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Objective: To characterize on-the-road, behind-the-wheel driving abilities and related laboratory performances of subjects with mild Alzheimer's disease (AD) and vascular dementia.Design: Prospective, experimental study involving two mild dementia and three age and health control groups. Road test reliability and validity were assessed.Setting: Greater western Los Angeles. Subjects were enrolled from the community by referral and from the Veterans Affairs dementia and diabetes clinics.Participants: Eighty-seven driving subjects were enrolled; 83 completed the study. A sample of eligible dementia clinic subjects consisting of 15 mild AD patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association probable AD criteria, while 12 met Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and Hachinski diagnostic criteria for multi-infarct dementia (vascular dementia). Clinic control subjects consisted of 15 age-matched patients with diabetes and without a history of stroke or dementia. Community controls consisted of 26 healthy, age-matched, older subjects (> 60 years) and 16 young subjects (20 to 35 years).Main Outcome Measures: Drive score from the Sepulveda (Calif) road test and laboratory measures of attention, perception, and memory.Results: The drive scores in the mild AD group (mean, 22.1; SD, 3.8) and in the vascular dementia group (mean, 24.0; SD, 7.8) differed significantly (P < .001 studentized range test) from the drive scores in the diabetic control group (mean, 31.5; SD, 3.9), the older control group (mean, 32.6; SD, 2.8), and the young control group (mean, 33.6; SD, 3.2). Drive score among the three control groups did not vary significantly. Short-term memory (Sternberg), visual tracking, and Folstein Mini-Mental State Examination scores correlated best with drive score, with a cumulative R2 of 0.68. Drive score and number of collisions and moving violations per 1000 miles driven were negatively correlated (r = -0.38; P < .02).Conclusions: Based on this study, type and degree of cognitive impairment are better predictors of driving skills than age or medical diagnosis per se. Specific testing protocols for drivers with potential cognitive impairment may detect unsafe drivers more effectively than using age or medical diagnosis alone as criteria for license restriction or revocation. [ABSTRACT FROM AUTHOR]

Frontotemporal dementia (FTD) is a common neurodegenerative dementia syndrome. Compulsive behaviors frequently occur in FTD and may be presenting symptoms of this disorder. This study evaluated compulsive behaviors as presenting symptoms in 29 patients with FTD compared to 48 patients with Alzheimer's disease (AD) enrolled in the UCLA Alzheimer's Disease Center. The FTD patients met the Lund and Manchester criteria for FTD and had predominant frontal hypoperfusion on single-photon emission computer tomography neuroimaging. The AD patients met National Institute of Neurological and Communicative Disorders-Alzheimer's Disease and Related Disorders criteria for clinically probable AD. Compulsive behaviors occurred in 11 FTD patients (38%) versus 5 AD patients (10%) (X2 = 6.73, P < .01). This difference persisted after controlling for the younger age of the FTD group. There was a range of compulsive behaviors, with the most frequent being repetitive checking activities. Compulsive behaviors are common presenting symptoms among FTD patients and may result from an inability to inhibit urges to perform compulsive movements from damage to frontal-striatal circuits. (J Geriatr Psychiatry Neurol 1997; 10:154-157). [ABSTRACT FROM PUBLISHER]

Operational skills involved in controlling a motor vehicle were measured in two groups of very healthy elderly drivers and a young control group to test the hypothesis that there are age-related declines in operational performance that may influence driver safety. An actual behind-the-wheel, standardized road test was employed using a motor vehicle equipped with sensors to record speed, braking activity, and lane position, as well as direction and magnitude of front-wheel and eye-movement excursions. The data from these sensors were used as dependent measures of operational performance. Older drivers made fewer steering and eye-movement excursions and drifted across the center line more frequently than the young control group. Younger drivers drove significantly faster and executed more braking applications than did their older counterparts. The motor-vehicle operational performance of older healthy drivers was related to visual-spatial attentional declines and the useful field of vision associated with the normal aging process. (J Geriatr Psychiatry Neurol 1996; 9:136-141). [ABSTRACT FROM PUBLISHER]

Quantitative electroencephalography (EEG) was performed on eight of ten Alzheimer patients in a double-blind, inpatient-outpatient tetrahydroaminoacridine (THA) and lecithin trial. Neuropsychological measures were related to EEG activity. Patient baseline dominant parietal rhythms (DPRs) and power spectral distributions differed significantly from controls. Severity of cognitive impairment was related to the degree of parietal slowing. Inpatient THA treatment resulted in increased DPR frequency in six of eight patients. Four of eight inpatients demonstrated reduced power in the delta and theta bands. During the outpatient long-term treatment phase, six of the patients were able to continue. Three of these improved significantly on tests of cognition. Two of these improved patients demonstrated DPRs with increased fre quency. One of these patients also showed a decrease in slow-wave activity. Thus, THA may accelerate DPRs while re ducing power in the slower EEG bands. However, there appears to be only a tentative coupling between individual quantitative EEG measures and cognitive performance associated with THA administration (J Geriatr Psychiatry Neurol 1991;4:127-133). [ABSTRACT FROM PUBLISHER]

Objective: This goal of this study was to evaluate reading ability by assessing eye movements during reading among patients with Alzheimer disease (AD) compared with normal elderly controls., Background: Reading is disturbed in patients with AD. These patients may have changes in reading ability early in the course of their disease before clinical alexia or abnormalities are apparent on standard reading tasks., Method: Reading competence was evaluated by recording eye movements during reading in 14 patients with mild to moderate clinically probable AD and 14 age- and education-matched controls., Results: All patients with AD could recognize letters and words and could understand written material of similar difficulty. Despite successful reading comprehension among the patients with AD, their oculographs showed slowed reading and irregular eye movements. Compared with controls, the patients with AD did not differ in saccadic duration; however, they had significantly longer fixation times, more forward saccades per line of text, and more saccadic regressions. In addition, increased reading difficulty significantly correlated with a scale of dementia severity in the patients with AD., Conclusions: This pattern of eye movements corresponds to increased text difficulty and probably represents difficulty with lexical-semantic access in AD. These results suggest that disordered eye movements can signal difficulties in reading ability in AD even before complaints of reading difficulty or abnormalities on reading tests and may be a means of identifying linguistic impairment early in this disorder.

Patients with dementia and leukoaraiosis may have either Alzheimer's disease (AD) with cerebrovascular changes or a form of vascular dementia (VaD). The presence or absence of the characteristic AD pattern of bilateral temporoparietal hypometabolism on (18)FDG-PET was used to differentiate 30 patients with progressive dementia and severe leukoaraiosis. Compared to 18 patients with the typical AD pattern (group I), the remaining 12 (group II) had better recognition memory, and greater difficulty with sustained attention and serial reversals. Better recognition memory, confluent periventricular leukoaraiosis, and poorer sustained attention distinguished all group II patients from group I. Dementia patients with severe leukoaraiosis and bilateral temporoparietal hypometabolism may have predominant AD; those who lack this pattern and have confluent leukoaraiosis may have a greater contribution from VaD. Copyrightz1999S.KargerAG,Basel

Background: Alzheimer disease (AD) and vascular dementia (VaD) are the two most common age-associated dementias. Neuropsychologic studies have demonstrated visuoconstructional impairment in AD and in VaD., Objective: This study used the Rey-Osterrieth Complex Figure to assess and compare specific aspects of visuoconstructional deficits in patients with AD, patients with VaD, and normal age-matched subjects., Method: Thirteen normal controls, 20 patients with AD, and 20 patients with VaD were given a neuropsychologic battery as part of a comprehensive evaluation for dementia. The groups were similar in age and education, and the VaD and AD groups had comparable levels of dementia. Based on their previous research on visual deficits in AD, the authors devised a new scoring system that divided the Rey-Osterrieth Complex Figure into six perceptual categories: right, left, upper, lower, basic gestalt, and inner detail., Results: Patients with AD and patients with VaD had significant deficits in all six Rey-Osterrieth Complex Figure scoring categories compared with normal controls. Patients with AD exhibited a pattern of deficits similar to that of patients with VaD, with one significant exception: The patients with AD had increased left-sided errors or inattention., Conclusions: These results suggest that left hemispatial inattention contributes to impaired performance on visuoconstructional tasks in AD.

This study evaluated information processing differences between 30 vascular dementia (VaD) patients, 30 Alzheimer's disease (AD) patients, and 30 normal elderly (NE) controls. They were administered a complex reaction time test, a continuous performance test (CPT), and a neuropsychological battery. Compared to NE, both dementia groups had significantly slower motor reaction times and made more errors on the CPT. Compared to AD patients, the VaD patients were slower in stimulus categorization time and had increasing omission errors and persistent commission errors throughout the CPT trial, VaD, which usually includes frontal-subcortical circuit injury, can impair mental speed and stimulus response initiation.

Objective: After Alzheimer's disease, vascular dementia (VaD) and frontotemporal dementia (FTD) are among the most common dementing illnesses. FTD may have a neuropsychological profile similar to that of VaD, and patients with these dementias may be difficult to distinguish on clinical examination. The purpose of this study was to elucidate distinct cognitive profiles of a large group of FTD and VaD patients on a brief, clinical mental status examination., Design: A comparison of 39 FTD patients and 39 VaD patients on a brief, clinical mental status examination., Setting: A Dementia Research Center and affiliated, university hospitals., Methods: The FTD patients were diagnosed by noncognitive clinical and neuroimaging criteria, and the VaD patients met NINDS-AIREN criteria for vascular dementia. The two dementia groups were comparable on three dementia assessment scales., Measurements: The mental status measures included the neuropsychological battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), plus supplementation from the Neurobehavioral Cognitive Status Examination (NCSE) for cognitive areas not assessed by the CERAD)., Results: The FTD and VaD groups differed significantly on the mental status examination measures. FTD patients performed significantly better than the VaD patients on digit span and constructions, despite comparable performance by both groups on calculations. Although not statistically significant, the FTD group performed worse than the VaD group on verbal fluency and abstractions. These differences were not explained by group differences in age and education., Conclusion: These results suggest that cognitive differences between FTD and VaD groups reflect greater frontal pathology in contrast to relative sparing of posterior cortex and subcortical white matter in FTD. These cognitive differences as measured by a mental status examination may help distinguish between these two dementia syndromes.

Frontotemporal dementia (FTD) is a common neurodegenerative dementia that can be difficult to distinguish clinically from Alzheimer's disease (AD). The differential distribution of pathology in FTD and AD predicts the presence of differential cognitive features on mental status examination. We compared 39 FTD patients with 101 AD patients on the Consortium to Establish a Registry in AD examination supplemented by cognitive areas from the Neurobehavioral Cognitive Status Examination. The FTD patients were diagnosed using noncognitive clinical and neuroimaging criteria and were comparable to the AD patients in terms of gender, educational level, and dementia severity ratings. The FTD patients performed significantly better than the AD patients on constructions and calculations. These findings were at the lower limits of normal for older normal controls and persisted after covarying for younger age and higher Mini-Mental Status Examination scores in the FTD group. In addition to personality and neuroimaging features, relatively preserved performance of elementary drawings and calculations in FTD suggests additional features for distinguishing FTD patients from comparably demented AD patients.

Forced thinking is an incompletely understood and rarely described epileptic aura. We studied three patients with forced thinking from left frontal lesions, two neoplastic and one vascular. All three experienced repetitive, intrusive thoughts at the onset of seizures. Their forced thinking was associated with the desire to vocalize, orobuccal movements, and speech arrest. The episodes occurred with other ictal manifestations and responded to antiseizure therapy. These patients suggest that epileptic forced thinking is a heterogeneous phenomenon; forced thinking from left frontal lesions is a manifestation of expressive language and is distinct from experiential thoughts arising from temporal limbic foci.

Quantitative SPECT brain imaging was performed in five normal subjects and in six ambulatory patients with Alzheimer's disease before the initiation of treatment with tetrahydroaminoacridine (THA) and lecithin. Imaging data were acquired with a single-head SPECT camera and a high-resolution collimator after the intravenous injection of 5 mCi of (p,5n) I-123 IMP. Uptake per pixel in 28 regions of interest in the transverse projection of each study was normalized to uptake per pixel in the cerebellum. Perfusion in the patients with Alzheimer's disease was decreased compared with that of the subjects. Perfusion was decreased greater than 2 SD below the mean in the posterior parietal cortex of 5/6 patients, in the temporal cortex of 3/6 patients, and in the frontal cortex of 2/6 patients with Alzheimer's disease. SPECT imaging was repeated in the six patients after initial titration to peak therapy with oral THA (75 to 200mg per day). The same abnormalities were again seen in the same patients. No dramatic clinical or behavioral change in cerebral perfusion was observed from initial treatment of Alzheimer's disease with THA and lecithin.

BMY 21502 is a novel pyrrolidinone nootropic with demonstrated ability to reverse electroconvulsively induced amnesia in rodents. We administered BMY 21502 intramuscularly to four monkeys (Macaca radiata) during testing using two separate paradigms. The first test involved the acquisition of a visual shape discrimination task where each monkey learned to select the correct lighted panel. In the second task, memory retention was tested by having the monkeys select and press the correct lighted panel using a delayed matching-to-sample procedure. A dose-response relationship was established for the acquisition of shape discrimination for each monkey. Two performance-enhancing doses in the visual discrimination task were then employed to test for effects on memory retention at different delay intervals in the delayed-matching-to-sample task. Results indicate that BMY 21502, when administered over a wide dose range, enhanced acquisition of shape discrimination in three of four monkeys when combined drug scores were compared to vehicle-only scores (p less than 0.02). However, BMY 21502 produced no significant improvement in memory retention at any of seven different delay intervals when low-dose and high-dose scores for the three responding monkeys were compared to vehicle-only scores.

Ten Alzheimer's disease patients underwent a trial of oral tetrahydroaminoacridine (THA) and lecithin. After 3 inpatient weeks there was no clear therapeutic effect. Three of six patients able to continue in long-term treatment showed measurable cognitive improvement, but only one displayed clinically obvious improvement.

Unilateral trigeminal tractotomy was carried out at the level of the obex, just rostral to the subnucleus caudalis, in five young adult Macaca fascicularis monkeys. The animals had been trained previously to perform a behavioral shock avoidance task in response to electrical stimulation of dental pulp and facial skin. Tractotomy produced an elevation in the stimulus strength which elicited escape behavior when facial skin was stimulated but not when the tooth pulp was stimulated. Unit activity, evoked by electrical stimulation of the tooth pulp and facial skin as well as innocuous and noxious mechanical stimulation of orofacial regions, was recorded from neurons in the trigeminal main sensory nucleus and the subnuclei oralis and interpolaris of the spinal nucleus 8 to 12 weeks after tractotomy. Primary afferent input to these nuclei is unaffected by the tractotomy which is located more caudally. The tractotomy interrupts primary afferent input into the trigeminal nucleus caudalis and also intranuclear connections between caudalis and the more rostral nuclei. Forty-one units contralateral and 47 ipsilateral to the tractotomy were studied. Thirty-six of the units responded only to low-threshold mechanical or electrical stimulation of orofacial zones, 46 were responsive to innocuous mechanical and electrical stimulation of orofacial zones and also to electrical stimulation of the dental pulp. Six units responded only to dental pulp stimulation. No statistically significant differences between the populations of neurons ipsilateral and contralateral to the tractotomies were found relating to the size or location of the peripheral receptive fields, latencies, thresholds, mean firing densities, or responsiveness to the various forms of stimulation. The behavioral results suggest that trigeminal relay neurons rostral to the obex are able to signal dental pain sensation, and the physiological studies confirm that the firing of such neurons is unaffected by tractotomy. The physiological studies demonstrate that the firing patterns of relay neurons activated by natural and electrical cutaneous facial stimuli and which are located in trigeminal brain-stem nuclei rostral to the obex are also not affected by tractotomy. The cutaneous facial analgesia observed after tractotomy thus appears to be due to deafferentation of relay neurons in trigeminal nucleus caudalis rather than to alterations in coding patterns in rostrally located trigeminal neurons due to interruption of the intratrigeminal pathway between the caudal and rostral nuclear groups.

Visual-evoked potentials (VEPs) and auditory-evoked potentials (AEPs) were elicited from amygdala nuclei and inferior temporal (IT) cortex in chaired, alert squirrel monkeys to diffuse flash and click stimuli. VEPs were recorded from electrodes placed in basalis lateralis amygdalae (BLA) and basalis medialis amygdalae (BMA) while AEPs could also be obtained from additional electrode sites in basalis accessorius medialis (BAM), centralis amygdalae (CeA), and lateralis amygdalae (LA). The amygdala-evoked potentials resulting from stimulation of the two modalities were similar in terms of component configuration. AEPs recorded from the IT cortex had shorter latencies than the amygdala VEPs that were recorded. Both modalities of stimulation elicited potentials with shorter onset latencies in the amygdala than those recorded from the surface of IT cortex. Bilateral ablation of the IT cortex eliminated VEPs recorded from the BMA but not the BLA amygdala region. AEPs recorded from BMA as well as other amygdala areas were not consistently affected by these IT cortical ablations.

Radiotelemetry of slow wave activity of the amygdala was recorded under a variety of conditions. Power, and the percentage of power in the delta band, increased in response to stimulation. Recordings of monkey vocalizations and slides of ethologically relevant, natural objects produced a greater increase in power than did control stimuli. The responses to auditory stimuli increased when these stimuli were presented in an unrestrained, group setting, yet the responses to the vocalizations remained greater than those following control stimuli. Both the natural auditory and visual stimuli produced a reliable hierarchy with regard to the magnitude of response. Following lesions of inferior temporal cortex, these two hierarchies are disrupted, especially in the auditory domain. Further, these same stimuli, when presented after the lesion, produced a decrease, rather than an increase, in power. Nevertheless, the power recorded from the natural stimuli was still greater than that recorded from control stimuli in that the former produced less of a decrease in power, following the lesion, than did the latter. These data, in conjunction with a parallel report on evoked potentials in the amygdala, before and after cortical lesions, lead us to conclude that sensory information, particularly auditory, available to the amygdala, following the lesion, is substantially the same, and that it is the interpretation of this information, by the amygdala, which is altered by the cortical lesion.

No influences of chronic cerebellar stimulation were found in 10 different controlled experiments in 5 different monkeys with chronic alumina-induced psychomotor seizures. The stimulation parameters used were comparable to those used in human epileptics, and continuous daily EEG and behavioral monitoring allowed all seizures to be measured for daily frequency and duration over the several weeks of the experiments. Nocturnal seizures were similarly quantified in 3 monkeys to verify that cerebellar stimulation did not affect them. Motor cortex potentials evoked by cerebellar pulses confirmed that the stimulations were activating the cerebellum throughout the experiments, and measures of electrode access resistance and impedance verified that the electrodes remained in contact with the cerebellum. In one monkey given phenobarbital medication, interictal morbid behavior appeared to be improved by chronic stimulation of either cerebellum or dorsolateral frontal cortex, thus indicating an arousal influence of brain stimulation not due to cerebellum per se.

Intravenous procaine HCl given at low doses (0.5-2.5 mg/kg) to two monkeys with bilateral alumina hippocampal foci depressed interictal spiking or had little effect. At 5.0 mg/kg unilateral limbic activation occurred. At 10.0 mg/kg unilateral or bilateral limbic activation and generalized seizures could be evoked within 3-10 min. At higher doses (15 and 20 mg/kg) bilateral limbic activation or brief (one min) generalized seizures occurred. The unilateral-onset psychomotor seizures were not identical to spontaneous psychomotor seizures, and the generalized seizures never occurred spontaneously in these monkeys. However, these results do indicate that procaine challenges may selectively activate limbic epileptogenic areas without activation of debilitating generalized tonic-clonic seizures.

Eleven Macaque monkeys underwent a variety of lesions in the trigeminal afferent system; namely, tractotomy, rhizotomy, and radiofrequency destruction of various components of the bulbospinal trigeminal nuclear complex. Behavioral responses were evaluated before and after the lesions using a quantitative paradigm which measured lever-pressing in response to electrical stimulation of the dental pulp or facial skin, and by assessing adversive responses to facial cutaneous and intraoral pin-scratch. Thresholds for lever-pressing in response to cutaneous facial stimulation were elevated by tractotomy, elevated further by a combination of tractotomy and rhizotomy of the seventh, ninth, and 10th cranial nerves and cervical dorsal roots C1-3, and maximally elevated by complete radiofrequency destruction of the trigeminal nucleus caudalis. These lesions also abolished adversive responses to cutaneous facial pin-scratch. None of these lesion combinations, however, altered lever-pressing responses to dental pulp stimulation. Radiofrequency destruction of the trigeminal nuclei principalis, oralis, and interpolaris caused elevations of lever-pressing thresholds in response to dental pulp stimulation, and also smaller but statistically significant elevations on cutaneous electrical stimulation. Mild reductions in adversive responses to cutaneous pin-scratch were also produced by these rostral nuclear lesions, suggesting analgesia. The experiments suggest that primary afferent fibers for dental pain perception travel only in the trigeminal nerve and that these fibers relay via the trigeminal brain-stem nuclei principalis, oralis, and interpolaris. Primary afferent fibers for cutaneous facial pain perception travel in the trigeminal, facial, glossopharyngeal, and vagus nerves, and the upper cervical dorsal and ventral roots, and these afferents relay mainly in the trigeminal nucleus caudalis.

Trigeminal tractotomy near the level of the obex was carried out in 10 macaque monkeys. Behavioral responses were evaluated by a quantitative paradigm measuring lever-press responses to electrical stimulation of the dental pulp or facial skin, and by assessing facial response to cutaneous pin-scratch before and after the tractotomy. Two pharmacological agents, strychnine and L-dopa, were administered and their effect on behavioral responses to these stimuli was studied. Tractotomy did not produce dental analgesia. Thresholds for escape from cutaneous electrical stimulation of facial skin, however, were elevated, consistent with marked hypalgesia to pin-scratch. The adversive responses to pin-scratch were absent in peripheral portions of the face, but near the midline and inside the oral cavity they were usually decreased or normal. Pharmacological agents caused a reduction in escape thresholds to cutaneous electrical stimulation and a shrinkage or abolition of the zone of analgesia to pin-scratch. The results imply that trigeminal nucleus caudalis, which undergoes deafferentation by tractotomy, may not be essential for processing of nociceptive information from the teeth, oral cavity, and midline facial zones. This findings is contrary to long-held hypotheses concerning facial pain mechanisms. The ability of strychnine and L-dopa to alter nociceptive escape thresholds is consistent with the idea, suggested by Denny-Brown, that facial nociception depends on central summation in the entire spinal trigeminal nucleus from overlapping afferent inputs contained in the trigeminal nerve, other cranial nerves, and the upper cervical nerve roots.

Single unit responses were recorded in the pulvinar nucleus of the squirrel monkey (Saimiri sciureus) while awake and alert, with the head fixed but free to make eye movements. Peri-saccadic time histograms revealed only post-saccadic responses to eye movements made spontaneously in the dark or in a uniformly illuminated field (Ganzfeld), or to trained eye movements made in response to a spot of light in the periphery. Of 120 pulvinar neurons that responded to eye movements in the light, approximately one-quarter was responsive to eye movements in the dark. In one group of monkeys about half of the eye movement-responsive cells in the light were responsive to light flash in the dark; in another group approximately half of the eye movement-responsive cells in the light were also responsive to trained eye movements. Of particular interest is the fact that pulvinar neurons responsive to eye movements were located within a restricted region oriented vertically and cutting across lateral and inferior pulvinar, rostrally, and lateral and medial pulvinar, caudally. The results have been interpreted as supporting the concept of convergence and integration of visual and oculomotor input in the pulvinar and also its potential role in the mediation of visual attention.