Longitudinal visual evoked potentials in Alzheimer's disease: a preliminary report.
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Biomedical subjects
D Coakley
Publications and source records attributed to D Coakley.
Utility of ischemic scores in the differential diagnosis of Alzheimer's disease and ischemic vascular dementia.
Despite new developments in the concept of vascular dementia, the Hachinski Ischemic Score (HIS) and its modified versions continue to be widely used in the clinical differentiation of Alzheimer's disease (AD) and ischemic vascular dementia (IVD). The sensitivity of the HIS and two modified versions in the diagnosis of AD, IVD, and single infarcts in a large, geriatric population with mild cognitive impairment (N = 100) was evaluated. Sensitivity for identification of AD was greater than 90% but was less than 70% for IVD. Over one third of patients with one or more infarcts on computed tomographic brain scans and 63% of mixed cases were classified as having probable AD. It is concluded that ischemic scores may be useful at predicting prevalence rates if individual case accuracy is ignored. Despite being sensitive to identifying AD, ischemic scores are insensitive to both cerebral infarction and IVD and cannot reliably exclude IVD. Finally, patients with mixed dementia should not be expected to have intermediate scores.
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Event-related potential prolongation in Alzheimer's disease signifies frontal lobe impairment: evidence from SPECT imaging.
BACKGROUND: The N2 and P3 components of auditory event-related potentials (ERPs) and single-photon emission computed tomographic (SPECT) images are separate independent biological markers of cerebral function and are abnormal in Alzheimer's disease (AD). The relationship between ERP N2 and P3 latencies and regional cerebral perfusion abnormalities in AD is unknown. METHODS: ERP and SPECT data were obtained one week apart in 18 patients with "probable" AD of mild or moderate severity, and 12 healthy age-matched elderly controls. Average premotor frontal, anterior temporal, inferior parietal, and occipital cortical/cerebellar perfusion ratios were calculated from the SPECT data and correlations with ERP N2 and P3 latencies derived for AD and control groups separately. RESULTS: ERP N2 latency was correlated significantly with the average frontal perfusion ratio (r = -.59; p < .009), but correlations with average temporal, parietal, and occipital ratios were nonsignificant in the AD group. Similarly, ERP P3 latency was correlated significantly with the average frontal perfusion ratio (r = -.65; p < .004), but not with the other perfusion ratios in the AD group. In the control group, a partial correlation between the average frontal perfusion ratio and the ERP N2 latency was noted (r = -.52; p < .09), but no other ERP/SPECT correlations approached statistical significance. CONCLUSION: ERP N2 and P3 latency delay in AD is a function of differential frontal lobe hypoperfusion.
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Clinical application of electrophysiological markers in the differential diagnosis of depression and very mild Alzheimer's disease.
BACKGROUND: Current evidence indicates that, on their own, neither flash visual evoked responses (FVEPs) nor event related potentials (ERPs) are sufficiently useful to the clinician in the very early stages of memory dysfunction. However, the possibilities for the combined use of these measures has not been fully explored. METHODS: This study examined the clinical utility of combined FVEP and ERP-P300 component latencies as predictive markers in 16 patients with Alzheimer's disease, 15 patients with depression, and 21 control subjects. RESULTS: There were significant group differences in FVEP P2 latency (P = 0.004) between the controls and both the depressive patients and those with very mild Alzheimer's disease. There were no statistically significant group differences for the ERP component (N2/P300) amplitudes or latencies. The P300 component latency was positively correlated with both the FVEP N2 and FVEP P2 component latencies in the patients with Alzheimer's disease but not in the control subjects or the depressed patients. A discriminant function, using two ERP and two FVEP component measures, gave an overall correct classification rate for dementia of 78%. In this study of very mildly impaired patients the FVEP latencies provided a more sensitive marker for the presence of cognitive dysfunction than P300 latency delay. CONCLUSIONS: The findings support the use of multimodal evoked potentials in the differential diagnosis of very mild Alzheimer's disease and normal aging.
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Are hydrogen breath tests valid in the elderly?
Hydrogen breath testing (HBT) is frequently used as an alternative to small bowel aspiration in the diagnosis of small intestinal bacterial overgrowth (SIBO). The role of the glucose HBT was assessed in 30 elderly patients. A positive HBT was recorded in 15 of 20 SIBO cases and 7 of 10 culture negatives (sensitivity 75% and specificity 30%). The correlation coefficients between hydrogen gas (H2) rise and total bacterial count (r = 0.21) and H2 rise and anaerobic count (r = 0) were not significant. Fasting H2 levels were raised in only 4 of the 20 SIBO cases. This study indicates that the HBT is not reliable in the diagnosis of SIBO in the elderly. There was no evidence from the data that different H2 levels or bacterial counts would significantly alter the reliability of the HBT. This work suggests that factors other than small bowel bacteria are involved in the production and expiration of H2 in the elderly, and that these factors need to be considered in the interpretation of this breath test.
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Haemagglutination properties of Moraxella (Branhamella) catarrhalis.
The ability of 30 isolates of Moraxella (Branhamella) catarrhalis to haemagglutinate erythrocytes of five species was examined. Two haemagglutination phenotypes of M. catarrhalis were observed: phenotype I isolates (n = 10) agglutinated human erythrocytes, while phenotype II isolates (n = 7) agglutinated both human and rabbit erythrocytes. No haemagglutination was observed with chick, sheep or horse erythrocytes. Haemagglutination by both phenotype I and II isolates was abolished following treatment of these isolates with pronase and trypsin, while heat treatment at 70 degrees C markedly reduced the level of haemagglutination by both sets of isolates. Haemagglutination by phenotype II isolates was inhibited by galactose, whereas haemagglutination by phenotype I isolates was not inhibited by this carbohydrate. Transmission electron microscopy (TEM) studies showed that very close cell-surface interactions occurred when both phenotypes of M. catarrhalis adhered to the human erythrocyte. Fimbrial attachment was not apparent. Haemagglutinating isolates of both phenotypes had a trypsin-sensitive outer fibrillar coat when examined by TEM.
Animals↗
Arterial closing pressure correlates with diastolic pseudohypertension in the elderly.
BACKGROUND: Pseudohypertension has frequently been reported in the elderly population, with the diastolic measurement being the most frequent source of error. There is no satisfactory noninvasive method of calculating the error in the blood pressure reading. We investigated the role of arterial closing pressure in the diagnosis of diastolic pseudohypertension. METHODS: Indirect and direct blood pressure were measured in 24 elderly patients. Brachial artery closure was visualized by ultrasound in all subjects. Arterial closing pressure (ACP) was recorded as zero if the vessel was seen to close spontaneously when it was isolated from central arterial pressure. If the vessel did not close spontaneously, a water cuff was applied externally over the artery and the additional pressure required to close it was recorded. RESULTS: Diastolic pseudohypertension was noted in 8 subjects. Spontaneous closure of the brachial artery occurred in the 16 without pseudohypertension; i.e., ACP = 0. Additional pressure of the water cuff (range: 30-158 mm Hg) was required to collapse the artery (ACP) in those with diastolic pseudohypertension. ACP correlated with the extent of diastolic pseudohypertension (range: 5-17 mm Hg); r = .85, p < .001). CONCLUSION: We propose that ACP may be used to diagnose the presence and extent of pseudohypertension.
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1994 de Villers Lecture--tribute to Denis Burkitt.
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Burkitt Lymphoma↗
Relation between aortic atherosclerosis and blood pressure.
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Aorta, Abdominal↗
Sources of variance in ocular microtremor.
This study presents a preliminary investigation of the sources of variance in the measurement of ocular microtremor frequency in a normal population. When the results from both experienced and relatively inexperienced operators are pooled, factors that contribute significantly to the total variance include the measurement procedure (p < 0.001), day-to-day variations within subjects (p < 0.001), and inter-subject differences (p < 0.01). Operator experience plays a role in determining the measurement precision: the intra-subject coefficient of variation is about 5% for a very experienced operator, and about 14% for a relatively inexperienced operator.
Adult↗
Small intestinal bacterial overgrowth--an incidental finding?
OBJECTIVES: To assess the prevalence of typical clinical features and need for treatment of small intestinal bacterial overgrowth (SIBO) in the elderly. DESIGN: Random selection of patients, regardless of their nutritional status. SETTING: Acute admissions ward in the Dept. of Medicine for the Elderly. PATIENTS: Thirty elderly patients between 68 and 90 years of age. MEASUREMENTS: Active clinical problems, including the presence of recent weight loss and diarrhea, were recorded. Routine blood tests, including serum vitamin B12, red cell folate, albumin and calcium, and qualitative small bowel bacteriology results, were analyzed. The effect of age on all variables was studied. RESULTS: Twenty of the 30 small bowel aspirates had proven SIBO, and strict anaerobes were isolated in 15. The mean blood test values did not differ significantly between culture-positive and culture-negative patients. There was no significant correlation between those variables and the total bacterial counts. Of the 20 proven SIBO cases, eight had anemia, five had hypoalbuminemia, five had diarrhea, four complained of recent weight loss, and none had B12 deficiency. Alternative causes other than SIBO were identified for many of these abnormalities. Advancing age correlated significantly with rising counts of small bowel strict anaerobes. CONCLUSIONS: These data suggest that age may be a predisposing factor in the development of anaerobic overgrowth but that SIBO is a benign entity in the elderly. Contrary to previous recommendations, treatment of this condition is not routinely indicated.
Age Factors↗
Differential diagnosis of dementia: a prospective evaluation of the DAT Inventory.
OBJECTIVE: To compare prospectively the concordance between the diagnosis of dementia based on clinical criteria and using the DAT Inventory. DESIGN, SETTING, AND PARTICIPANTS: A prospective study of 81 consecutive patients referred to a Memory Clinic. Only patients for whom a definitive diagnosis of dementia was established after 8 to 20 months follow-up were retained in the study (n = 76). MEASUREMENTS: The sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy of the DAT Inventory were calculated. Kappa values were also computed. RESULTS: Based on all patients (n = 76), sensitivity and specificity were 71% and 95%, respectively, with 98% positive prediction, 56% negative prediction, 78% overall accuracy, and kappa of 0.54. Of 21 cases not meeting NINCDS/ADRDA criteria for DAT, one patient with multi-infarct dementia was misclassified as DAT on the DAT Inventory. Of 55 DAT cases (NINCDS/ADRDA criteria), 16 patients, predominantly very mild or mixed cases, were classified as non-DAT on the DAT Inventory. When mixed, very mild, and borderline cases were excluded (remaining n = 54), DAT Inventory sensitivity increased to 94%, and specificity remained unchanged at 95%, with 97% positive and 91% negative prediction, 94% overall accuracy, and kappa of 0.88. CONCLUSIONS: In general, scores above the designated cutoff point (> 14/20) on the DAT Inventory are consistent with a clinical diagnosis of DAT (NINCDS/ADRDA criteria). Concordance is best in cases of mild to moderate dementia (Clinical Dementia Rating 1-2). The Inventory is less discriminating as a differential diagnostic instrument in cases of very mild dementia, atypical presentations of DAT, or in cases of mixed pathology.
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Phase I trial of valaciclovir, the L-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease.
Valaciclovir, the L-valyl ester of acyclovir, is rapidly and extensively converted in humans to acyclovir after oral administration by first-pass metabolism. A phase I study was conducted in two cohorts of volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count of < 150 cells per microliters) who received oral valaciclovir at dosages of 1,000 or 2,000 mg four times daily for 30 days. All patients were clinically stable without any changes in underlying HIV-related medications for > or = 6 weeks prior to entry in study; these medications were continued throughout the study. Multiple-dose administration of valaciclovir showed a generally favorable safety profile. Nausea, vomiting, diarrhea, and abdominal pain each were reported in < or = 31% of the patients; of these symptoms, only one episode of diarrhea was considered causally related to valaciclovir exposure. Four patients developed neutropenia (two at each dose level) which was not clinically significant. There were no renal or neurologic adverse events. Valaciclovir was rapidly absorbed and converted to acyclovir, with plasma valaciclovir levels generally undetectable or levels of < or = 0.4 microgram/ml. After 3 h postdosing, valaciclovir was not detectable in plasma. Acyclovir was measurable in plasma as early as 15 min following valaciclovir dosing, and plasma concentrations of acyclovir greatly exceeded those of valaciclovir. The mean values for the maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, area under the concentration-time curve from 0 h to infinity, and apparent half-life of acyclovir obtained after single- and multiple-dose valaciclovir administration in HIV-infected patients were similar to those reported in normal healthy volunteers. The time to maximum concentration in serum and half-life of acyclovir after valaciclovir administration were approximately 2 and 3 h, respectively, which were similar to those reported after oral administration of acyclovir itself. The mean trough and peak acyclovir concentrations and the daily area under the concentration-time curve acyclovir values at steady state were 2.5 and 8.4 micrograms/ml and 120 h micrograms/ml, respectively, after a dosage of 2,000 mg of valaciclovir four times daily. These values were approximately fivefold greater than those achieved with high dosages of oral acyclovir (800 mg, five times daily) and were not affected by continued use of medications necessary for management of advanced HIV disease. Thus, 2,000 mg of valaciclovir given orally four times daily should be evaluated for its potential efficacy in suppressing cytomegalovirus and other herpes group virus infections not optimally managed with current oral acyclovir therapy.
Acyclovir↗
Primary auditory pathway and reticular activating system dysfunction in Alzheimer's disease.
Patients with Alzheimer's disease (AD) have pathologic involvement of several important components of the primary auditory pathway, including the inferior colliculus, medial geniculate body, primary auditory cortex, and secondary auditory cortex. The main components of the brainstem auditory evoked response (BAER) and middle latency response (MLR) reflect the function of portions of the primary auditory pathway, including those affected pathologically in AD. The amplitude of the P1 component of the MLR reflects the degree of neuronal activity of midbrain portions of the ascending reticular activating system (ARAS) with cortical cholinergic projections. To determine whether there is dysfunction of the primary auditory pathway and ARAS in AD, we compared simultaneous BAER and MLR component latency and amplitude measurements in patients with mild-moderate AD (n = 35) and age-matched healthy elderly controls (n = 34). There were significant latency delays in brainstem transmission time (BAER I-V interpeak latency; p < 0.05) and in primary auditory cortex evoked potential generation (MLR Pa latency; p < 0.05) in the AD group compared with controls. In addition, there was a significant reduction in the P1 component amplitude of the MLR in the AD group (p < 0.01). These results indicate dysfunction of the primary auditory pathway and ARAS in patients with mild-moderate AD and support the hypothesis that impairment of auditory function and of arousal are intrinsic features of AD.
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The discriminant value of semiquantitative SPECT data in mild Alzheimer's disease.
UNLABELLED: In most semiquantitative SPECT studies, overlap between groups of patients with Alzheimer's disease (AD) and age-matched elderly controls is such that single posterior cortical perfusion measurements lack sensitivity. In the present study, the value of a combination of semiquantitative temporoparietal SPECT parameters was examined. METHODS: Supratentorial transaxial perfusion measurements were obtained in frontal, anterior temporal, posterior temporoparietal and occipital cortical areas in both hemispheres, in a baseline population of 10 healthy elderly controls and 30 mild to moderately impaired AD patients, as well as in a prospective group of 15 patients with mild cognitive impairment, 12 patients with a diagnosis of probable AD and individual cases of multi-infarct dementia, dementia-frontal type and paranoid psychosis. A linear discriminant function (LDF) was calculated from the baseline subjects' data to classify control and AD subjects individually. RESULTS: Highly significant hypoperfusion was noted in both the anterior temporal and posterior temporoparietal regions of interest in the AD group compared with controls, but with significant overlap. Using an LDF incorporating these perfusion measurements in both hemispheres, 10/10 (100%) controls and 26/30 (87%) AD baseline subjects were correctly classified. Using the baseline LDF in the prospective 15 mildly impaired cases, 11/12 new mild AD cases and none of the 3 non-AD cases were classified in the AD group. CONCLUSION: These results support the use of a combination of semiquantitative SPECT perfusion estimates from cortical areas with predictable pathological involvement in AD in a linear discriminant format in the clinical assessment of patients with suspected AD.
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Ocular microtremor measurement system: design and performance.
The frequency of ocular microtremor (OMT) is related to the functional status of the brain stem, and thus OMT may be useful in the diagnosis and management of brain stem disorders. The paper discusses the design of an OMT measurement system and reports quantitative specifications for three portable systems. All systems use a piezo-electric element as the transducer, which measures the displacement of the sclera during eye rotations. The systems differ in the manner in which the signal is recorded. All systems can detect eye movements corresponding to displacements of the sclera ranging from 12 to over 3000 nm. The frequency responses of all systems are flat (< 2 dB deviation from peak response) between 20 and 150 Hz. The phase response shows deviations (< pi) at the extremes of this range, but qualitative comparison of input and measured signals demonstrates that phase distortion is not excessive. Thus all systems are acceptable for clinical studies involving OMT.
Biomedical Engineering↗
Observing the brachial artery through a pressure cuff.
A technique is described which enables ultrasonic imaging of the brachial artery whilst pressure is applied via a pressure cuff. This involves a new instrument--a sphygmomanometer, which uses water as opposed to air as the pressure medium, in order to permit ultrasonic imaging through the cuff. The technique was found to be acceptable in the clinical setting, and gave a measurement of the systolic blood pressure which correlated with the conventional cuff measurement in eleven elderly subjects (r = 0.89, p < 0.001). The technique should have an important role to play in studying the origin of differences which occur between direct and indirect blood pressure measurements.
Blood Pressure Determination↗
Measurement of arterial closing pressure.
It has been suggested that certain artifacts in blood pressure measurement by auscultation stem from stiffness of the tissues underneath the pressure cuff, resulting in a component of cuff pressure being required to overcome resistance to brachial artery collapse. This paper describes a technique for measuring the pressure required to collapse a segment of the brachial artery which has been isolated from central arterial pressure. This measurement is termed the arterial closing pressure. In a study of eleven elderly subjects, the artery collapsed spontaneously (zero closing pressure) after being isolated from central pressure in seven subjects. The remaining four required external pressures ranging from 4.6 to 10.7 kPa (35 to 81 mmHg) in order to collapse the artery. Thus arterial closing pressure may frequently be a significant fraction of arterial blood pressure in the elderly population, and may contribute to error in the measurement of blood pressure by auscultation. Arterial closing pressure may be a useful tool for investigating the origin of differences between indirect and direct blood pressure measurements, and also in the investigation of spontaneous arterial closure.
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