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Biomedical subjects

R Mayeux

Publications and source records attributed to R Mayeux.

At least 181 records · Page 10Linked to original sources
PubMed1989

A pilot study of haloperidol treatment of psychosis and behavioral disturbance in Alzheimer's disease.

Nine outpatients meeting research criteria for probable Alzheimer's disease who had psychosis or behavioral disturbance participated in a single-blind, placebo-controlled pilot study. Oral haloperidol in doses of 1 to 5 mg daily improved target symptoms, confirmed by double-blind ratings of videotaped interviews. Patients could not be maintained on more than 4 mg of haloperidol daily due to the severity of extrapyramidal side effects. Modified Mini-Mental State scores worsened while taking haloperidol, with only partial recovery in the final 4-week placebo phase. Severe extrapyramidal side effects and decline in cognitive function may compromise the efficacy of commonly used doses of neuroleptic drugs in patients with Alzheimer's disease.

Activities of Daily Living↗
PubMed1989

Coexisting dementia and depression in Parkinson's disease.

Dementia and depression in patients with Parkinson's disease have been reported separately, but their prevalence is controversial. This study examines the coexistence of these two problems and suggests a common underlying biochemical system. We examined these two entities by retrospective chart review and cerebrospinal fluid biochemistry. We found a prevalence of 10.9% for dementia, 51% for depression, and 5.4% for coincident depression and dementia. In a prospective study of patients with Parkinson's disease we found a continuum of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. Patients who were either depressed or demented had lower concentrations of this metabolite than other patients with Parkinson's disease, but patients who were depressed and demented had the lowest levels. These results suggest that the coexistence of dementia and depression represents a unique clinical entity in Parkinson's disease. The serotonergic system may be involved in depression and dementia because evidence of a cumulative effect on this biochemical system is present.

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PubMed1989

Gray-matter degeneration in presenile Alzheimer's disease.

Previous comparisons between presenile Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT) did not control for disease severity and duration. In the current study, 18 patients with each diagnosis were matched for disease duration, cognitive dysfunction, and behavioral symptoms (using the modified Mini-Mental Status [mMMS] examination and the Blessed Dementia Rating Scale [BDRS] ). Regional cerebral blood flow (rCBF) was quantified by the 133xenon inhalation technique, and several indices of tissue perfusion were examined. The two variables of primary interest were relative gray-matter relative weight (35% in presenile patients versus 39% in senile patients and healthy control subjects, p = 0.006), with neither perfusion nor disease severity differences between the two dementia samples. This loss of gray matter was significantly related to both severity and duration of disease in the patients with presenile AD, but not in patients with SDAT. These findings lend support ot previous suggestions of greater degenerative process in presenile AD and confirm the need to examine and control age of onset in future investigations of AD. Further, correlation analysis suggests greater proportion of common variance among clinical and physiological indices in presenile AD.

Age Factors↗
PubMed1989

The pedunculopontine nucleus in Parkinson's disease.

This study demonstrated a significant loss of neurons within the lateral part of the pedunculopontine nucleus pars compacta in individuals with idiopathic Parkinson's disease and in individuals with combined Parkinson's and Alzheimer's disease. We also examined the extent of neuronal loss within the substantia nigra pars compacta, locus ceruleus, dorsal raphe nucleus, and nucleus basalis of Meynert. The number of pedunculopontine nucleus pars compacta neurons in the patients with Parkinson's or Parkinson's and Alzheimer's disease was reduced (average, 40%) in comparison with the number in control subjects or patients with Alzheimer's disease (p less than 0.01). This finding correlated significantly with the extent of loss of substantia nigra pars compacta neurons (p less than 0.01).

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PubMed1988

An estimate of the prevalence of dementia in idiopathic Parkinson's disease.

A review of the records for evidence of dementia using criteria adapted from the third edition of the Diagnostic and Statistical Manual of Mental Disorders in every patient (hospitalized and outpatient) with parkinsonism at a major medical center during an 18-month period revealed an overall prevalence of 10.9% in 339 patients with idiopathic Parkinson's disease. Demented patients were older, had a later age at onset of motor manifestations, and a more rapid progression of physical disability than nondemented patients. Duration of illness and levodopa use and the presence of tremor or depression were similar in demented and nondemented patients. Demented patients more often responded poorly or developed adverse effects to levodopa than nondemented patients. When Parkinson's disease began after age 70 years, dementia was noted over three times more frequently than when the disease began at an earlier age. The age-specific prevalence rate of dementia for patients older than 70 years was more than twice that for younger patients. Moreover, the number of records with evidence for dementia with idiopathic Parkinson's disease was 3.75 times greater than expected in comparison with data from a study of the prevalence of dementia in the elderly.

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PubMed1988

Familial Alzheimer's disease with myoclonus and 'spongy change'.

"Spongy change," or vacuolar change, was observed in the neocortex of temporal and frontal lobes in four of 27 patients with clinical and pathologic characteristics of Alzheimer's disease. All four cases had the autosomal dominant form of the disease, and aside from severe dementia, all developed myoclonus and became mute before death. The degeneration observed was unlike that seen in Creutzfeldt-Jakob disease because it lacked astrocytosis and had a different distribution of lesions. Moreover, the abundance of neurofibrillary changes and senile plaques was consistent with Alzheimer's disease. None of the other 23 cases were familial, and none developed myoclonus or mutism; three of them had minor vacuolation limited to the temporal lobe. The four cases with severe spongy change described are the first, to our knowledge, in which vacuolar or spongy change has been associated with the familial form of Alzheimer's disease.

Aged↗
PubMed1988

The relationship of serotonin to depression in Parkinson's disease.

We have previously reported a correlation between depression in patients with idiopathic Parkinson's disease and decreased concentrations of the cerebrospinal fluid content of the serotonin metabolite, 5-HIAA. To further examine this relationship, we repeated the study in a new cohort of patients while they remained on dopaminergic medications, conducted follow-up interviews and examinations in our original cohort, and conducted an open trial of the serotonin precursor, 5-hydroxytryptophan in a group of new patients with depression. We were again able to demonstrate a significant reduction in cerebrospinal 5-HIAA in depressed patients in comparison to controls and patients without depression. Demented patients with Parkinson's disease, particularly those with concurrent depression, had the lowest values of 5-HIAA. No new cases of depression occurred in our original cohort after 2 1/2 years of follow-up, and depression remitted following conventional or experimental treatment in four patients. Depression improved in six of the seven new patients following oral 5-hydroxytryptophan. Three of these patients allowed a repeat lumbar puncture, and the concentration of 5-HIAA increased following 5-hydroxytryptophan. These three studies support our hypothesis that depression in idiopathic Parkinson's disease is associated with a reduction in brain serotonin. However, it also suggests that other factors, biological or environmental, may be causal factors.

5-Hydroxytryptophan↗
PubMed1988

Prism adaptation in Parkinson's disease.

Prism adaptation is impaired by lesions in the basal ganglia in non-human primates, suggesting that this area is involved in this form of visuomotor learning. We investigated the ability of patients with Parkinson's disease to prism adapt. Patients and controls wore prisms which deflected vision laterally by 11 degrees. After baseline testing with a localisation task that permitted no feedback about performance accuracy, prism adaptation was tested at 4 minute intervals over a 28 minute trial. All subjects erred initially, reaching too far to the left of the target, but a separate pointing task encouraged adaptation and reaching error decreased at a similar rate in Parkinsonians and controls. Immediately after the prisms were removed, all subjects reached to the right of the target. This negative after effect was present in controls but not patients when assessed 4 minutes later, suggesting that the patients could not maintain the new sensorimotor relationship imposed by the prisms after their removal. This is similar to performance on visuospatial and executive tasks in Parkinsonians, where ongoing behaviour cannot be modulated without external guidance.

Adaptation, Ocular↗
PubMed1988

Long-term administration of oral physostigmine in Alzheimer's disease.

Minimal short-term benefits with oral physostigmine have been reported in Alzheimer's disease. We examined long-term oral physostigmine therapy in 14 patients with probable Alzheimer's disease in an extended double-blind crossover trial in which they received physostigmine for five intervals of 4 to 6 weeks in length and placebo for one interval determined at random. At each interval a Selective Reminding Test was administered and three indexes were examined: total recall, long-term recall, and intrusions. As a group, patients' memory test scores were significantly better during the drug period. Two patients who previously had performed worse on drug than on placebo in a short-term trial continued to do so. Nine of the remaining 12 patients performed better on two or more measures on physostigmine compared with placebo. In some cases scores improved up to 50% over placebo values. This improvement was not predicted by response to medication in the earlier short-term trial. Seven patients completed an additional six-interval crossover trial. All but one continued to have improved performance with oral physostigmine and, in grouped data, memory measures remained significantly improved. These results suggest that long-term administration of physostigmine in Alzheimer's disease may be more effective than short-term. This benefit can be sustained for up to a year in some patients.

Administration, Oral↗
PubMed1988

Reductions in [3H]nicotinic acetylcholine binding in Alzheimer's disease and Parkinson's disease: an autoradiographic study.

In Alzheimer's disease (AD) and Parkinson's disease (PD), dysfunction in the basal forebrain cholinergic system is accompanied by a consistent loss of presynaptic cholinergic markers in cortex, but changes in cholinergic receptor binding sites are poorly understood. In the present study, we used receptor autoradiography to map the distribution of nicotinic [3H]acetylcholine binding sites in cortices of individuals with AD and PD and matched control subjects. In both diseases, a profound loss of nicotinic receptors occurs in all cortical layers, particularly the deepest layers.

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PubMed1988

Cerebral perfusion as a diagnostic marker of early Alzheimer's disease.

Clinical diagnosis of Alzheimer's disease (AD) is not fully satisfactory, and laboratory markers of this disease are not yet established. We report substantial regional Cerebral Blood Flow (rCBF) abnormalities in patients with documented early stages of the disease, when differential diagnosis is most critical. Thirty-six patients with carefully documented clinical diagnosis of early AD (mean disease duration, 3.25 +/- 1.80 years) and 12 elderly healthy controls participated in rCBF studies using the 133Xe inhalation method. Whole-brain perfusion was significantly (p less than 0.001) lower in the AD group, and a characteristic perfusion deficit was consistently found in temporoparietal cortex of the AD patients. Discriminant analyses demonstrated over 90% correct classification of the two groups. Two subgroups of patients with mildest disease manifestations were equally well discriminated. The similarity of these findings to those in late stages, which have been validated neuropathologically, offers indirect confirmation of validity and specificity. These results suggest that rCBF procedures may provide an accurate and sensitive laboratory marker for early AD.

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PubMed1987

Aminergic systems in Alzheimer's disease and Parkinson's disease.

Biochemical markers for serotoninergic and catecholaminergic neurons in frontal and temporal poles were examined post mortem in brains of patients with Alzheimer's disease, Parkinson's disease, and the two combined. Binding of [3H] citalopram to serotoninergic uptake sites and levels of serotonin were decreased by 40 to 50% in brains of persons in each disease category. In contrast, significant reductions of catecholaminergic markers were not detected. In all three disease groups, the choline acetyltransferase activity was reduced by 50 to 60%. Binding sites for adenosine (A1), muscarinic cholinergic, phencyclidine, beta-adrenergic, and calcium antagonist receptors were unchanged. We conclude that substantial damage to serotoninergic neurons occurs in persons with Parkinson's and Alzheimer's diseases.

Alzheimer Disease↗
PubMed1987

Effects of oral physostigmine in Alzheimer's disease.

Previous studies of oral physostigmine in the treatment of Alzheimer's disease have: (1) assumed physostigmine is effective only in mildly affected patients; (2) relied on an initial "dose-finding" phase to determine the most effective dose and excluded nonresponders; and (3) primarily assessed memory. We examined the response of 22 patients to six different daily dosages of oral physostigmine, using selective reminding tests that were administered twice daily. Nine patients had a "best" dose/day (mode = 13 mg/day), which was used in a subsequent double-blind crossover study. The other 13 were given the highest tolerated dose. The selective reminding test and a full neuropsychological battery were given during the drug and placebo periods. As a group, the 22 patients improved significantly on the Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest and a shape cancellation task (p less than 0.05). Nine patients showed improved performance on the selective reminding test during physostigmine treatment, and 9 showed no response; 4 patients performed better during placebo treatment. Dose finding did not help in predicting response in the crossover study; only 2 of the 9 who showed improvement had a best dose. Dementia severity did not predict crossover response. This suggests that: (1) physostigmine as administered had no pronounced effect on memory in Alzheimer's disease; (2) oral physostigmine produces no greater benefits on memory in mildly than in moderately demented patients; (3) response in a dose-finding phase does not predict response in double-blind crossover; and (4) Digit Symbol and cancellation tasks may be more sensitive than memory tests to the effects of oral physostigmine.

Administration, Oral↗
PubMed1987

Diffuse Lewy body disease. Neuropathological and biochemical studies of six patients.

Post-mortem pathological and biochemical studies are reported on six patients with progressive dementia. The characteristic pathological finding was neurofilament-containing cytoplasmic inclusions in cortical and subcortical neurons. The clinical and pathological findings were consistent with so-called diffuse Lewy body disease. The patients had variable changes of the Alzheimer type, with five of six patients displaying "plaques only" Alzheimer's changes. Biochemical studies showed profound decreases in neocortical choline acetyltransferase (ChAT) activities that correlated with marked neuronal loss in the basal nucleus of Meynert. ChAT activities were normal in the hippocampus in three patients who also had no significant Alzheimer type hippocampal changes. All patients had decreased cortical somatostatin-like immunoreactivity. Our observations suggest that dementia in diffuse Lewy body disease bears biochemical similarities to Alzheimer's disease, in that biochemical markers for both intrinsic cortical neurons and ascending cholinergic neurons are affected.

Aged↗
PubMed1987

Predictors of disease course in patients with probable Alzheimer's disease.

The presence of extrapyramidal signs or psychosis may indicate greater disability in patients with probable Alzheimer's disease. We evaluated the ability of these signs, noted at a patient's first visit, to predict one of two specific clinical endpoints: (1) a preselected score on the modified Mini-Mental State examination (cognitive endpoint), and (2) a preselected score on the Blessed Dementia Rating Scale (functional endpoint). Sixty-five patients were followed either until they reached the endpoints or to the end of the study period. Survivorship curves were drawn to predict the distribution of time to onset of an endpoint in patients with and without the clinical signs. Time to reach the cognitive endpoint was shorter for patients with extrapyramidal signs or psychosis compared with those without these signs and symptoms. These clinical signs did not predict the functional endpoint. We conclude that extrapyramidal signs and psychosis may be useful predictors of intellectual decline in Alzheimer's disease.

Activities of Daily Living↗