Oculomotor reaction time in dementia reflects degree of cerebral dysfunction.

The effects of diffuse cerebral dysfunction on oculomotor reaction time were assessed in patients with dementia of presumed Alzheimer's etiology and in normal age-matched control subjects. Patients were classified into mild, moderate, and severe groups on the basis of independent neurological, neuropsychological, and neuroradiological ratings for disease severity. Saccadic latencies to targets appearing in parafoveal and near peripheral vision showed significant increases from the normal controls to dementia groups, with each severity subdivision clearly differentiated from the others in terms of mean oculomotor reaction time. These data offer strong evidence for a direct relationship between degree of cortical structural integrity and simple oculomotor reaction time and suggest a higher cortical regulatory role in sensory-motor integration.

Simple and choice reaction time in dementia: clinical implications.

The present study investigated differences between normal elderly subjects matched for age and education and patients with dementia of the Alzheimer's type (DAT) on two measures of reaction time (RT). Statistically significant group differences clearly demonstrate that normal elderly subjects have faster RT than subjects with senile dementia on all RT tasks. The DAT patients were most clearly differentiated in terms of overall group means and clinical classification from their age-matched counterparts on the choice of RT task. Eleven of 12 (92%) DAT patients displayed choice RT's 2 or more standard deviations above those of age-matched normals. While both RT measures were discriminative between patients and normals, the overall results argue for increased sensitivity when choice is required in RT in accessing the cognitive deficits in DAT.

Establishing the limits of the Mini-Mental State. Examination of 'subtests'.

It has been suggested that the Mini-Mental State examination can be used to examine a patient's cognitive profile. We therefore examined the validity of Mini-Mental State subtests and individual items. The memory item, attention-concentration items, and constructional item had satisfactory sensitivity-specificity and correlated significantly with scores on neuropsychological tests. In contrast, four of the five Mini-Mental State language items had very low sensitivity, and three of five failed to correlate with neuropsychological test scores. These findings establish limits with regard to the ability of the Mini-Mental State to generate a cognitive profile. Our data also provide information regarding validity, difficulty level, and optimal cutoff scores for widely used mental status tasks.

Brain choline acetyltransferase and mental function in Alzheimer disease.

OBJECTIVE: To determine whether higher brain levels of choline acetyltransferase (ChAT) are associated with improved neuropsychological function in patients with Alzheimer disease (AD). DESIGN: Case series with single-blind post hoc analysis of biopsy specimens. SETTING: Urban hospital and medical school. PATIENTS: A consecutive sample of 8 patients with AD undergoing brain biopsy and surgical implantation of intraventricular pumps for administration of potential chemotherapeutic agents. INTERVENTIONS: Brain biopsy, surgical implantation of intraventricular pumps, and, in 1 patient, ventriculoperitoneal shunt placement. MAIN OUTCOME MEASURES: All patients underwent neuropsychological testing no more than 2 weeks before surgical biopsy. Levels of ChAT were determined in fresh brain tissue from biopsy samples. RESULTS: Significant positive correlations were found between ChAT levels and 2 neuropsychological test scores, Mini-Mental State Examination and the Logical Memory subtest of the Wechsler Memory Scale. CONCLUSION: Degeneration of the cholinergic system in vivo correlates with decreasing cognitive function in patients with AD.

The heterogeneity of Parkinson's disease: clinical and prognostic implications.

In 334 patients with idiopathic Parkinson's disease, deterioration in mental status paralleled severity of bradykinesia, postural instability, and gait difficulty. Tremor was relatively independent of the other cardinal signs and was associated with relative preservation of mental status, earlier age at onset, family history of parkinsonism, and more favorable prognosis. There seem to be at least two Parkinson's subgroups: one with postural instability and gait difficulty and another with tremor as the dominant feature.

Relationship of motor symptoms to intellectual deficits in Parkinson disease.

We studied 60 patients with idiopathic Parkinson disease with motor and neuropsychologic tests to ascertain whether the severity of motor symptoms was associated with the degree of neuropsychologic deficity. Significant correlations were found between the severity of brady kinesia and impaired performance on tests assessing visual-spatial reasoning and psychomotor speed. More severe tremor was associated with better performance on a spatial orientation memory test. There relationships remained when age, age at onset, and self-rated depression were controlled. The findings suggested that cognitive impairment may result from the same subcortical lesions that cause motor symptoms.

Clinical, biochemical, and neuropathologic findings following transplantation of adrenal medulla to the caudate nucleus for treatment of Parkinson's disease.

We transplanted autologous adrenal medullary tissue into the caudate nucleus of 3 patients with advanced Parkinson's disease. The 1st patient, a 59-year-old man with parkinsonian symptoms for 15 years, had mild improvement in his motor functioning after the operation. However, his postoperative course was characterized by prolonged drowsiness and complex visual hallucinations. The patient died suddenly 8 months after the transplant, and an autopsy revealed coronary atherosclerosis. Examination of the graft site showed necrotic adrenal medullary tissue surrounded by inflammatory cells. The 2nd patient, a 50-year-old man with a 21-year history of parkinsonian symptoms, improved the most after the procedure. The 3rd patient, a 43-year-old man with 12 years of parkinsonian symptoms, had mild improvement in his motor functioning. CSF homovanillic acid increased postoperatively in the 3 patients, but then returned to preoperative levels in all except the 2nd patient. The anatomic, neurochemical, and physiologic basis for the modest clinical improvement shown in these patients is not yet understood.

Intracerebroventricular bethanechol chloride infusion in Alzheimer's disease. Results of a collaborative double-blind study.

The use of intracerebroventricular bethanechol chloride infusion in patients with Alzheimer's disease was first reported in 1984. An initial trial in four patients demonstrated the feasibility of this approach for cholinergic drug delivery to the brain, but objective improvement in cognitive function was not documented. A collaborative placebo-controlled double-blind crossover study has now been carried out in 49 patients with biopsy-documented Alzheimer's disease. The results demonstrate a statistical improvement in Mini-Mental State scores and significantly slower performance on Trails A testing during drug infusion. Other neuropsychological test scores were not similarly affected. The degree of improvement was not sufficient to justify further treatment of Alzheimer's disease patients by intracerebroventricular infusion of bethanechol chloride. The drug delivery system used in the study was well tolerated, with two irreversible complications in more than 50,000 patient days.

Progressive nonfluent aphasia with dementia: a case report.

We report a patient with progressive nonfluent aphasia and mild dementia. On 9-month follow-up evaluation, there was significant deterioration in both language and cognition. Unlike in Alzheimer's disease, the aphasia was of the Broca's type. In contrast with primary progressive aphasia, a dementia was present and the cognitive and language decline showed a rather rapid course.

Mental status assessment of insight and judgment.

Although a traditional part of the mental status examination, assessment of insight and judgment has received scant attention from researchers and clinicians. This is unfortunate, because few abilities are more crucial to decisions about whether a patient can continue to live independently or what level of supervision is needed. The authors discuss current and evolving methods for the assessment of insight and judgment, and also address neuroanatomic substrates and theoretical conceptions of these functions.

Other neurologic diseases with dementia as a sequela.

Less-common causes of dementia are briefly discussed. Disorders covered include Pick's disease, primary progressive aphasia, progressive supranuclear palsy, Huntington's disease, olivopontocerebellar atrophies, closed head injury, dementia pugilistica, and Creutzfeldt-Jakob disease. Pseudodementia is also discussed. These disorders are compared and contrasted with the more common etiologies of dementia that are reviewed in other articles in the issue. Topics covered include treatment, differential diagnosis, clinical features, and pathogenesis.

Neuropathological and neuropsychological changes in Alzheimer's disease. Relationship of biologic markers to behavioral markers.

Alzheimer's disease is the fourth most common cause of death in the United States, and is the leading cause of functional disability in the elderly. This article analyzes the pathologic validity of mental status tests and the biochemistry of Alzheimer's disease patients.

A developmental study of the auditory Stroop effect.

A pediatric auditory version of the Stroop procedure was developed and administered to 48 normal children from 3 to 6 years of age. Our purpose was to define the developmental course characterizing interaction between auditory and semantic speech dimensions in young children. The procedure was a reaction time (RT) task that required children to respond as quickly and as accurately as possible to words spoken by a male or a female voice. Children were instructed to ignore what was said and to push the "Mommy" button if Mommy was talking or the "Daddy" button if Daddy was talking. Performance was obtained for words with neutral, congruent, and conflicting semantic content. Preschool children manifested processing dependencies that were similar to those observed in adults on the visual Stroop procedure. Conflict between semantic and auditory dimensions significantly increased RT and congruence between the two dimensions significantly decreased RT relative to the neutral condition. The pattern of results indicated that the meaning of words was processed automatically in the normal children. The magnitude of the Stroop effect reflected developmental change with increasing age.

The separability of central auditory and cognitive deficits: implications for the elderly.

After viral encephalitis a 40-year-old man showed both central auditory deficit and severe cognitive deficits. The asymmetric central auditory deficit was revealed by speech audiometry. The effect could be explained neither by peripheral sensitivity loss nor by cognitive status. Results highlight the separability of central auditory and cognitive deficits. Implications for the elderly are discussed.

Impact of central auditory processing disorder and cognitive deficit on the self-assessment of hearing handicap in the elderly.

We studied the impact of central auditory processing disorder (CAPD) and cognitive deficit (CD) on the self-assessment of hearing handicap in 122 elderly subjects. Self-assessment was quantified by means of the Hearing Handicap Inventory for the Elderly (HHIE). Results showed that cognitive impairment exerted no significant effect on the self-assessment of hearing handicap. Subjects with CAPD, however, rated themselves as significantly more handicapped than non-CAPD subjects. Furthermore this difference did not interact with degree of loss. It was present even in subjects without significant peripheral sensitivity loss. These results support the conclusion that CAPD status is a relevant dimension in the evaluation of the elderly subject with or without peripheral hearing loss.

Unsuccessful use of binaural amplification by an elderly person.

An elderly person who preferred and performed better with monaural than with binaural amplification was extensively studied, both audiologically and neuropsychologically, in search of an explanation for the phenomenon. Particular emphasis was placed on the study of dichotic speech perception, both behaviorally and electrophysiologically. Results suggest that age-related changes in interhemispheric transfer of auditory input via corpus callosum may underlie the preference for monaural amplification. Implications for the evaluation of amplification potential in elderly persons are discussed.

Central auditory processing disorder: a case study.

We carried out extensive audiologic, electrophysiologic, and neuropsychologic testing on a young woman who complained that she had difficulty hearing in her educational environment. Conventional audiometric results, including pure-tone, speech, and immittance audiometry, were all within normal limits. The subject performed normally on tests involving the processing of rapidly changing temporal information, interaural time and intensity difference detection, and both absolute and relative sound localization. Early, middle, late and task-related auditory evoked potentials were essentially normal, although some asymmetry was observed in the middle latency (MLR) and late (LVR) responses. There was, however, a consistent left-ear deficit on dichotic sentence identification, on threshold and suprathreshold speech measures in the left sound field when various types of competition were delivered in the right sound field, and on cued-target identification in the left sound field in the presence of multitalker babble. Results suggest a central auditory processing disorder characterized by an asymmetric problem in the processing of binaural, noncoherent signals in auditory space. When auditory space was structured such that the target was directed to the left ear, and the competition to the right ear, unwanted background was less successfully suppressed than when the physical arrangement was reversed.

Lateral asymmetries in visual perception: a review of tachistoscopic visual half-field studies.

Experiments using the visual half-field paradigm are reviewed with special reference to the three theories which purport to account for perceptual asymmetries: the left-to-right internal scanning mechanism theory, the direct anatomical access theory, and the attentional bias theory. Recent evidence has clearly shown that the direct anatomical access theory can account for virtually all lateral asymmetries in the perception of verbal and spatial stimuli. The results of the studies reviewed strongly support a model of brain function which suggests that the simultaneous processing of verbal and spatial stimuli does not constrict the attention of either hemisphere. The difficulty in separating the factors of hemispheric processing and stimulus characteristics is discussed. It is suggested that a reliable conclusion about the role of the cerebral hemispheres can only be made when a better description of the operating characteristics of the hemispheres is available.

Application of Hick's law of response speed in Alzheimer and Parkinson diseases.

Reaction time in normal subjects is known to increase in a log-linear fashion relative to the number of alternative choices. However, this relationship (formalized as "Hick's law") has received limited investigation in populations with neurological cognitive impairment. The present study used timed sorting of standard playing cards to test Hick's law for 20 young control subjects, and 20 each of age-matched elderly subjects with Alzheimer disease, Parkinson disease, and no cognitive abnormalities. Although Parkinson patients were slowest in the simple tasks of dealing out the cards and sorting by color, Alzheimer patients showed the greatest slowing for the more cognitively complex conditions of sorting by suit and rank of the cards. The performance of all four groups followed Hick's law in displaying a significant linear relationship between response time and log2 of the number of choices. These findings suggest that, although limitations of information-processing speed in Alzheimer and Parkinson disease affected choice response time, there may be sparing of fundamental cognitive organization in these disorders.

Oculomotor programming disturbances in the dementia syndrome.

Three types of oculomotor programming disturbances are described in patients with the dementia syndrome. This report describes two of these abnormalities, poorly regulated gaze patterns and a programming type of gaze perseveration. All patients showed poorly regulated gaze patterns in contrast to the normal controls, whereas on the whole only the moderately affected patients showed the programming type of gaze perseveration. The third type of oculomotor programming disturbance is efferent perseveration of gaze (a hypokinetic, "staring" type of gaze pattern) and can be seen with severe dementia. The possible significance of these findings is discussed.