Double-blind placebo-controlled study of velnacrine in Alzheimer's disease.

The present study assessed the safety and efficacy of the cholinesterase inhibitor, velnacrine, for treating the cognitive symptoms of Alzheimer's disease. Patients (N = 236) meeting NINCDS-ADRDA criteria for Alzheimer's disease entered a double-blind, placebo-controlled dose-ranging protocol (30, 75, 150, 225 mg/day each for one week) to identify velnacrine responders (> or = four point improvement on the cognitive subscale of the Alzheimer's Disease Assessment Scale [ADAScog]). After a two week drug washout, velnacrine responders were randomly assigned to their best velnacrine dose or placebo in a six week dose-replication protocol employing the ADAScog and the Clinical Global Improvement scale as primary outcome measures. During dose-replication, intent-to-treat analysis revealed that velnacrine patients scored significantly better than placebo patients on the ADAScog after two (p < 0.004), four (p < 0.025) and six (p < 0.001) weeks of treatment. No significant treatment effect on Clinical Global Improvement scores was observed. The primary adverse event was an asymptomatic elevation of liver transaminases found among 28% of the 236 treated patients. Cholinergic side effects including diarrhea (14%), nausea (11%) and vomiting (5%) were observed and 8% of patients experienced skin rash. The present study identified a subgroup of Alzheimer's patients who demonstrated a significant, but modest, improvement during velnacrine treatment on structured cognitive testing.

Effects of sudden insight on long-term sentence priming in Alzheimer's disease.

The purpose of this study was to demonstrate spared, long-term sentence priming in individuals with Alzheimer's Disease (AD) using a sentence puzzle task. The sentence puzzle task required a decision--either yes or no--regarding the correctness of an answer supplied for a sentence puzzle. Twelve persons with AD, 12 older controls, and 12 younger controls took part. Speed of response (deciding if a puzzle answer was correct or incorrect) was recorded, with increased speed at retesting after 30-min and 1-week delays used as an index of priming. Individuals with AD demonstrated sentence priming over both a 30-min and 1-week delay, comparable in form to that of controls. In addition, persons with AD were affected by stimulus parameters (correct/incorrect puzzle answers; difficult/easy puzzles) in a similar manner as were controls.

Multi-infarct dementia.

Vascular dementia and its most common subtype, multi-infarct dementia, are pathologically proven clinical entities. Their prevalence is not as high as previously thought, but they do represent a significant percentage of the population of demented patients. The diagnosis is more difficult to make than is the diagnosis of Alzheimer's disease; however, there are excellent criteria to guide the physician in making the diagnosis. At present the only treatment available is to control the risk factors responsible for the basic disease process; in the majority of cases this requires controlling hypertension.

Frontal lobe syndrome in a patient with bilateral globus pallidus lesions.

This article describes a patient who experienced the rapid onset of an irreversible behavioral change while vacationing in La Paz, Bolivia (altitude, 4070 m). The only lesions demonstrated on a magnetic resonance imaging scan were bilateral hemorrhages in the globus pallidus. The behavior change was characterized by apathy and lack of motivation, features commonly associated with bilateral frontal lobe disease. This case is a further demonstration of how subcortical lesions can produce behavioral syndromes that are clinically indistinguishable from classic cortical syndromes. It is cases such as this that show how a strict localizationist concept of behavioral function is too restrictive and how it is necessary to consider a wide network of neuronal interconnections when explaining the mechanism of a dissolution of complex higher functions.

Anomalous dominance in sibling stutterers: evidence from CT scan asymmetries, dichotic listening, neuropsychological testing, and handedness.

Two left-handed siblings with developmental stuttering are comprehensively described. The methods of study included speech and language evaluation, neurological and neuropsychological examinations, dichotic listening, auditory evoked responses, electroencephalogram, and CT scan asymmetry measurements. The data from each sibling showed evidence of anomalous cerebral dominance on many of the variables investigated. The CT scan measurements showed atypical asymmetries, especially in the occipital regions. These findings support the theory that stuttering may be related to anomalous cerebral dominance, both on functional as well as structural bases. Implications of anomalous dominance and the resultant effect of hemispheric rivalry on speech fluency are discussed.

Memory assessment using the Strub-Black Mental Status Examination and the Wechsler Memory Scale.

A systematic mental status exam often can differentiate accurately patients with organic brain disease from normal persons and those with functional disorders. The present study attempts to validate the memory portion of the Strub-Black Mental Status Exam by comparing it to the Wechsler Memory Scale. Twenty-five brain-damaged and 25 routine medical patients were given Form I of the Wechsler Memory Scale and the memory portion of the Strub-Black Mental Status Exam at their hospital bedside. Results indicate significant differences in almost all scores between the brain-damaged and normal groups on both the Wechsler Memory Scale and Mental Status exam; the Mental Status Exam differentiated between groups at a higher level of significance of ANOVA and ANCOVA comparisons of total memory scores, as well as several subtests. In these samples, age, more than education, was an important factor that affected memory test performance. The Mental Status Examination appears valid for the differentiation of clinical samples and for the documentation of specific aspects of memory dysfunction in individual brain-damaged patients. This study represents a beginning step in providing normative data on components of the Strub-Black mental status examination.

Long-term effects of focal, cortical injuries upon articulation and discrimination performance.

Residual, long-term effects of cortical injuries upon speech production are rarely examined. In this study, we examined the articulation and discrimination abilities in twelve subjects who received focal, cortical injuries in Vietnam during 1968-1971. The subjects were divided into two groups based upon the hemisphere (right or left) of lesion. Data revealed the left-hemisphere injured group produced a greater number of articulation and discrimination errors than the right-hemisphere injured group. Articulation errors occurred more often than discrimination errors in both groups. However, a feature analysis revealed the left-hemisphere injured group made predominantly combination errors and the right-hemisphere injured group made predominantly place errors. Taken overall, the data suggest the left-hemisphere injured group may experience residual difficulties with the encoding of phonological units while the right-hemisphere injured group appears to have residual problems that may be related to the spatial correlates of speech.

The correlation between surgical and CT estimates of brain damage following missile wounds.

The occurrence of distant brain damage following an apparent focal missile injury to the brain has not been well documented until computerized tomography scanning demonstrated this phenomenon. Mechanisms of additional or distant damage within the brain may include a high deposit of kinetic energy from the penetrating missile, additional vascular damage, and possibly neuronal and axonal degeneration. Widespread and distant brain changes may explain some instances of late neuropsychological and psychiatric dysfunction or rehabilitation failure following a brain wound. Brain imaging should be used to properly evaluate the full extent of brain damage following wounding.

The clinical utility of reproduction drawing tests with low IQ patients.

Bedside mental status testing in low IQ, poorly educated patients is often difficult. These patients, who comprise a significant proportion of the population served by major inner city public hospitals, have a limited ability to perform adequately on many higher cortical function tests. Because of this, it is often difficult to accurately differentiate between an organic brain syndrome and the effect of depressed intelligence in these patients. Copying line drawings and other constructional tasks are a very important element in a complete mental status examination, as they are frequently failed by patients with organic brain disease. The applicability of drawing tasks in the low IQ patient is an important issue; this study demonstrates that selected drawings can be effectively utilized to identify brain dysfunction in this low IQ population.

Digit repetition performance in patients with focal brain damage.

Digit span forward and backward was investigated in well-matched samples of patients with discrete quadrant brain lesions. The incidence of significantly impaired digit repetition performance and the incidence of large forward and backward digit span discrepancies were also studied. Correlational data of digit span performance and various intellectual, memory, and constructional measures was examined. Approximately 60% of all brain-damaged patients showed an impairment of digit span forward, while only 5% showed a similar impairment on the digit span backward task. These data indicate that digit span forward is a more sensitive measure of brain dysfunction from focal brain lesions. No difference was found in the performance of patients with right or left hemisphere lesions; however, the low incidence of aphasia (8%) in this sample may account in part for the relatively adequate performance by the left hemisphere patients. Although the current data regarding visual constructive deficits and impaired ability to repeat digits backward is inconclusive, there did not appear to be a strong relationship between these two functions for these patients. Digit repetition performance does appear to be related to both general intellectual ability and to performance on the Wechsler Memory Scale.

Constructional apraxia in patients with discrete missile wounds of the brain.

Sixty patients with missile wounds confined to one of the four quadrants of the brain were investigated. All patients had neurosurgical verification of the limits of their lesions. The incidence and severity of constructional apraxia was studied using the WAIS Block Design and Object Assembly subtests, and the Bender Gestalt Test. A uniformly significant caudality effect was obtained with more posteriorly localized lesions resulting in more severe constructional apraxia. A significant laterality effect was obtained on two of three criterion measures with uniformly inferior performance by patients with right hemisphere lesions. The magnitude of the laterality effect, however, was less than that of the caudality effect for all criterion variables. The degree of severity of constructional apraxia in patients with right posterior lesions was uniformly greater than that of patients with other quadrant loci. The incidence of constructional apraxia in the four quadrants varied as expected with the left anterior lesion sample showing very little evidence of constructional apraxia, while the right posterior sample showed a high incidence of such deficits. The absolute incidence of significant constructional apraxia in all samples was suprisingly low. This finding might be partially accounted for by the age and general good health of the subjects studied, the relative absence of general cognitive impairment in the majority of subjects, and the discrete nature of the lesions.