular dementia (VaD) or Alzheimer's disease (AD). In the first community-based sample, the 1524 + 95A-->G mutation, which is known to be associated with ASA-PD, was present in 35% of VaD cases and none of the AD cases. In a second sample of cases drawn from a Dementia Register, the mutation rates were 18% (VaD) and 16% (AD). Brain DNA from a post-mortem sample revealed the ASA-PD mutation in 60% of VaD cases and 34% of AD cases. These rates are higher than previous studies of culturally similar populations and suggest that ASA-PD may be a risk factor for dementia.     

The distressed psychologist: Prevalence and treatment considerations.

Investigated the level and types of distress in a sample of 379 psychologists, using survey methodology. Overall, Ss were healthy and satisfied with work and interpersonal relationships. 10% of Ss experienced distress in the areas of depression, marital/relationship, physical illness, alcohol use, and loneliness. A distress band was calculated and ranged from 9% for multiple categories to 19% for single categories of distress. A subsample of Ss in distress from alcohol use was characterized by use of controlled drinking strategies with notable failure of these options to reduce distress levels. The authors conclude that (a) distress is a multifaceted phenomenon requiring careful examination on several levels; (b) controlled drinking strategies do not function to reduce distress among problem-drinking psychologists; and (c) verification of the distress band prevalence is needed to guide planning of intervention efforts on a state and national basis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modifying psychotropic drug prescription patterns: a follow-up survey

Blood flow to the rat ventral prostate (VP), dorsolateral prostate (DP), and Dunning R3327 prostatic tumors was measured at different times up to 7 days after castration, using the microsphere method. In the VP organ weight was decreased from day 3 onwards. Blood flow was, however, already significantly decreased from day 1. The reduced blood flow in VP in 1-3 and 7-day castrated animals could be reversed by testosterone treatment. Organ weight was slightly decreased but blood flow was unaffected by castration in DP. Castration left Dunning tumor volume and blood flow unaffected. Using immunohistochemistry, androgen receptors were observed in epithelial and stromal cells in VP, DP and Dunning tumors, but not in blood vessels. Castration is known to induce apoptosis in the VP, but not in the DP or in Dunning tumors. This suggests that a reduction in blood flow might be an important component for the castration-induced involution and apoptosis in prostatic tissue. The reason why castration reduces blood flow only in the VP, and not in the DP or Dunning tumor is unknown.     

Re-evaluating the role of vascular changes in the differential diagnosis of Alzheimer's disease and vascular dementia

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common causes of dementia, and much effort has been devoted to their differential diagnosis. However, current epidemiological, clinical and neuropathological evidence points to a substantial overlap between AD and VaD and suggests that vascular pathology, the traditional cornerstone of the differential diagnosis between the two entities, may not represent as clear a line of demarcation as originally believed. It may be time to reevaluate the dichotomy between AD and VaD.     

APOE-epsilon 4 in patients with Alzheimer disease and vascular dementia

This study reports seven cases of epulis excised by the CO2 laser without anesthesia. The laser was used in a continuous wave mode at power setting of 2-4 W. All lesions were excised completely, and no patients felt pain during laser irradiation. The operation was successful without using surgical packs, and there was no postoperative discomfort. There has been no evidence of recurrence after operation.