Biomedical subjects

S Darvesh

Publications and source records attributed to S Darvesh.

12 recordsLinked to original sources

PubMed2005

The behavioural neurology assessment.

BACKGROUND: We present information regarding the standardization, reliability and clinical validity of two versions of the Behavioural Neurology Assessment (BNA). The BNA-Long Form consists of 24 subtests within separate domains: Attention, Memory, Language, Visuospatial Function, Executive Function, and Praxis. The BNA-Short Form consists of 13 subtests within the domains of Attention, Memory, Naming, Visuospatial Function and Executive Function. In addition to individual domain indices, a Grand Total score was calculated for both BNA versions. OBJECTIVE: To standardize the administration and scoring and validate the BNA for detection of dementia. METHODS: Standardized normative data were obtained on 115 healthy subjects ranging in age from 50 to 95. Test-retest stability was obtained on 19 subjects and clinical validity was investigated by administering the BNA and Mini-Mental Status Examination (MMSE) to 29 patients with dementia and 29 age-matched healthy subjects (controls). RESULTS: Age had a significant effect on all but the Visuospatial and Praxis indices of the BNA-Long Form and an effect on Naming and Grand Total score of the Short-Form. Internal consistency (Cronbach's coefficient alpha) was .87 and .67 for the Long and Short Forms (.95 and .96 for dementia and control groups combined). Test-retest stability was acceptable. Grand Total indices of both BNA versions showed significant, positive correlations with the MMSE. Both BNA versions had superior sensitivity to dementia relative to the MMSE (.93 versus .79). Specificity was equivalent to the MMSE (.93 versus .97). CONCLUSIONS: Positive predictive values of the BNA and MMSE are equivalent but the BNA provides superior negative predictive value.

Age Factors↗

PubMed2001

Butyrylcholinesterase and cognitive function.

Butyrylcholinesterase (BuChE) is expressed in brain structures involved in cognition, but the effect of selective BuChE inhibitors on human cognitive function is unknown. We report a patient whose cognitive function deteriorated following a reduction and improved following reinstitution of ethopropazine, a selective BuChE inhibitor. We suggest that, because neurons expressing BuChE may be involved in cognition, there is merit to further evaluation of selective BuChE inhibitors in treating cognitive dysfunction.

Adult↗

PubMed2001

Estimating the prevalence of dementia in elderly people: a comparison of the Canadian Study of Health and Aging and National Population Health Survey approaches.

The Canadian Study of Health and Aging (CSHA) and the National Population Health Survey (NPHS) collected data on the prevalence of dementia in differing fashions. The CSHA used a two-stage method with objective testing and expert judgment, and the NPHS used self-report and proxy data. The present report compares estimates of prevalence and the methodology for ascertainment in the two surveys. The more detailed approach of the CSHA offers the more valid means of estimating prevalence and providing data on subtypes, and can be used in naturalhistory studies. TheNPHSmeasures, including a self/proxy report of diagnosed dementia and a derived cognitive measure, are not sufficiently valid for useful inferences to be made. However, the NPHS method can be improved through supplementation with data on functional disability, providing age group-specific point estimates closer to the CSHA's estimates of cognitive impairment and dementia from the community sample. Future waves of the NPHS may wish to include objective cognitive function measures as a cost-efficient and more accurate method of estimating the prevalence of the dementia syndrome without attempting to estimate the prevalence of particular causes of that syndrome.

Aged↗

PubMed2001

Butyrylcholinesterase-Mediated enhancement of the enzymatic activity of trypsin.

1. Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC 3.1.1.8) are enzymes that catalyze the hydrolysis of esters of choline. 2. Both AChE and BuChE have been shown to copurify with peptidases. 3. BuChE has also been shown to copurify with other proteins such as transferrin, with which it forms a stable complex. In addition, BuChE is found in association with beta-amyloid protein in Alzheimer brain tissues. 4. Since BuChE copurifies with peptidases, we hypothesized that BuChE interacts with these enzymes and that this association had an influence on their catalytic activities. One of the peptidases that copurifies with cholinesterases has specificity similar to trypsin, hence, this enzyme was used as a model to test this hypothesis. 5. Purified BuChE causes a concentration-dependent enhancement of the catalytic activity of trypsin while trypsin does not influence the catalytic activity of BuChE. 6. We suggest that, in addition to its esterase activity, BuChE may assume a regulatory role by interacting with other proteins.

Acetylcholinesterase↗

PubMed2000

Enhancement of survival of stored dopaminergic cells and promotion of graft survival by exposure of human fetal nigral tissue to glial cell line--derived neurotrophic factor in patients with Parkinson's disease. Report of two cases and technical considerations.

The authors have studied the ability of glial cell line-derived neurotrophic factor (GDNF) to promote survival of human fetal dopaminergic tissue after a storage period of 6 days and subsequent implantation into the human putamen. The results indicate that GDNF promotes survival of stored dopaminergic cells. Cells stored without GDNF had a 30.1% decrease in survival time compared with those exposed to GDNF. Two patients with Parkinson's disease received bilateral putaminal implants of fetal dopaminergic cells exposed to GDNF for 6 days and showed enhancement of graft survival as assessed by positron emission tomography scanning. A mean increase of 107% in putaminal fluorodopa uptake from baseline values was observed 12 months postgrafting.

Aged↗

PubMed1999

Spectrum of disease in vascular cognitive impairment.

The recognition that cognitive impairment of vascular origin is not limited to multi-infarct dementia has led to the development of several sets of new criteria for vascular dementia (VaD). We set out to define the spectrum of disease in patients presenting with vascular cognitive impairment (VCI). Of 412 patients consecutively seen at a memory clinic, 80 had VCI. These patients had vascular cognitive impairment not dementia (n = 19), VaD (n = 48), and mixed Alzheimer's disease-VaD (n = 13). Radiographic patterns were: white matter changes only (40%); multiple infarcts (30%); single strategic stroke (14%), and no identified lesion (16%). Of note, 19 (24%) of these patients meet none of the currently published criteria for VaD. To better understand and treat ischaemic causes of cognitive impairment, the concept of VaD should be expanded to include patients who do not meet traditional dementia criteria.

Aged↗

PubMed1998

Cholinesterases in cardiac ganglia and modulation of canine intrinsic cardiac neuronal activity.

Cholinergic neurotransmission plays a significant role in intrinsic cardiac ganglia with the action of acetylcholine being terminated by acetylcholinesterase (AChE, EC 3.1.1.7). Anatomical studies were performed to characterize neurons associated with AChE and a closely related enzyme, butyrylcholinesterase (BuChE, EC 3.1.1.8), in canine intrinsic cardiac ganglia. Histochemical staining for AChE and BuChE in canine right atrial neurons showed that there were four neuronal populations, namely, those that contained AChE only, BuChE only, both AChE and BuChE, and those that did not contain either enzymes. The neuronal activity of intrinsic cardiac neurons in response to substrates and inhibitors of cholinesterases were studied in anesthetized dogs. The activity of intrinsic cardiac neurons, as measured by changes in the number of action potentials, increased by local application of acetylcholine. However, local application of butyrylcholine led to a considerably greater increase in the activity of intrinsic cardiac neurons. In keeping with the neurochemical heterogeneity in intrinsic cardiac ganglia with respect to cholinesterases, the activity generated by most butyrylcholine-sensitive neurons was not influenced by acetylcholine and the activity generated by the most acetylcholine-sensitive neurons was not influenced by butyrylcholine. This suggests that these two agents preferentially influence different populations of intrinsic cardiac neurons. Enzyme kinetic studies demonstrated that canine AChE preferentially catalyzed the hydrolysis of acetylcholine while canine BuChE preferentially catalyzed the hydrolysis of butyrylcholine. Cholinesterase inhibitors Ro 2-1250 and Ro 2-0638 inhibited both canine cholinesterases, while huperzine A preferentially inhibited canine AChE and ethopropazine inhibited canine BuChE. The activity of neurons in the intrinsic cardiac ganglia significantly increased when Ro 2-1250 or Ro 2-0638 was administered locally. The activity of neurons was not affected when huperzine A or ethopropazine was administered, indicating that both cholinesterases must be inhibited to increase neuronal activity. In summary, these data show that in addition to AChE, intrinsic cardiac ganglia also contain distinct populations of neurons that are associated with BuChE, and the activity generated by these neurons is differentially influenced by their substrates. Because simultaneous inhibition of AChE and BuChE leads to increased neuronal activity, it is concluded that AChE- and BuChE-positive intrinsic cardiac neurons may act synergistically to influence the overall tonic activity of intrinsic cardiac ganglia.

Acetylcholine↗

PubMed1998

Distribution of butyrylcholinesterase in the human amygdala and hippocampal formation.

The distribution of the major cholinergic regulatory enzyme acetylcholinesterase (AChE, EC 3.1.1.7) has been extensively studied in the human brain, but the distribution of the closely related enzyme butyrylcholinesterase (BuChE, EC 3.1.1.8) is largely unknown. Because of the importance of BuChE and AChE in Alzheimer's disease, we have studied the distribution of BuChE in the normal human amygdala and hippocampal formation and compared it with that of AChE by using histochemical techniques. In the amygdala, the distribution of BuChE differed significantly from that of AChE in that BuChE was found primarily in neurons and their dendritic processes, whereas AChE was found predominantly in the neuropil. BuChE-positive neurons were present in up to 10% of the neuronal profiles in lateral, basolateral (basal), basomedial (accessory basal), central, cortical, and medial amygdaloid nuclei. AChE was found primarily in the neuropil in these nuclei with only a few AChE-positive neurons. In the hippocampal formation, BuChE was also found in neurons and not in the neuropil, whereas AChE was found in both neurons and in the neuropil. BuChE and AChE neurons were present in the polymorphic layer of the dentate gyrus, as well as the stratum oriens and stratum pyramidale of the hippocampus proper. There was considerable overlap in shapes, sizes, and numbers of BuChE- and AChE-positive neurons, suggesting that the enzymes were colocalized in neurons of the hippocampal formation. The distinct distribution of BuChE suggests that it may have specific functions including coregulation of cholinergic and noncholinergic neurotransmission in human amygdala and hippocampal formation.

Acetylcholinesterase↗

PubMed1998

Retrospective diagnosis of dementia using an informant interview based on the Brief Cognitive Rating Scale.

The accuracy of a dementia diagnosis by specialist physicians, as verified at an autopsy, is greater than 90% in many series. Donations of brains to the Maritime Brain Tissue Bank (MBTB) by individuals who did not have expert dementia diagnoses before death led us to investigate whether clinical features could also be detected retrospectively. Informants for 36 individuals whose brains were in the MBTB (18 women, mean age = 79 years; pathologic diagnoses: 75% Alzheimer's disease [AD]; 8.4% vascular or mixed dementia) were interviewed by specialist physicians using a semistructured retrospective interview based on the Brief Cognitive Rating Scale (BCRS) (range = 1 [no impairment] to 7 [terminal dementia]). The mean duration of dementia was 8.5 +/- 12.8 years based on proxy reports, and most cases suggested severe dementia--(stage 6 [severe] or 7 [terminal])--on the retrospective BCRS (RetroBCRS) before death. A score of 4 or more on the RetroBCRS had 100% sensitivity and specificity in detecting dementia. The RetroBCRS score correlated moderately with duration (.51). In linear and logistic regression models adjusted for age and sex, RetroBCRS staging helped explain 93% of the variation in duration. The accuracy of the retrospective diagnosis of the cause of dementia, compared with autopsy, was 92%. The RetroBCRS used by an expert physician with a reliable informant is a valid method of detecting dementia and determining whether AD was present.

Aged↗

PubMed1996

Subcortical dementia: a neurobehavioral approach.

The subcortical dementias are a heterogeneous group of disorders in which the predominant pathological lesions occur in subcortical structures such as basal ganglia, brainstem nuclei, and the cerebellum. When the cerebral cortex is involved, the lesions are most often in the frontal lobes. These pathologic lesions are associated with cognitive changes that include bradyphrenia, personality change (apathy, depression, irritability), memory impairment, and impaired manipulation of acquired knowledge (calculation, abstraction). Aphasia, apraxia, and agnosia are commonly seen in the cortical dementias, but are absent in the subcortical dementias. Progress in research on the anatomy and connectivity of cortical-subcortical structures has led to refinement in our understanding of the cortical dementias. Despite the connectivity between the cortical and subcortical structures, patterns of cognitive impairment in subcortical dementias remain distinct.

Aphasia↗

PubMed1987

Distribution of neuropeptide-like immunoreactivity in intact and chronically decentralized middle cervical and stellate ganglia of dogs.

Neuropeptide-like immunoreactivity to antisera raised against Leu- and Met-enkephalin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and substance P (SP) have been studied immunohistochemically in middle cervical and stellate ganglia of dogs. To investigate the relationship of the peptides to one another as well as to preganglionic and postganglionic neurons, intact and chronically decentralized middle cervical and stellate ganglia were studied. Ganglia were processed for immunohistochemistry in unoperated dogs and in dogs two weeks after unilateral ganglionic decentralization. The immunoreactivity for each peptide had a characteristic distribution in the ganglia. These distributions differed from one another and from the distribution of cardiac postganglionic sympathetic neurons. Camera lucida drawings of peptide distributions were made to compare different peptides and counts were made to determine the percentages of cells immunoreactive for a given peptide. The results demonstrated that enkephalin-like immunoreactivity in axons was present in both the stellate and middle cervical ganglia, but was heaviest in the caudal 2/3 of the stellate ganglia. Enkephalin-like immunoreactive fibers formed pericellular baskets around stellate ganglion neurons. VIP-like immunoreactive cell bodies and processes were distributed sparsely, but widely, in the stellate ganglia and to a lesser extent in the middle cervical ganglia. One of two commercial antisera to SP resulted in immunoreactive staining of cell bodies and processes in the stellate ganglia. SP-like immunoreactivity in neurons represented about 10% or less of the cells in the stellate ganglia. At least 80-85% of the neurons in the stellate and middle cervical ganglia were immunoreactive for NPY antisera. Decentralization eliminated enkephalin-like immunoreactive staining in the middle cervical and stellate ganglia, but not the VIP-, NPY- and SP-like immunoreactive staining of neurons in these ganglia. In summary, the enkephalin-like immunoreactive axons in the thoracic autonomic ganglia appear to be derived from extrinsic neurons, most likely from preganglionic spinal neurons. VIP-, SP- and NPY-like immunoreactivity were not significantly affected by decentralization. The results provide anatomical evidence for substrates related to neuropeptidergic synaptic mechanisms in thoracic autonomic ganglia.

Animals↗

PubMedDate not supplied

Inter-rater reliability of the diagnosis of vascular cognitive impairment at a memory clinic.

Consensus criteria for the diagnosis of vascular dementia (VaD) are gradually being replaced with data-based criteria. We report the inter-rater reliability of a new set of empirically-derived criteria for vascular cognitive impairment (VCI). Stratified sampling, with optimal allocation, was employed to randomly select 36 patients from the Queen Elizabeth II Health Science Centre's Memory Disability Clinic. Chart reviews were conducted independently by 4 physicians. Each physician classified the patients as having either: no cognitive impairment, VCI or Alzheimer's disease (AD). VCI was further classified both clinically (VCI without dementia, VaD or AD with a vascular component) and radiographically (infarcts, white matter changes, single strategic stroke). The intraclass correlation coefficient (ICC) for the diagnosis by physicians of VCI or otherwise was based on a repeated-measures analysis of variance with raters as the independent variable. A significant coefficient of reliability (average ICC = 0.88, 95% CI = 0.80-0.93) was obtained (H(o): rho </= 0.80, p = 0.03). Where differences in diagnosis occurred, the discrepancies most commonly resulted within the subtypes of VCI (9 cases) or between the diagnoses of AD and VCI (9 cases). Instances of diagnostic incongruity were typically due to the disagreement of a single rater (10 cases). This study demonstrates a high degree of reliability of criteria for VCI by physicians in a memory clinic, and can also be understood as an aspect of construct validation of those criteria. In the absence of a readily available biological marker for VCI, clinical criteria are necessary and can be reliably employed.

Activities of Daily Living↗