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Biomedical subjects

I Litvan

Publications and source records attributed to I Litvan.

At least 109 records · Page 6Linked to original sources

Neuropsychological features of progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is the epitome of a subcortical dementia process. Due to its relative rarity, there is only a small literature on the neuropsychological consequences of PSP. The findings to date demonstrate that PSP patients have dramatically slowed information processing and motor execution, rapid forgetting, problems in orienting attentional resources, and difficulty in planning and shifting conceptual sets. The pattern and severity of these deficits are unique to PSP and suggest that the study of PSP patients can provide a special insight into brain-behavior relations.

Brain↗

What can preservation of autobiographic memory after muscarinic blockade tell us about the scopolamine model of dementia?

Autobiographic memory is reported to be impaired in patients with Alzheimer's disease (AD). To determine if cholinergic blockade fully reproduces the amnestic disorder found in dementia, we evaluated aspects of autobiographic and episodic memory in six healthy elderly controls after both scopolamine and placebo administration compared with untreated age- and education-matched patients with AD. The performance of patients with AD was significantly worse than that of controls after both treatment conditions. Scopolamine impaired episodic but not autobiographic memory. Thus, even though the cholinergic system is severely affected in patients with AD, muscarinic blockade alone does not seem to be a good model of this disorder.

Aged↗

Pharmacological evaluation of the cholinergic system in progressive supranuclear palsy.

Severe cholinergic loss occurs in the brains of patients with progressive supranuclear palsy. To evaluate the functional implications of this neuronal deficit, dose-response curves were obtained in patients with progressive supranuclear palsy and normal control subjects undergoing intravenous cholinergic blockade (scopolamine) and stimulation (physostigmine). Physostigmine had no significant neurobehavioral effects at any dose in patients with progressive supranuclear palsy. Scopolamine, at low and medium doses, significantly impaired memory performance of both groups, but worsened the gait of only the patients. High-dose scopolamine, which could not be tolerated by the patients, resulted in gait deterioration among control subjects. Thus, patients with progressive supranuclear palsy have increased sensitivity to cholinergic blockade compared to control subjects. Since loss of cholinergic neurons appears to contribute to the pathogenesis of certain cognitive and motor deficits found in progressive supranuclear palsy, the use of oral anticholinergics should ordinarily be avoided in this disorder. On the other hand, physostigmine at clinically tolerated dose levels seems to be therapeutically ineffective.

Aged↗

Cholinergic approaches to the treatment of progressive supranuclear palsy.

In spite of the severe loss of cholinergic neurons in the brains of patients with progressive supranuclear palsy (PSP), marginal or null benefits are seen in clinical trials after the administration of physostigmine, a cholinesterase inhibitor, or RS-86, a cholinergic agonist. The possible role of cholinergic therapy in PSP is reevaluated.

Cholinergic Agonists↗

Cognitive disturbances in progressive supranuclear palsy.

The cognitive disturbances in progressive supranuclear palsy (PSP) gave rise to the term "subcortical dementia." PSP patients demonstrate prominent recall deficits and moderate forgetfulness although their short-term and implicit perceptual memory processes are intact. PSP patients have both slowed motor responses and dramatically slowed information processing speed. Executive dysfunction appears early in the course of the disease and is relatively severe. The combination of severely slowed information processing and marked executive dysfunction are characteristic of PSP and differentiates it from other dementias. In their landmark description of progressive supranuclear palsy (PSP) as a clinicopathological entity, Steele et al. (1964) reported that cognitive disturbances were present in seven out of their nine patients. Ten years later, Albert et al. (1974) characterized these changes to be part of a "subcortical dementia," They analyzed 5 of their own PSP cases and also reviewed the published literature; they found a common cluster of symptoms, including the presence of forgetfulness, slowness of thought process, emotional or personality changes, and impaired ability to manipulate acquired knowledge. Albert et al. analysis was qualitative, but in the authors' view, clearly differentiated PSP patients from patients with "cortical dementia" who presented with aphasia, apraxia, and/or agnosia. They also suggested that the symptoms found in PSP were similar to those that had previously been described in patients with frontal lobe lesions.

Cognition Disorders↗

Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy).

We present the preliminary neuropathologic criteria for progressive supranuclear palsy (PSP) as proposed at a workshop held at the National Institutes of Health, Bethesda, MD, April 24 and 25, 1993. The criteria distinguish typical, atypical, and combined PSP. A semiquantitative distribution of neurofibrillary tangles is the basis for the diagnosis of PSP. A high density of neurofibrillary tangles and neuropil threads in the basal ganglia and brain-stem is crucial for the diagnosis of typical PSP. Tau-positive astrocytes or their processes in areas of involvement help to confirm the diagnosis. Atypical cases of PSP are variants in which the severity or distribution of abnormalities deviates from the typical pattern. Criteria excluding the diagnosis of typical and atypical PSP are large or numerous infarcts, marked diffuse or focal atrophy, Lewy bodies, changes diagnostic of Alzheimer's disease, oligodendroglial argyrophilic inclusions, Pick bodies, diffuse spongiosis, and prion protein-positive amyloid plaques. The diagnosis of combined PSP is proposed when other neurologic disorders exist concomitantly with PSP.

Brain↗

CSF galanin and neuropeptide Y immunoreactivity in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) has been associated with degenerative changes in cholinergic and dopaminergic neurons in several brain regions. Since acetylcholine is colocalized with the neuropeptide galanin in certain neuronal populations, we measured the concentration of this neuropeptide and neuropeptide Y in cerebrospinal fluid (CSF) of 11 patients with PSP and in 16 age-matched healthy controls. No significant alterations in the CSF levels of galanin or neuropeptide Y were found.

Aged↗

Cognitive planning deficit in patients with cerebellar atrophy.

We compared the performance of 12 patients with cerebellar atrophy (CA) and 12 normal controls matched for age and education on the Tower of Hanoi, a nine-problem task that requires cognitive planning. CA patients performed significantly worse than controls on this task despite no difference in planning and between-move pause times. A reanalysis of the data using just the subgroup of patients with pure cerebellar cortical atrophy (CCA) (N = 9) replicated the above results and also showed that CCA patients had significantly increased planning times compared with controls. Neither age, sex, education level, severity of dementia, word fluency, response time, memory, nor visuomotor procedural learning predicted CA or CCA performance. This deficit in cognitive planning suggests a functional link between the cerebellum, basal ganglia, and the frontal lobe concerning specific cognitive processes. However, the exact role of the cerebellum in cognitive planning remains undetermined.

Adult↗

Differential memory and executive functions in demented patients with Parkinson's and Alzheimer's disease.

Selected aspects of verbal memory and executive function were compared in 11 demented Parkinson's disease (PD) patients and 11 Alzheimer's disease (AD) patients with equally severe dementia, with 11 healthy controls matched for age and education. Semantic and episodic memory were impared in all patients compared with controls, but to a relatively greater degree in AD patients than in those with PD. In contrast, demented PD patients were relatively more compromised on executive tasks. These findings, taken in the context of the neuropathological and neurochemical overlap between demented PD and AD patients, suggest that differences in neurobehavioural patterns in patients with these diseases are relative, rather than absolute.

Aged↗

Cerebrospinal fluid acetylcholinesterase in progressive supranuclear palsy: reduced activity relative to normal subjects and lack of inhibition by oral physostigmine.

Acetylcholinesterase (AChE) activity was measured in lumbar cerebrospinal fluid (CSF) of 11 patients with progressive supranuclear palsy (PSP) and 18 age-matched healthy control subjects. Mean CSF AChE activity in PSP subjects was significantly reduced by 31% relative to control subjects (p less than 0.002). In the light of evidence of a central cholinergic deficit, physostigmine was administered orally (0.5-2.0 mg every two hours, six times a day for 10 days) to eight of the 11 PSP patients. CSF was sampled when the patients were on placebo and when receiving physostigmine and CSF AChE and butyrylcholinesterase (BChE) activities were measured. There was no significant change in either CSF AChE or BChE activities following physostigmine treatment. These data suggest that the doses of physostigmine used were insufficient to produce marked inhibition of AChE within the central nervous system.

Acetylcholinesterase↗

Progressive supranuclear palsy: altered sensory processing leads to degraded cognition.

We studied the latencies, amplitudes, and scalp distributions of the early and late components of the event-related brain potential (ERP) in patients with progressive supranuclear palsy (PSP) and matched normal controls. In separate choice reaction time (RT) tasks, the subjects pressed buttons to visual stimuli presented randomly at probabilities of either 20/80 or 50/50. Compared with normal controls, PSP patients had significantly reduced amplitudes and increased latencies for both the visual P2 and P300 components at all levels of probability. RTs and percent errors were significantly greater in the patients compared with controls. Neither the amplitude nor latency of the visual N1 component was significantly altered in these patients. There were no significant group differences in the distribution of electrical activity over the scalp for any of these ERP components, a finding which suggests that the neural structures responsible for generating these potentials were intact in these patients. The decreased ERP component amplitudes and increased ERP component latencies, combined with intact scalp distributions and increased RTs and error rates, present a pattern of results suggesting that the stimulus identification or categorization processes in these patients are significantly degraded.

Analysis of Variance↗

Frontal lobe function in progressive supranuclear palsy.

Performance on tasks evaluating "executive and attentional" processes presumably subserved by prefrontal cortex were compared in patients with progressive supranuclear palsy and with age- and education-matched control subjects. The results indicated that patients with progressive supranuclear palsy were particularly impaired when a task required sequential movements, conceptual shifting, monitoring the frequency with which stimuli are presented, or rapid retrieval of verbal knowledge. These deficits could not simply be accounted for by slowed information processing or by a deficit in representational knowledge. Conceivably, "weak activation" of frontal lobe representational knowledge characterized by an observed attentional deficit results in the neuropsychological impairments noted in patients with progressive supranuclear palsy. The oral administration of physostigmine, under double-blind placebo-controlled conditions, did not facilitate executive or attentional performance as evaluated by our tasks.

Affect↗

Effects of physostigmine on spatial attention in patients with progressive supranuclear palsy.

We tested patients with progressive supranuclear palsy and control subjects on a task of visuopatial attention. Targets preceded by cues on the same side were termed validly cued; and those on the opposite side, invalidly cued. For all subjects, validly cued targets were responded to faster than those that were invalidly cued. The difference between reaction times for invalidly and validly cued targets, which is hypothesized to measure attentional movement, was significantly increased for the patients. The performance of the controls on certain neuropsychological tests was correlated with their attentional ability. These correlations were altered by progressive supranuclear palsy. Physostigmine treatment of the patients induced a speeding of responses to invalidly cued targets as a function of the duration of the disease. These studies show defects in cognition and attention in patients with progressive supranuclear palsy and demonstrate that physostigmine reduces some of the abnormal visual attentional performance.

Aged↗

Selective deficits in Alzheimer and parkinsonian dementia: visuospatial function.

Deficits in visuospatial cognition are frequently cited as an important component of the cognitive changes accompanying Parkinson's disease. To characterize possible differences between Parkinson's (PD) and Alzheimer's (AD) dementia, patients from both groups, matched for overall dementia severity, age and education, were contrasted neuropsychologically. Visuospatial tasks dissociated from memory, were significantly compromised in both patient groups. Differential impairment was evident on visuospatial abstraction and reasoning (Object Assembly), which was most deficient in PD. Visuospatial cognition associated with memory, classified both patient groups as impaired compared to controls, but AD patients demonstrated substantially lower performance levels than those with PD. Parkinsonian dementia thus appears to have some distinct features compared to Alzheimer's disease, which may indicate differences in underlying pathogenic mechanisms.

Adult↗

Implicit learning in patients with Alzheimer's disease.

We examined implicit memory using priming and procedural learning tasks in patients with probable Dementia-Alzheimer's Type (DAT) to examine whether priming and procedural processes could be dissociated and whether task specificity was a factor in DAT patient performance. Priming was tested using a word recognition paradigm (perceptual priming) and by repeated administrations of a fragmented objects test (long term priming). Procedural learning was tested using repeated and random sequences on a choice serial reaction time task and by repeated administration of a puzzle map of the United States. DAT patients were compared to hospitalized depressed patients, patients suffering from Progressive Supranuclear Palsy (PSP), and normal controls. We found that DAT patients demonstrated marginal but significant implicit learning on both procedural learning and perceptual priming tasks. DAT patients performed relatively better on the procedural learning task than a perceptual priming task compared to PSP patients, suggesting that priming of meaningful stimuli is subserved by cortical structures whereas procedural motor responses to simple serial visual stimulus patterns can be maintained by subcortical systems. Furthermore, our findings suggest that priming and procedural processes can be dissociated and that task specificity is a factor in interpreting the results of implicit learning paradigms in DAT patients. The implications of these results for models of knowledge representation and memory processes as well as the way they can serve as models for testing nootropic drug effects are discussed.

Aged↗

Selective deficits in cognition and memory in high-functioning parkinsonian patients.

To evaluate the profile and extent of cognitive deficits in Parkinson's disease, afflicted patients of exceptional professional distinction, who continue to function successfully in leadership positions, were compared neuropsychologically to neurologically normal individuals, matched for sex, age, education and professional standing. While patients showed relative preservation of verbal skills and higher executive function, they exhibited a significant reduction in episodic memory and visuospatial function. The observation of circumscribed impairment in this select group of Parkinsonian patients further implicates cognitive and memory deficits as consistent features of Parkinson's disease.

Adult↗

Memory impairment in patients with progressive supranuclear palsy.

Verbal memory was compared in 12 patients with progressive supranuclear palsy and 12 healthy control subjects matched for age, sex, and education. Learning, consolidation, and retrieval were significantly impaired in patients with progressive supranuclear palsy. Information scanning, which requires the use of short-term memory processes, remained intact. Duration of symptoms and degree of motor dysfunction correlated with intrusions during learning. No relation between central dopamine metabolism and memory dysfunction could be established.

Aged↗

Physostigmine treatment of progressive supranuclear palsy.

Cognitive and extrapyramidal effects of cholinomimetic therapy were evaluated in 8 patients with progressive supranuclear palsy. Each was randomized to a 10-day double-blind crossover trial of physostigmine and placebo. Physostigmine treatment was associated with marginal and inconsistent changes in long-term memory, suggesting that cholinergic therapy alone is insufficient to restore cognitive function. Motor scores remained unchanged.

Aged↗