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.

Effects of methylphenidate in HIV-related depression: a comparative trial with desipramine.

This report is a randomized, double-blind, comparative trial of desipramine with the psychomotor stimulant methylphenidate. Twenty HIV antibody-positive patients with depressive symptoms were randomly assigned to either drug. After individual dose titration, the mean daily dose of desipramine was 150 mg. and methylphenidate 30 mg. daily. The differences in responses between desipramine and methylphenidate were not statistically significant on various measures of depression. The antidepressant effect of methylphenidate did not occur any faster than that of desipramine. Both significantly reduced depressive and anxious symptomatology over the blinded portion of the treatments. Thus, methylphenidate relieves depressive symptomatology with efficacy similar to that of desipramine, offering an alternative to patients who are unable to tolerate standard tricyclic antidepressant therapy. The dopaminergic effects of methylphenidate are likely to mediate its antidepressant effects.

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.

Raven's colored progressive matrices: a normative study of a random sample of healthy adults.

Raven's Colored Progressive Matrices Test (RCPM) was administered to 894 normal healthy adults who were randomly selected in six Italian cities and in the Republic of San Marino. Gender, age, and education significantly influenced overall test performance, and performance on different RCPM subsets. Findings from this large random sample provide demographic corrections to test scores for use in clinical practice.

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.

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.

Structured assessment of independent living skills: preliminary report of a performance measure of functional abilities in dementia.

Assessment of functional abilities is integral to the diagnosis and management of elderly patients with dementia. We present a measure of activities of daily living, the Structured Assessment of Independent Living Skills (SAILS), and report preliminary reliability and validity data for 18 patients with Alzheimer's disease (AD) and 18 age- and education-equivalent controls. The SAILS utilizes behaviorally anchored rating scales to directly assess 10 areas of everyday functioning: Fine Motor Skills, Gross Motor Skills, Dressing, Eating, Expressive Language, Receptive Language, Time and Orientation, Money-Related Skills, Instrumental Activities, and Social Interaction. AD patients scored significantly worse than controls in all 10 areas. High correlations were obtained between the SAILS, visuospatial abilities, attention, and visual memory. In contrast, verbal memory, degree of depression, and praxis were not significantly correlated with the SAILS. The SAILS offers a criterion-based means of quantifying patient functional status for both clinical and research applications.

Insight for impairment in independent living skills in Alzheimer's disease and multi-infarct dementia.

Dementing diseases cause a deterioration in the capacity for independent living skills (ILS). The present study investigated the level of insight in ILS impairment in 12 Alzheimer's disease (AD) patients, 12 multi-infarct dementia (MID) patients, and 12 normal elderly controls, using two different measurement techniques: informant report and patient self-report. Pairwise comparisons at the .05 level revealed a significantly greater loss of insight for ILS impairment in AD patients as compared to both controls and MID patients. Additional analyses revealed that loss of insight, operationally defined as the discrepancy between informant report and patient self-report, was not significantly related to age, education, mental status, or level of depression, but was significantly related to degree of caregiver burden. These results indicate that intervention strategies are needed that take into consideration the level of patient insight for ILS impairment, as well as the caregiver's perception of the patient's capabilities and the degree of burden experienced by the caregiver.

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.

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.

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.

Latency and accuracy of word recognition in dementia of the Alzheimer type.

The sensitivity of reaction time (RT) measurement in assessing cognitive decline in dementia of the Alzheimer type (DAT) was evaluated. Sixteen DAT patients and 16 normal elderly controls, matched for age and education, read 50 stimulus words presented individually on a cathode-ray tube. DAT patients exhibited a significantly greater cognitive impairment as shown by multivariate analysis of variance (p less than 0.0001). Canonical variate correlations revealed RT (0.961) to be more sensitive to decline in cognitive functioning in dementia than the measure of number of reading errors (0.559). Results confirm that RT is a highly sensitive measure of central nervous system integrity, which allows for a more refined investigation of a patient's cognitive deficit than is obtainable with traditional test measures. These findings suggest that chronometric measures should be incorporated in clinical and research studies attempting to document the existence and severity of cognitive impairment in neurodegenerative disease.

Choice reaction time modifiability in dementia and depression.

The effects of cognitive impairment resulting from either dementia of the Alzheimer type (DAT) or major depression (pseudodementia) on choice reaction time were examined in two conditions hypothesized to influence group performance selectively. Elderly controls had shorter reaction times than depressed patients who, in turn, were faster than dementia patients in the standard choice reaction time test. Elderly control and depressed subjects responded more quickly under conditions designed to reduce task demands. However, no effect was detected for DAT patients, presumably due to the neural constraints imposed on cognitive functioning in dementia. These results highlight the different etiologies for the intellectual decline in dementia and pseudodementia.

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.