Neuropathologic diagnosis of Alzheimer disease: interrater reliability in the assessment of senile plaques and neurofibrillary tangles

The potential advantages of using digital techniques instead of film-based radiography have been discussed extensively for the past 10 years. A major future application of digital techniques is computer-assisted diagnosis: the use of computer techniques to assist the radiologist in the diagnostic process. One aspect of this assistance is computer-assisted detection. The detection of small lung nodule has been recognized as a clinically difficult task for many years. Most of the literature has indicated that the rate for finding lung nodules (size range from 3 mm to 15 mm) is only approximately 65%, in those cases in which the undetected nodules could be found retrospectively. In recent published research, image processing techniques, such as thresholding and morphological analysis, have been used to enhance true-positive detection. However, these methods still produce many false-positive detections. We have been investigating the use of neural networks to distinguish true-positives nodule detections among those areas of interest that are generated from a signal enhanced image. The initial results show that the trained neural networks program can increase true-positive detections and moderately reduce the number of false-positive detections. The program reported here can perform three modes of lung nodule detection: thresholding, profile matching analysis, and neural network. This program is fully automatic and has been implemented in a DEC 5000/200 (Digital Equipment Corp, Maynard, MA) workstation. The total processing time for all three methods is less than 35 seconds. In this report, key image processing techniques and neural network for the lung nodule detection are described and the results of this initial study are reported.     

Evaluation of the structures of agreement and disagreement in reliability studies

AIMS: To investigate, in healthy volunteers, the relationships between the plasma concentrations (C, ng ml(-1)) of zabiciprilat, the active metabolite of the angiotensin I-converting enzyme inhibitor (ACEI) zabicipril, and the effects (E) induced on plasma converting enzyme activity (PCEA, nmol ml(-1) min(-1)), brachial and femoral artery flows (BAF, FAF, ml min(-1)), and brachial and femoral vascular resistances (BVR, FVR, mmHg x s ml(-1)) after a single oral administration of two doses (0.5 and 2.5 mg) of zabicipril. METHODS: The study was placebo-controlled, randomized, double-blind and crossover. E was related to C by the Hill model, E = Emax x Cgamma/(CE50gamma + Cgamma), fitted to the data of both doses simultaneously. RESULTS: We obtained (mean +/- s.d.) Emax = -99 +/- 1%, CE50 = 2.2 +/- 1.0 ng ml(-1) and gamma = 1.0 +/- 0.4 for PCEA, Emax = 55 +/- 26 ml min(-1), CE50 = 5.1 +/- 4.0 ng ml(-1) and gamma = 2.4 +/- 1.6 for BAF, and Emax = -45 +/- 10%, CE50 = 2.0 +/- 1.3 ng ml(-1) and gamma = 2.3 +/- 1.4 for BVR. The parameters obtained for FAF and FVR were similar to those obtained for BAF and BVR, respectively. The CE95 (C required to induce 95% of Emax) varies from 7 to 17 ng ml(-1) for haemodynamic effects. CONCLUSIONS: As zabiciprilat peak plasma concentrations average 20 ng ml(-1) after the 2.5 mg dose of zabicipril, this dose of the drug should be sufficient to induce optimal haemodynamic effects.     

Status of risk factors for dementia associated with stroke

This study presents a brief investigation into sex differences of speakers in the voice onset time of English plosives that are stressed in both word-initial and prevocalic position. 72 short phrases were presented to 5 men (range 25 to 37 years, mean age 34.2 yr.) and five women speakers (range 28 to 38 years, mean 32.6 yr.). Analysis showed that the women as speakers had on average, longer voice onset time values than their male peers.     

Neuropsychologic method in diagnosis of mild dementia in elderly and senile patients

Clinical neuropsychologic investigation was performed in 95 patients of elderly and senile age with mild dementia: 20 individuals with Alzheimer's disease (AD), 25 patients with senile dementia of Alzheimer's type (SDAT), 25 patients with vascular dementia (VD) and 25 patients with combined dementia of vascular and Alzheimer's types (DAT/VD). Clinical diagnosis of mild dementia was performed according to ICD-10. Neuropsychologic study was based on the theory and method of A.R. Luria. Syndrome of disorder of high psychic functions (HPF) in patients with mild SDAT was characterised by pathology of frontal cerebral structures and by significantly less defects of profound cerebral structures. According to the examination results the group of patients with mild AD was divided into 2 subgroups: 1) patients in which syndrome of HPF disorders was determined by pathology of parietal-temporal and profound cerebral structures and 2) patients with dysfunction of profound and frontal cerebral structures. Symptoms associated with profound cerebral structures were the main ones in patients with mild VD. Syndrome of HPF disorder included in mild DAT/VD symptoms connected with subcortical and profound brain structures as well as with frontal structures too. Besides, there were also defects in posterior frontal and parietal structures of the brain.     

A meta-analysis of interrater and internal consistency reliability of selection interviews.

A meta-analysis of 111 interrater reliability coefficients and 49 coefficient alphas from selection interviews was conducted. Moderators of interrater reliability included study design, interviewer training, and 3 dimensions of interview structure (standardization of questions, of response evaluation, and of combining multiple ratings). Interactions showed that standardizing questions had a stronger moderating effect on reliability when coefficients were from separate (rather than panel) interviews, and multiple ratings were useful when combined mechanically (there was no evidence of usefulness when combined subjectively). Average correlations (derived from alphas) between ratings were moderated by standardization of questions and number of ratings made. Upper limits of validity were estimated to be .67 for highly structured interviews and .34 for unstructured interviews. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ensemble-averaged impedance cardiogram: an evaluation of scoring methods and interrater reliability

It has been shown that an appreciable percentage of patients presenting with primary, apparently sporadic phaeochromocytomas may in fact have von-Hippel-Lindau (VHL) disease. In order to investigate this, we retrospectively screened 68 patients, who had been operated on for phaeochromocytomas, for the presence of germline mutations in the vhl gene. DNA was isolated from peripheral-blood leukocytes and used to screen the entire coding sequence and the intron-exon boundaries of the vhl gene for mutations, using a PCR-based SSCP strategy. When an abnormal pattern was found in the SSCP analysis, sequence analysis was carried out. We found SSC variants in the vhl gene in 8 of the 68 patients. Of 6 patients, 2 turned out to be related (an uncle and his nephew), and they carried the same mis-sense mutation: R64P. In 4 other patients, mis-sense mutations, P25L, L63P, G144Q and I147T, were also identified. None of these mutations has been described, and 3 of them (P25L, L63P and R64P) are located closer to the N terminus of the vhl protein than any reported vhl mutation. In the remaining 2 cases, the mutations were localized not in the coding sequence but in the intronic sequence (but not within splice-sites), adjacent to the exon, so they were probably not related to the disease. Our results show that a relatively high proportion (6/68, or 8.8%), though not as high as the 20% reported earlier, of patients with apparently sporadic phaeochromocytomas may carry germline mutations in the vhl gene.     

Differences and disagreement as factors in creative group problem solving.

"This experiment was designed to test the following hypothesis: conflict generated by increasing the resistance of subordinate members of a group to a solution offered by member in an authority position increases the frequency of high quality solutions. The supplementary hypothesis that mixed-sex composition in interaction with such conflict further enhances the production of high quality solutions was also tested… . The results support the major hypothesis." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Simultaneous palpation of the craniosacral rate at the head and feet: intrarater and interrater reliability and rate comparisons

BACKGROUND AND PURPOSE: The main purpose of this study was to determine the interrater and intrarater reliability of measurements obtained during palpation of the craniosacral rate at the head and feet. Palpated craniosacral rates of head and feet measured simultaneously were also compared. Subjects. Twenty-eight adult subjects and 2 craniosacral examiners participated in the study. METHODS: A within-subjects repeated-measures design was used. A standard cubicle privacy curtain, hung over the subject's waist, was used to prevent the examiners from seeing each other. RESULTS: Interrater intraclass correlation coefficients (ICCs) were .08 at the head and .19 at the feet. Intrarater ICCs ranged from .18 to .30. Craniosacral rates simultaneously palpated at the head and feet were different. CONCLUSION AND DISCUSSION: The results did not support the theories that underlie craniosacral therapy or claims that craniosacral motion can be palpated reliably.     

Crystallized and fluid intelligence in elderly patients with mild dementia of the Alzheimer type

OBJECTIVE: To describe a systematic procedure for adapting, or 'tailoring' the World Health Organisation's 'global guidelines for the management of HIV/AIDS in adults and children' for use in two developing countries: Malawi and Barbados. DESIGN: In order for these guidelines to achieve reproducibility, clinical flexibility, and clinical applicability, a systematic procedure is needed to tailor the guidelines to the local practice conditions of specific settings. METHODS: A group of local experts in each country used a nominal group process to modify the global program on AIDS (GPA) guidelines for local use. Semantic analysis techniques, known as clinical algorithm nosology (CAN), were used to compare the two modified guidelines with the global ones to determine the extent and type of differences between sets of guidelines. RESULTS: Standard, locally-tailored algorithm map guidelines (AMG) were developed within 4 months. CAN semantic analysis showed that guideline structure was maintained; 572/858 (66.6%) decision nodes were found to be the same in the GPA/Malawi, GPA/Barbados and Malawi/Barbados comparisons. However, different guideline versions managed patients quite differently, as evidenced by clinical algorithm patient abstraction (CAPA) scores of between 0 and 8.46 (0 = different; 8 = similar; 10 = identical). Analysis of the 197 specific differences found in these abstractions showed that 83% were in approaches to diagnosis and therapy, while the remaining 17% related to disease prevalence. CONCLUSIONS: Standard techniques involving consensus used to develop clinical guidelines can also be employed to tailor these guidelines to local settings. Semantic analysis shows that the tailoring preserves structure but may involve significant modification to the processes of clinical care that could in turn affect care outcomes.     

Hippocampal sclerosis contributes to dementia in the elderly

OBJECTIVE: To assess the relevance of hippocampal sclerosis (HS) to dementia in the elderly. BACKGROUND: HS is a prominent pathologic finding in some demented elderly, but the anatomic substrate and cognitive profiles of this dementia have not been well established. DESIGN/METHODS: An autopsy series, including dot-immunobinding assay to estimate neocortical synaptic density, of eight patients (three men, five women) with HS on whom extensive antemortem neuropsychological testing was available. RESULTS: Mean age at onset was 72.0 (+/-9.8) (range, 59 to 89) with a mean duration of symptoms of 6.5 (+/-2.9) years. Patients were only mildly impaired with a mean MMSE of 20.9 (+/-4.9) and a mean DRS of 103.1 (+/-12.5) at presentation. Cardiovascular disease was present in 88%, with a mean Hachinski score of 3.4 (+/-2.2). No patient had a history of seizures. Sixty-three percent had depression or depressive symptoms. Neuropsychologically, most patients presented with prominent memory and language deficits and became progressively demented. Neuropathologically, isolated HS was a rare finding; many patients had either very mild or neocortical "plaque only or plaque predominant" Alzheimer's disease (AD) in addition to HS changes. Midfrontal neocortical synaptophysin counts were significantly reduced in all HS patients compared with controls (p = 0.0006). CONCLUSIONS: In the elderly, HS can be a neuropathologic substrate of dementia. Clinically, it can be associated with a course that is difficult to distinguish from AD although cardiac disease and depression are frequent concomitants. Deterioration of cognitive function in these subjects may relate to other pathologic features such as neocortical synapse loss.     

Abnormality of bone mineral metabolism in elderly female patients with dementia

In order to clarify the relationship between dementia and osteoporosis, bone mineral metabolism was studied in elderly female patients with dementia. We measured bone mineral densities of the vertebral body and the femoral neck using DEXA, and evaluated Ca-related factors in 22 patients with dementia of the Alzheimer type (DAT), 23 patients with vascular dementia (VD), and 22 age-matched controls (C). Activity of daily living was significantly poorer in VD patients than controls, but no difference was shown between DAT and C groups. Bone mineral density values of the vertebral body and the femoral neck were significantly decreased in both DAT and VD groups when compared to C group. DAT patients showed significant decreases in serum Ca and Ca2+ ion, increase in serum parathyroid hormone, and decrease in serum 1,25-dihydroxyvitamin D, a tendency towards decrease in serum calcitonin, and a tendency towards increase in urinary Ca. However, VD patients showed only significant increase in urinary Ca and a tendency towards decrease in serum 1,2-dihydroxyvitamin D, without showing other changes of Ca-regulating hormones. These results suggest that patients with dementia are more often associated with osteoporosis, and that in DAT several abnormalities of Ca-regulating factors play an important role in the development of osteoporosis, while in VD limited physical activities contribute to bone mineral loss.     

Is the diagnosis of dementia stable over time among elderly immigrant Gujaratis in the United Kingdom (Leicester)?

BACKGROUND: The single largest ethnic elder group in the United Kingdom originates from the Indian subcontinent and their numbers are increasing. METHOD: Elderly Gujarati subjects, with a diagnosis of dementia ascertained during an epidemiological field study in Leicester, were reexamined at a median follow-up interval of 27 months to establish stability of the original diagnosis and cognitive decline. RESULTS: Seven of the original 11 subjects with dementia were alive at the follow-up and they were reexamined by a Gujarati psychiatrist. In six of these seven subjects the diagnosis of dementia was reconfirmed with concomitant cognitive decline on the CAMDEX dementia severity index. Informant history in three of the four original dementia subjects provided evidence of cognitive decline between the original interview and death. CONCLUSION: The diagnosis of dementia in elderly Gujaratis was stable at follow-up with concurrent evidence of decline. This also provided further support for the validity and performance of the Gujarati MMSE in the original study.     

Occurrence of dementia and depression in an elderly Danish population

A community survey of all Danish speaking residents above the age of 64 in a geographically delimited area was performed. The aim of the survey was to establish the prevalence of dementia disorders and depression by the use of international screening tools: the Mini Mental State Examination for dementia and the Beck's Depression Inventory for depression. The screening was performed during the period of one year in the municipality of Karlebo and the interviews took place in the homes of the participants. Six hundred and sixty-four (66%) of the 1,008 eligible persons entered the study. Six percent were residents in nursing homes. Thirteen point seven percent were found to be suffering from dementia. Nine point six percent had symptoms of depression. These prevalences would indicate that more than 6,000 persons in Frederiksborg county suffer from dementia while more than 4,000 might be suffering from depression. The study confirms knowledge obtained in other studies, indicating that one out of seven of the elderly suffers from dementia. We do not conclude, however, that nine point six percent suffer from depression, but rather that they need further examination to make it possible to decide whether they are indeed depressed.