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We examined the clinical characteristics of six right-handed patients who developed speech motor control disorders after human immunodeficiency virus (HIV) infection. They exhibited an ataxic dysarthria, characterized by irregular articulatory breakdowns in consonant and vowel timing; were slow in timed decision-making tasks; and had impaired procedural learning. Other aspects of the neurologic examination revealed signs of diffuse CNS involvement including action-intention tremors, ataxic gait, and release signs. None developed HIV-associated dementia during 1 year of follow-up. Motor speech control disorder appears to be related to a cerebellar dysfunction.

Objective: To describe temporal trends in the incidence of human immunodeficiency virus (HIV)-related neurologic diseases in the Multicenter AIDS Cohort Study from 1985 to 1992., Methods: The incidence rates of six neurologic disorders were examined: toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, progressive multifocal leukoencephalopathy, HIV dementia, and sensory neuropathy. Poisson modeling was used to test linear trends over time and the effects of progressive immunosuppression, antimicrobial prophylaxis, and antiretroviral drug therapy., Results: There was an upward temporal trend in all incidence rates, except for HIV dementia. Progressive immunosuppression in the cohort explained all calendar trends except for sensory neuropathy, where an increasing temporal trend remained even after adjusting for CD4+ cell count, and for HIV dementia where a slight decline was noted, although the effects were not statistically significant. We noted a protective trend of antimicrobial prophylaxis on toxoplasmosis and cryptococcal meningitis, but, in contrast, use of antiretroviral agents was not protective against HIV dementia. Men receiving didanosine, zalcitabine, or stavudine were more likely to develop sensory neuropathy., Conclusion: Despite the earlier and more widespread use of antimicrobial and antiretroviral agents, neurologic conditions still occurred frequently in this cohort, with annual rates above 1.5 per 100 person-years for HIV dementia and sensory neuropathy. Sensory neuropathy seems to be increasing in incidence and HIV dementia declining slightly in this cohort. As the epidemic matures and more people with profound immunosuppression live longer, the overall incidence of HIV-related neurologic diseases can be expected to rise.

We evaluated the reliability of clinical diagnoses using the recently standardized criteria for the diagnosis of vascular dementia (VaD) developed by the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN). Two neurologists and two psychiatrists independently reviewed clinical data abstracted from those of 42 demented subjects participating in a longitudinal study of dementia at the University of Pittsburgh. For each patient we abstracted the clinical data on a standardized form. Each physician diagnosed each case according to the NINDS-AIREN criteria, using both clinical information and MRIs. We calculated the interrater agreement for all two-way combinations of clinicians with kappa statistics, which ranged from 0.46 (moderate agreement) to 0.72 (substantial agreement). The moderate reliability observed in this study may be attributable to patient-, clinician-, or criteria-centered sources of variance.

Objective: We describe the sampling, initial evaluation, and final diagnostic classification of subjects enrolled in a natural history study of Alzheimer's disease (AD)., Design: Volunteer cohort study., Setting: Multidisciplinary behavioral neurology research clinic., Patients or Other Participants: Three-hundred nineteen individuals were enrolled in the Alzheimer Research Program between March 1983 and March 1988. Of these, 204 were originally classified with AD, 102 were normal elderly control subjects, and 13 were considered special cases., Main Outcome Measures: Final consensus clinical diagnosis, final neuropathologic diagnosis, and death., Results: Of the 204 patients enrolled in the study, re-review after as many as 5 years of follow-up resulted in a final clinical classification of 188 with probable AD. Seven patients were believed to have a significant vascular component to the dementia, three were found to have developed depression, and six were excluded on other clinical grounds. Neuropathologic examination of 50 brains indicated definite AD in 43. After removing these seven misdiagnosed patients, the final group of probable/definite AD totaled 181 individuals. Accuracy of the baseline clinical diagnosis relative to neuropathology was 86%, and when follow-up clinical data were considered, 91.4%. Detailed neuropsychological testing yielded high sensitivity (0.988) and specificity (0.983) to dementia. Analyses of survival time from study entry until death revealed that older patients were significantly more likely to die during follow-up, but neither sex, years of education, nor pattern of cognitive impairment were related to survival., Conclusions: These data provide the descriptive basis for future studies of this cohort. They indicate that longitudinal follow-up of demented cases increases accuracy of diagnosis, and that detailed cognitive testing aids in early classification.

The purpose of the present study was to investigate the imagery ability of 8 "probable" Alzheimer disease patients using a standard task sensitive to the disruption of the imagery system. These patients were selected based on their good performance on a prerequisite clock-setting task, and with 8 matched control subjects were then required to compare the angles made by the hands on clock faces using only imagined stimuli. There were no significant differences between patients and controls in performance on the clock-imagery task. These data are consistent with models of information processing which postulate the relationships between visual imagery and a short-term memory store and include a central executive system for allocation of cognitive resources.

Previous studies have identified age as a risk factor for many neurologic disorders, and a "cerebral reserve" factor has been postulated to explain these findings. This study examined whether age represents a risk factor for HIV-1-related neuropsychological dysfunction. Subjects for study 1 were primarily asymptomatic seropositive (n = 1,066) and seronegative (n = 1,004) nonelderly male community volunteers who completed neuropsychological and reaction time measures. Data analyses revealed a significant effect for age on reaction time and timed neuropsychological measures, but no interaction between age and serostatus. Study 2, employing a similar neuropsychological battery, consisted of 76 seropositive men (29 over age 55) recruited from community outpatient clinics and 47 seronegative controls. We found serostatus and age to have main effects on a number of measures, but a trend for an effect of age-serostatus interaction on only one measure.

This study presents a structural and clinical description of a patient with dementia of motor neuron disease (D-MND), and compares and contrasts the neuropsychological characteristics of this patient with those of a group of patients with Alzheimer's disease (AD) matched by severity of dementia. The D-MND patient as well as the AD patients performed abnormally on all tasks that assessed executive/frontal functions. However, the D-MND patient tended to be more impaired than AD patients on tasks that required high speed decisions and on shifting from one strategy to another. Deficits in memory, language, and lexical-semantic abilities were also apparent in this patient. The co-occurrence of signs and symptoms characteristics of 'subcortical' dementia with those of 'cortical' dementia suggest that the executive system dysfunction may be secondary to subcortical pathology.

We examined the relationship between unawareness of cognitive deficits and psychiatric and neuropsychological manifestations in 181 patients with probable Alzheimer's disease (AD). Patients unaware of their cognitive deficits were more cognitively impaired, as measured by the Mini-Mental State Examination, and had a specific defect in 'frontal/executive' functions. The presence of major depression, delusions and hallucinations was no more likely among patients who were aware of their cognitive impairment than among those who were not. These findings have important implications for the understanding of anosognosia and deficit awareness in dementia.

The functional neuroanatomy of verbal memory was investigated using verbal free recall during H2 (15) O positron emission tomography (PET). Twelve young (25-40 years old) normal control subjects participated in eight scans during a single scanning session during which they performed three memory tasks differing by word list length. Four subjects also had scans during a "rest" condition. Temporal lobe activation was observed during all tasks, including single-word repetition. The frontal cortices, specifically Brodmann areas 9 and 10, were activated only when the recall word lists exceeded the memory spans (i. e., 12 and 15 words). Activation was also observed in the anterior cingulate cortex (BA24 and BA32). These data, obtained using a within-subject design, extend previously reported findings that used mixed within-and between-subject designs and demonstrate important functional components of normal auditoryverbal short-term memory. © 1994 Wiley-Liss, Inc., (Copyright © 1994 Wiley-Liss, Inc.)

We determined incidence and future projections of dementia after AIDS onset in 492 homosexual men with AIDS in the Baltimore/Los Angeles sites of the Multicenter AIDS Cohort Study, 64 of whom developed dementia. We studied various risk factors for dementia, including demographic and clinical features, medical history, markers of immune status before AIDS, and zidovudine use. During the first 2 years after AIDS, HIV dementia developed at an annual rate of 7%. Overall, 15% of the cohort followed through death developed dementia. The median survival after dementia was 6.0 months. Using a proportional hazards model, risk factors for more rapid development of dementia were lower hemoglobin (relative hazard, 0.59 per additional 2 g/dl; p = 0.0005) and body mass index (relative hazard, 0.64 per additional 5 kg/m2; p = 0.05) 1 to 6 months before AIDS, more constitutional symptoms 7 to 12 months before AIDS (relative hazard, 1.68 per additional symptom, p = 0.005), and older age at AIDS onset (relative hazard, 1.60 per decade older; p = 0.009). In a multivariate model, pre-AIDS hemoglobin remained the most significant predictor of dementia. There were no significant risks defined from demographic characteristics, specific AIDS-defining illnesses, zidovudine use before AIDS, or CD4+ lymphocyte count before AIDS. We project that 12 months after the first AIDS diagnosis, 7.1% of survivors will have dementia. The observed association between anemia, low weight, constitutional symptoms, and dementia suggests a role for cytokines inducing both systemic and neurologic disease.

Neuropsychological and psychiatric evaluations were made of 39 subjects with possible Alzheimer's disease and a history of excessive alcohol consumption (AD + ETOH), who had been abstinent or had drunk minimally for at least three months before evaluation, and 225 patients with probable Alzheimer's disease (PAD) of comparable age, years of education, and baseline global impairment. At baseline, there were no significant differences between the groups in terms of age of onset of dementia, neuropsychological test scores, or current behavioural or psychiatric symptoms. One year later, no differences in rates of decline between 20 abstinent AD + ETOH patients and 88 PAD subjects could be shown. Thus, past heavy alcohol consumption does not appear to modify the presentation of dementia of the Alzheimer's type, nor does it modify progression over a one-year interval.

The present study reports new and unexpected results of cognitive abnormalities among human immunodeficiency virus type 1 (HIV-1) asymptomatic subjects in the Multicenter AIDS Cohort Study. The major purpose of our analyses is to estimate the separate and combined effects of serostatus and education level on the prevalence of cognitive abnormality. Cognitive "abnormality" was defined as performance that deviated > or = 2 SDs below the mean of the total seronegative group on at least one of the five neuropsychological screening tests (Grooved Pegboard, Verbal Fluency, Digit Span, Symbol Digit Modalities, Rey Auditory Verbal Learning). The predicted prevalence of cognitive abnormality was 38% in seropositive individuals with no more than 12 years of education, compared with < 17% in the other education-serostatus groups. This interaction between education level and serostatus remained after controlling for the possible confounding effects of age, ethnicity, CD4 level, depression, prior drug history, and learning disability using logistic regression. To account for these findings, we suggest that low education might reflect an indirect index of lower reserve capacity (i.e., a risk factor) that lowers the threshold for neuropsychological abnormalities in cases of early HIV-1 infection.

Immediate memory for visuospatial information was assessed in patients affected by Alzheimer-type dementia but with unimpaired visuo-perceptual functions. Patients were given two tasks: one was a traditional visuospatial memory task (Corsi's block tapping test), the second explored specifically immediate memory for visuospatial patterns. The experiment was conducted in two parallel groups of patients in Italy and the United States, each with its own appropriate sample of normal control subjects. Results showed a specific deficit of visual working memory in demented patients, even in a task in which control subjects achieved error-free performance. These data are interpreted in the light of the Working Memory Model, and suggest that in dementia the functions of the Visuospatial Scratchpad, unlike the functions of the verbal subsystems, may be impaired.

Current theories of memory and memory dysfunction emphasize the importance of the use of contextual information in the storage and retrieval of specific episodes. Patients with lesions primarily in the diencephalon perform poorly on a measure of temporal recency, while those with temporal lobe amnesia are significantly better. The present study evaluated the ability of Probable AD patients to utilize information about temporal recency in the context of a recognition memory task. The performance of the AD patients was significantly impaired and resembled that of patients with Korsakoff's syndrome. The pattern of performance suggested that they were able to recognize which stimuli had been previously presented, but were unable to recall the correct temporal context. Further, there were no significant correlations between measures of temporal recency and those of frontal lobe function. These data suggest that AD patients, like other groups of patients with severe memory defects, are impaired at the use of context information in their attempts to remember recent events.

This study extends previous work analysing functional dissociations occurring in patients with Alzheimer's disease (AD) by demonstrating that material-specific memory loss is common. The pattern of neuropsychological dysfunction in 191 patients with probable AD was examined and 13% presented with material-specific memory loss. Thirteen patients had impaired immediate verbal recall, but normal non verbal recall and 12 had impaired non verbal recall and normal verbal memory. These patterns appeared to be related to a specific memory deficit and were probably not secondary to associated cognitive impairments. These data confirm earlier observations that the memory defect in AD can be material-specific, and suggest that these patterns of impairment should be viewed as a focal sparing of function.

We evaluated the neuropsychological functions, rate of disease progression, and psychiatric characteristics of 22 patients with probable Alzheimer's disease in whom periventricular white-matter radiolucencies (PWMRs) were seen on the computed tomographic scan of the brain and compared them with 22 matched patients with Alzheimer's disease without PWMRs. Executive/attention, lexical/semantic, memory/learning, and visuospatial functions did not differ between the two groups at baseline or at the 1-year follow-up examination. The frequency of major depression, delusions, and hallucinations did not differ between the groups. However, patients with PWMRs had significantly higher Hachinski Rating scores at both visits and were more likely to develop cerebrovascular disease during follow-up than were controls with Alzheimer's disease. These preliminary results suggest that the presence of PWMRs is not associated with specific cognitive and psychiatric features or with an altered rate of progression of Alzheimer's disease but does predict the development of clinically significant cerebrovascular disease.

The memory deficit in Alzheimer's disease (AD) has been characterized as consisting of multiple components. The purpose of this study was to confirm the utility of a two-process model, and to examine changes in the nature and extent of the neuropsychological deficits after a one-year interval. The results replicate the initial observation that the memory loss in AD can be described as consisting of a focal amnesic syndrome and a dysexecutive syndrome characterized by failure of rapid information processing and search of both episodic and semantic memory. One year after the initial observation, all dysexecutive patients and the majority of the amnesic patients had become non-focal. No patient developed a dysexecutive syndrome, but 18 patients developed amnesic syndromes. These results suggest that, like other aspects of the cognitive deficits of AD, the memory loss is multifactorial. These results have implications for understanding the pathophysiology of AD, and for designing pharmacotherapeutic intervention.

This study evaluated the self-reported patterns of handedness among a large subsample (n = 1612) of the gay/bisexual men comprising the Multicenter AIDS Cohort Study (MACS). There was a small but significant elevation in left-handedness among gay/bisexual men compared to available normative data. However, there were no differences within the cohort in measures of immune function, self-reported autoimmune disorders, asthma, or hay fever, although there was an association between handedness and allergy. Performance on neuropsychological tests also did not differ as a function of handedness.

This study reports normative data for a group of 733 homosexual/bisexual men stratified by age (range 25 to 54 years) and by education on the following six neuropsychological tests: (1) Digit Span (WAIS-R), (2) Rey Auditory Verbal Learning Test, (3) Symbol Digit Modalities Test, (4) Controlled Oral Word Association Test, (5) Grooved Pegboard, and (6) The Trail Making Test. Analysis demonstrates that both age and education are important determinants of performance for several of these measures.

We longitudinally evaluated the neuropsychological functions, rate of progression, and waking EEG findings in 17 patients with probable Alzheimer's disease (AD) with delusions and hallucinations, and compared them with those of matched AD patients without delusions and hallucinations. AD patients with delusions and hallucinations had a more rapid rate of decline, as measured by the Mini-Mental State Examination, a specific defect in receptive language, and a greater frequency of aggression and hostility. Visual EEG analysis showed that these patients had a significantly greater proportion of moderately abnormal EEGs, and spectral analysis confirmed the increased amount of delta and theta activity. These data demonstrate that AD patients with delusions and hallucinations have a greater degree of cerebral dysfunction and a relatively focal neuropsychological defect, which may indicate a localized pathologic abnormality.

Age of onset and aphasia are frequently proposed as predictors of decline in Alzheimer's disease (AD). We compared longitudinally the neuropsychological test performance of AD patients classified as Fast Decliners (FD, N = 18) based on the rate of change of their scores on the Mini-Mental State Examination (MMS) and a group classified as Slow Decliners (SD, N = 15). There was no statistical difference in the age of onset of AD or in severity of dementia at first visit. Performance on verbal tests was the best predictor of rapid cognitive decline, even after the influence of the overall degree of dementia had been accounted for. Among the language tasks, performance on a naming test was the best predictor. The results of this study do not support age of onset as a predictor of the course of AD. On the other hand, poor performance on language tests does predict a more rapid rate of decline in AD.

We studied motor impersistence syndrome (MIS) in patients with a clinical diagnosis of probable Alzheimer's Disease (AD). MIS was found in 16 (10%) of the 166 patients examined; all 16 were moderately to severely demented (Mini-Mental State scores ranging from 17 to 2). We compared the neuropsychological features between these AD patients with MIS and AD patients without MIS matched by the severity of dementia. We found no significant difference between the two groups in terms of orientation, memory, language, attention, and visuoconstructional and visuoperceptual abilities. Buccolingual and limb praxis also failed to reveal differences between the groups. Although MIS has been related to visuoconstructional disorders and apraxia, the phenomenon as it occurs in AD seems not to be related to any specific cognitive domain.

We examined whether 644 homosexual men who engaged in receptive anal intercourse were at particularly elevated risk for seroconversion if they also possessed specific behavioral, health or psychosocial vulnerability characteristics. Of 11 potential factors examined, heavy drinking, moderate to heavy drug use, and younger age were significantly related to seroconversion. These variables were also associated with an increased number of sexual partners, anonymous sex, and failure to use condoms.

Rigorous and standardized assessment of cognitive function is an important component of any multidisciplinary study of chronic fatigue syndrome. The present paper describes some methodologic issues that need to be addressed to maximize the yield from any neuropsychiatric evaluation of the syndrome.

Although the NINCDS-ADRDA Work Group has recently developed uniform clinical criteria for the diagnosis of Alzheimer's disease (AD), inter-rater reliability studies of these criteria are few. We report a study in which 2 neurologists and 2 psychiatrists independently reviewed clinical data abstracted from the records of 30 demented subjects and 10 nondemented control subjects participating in a longitudinal study of AD at the University of Pittsburgh. We recorded the clinical data on a standardized form; the subjects' identity and clinical and pathologic diagnoses were omitted. Each physician diagnosed each case according to the NINCDS-ADRDA criteria. We calculated the inter-rater agreement for all possible 2-way combinations of clinicians with the Kappa statistic, which ranged from 0.36 (fair agreement) to 0.65 (substantial agreement). We conclude that current NINCDS-ADRDA criteria enable moderate levels of agreement among clinicians in general.

The authors longitudinally evaluated the cognitive functions of patients with probable Alzheimer's disease who also met criteria for major depression and compared them with matched patients with Alzheimer's disease who were not depressed. They found no significant difference in the pattern of neuropsychological deficits between the two groups; composite scores on attention, language, memory, learning, and visuospatial functions did not differentiate the two groups at baseline or at 1-year follow-up. The results of this preliminary report suggest that depression does not modify the neuropsychological features and the rate of progression of Alzheimer's disease.

We administered a battery of standardized neuropsychological measures to assess cognitive functions in a group of 769 HIV-1 seronegative, 727 asymptomatic HIV-1 seropositive (CDC Groups 2 and 3), and 84 symptomatic HIV-1 seropositive (CDC Group 4) homosexual/bisexual men enrolled in the Multicenter AIDS Cohort Study (MACS). Measures included tests of attention, memory, and psychomotor speed. Comparison of group means revealed significant differences in performance between HIV-1 seronegative and symptomatic HIV-1 seropositive subjects on measures of memory and on measures with strong motor and psychomotor timed components. These findings support the sensitivity of these neuropsychological instruments for detecting cognitive changes that may be related to HIV-1, and are consistent with other reports of neuropsychological abnormalities in symptomatic HIV-1-infected individuals. Asymptomatic seropositive men, on the other hand, did not differ significantly from seronegative subjects on any of the neuropsychological measures. Only 5.5% of the asymptomatic HIV-1 seropositive men showed abnormal performance on individual tests. This proportion did not differ significantly from that of seronegative controls. Further, among asymptomatic seropositive subjects, we found no statistically significant differences as a function of duration of HIV infection or level of immune system functioning. Thus, results from this study support the hypothesis that the frequency of neuropsychological abnormalities in asymptomatic HIV-1-infected homosexual men is low, and not statistically different from that of seronegative controls.

The memory loss in alcoholic Wernicke-Korsakoff syndrome has been well characterized. However, it has been suggested that some of the neuropsychological defects seen in these patients are due to frontal lobe dysfunction resulting from chronic alcohol abuse. The present report details the nature and extent of the amnesia in a Wernicke-Korsakoff patient who did not have a history of alcoholism. In spite of her normal performance on measures of frontal lobe function, this patient showed many characteristics similar to those seen in alcoholic Wernicke-Korsakoff syndrome including a graded loss of remote memories and abnormal semantic information processing. Thus, the extent of the "core" features of this amnesic syndrome may be greater than was previously thought.

Magnetic resonance (MR) scans were performed as part of a prospective neuropsychological study within the Multicenter AIDS Cohort Study. Fifty HIV-1-seronegative men, 85 HIV-1-seropositive men without constitutional symptoms, and 14 with symptomatic HIV disease underwent MR imaging using a uniform protocol. Scans were rated by neuroradiologists blinded to all clinical details except age. The majority of MR scans were normal in all of the clinical groups and no covert mass lesions or diffuse white matter abnormalities were identified. Focal hyperintensities in the white matter were observed in 24% of the HIV-1 seronegatives, 26% of HIV-1 asymptomatic seropositives (CDC II/III), and 17% of those with ARC/AIDS. No significant associations were noted between the white matter hyperintensities and HIV-1 serostatus, neurological abnormalities, CD4 count, alcohol or drug use, hypertension, or smoking. In one individual classified with early HIV-1 dementia, MR demonstrated several hyperintensities in the deep parietal white matter, but at autopsy no microscopic abnormalities corresponding to the MR findings were identified. Our studies imply that focal white matter hyperintensities identified on MR are not specific for HIV-1 infection and are probably incidental and of no clinical significance.

The memory loss associated with Alzheimer's Disease (AD) may have multiple cognitive components. Working Memory appears to be impaired due to failures of a Central Executive System. Secondary Memory, on the other hand, is affected due to poor encoding or mediational processes. An analysis of the performance of 71 AD patients on tests related to these neuropsychological constructs revealed that they could indeed be dissociated. In fact, individual patients were identified with significantly different, and unique, patterns of impairment which were consistent with the two-component model. These data, therefore, lend preliminary support for the notion of multiple cognitive impairments being responsible for the memory loss in AD.

Recent work has suggested that patients with damage to temporal lobe structures, such as patients with Alzheimer's Disease (AD), lose information from memory at an abnormally rapid rate. In contrast, data from other studies suggest that the rate of forgetting in AD is normal. In the present study, 62 patients with mild to moderate AD and 64 elderly controls were tested for their immediate and delayed recall of a short verbal passage and a modified Rey complex figure. The results suggest that although AD patients recalled less than controls, they did not forget at a faster rate during the 30 minute retention interval, supporting the finding that these memory impaired patients do not have an abnormal rate of forgetting. The data also suggest that poor initial encoding of the stimuli may be the cause of the AD patients' impaired recall.

Smooth pursuit eye movements were studied in three patients with alcoholic Korsakoff's syndrome, one with Wernicke's encephalopathy, and an age-matched control. Horizontal smooth pursuit eye movements were abnormal in all patients: peak eye velocity and the ability to sustain smooth eye velocity were reduced. Also, smooth pursuit gain began to decrease at relatively low target velocities (i.e., 8-10 degrees). These data demonstrate a severe disturbance in smooth pursuit function long after the clinically apparent oculomotor abnormalities have passed.

The performance of alcoholics and alcoholics with Korsakoff's syndrome was compared with that of nonalcoholic controls on a task which required the generation of a series of questions for the solution of object and digit/letter identification problems. Each subject attempted to determine which of a set of stimuli (objects, letters, or numbers) the examiner had arbitrarily preselected as correct. The nonalcoholic control subjects asked constraint-seeking questions which reduced alternatives by inquiring about general categories (e.g., "Is it a tool?"). In contrast, the two groups of alcoholic patients assumed the far less efficient strategy of asking hypothesis-scanning and pseudo-constraint questions which provided information only about one of the possible stimuli (e.g., "Is it the saw?"). This similarity in the problem-solving strategies of alcoholics both with and without Korsakoff's syndrome is consistent with the hypothesis that the problem-solving deficits of Korsakoff patients are apparent before the acute onset of their amnesic symptoms. These deficits may be due to alcohol-induced damage to the anterior and posterior cerebral cortical association areas which mediate problem-solving and visuoperceptual functions.

The learning ability of 12 patients with Parkinson's disease (PD) was studied using a verbal paired-associate learning task, and was compared with that of ten patients with Alzheimer's Disease (AD) and 12 controls (NC). Overall, the PD patients performed significantly better than the AD patients but significantly worse than the NC subjects. Their performance was not related to their overall level of cognitive functioning as measured by the Mattis' Dementia Rating Scale, but was unequally distributed suggesting that the PD population actually consisted of more than one subgroup. A low error group performed like controls, while a high error group had a learning impairment comparable to that of AD patients. It is concluded that PD patients may have three patterns of neuropsychologic performance: some are unimpaired, some have "focal" abnormalities, and some have a generalized impairment of cognitive function.

Saccadic eye movements from three patients diagnosed as having Korsakoff's syndrome and one patient who had suffered the acute Wernicke stage of the disorder were examined for changes in saccadic characteristics. The three Korsakoff patients showed increased saccadic latencies; two of the three also had reduced saccadic peak velocities and increased saccadic durations. A higher than expected incidence of hypometric saccades was also found in all four patients; saccadic intrusions were recorded in two Korsakoff patients. These abnormal oculomotor responses were found 2-7 years after the onset of the Korsakoff's syndrome and are consistent with the cerebellar and frontal lobe dysfunction reported in this patient group.

The performance of a group of detoxified male chronic alcoholics was compared with that of age-matched nonalcoholic controls on a memory task which at face value seemed relevant to daily life--i.e., learning to associate people's names with their faces. The alcoholics not only made more errors while learning the face-name associations than did the controls, but fewer of them were able to reach the learning criterion. However, 1 hour later, the alcoholics were nevertheless able to recognize all of the faces and names used during acquisition. The savings scores for the alcoholics, an index of the relative number of face-name associations retained during the 1-hour interval, did not differ significantly from those of the controls. These results demonstrate that the alcoholics' paired-associate learning deficit on this ecologically relevant task is related to their failure to form associations rather than to deficiencies in recognition memory or perceptual processes.

Two patients with Wernicke's encephalopathy were evaluated with quantitative vestibulo-ocular reflex and ocular motor testing. Vestibulo-ocular reflex testing included caloric irrigation, earth vertical axis rotational sinusoids, and rotational impulses. Both patients demonstrated hypoactive vestibular responses to both caloric and rotational stimuli at the time of presentation. One patient had unbeating nystagmus that diminished with upgaze, downgaze, or convergence. Following treatment with thiamine, both patients' vestibular responses improved but remained abnormal, with a short vestibulo-ocular reflex time constant and increased low-frequency rotational phase lead. Impairment of the velocity storage element attributable to damage to the vestibular nucleus and nucleus prepositus hypoglossi may account for this permanent effect on the vestibulo-ocular reflex.

Although many brain areas have been implicated in spatial memory processes, recent investigations have focused on the hippocampal formation. The present experiment was designed to determine the relative importance of the hippocampal system as compared to the amygdala, the caudate nucleus, or the frontal cortex. Groups of rats were trained to perform on an eight-arm radial maze and then given lesions in one of these brain areas. The post-operative performance of rats with lesions in the fimbria-fornix was never significantly greater than that expected by chance. In contrast, the performance of rats with lesions in the amygdala, the caudate nucleus or the sucal frontal cortex was not significantly different from that of controls. The performance of rats with lesions in the medial frontal cortex was substantially impaired relative to that of the controls during the first few post-operative test sessions, but improved so that by the end of testing the rats were performing as well as were controls. The recovery of function by the rats with lesions in the medial frontal cortex was a function of experience testing on the maze and not simply the passage of time following surgery. Thus, only rats with functional hippocampal systems were able to perform the maze task accurately while thos rats with lesions in the hippocampal system were not.

Although patients with Alzheimer's disease (AD) generally have impairments in multiple areas of cognitive function, there are those patients who appear to have neuropsychological deficits more prominent in one domain than in other domains. We examined the neuropsychological status of 86 patients with probable AD and 92 elderly control subjects and identified the patterns of impairments in the patients with AD. Independent deficits of visuoconstructional and lexical/semantic abilities were identified in a subset of patients by a principal components analysis. Individual patients were identified who were predominantly impaired in one, but not the other, neuropsychological domain. There were no striking relationships between the demographic characteristics of the patients and their pattern of deficits at the initial evaluation. There were no significant differences in age at onset or rate of progression of dementia among patients with different patterns of cognitive dysfunction. A review of the results of this and other studies suggests that the language impairment in AD may be associated with two distinct neuropsychological abnormalities: a lexical/semantic impairment that is unrelated to onset or progression of symptoms, and a syntactic impairment that may be associated with earlier onset and more rapid progression of dementia.

Patients with Huntington's disease (HD), patients with alcoholic Korsakoff's syndrome, and normal control subjects were compared on tests of skill learning (mirror reading) and verbal recognition. Like previously reported results, the patients with Korsakoff's syndrome acquired the mirror-reading skill at a normal rate but were severely impaired in their recognition of the words used on the mirror-reading task. In contrast to the amnesic patients, the demented patients with HD were retarded in their ability to acquire this skill but showed normal verbal recognition. Besides emphasizing substantial differences in the anterograde substantial differences in the anterograde memory disorders of these two patient populations, the results suggest that the memory disorder of patients with HD may appear much more severe when recall rather than recognition test paradigms are employed. This failure of recall by the patients with HD may be due to an inability to generate strategies necessary to search their short- and long-term memories.

An overnight dexamethasone suppression test (DST) was performed on 66 nondepressed primary alcoholics, a mean of 20.79 +/- 11.5 days after last alcohol intake. The Beck Depression Inventory (BDI) was given concurrently. Only 6% of the subjects were nonsuppressors. There was no correlation between cortisol levels at 17 and 24 hours postdexamethasone and the age of the subjects or duration of abstinence. There was a low level correlation between cortisol values at 24 hours and the BDI scores. Review of published data indicates that the DST may be abnormal in alcoholics in the first 2 weeks of abstinence, probably a result of abnormal liver function and withdrawal phenomena. DST response of alcoholics resembles that of normal controls after more than 2 weeks of abstinence. Alcoholics with clinical features of depression and an abnormal DST after 2 weeks of abstinence may be candidates for antidepressant therapy or electroconvulsive therapy.

The purpose of this study was to assess two versions of the hypothesis that alcohol abuse results in premature aging of the brain and of cognitive functioning. The performances of detoxified long-term alcoholic was compared with that of nonalcoholic controls on three divided attention tasks known to be sensitive to aging. While both forms of the premature aging hypothesis predicted that alcoholics should perform more poorly than controls, the hypotheses differed in their predictions of the interactions between the effects of alcohol and normal aging. The results showed that while all three tasks were sensitive to age, only two were affected by long-term alcohol abuse. On one of the tests affected by both age and alcohol abuse, the performance of both young and old alcoholics was equally impaired whereas on the other, only the older alcoholics had significant difficulties. Based on these findings it was concluded that there was only partial overlap between the effects of alcohol and aging, and that neither of the two forms of the premature aging hypothesis could predict the observed pattern of results.

These experiments determined the extent to which the hippocampal system and the medial frontal cortex are selectively involved in cognitive mapping in spatial environments. Rats were trained to discriminate between two 3-dimensional objects based on either the location of the objects in the test environment, or on the stimulus characteristics of the objects themselves. Following the acquisition of one of these discrimination tasks, each rat was given a series of transfer tests to determine the extent to which a cognitive mapping strategy had been used to solve the task. Each rat was then given a lesion in the fimbria-fornix or the medial frontal cortex, or a control operation. In the location discrimination, rats with fimbria-fornix lesions, as compared to control rats: (a) performed poorly at the beginning of retention testing; (b) relearned the task to criterion performance; (c) performed normally during the transfer tests indicating that they used a cognitive mapping strategy, and (d) performed poorly in the discrimination reversals. In the object discrimination, these rats performed as well as controls during retention and transfer tests, but had a slight impairment during discrimination reversals. The performance of rats with lesions in the medial frontal cortex was worse than that of the controls during the retention of both discriminations, and during the reversal of the location, but not the object discrimination. These results are related to predictions of current theories implicating the hippocampus and medial frontal cortex in spatially organized behaviors, particularly those behaviors requiring cognitive mapping.

We used cognitive deficits detected by neuropsychological testing to evaluate clinical diagnosis of Alzheimer's disease. Deficits were defined with respect to performance of control subjects according to procedural guidelines set by a NINCDS-ADRDA Work Group. The most frequent deficits were in recent memory and lexical-semantic language abilities. Clinical diagnosis of Alzheimer's disease was compared with diagnosis based on a criterion of two or more cognitive deficits both on initial neuropsychological testing and on testing repeated a year later in some subjects. Initial clinical diagnosis identified 96% of cases who met the criterion when first tested and 100% of those with multiple deficits at follow-up. Specificity with respect to the criterion was 86% on initial testing and 89% at follow-up. These findings support the validity of clinical diagnosis of Alzheimer's disease using the NINCDS-ADRDA criteria.

Inpatient alcoholics (N = 54 men), nonhospitalized members of an Alcoholics Anonymous group (N = 15 men) and nonalcoholic inpatients (N = 10 men) were shown a 55-min film on alcoholism and were subsequently given memory tests for recall and recognition of information from the film. The performance of the inpatient alcoholics was impaired relative to that of the controls. Alcoholics who were tested earlier in treatment performed worse than those tested 3 or more weeks after their last drink. These results suggest that treatment-relevant information may not be well remembered by alcholics until they have been in treatment for at least 2-3 weeks.