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Biomedical subjects

K M Perryman

Publications and source records attributed to K M Perryman.

At least 19 recordsLinked to original sources

Eye movement abnormalities during reading in patients with Alzheimer disease.

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.

Aged↗

Performance on the Rey-Osterrieth Complex Figure Test in Alzheimer disease and vascular dementia.

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.

Aged↗

Behavioral differences between frontotemporal dementia and Alzheimer's disease: a comparison on the BEHAVE-AD rating scale.

Frontotemporal dementia (FTD) is a dementing syndrome characterized by the occurrence of neuropsychiatric features early in the clinical course. Patients with Alzheimer's disease (AD) also have neuropsychiatric symptoms, but these symptoms typically emerge later in the course after the development of memory and other cognitive impairment. The BEHAVE-AD, an instrument developed to evaluate neuropsychiatric features in dementia, may help characterize the behavioral features of FTD and differentiate FTD from AD. This study evaluated BEHAVE-AD results of 29 patients with the diagnosis of FTD compared to those of 29 patients with the diagnosis of probable AD of similar dementia severity. The FTD patients had significantly worse global BEHAVE-AD scores compared to the AD patients. Verbal outbursts and inappropriate activity characterized the FTD patients, and three BEHAVE-AD subscales correctly classified 69% of the patients. The assessment of neuropsychiatric symptoms with a standardized scale or inventory can help distinguish dementia patients with FTD and AD.

Age Distribution↗

Differences between Alzheimer's disease and vascular dementia on information processing measures.

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.

Aged↗

Frontotemporal dementia versus vascular dementia: differential features on mental status examination.

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.

Aged↗

Compulsive behaviors as presenting symptoms of frontotemporal dementia.

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%) (chi2 = 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.

Aged↗

Effects of normal aging on the performance of motor-vehicle operational skills.

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.

Adult↗

Epileptic forced thinking from left frontal lesions.

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.

Adult↗

Frontotemporal dementia versus Alzheimer's disease: differential cognitive features.

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.

Aged↗

Alzheimer and vascular dementias and driving. A prospective road and laboratory study.

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.

Adult↗

Influence of cholinesterase inhibitors on cortical slow-wave activity in aging nonhuman primate.

Substantial evidence has now accumulated suggesting that the cognitive decrements characteristic of Alzheimer's disease and, to a lesser degree, of normal aging, may result, at least in part, from degenerative changes in the cholinergic system innervating archi- and neocortices. This evidence for cholinergic degeneration in AD has provided the key rationale for many recent clinical trials utilizing cholinergic agents for the purpose of palliating cognitive loss. The basal forebrain cholinergic system plays an important function in electrocortical activation associated with behavioral arousal and cognitive functions. We recorded electrocortical changes from nonhuman primates following administration of potentially clinically useful cholinergic agonists as well as an antagonist. The cholinesterase inhibitors tacrine (THA) and, to a lesser extent, physostigmine (PHYSO) and amodiaquine (AMDQ), caused an upward shift in the frequency of the resting electrocortical activity, although scopolamine significantly slowed the activity below baseline levels. We believe these findings support the concept that the cholinergic system may play an important role in cognitive processes associated with cortical activation.

Aging↗

Delayed matching-to-sample performance during a double-blind trial of tacrine (THA) and lecithin in patients with Alzheimer's disease.

During a double blind, inpatient-outpatient study of THA (tacrine) and lecithin in Alzheimer's disease, data on a laboratory-based delayed-matching-to-sample (DMS) test was collected on six of 10 subjects. DMS measures proved more sensitive to drug effects than clinical measures of cognitive performance. Both clinical and DMS measures suggest that patients with mild to moderate impairment are more likely to show modest improvement in performance than advanced cases. Outcome measures are related to possible mechanisms of attention and memory.

Aged↗

SPECT brain imaging in Alzheimer's disease during treatment with oral tetrahydroaminoacridine and lecithin.

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.

Administration, Oral↗

Effect of BMY 21502 on acquisition of shape discrimination and memory retention in monkey.

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.

Animals↗

Slow wave changes in amygdala to visual, auditory, and social stimuli following lesions of the inferior temporal cortex in squirrel monkey (Saimiri sciureus).

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.

Amygdala↗