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.

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.

Comparison of conventional amplification and an assistive listening device in elderly persons.

OBJECTIVE: To assess the impact of personal amplification systems on quality of life of elderly persons and to compare conventional hearing aid with assistive listening device. DESIGN: Audiologic, neuropsychologic, and quality-of-life measures were prospectively administered to 180 elderly, hearing-impaired persons before and after randomized 6 wk trials of four treatment conditions-a no-amplification condition and three different types of amplification: 1) conventional hearing aid, 2) assistive listening device, and 3) a combination of the two systems. All subjects volunteered to participate in a study comparing different amplification systems and were paid for their participation. RESULTS: Both self-perceived handicap and speech understanding were improved significantly by all three amplification systems. There were no significant group differences between new users and previous users of amplification in self-assessed handicap after amplification use. Anecdotally, subjects preferred the sound quality of the assistive listening device, but an overwhelming majority (97.3%) still chose the conventional aid for use in daily living. CONCLUSIONS: Results affirm the significant impact of amplification on the quality of life of elderly persons. The strong preference for the conventional hearing aid in everyday use undoubtedly reflects the fact that elderly users usually are not willing to endure the difficulties associated with the use of remote-microphone systems.

Aging and memory: corrections for age, sex and education for three widely used memory tests.

The associate learning subtest from the Wechsler Memory Scale; Benton's Visual Retention test and a Controlled Word Association Task (FAS) were administered to a random sample of normal, healthy individuals whose age ranged from 20 to 79 years, recruited within the Italian peninsula. The neuropsychological examination took place on a mobile unit and the tests were given by the same team of neuropsychologists to reduce variability among examiners. The Research Project was known as Progetto Memoria. Corrections to the scores of these tests were calculated for age, sex, and education. These corrected values will allow clinicians to screen for memory impairment with greater precision among normally aging individuals, thus improving differential diagnosis between physiologic and pathologic deterioration of cognitive functions.

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.

Developmental trends in the interaction between auditory and linguistic processing.

The developmental course of multidimensional speech processing was examined in 80 children between 3 and 6 years of age and in 60 adults between 20 and 86 years of age. Processing interactions were assessed with a speeded classification task (Garner, 1974a), which required the subjects to attend selectively to the voice dimension while ignoring the linguistic dimension, and vice versa. The children and adults exhibited both similarities and differences in the patterns of processing dependencies. For all ages, performance for each dimension was slower in the presence of variation in the irrelevant dimension; irrelevant variation in the voice dimension disrupted performance more than irrelevant variation in the linguistic dimension. Trends in the degree of interference, on the other hand, showed significant differences between dimensions as a function of age. Whereas the degree of interference for the voice-dimension-relevant did not show significant age-related change, the degree of interference for the word-dimension-relevant declined significantly with age in a linear as well as a quadratic manner. A major age-related change in the relation between dimensions was that word processing, relative to voice-gender processing, required significantly more time in the children than in the adults. Overall, the developmental course characterizing multidimensional speech processing evidenced more pronounced change when the linguistic dimension, rather than the voice dimension, was relevant.

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.

Correlational analysis of speech audiometric scores, hearing loss, age, and cognitive abilities in the elderly.

A battery of speech audiometric measures and a battery of neuropsychological measures were administered to 200 elderly individuals with varying degrees of pure-tone sensitivity loss. Results were analyzed from the standpoint of the extent to which variation in speech audiometric scores could be predicted by knowledge of pure-tone hearing level, age, and cognitive status. For the four monotic test procedures (PB, SPIN-Low, SPIN-High, and SSI) degree of hearing loss bore the strongest relation to speech recognition score. Cognitive status accounted for little of the variance in any of these four speech audiometric scores. In the case of the single dichotic test procedure (DSI), both degree of hearing loss and speed of mental processing, as measured by the Digit Symbol subtest of the WAIS-R, accounted for significant variance. Finally, age accounted for significant unique variance only in the SSI score.

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.

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.

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.

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.

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.

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.

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.