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Event related potentials, reaction time, and cognitive performance in idiopathic Parkinson's disease.
Sixteen non-demented patients with idiopathic Parkinson's disease (PD) with varying degrees of cognitive impairment and sixteen age-, sex- and education-matched normal controls were examined with (1) an auditory oddball paradigm requiring counting or a motor response in separate determinations, (2) a reaction time task with movement time component and (3) a detailed clinical and neuropsychological test battery. Patients were impaired on a number of neuropsychological tests. They also showed an increased P2 and N2 latency, but no significant increase in P3 latency. Their response initiation times and reaction times during the oddball experiment were not different from controls, whereas movement time was significantly increased. Increased peak latencies, particularly for N2, were moderately associated with Parkinsonian motor impairment in patients and with the Benton Multiple Choice Visual Retention Test in patients and controls. Movement time was associated with P3 latency only in controls and in both groups with the Benton Multiple Choice Visual Retention Test. The observed pattern of results suggests that in non-demented PD patients ERP peak latencies, visuo-spatial task performance and Parkinsonian motor impairment share a significant degree of variance. While impairments in neuropsychological tests and delay in the earlier peaks P2 and N2 do not appear to be sensitive to medication with L-DOPA, normal P3 latencies might indicate good pharmacological symptom control in the absence of dementia.
The effect of different high-pass filter settings on peak latencies in the event-related potentials of schizophrenics, patients with Parkinson's disease and controls.
Eighteen schizophrenic patients, 16 patients with idiopathic Parkinson's disease, and the same numbers of age, sex and education matched controls were examined with oddball experiments for the generation of P3. Individual averages were high-pass filtered at different cut-off frequencies with single-pole digital filters with equivalent analogue Butterworth filter profiles. The purpose of this procedure was to simulate analogue high-pass filters used in clinical studies from different centres and to examine their potential effect on group differences. Increasing high-pass filters resulted in a phase lead for all peaks examined (N1, P2, N2, P3). The only group differences were found for P3, which showed a greater phase lead in controls than in the patient groups, usually resulting in a more pronounced group difference. Similar wave forms and filter properties could be modelled by synthetic wave forms consisting of sine waves of different frequencies.
Differential diagnosis in dementia using the cerebral blood flow agent 99mTc HM-PAO: a SPECT study.
One of the potential clinical uses of the new cerebral blood flow agent 99mTc-hexamethylpropyleneamineoxime (HM-PAO) is the investigation of dementia, in particular to differentiate between dementia of the Alzheimer type (DAT) and multiinfarct dementia (MID). In this study 27 patients, 17 with DAT and 10 with MID, and three normal volunteers were imaged both with single photon emission CT and magnetic resonance. The HM-PAO perfusion deficits were much more common in the DAT group than in the MID group, especially in the temporoparietooccipital (TPO) regions. The two groups of patients were found to be significantly different (p less than 0.02), as regards the frequency of occurrence of bilateral TPO perfusion deficits. Four of the 17 DAT patients did not have bilateral TPO deficits but these included the three least impaired patients as assessed by psychometric testing.
Nuclear magnetic resonance imaging and single photon emission tomography with radio-iodine labelled compounds in the diagnosis of dementia.
White matter lesions and T1 changes were identified using NMR and then compared between groups of patients suffering from dementia of the Alzheimer type (DAT), Multiple infarct dementia (MID) and normal controls. All DAT and MID patients were also imaged with a gamma camera using 123Iodo-n-isopropyl-amphetamine, a radiopharmaceutical whose uptake in the brain follows the regional blood flow. While NMR was not able to differentiate between DAT and MID, 19 out of 21 DAT patients compared to four out of 18 MID patients showed bilateral parietal lesions on IMP scans.
The structure of Cloninger's Tridimensional Personality Questionnaire in a British sample
This study adds to the very few published reports of the structure of the Tridimensional Personality Questionnaire (TPQ) at both the item and subscale levels. The TPQ was completed by 897 students from Universities within Edinburgh. Exploratory factor analysis was run on the items and the 12 subscales as described by Cloninger, Przybeck, and Svrakic (1991). Harm Avoidance showed high internal consistency both for the whole scale and the subscales; however, this was not the case for Reward Dependence and Novelty Seeking. A three factor solution was extracted from analysis at the scale level which gives support to Cloninger's model. However, when analysis was carried out at the item level, three and four factor solutions were extracted with only one factor, that of Harm Avoidance, resembling Cloninger's model. The four factors extracted were provisionally named Harm Avoidance, Conscientiousness, Sociability and Impulsiveness. These more closely resemble factors from the Five Factor Model (Costa & McCrae, 1992) and Eysenck's three factor model (Eysenck, Eysenck, & Barrett, 1985) than Cloninger's theory. It may be necessary to adapt Cloninger's model for a British sample, and more generally to question the psychometric structure of the TPQ. © 2003 Elsevier Ltd. All rights reserved.
A voxel-based analysis of cerebral perfusion in dementia and depression of old age.
Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.
Hypofrontality revisited: a high resolution single photon emission computed tomography study in schizophrenia.
Hypofrontality or reduced activity in the prefrontal cortex, measured as reduced frontal perfusion or glucose uptake, has gained the status of an established finding in the medical literature on schizophrenia. Many relevant studies, however, have potential sources of bias, such as small subject numbers, or unreliable performance of activation tasks by the patients during the scanning procedure. Seventy patients with non-affective and non-organic psychoses were recruited--most qualifying for DSM III-R schizophrenia or schizophreniform psychosis (n = 60)--together with 20 healthy volunteers. They underwent single photon emission computed tomography with 99mTc-exametazime, carried out at rest. Tracer uptake was normalised to the occipital cortex. Group differences in tracer uptake were predicted in anterior regions of interest (prefrontal cortex and mesial frontal/cingulate cortex). Actively psychotic (including schizophrenic) patients not taking any drugs showed increased uptake in the prefrontal cortex. Reduced tracer uptake occurred in the mesial frontal cortex of schizophrenic patients, particularly if they were taking drugs. Relatively increased prefrontal tracer uptake associated with relatively decreased mesial frontal uptake characterised the patients in comparison with the controls. Generalised hypofrontality is, therefore, not a feature of schizophrenic patients at rest whether taking drugs or not.
Serum iron and transferrin in acute neuroleptic induced akathisia.
Thirty acute psychiatric patients were examined prospectively at the beginning of neuroleptic treatment for acute psychotic symptoms and on average 16 days later. Two alternative hypotheses were examined: 1) neuroleptic treatment affects the levels of serum iron and transferrin; 2) acute akathisia developing during the initial few weeks of treatment is associated with low levels of serum iron and transferrin, either initially or at follow up or both. Serum iron levels did not change on repeat measurement, while there was a small, but significant decrease of serum transferrin. There was a significantly greater decrease in iron and transferrin levels in patients with akathisia on follow up compared with non-akathisics. In addition, akathisia ratings were highly correlated with serum transferrin levels on follow up.
Parkinson's disease in Aberdeen: survival after 3.5 years.
The increasing age of the general population and of patients suffering from Parkinson's disease suggests that a reappraisal of mortality rates and factors related to increased mortality should be carried out. A 3.5 year follow-up of a whole population sample of 267 patients and 233 controls matched by age, sex and general practitioner, yielded a relative mortality rate of 2.35 (99%-confidence interval: 1.60-3.43). Factors predicting death within the follow-up period were: cognitive impairment, old age, late age of onset, long history of smoking, lower blood pressure, and a variety of signs, symptoms and sequelae of Parkinson's disease associated with decreased mobility. However, age less than 70 years, age of onset before 66 years, absence of kyphosis or normal Webster posture score, mild impairment on the Hoehn & Yahr scale (1-2), or no impairment in a 10-question mental status questionnaire (9-10), were not associated with an increased risk of death.
fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia.
Schizophrenia is a highly heritable disorder that typically develops in early adult life. Structural imaging studies have indicated that patients with the illness, and to some extent their unaffected relatives, have subtle deficits in several brain regions, including prefrontal and temporal lobes. It is, however, not known how this inherited vulnerability leads to psychosis. This study used a covert verbal initiation fMRI task previously shown to elicit frontal and temporal activity (the Hayling sentence completion task) to examine this issue. A large (n = 69) number of young participants at high risk of developing schizophrenia for genetic reasons took part, together with a matched group of healthy controls (n = 21). At the time of investigation, none had any psychotic disorder, but on detailed interview some of the high-risk participants (n = 27) reported isolated psychotic symptoms. The study aimed to determine: (i) whether there were activation differences that occurred in all subjects with a genetic risk of schizophrenia (i.e. 'trait' effects); and (ii) whether there were activation differences that only occurred in those at high risk who had isolated psychotic symptoms ('state' effects). No activation differences were found in regions commonly reported to be abnormal in the established illness, namely the dorsolateral prefrontal cortex or in the temporal lobes, but group differences of apparent genetic cause were evident in medial prefrontal, thalamic and cerebellar regions. In addition, differences in activation in those with symptoms were found in the intraparietal sulcus. No significant differences in performance were found between the groups, and all subjects were antipsychotic naïve. These findings therefore suggest that vulnerability to schizophrenia may be inherited as a disruption in a fronto-thalamic-cerebellar network, and the earliest changes specific to the psychotic state may be related to hyperactivation in the parietal lobe.
Oral amino acid load mimicking hemoglobin results in reduced regional cerebral perfusion and deterioration in memory tests in patients with cirrhosis of the liver.
This study tests the hypothesis that administration of an oral amino acid load mimicking hemoglobin in patients with cirrhosis of the liver causes deterioration in neuropsychological function and a reduction in regional cerebral perfusion. Eight overnight fasted, metabolically stable cirrhotic patients with no evidence of overt hepatic encephalopathy were studied prior to and 4 h after simulating an upper gastrointestinal bleed by oral administration of 75 g of a solution mimicking the amino acid composition of hemoglobin. Neuropsychological function was measured using a test battery. Peripheral venous blood was collected for the measurement of ammonia and amino acid concentrations. Regional cerebral perfusion was measured using a head SPECT scanner following intravenous administration of technetium-99m hexamethyl propylamineoxime. The amino acid solution resulted in significant deterioration in the immediate and delayed story recall tests. Ammonia concentration increased from a median of 87 (range 67-94) micromol/L to 105 (98-112) micromol/L at 4 h after the simulated bleed (p < 0.01). The concentration of almost all amino acids increased; only isoleucine levels decreased following the upper gastrointestinal bleed. SPECT analysis showed a significant reduction in cerebral perfusion after the simulated bleed in both temporal lobes, left superior frontal gyrus, and right parietal and cingulate gyrus. An oral amino acid load mimicking hemoglobin in cirrhotic patients produces hyperammonemia and hypoisoleucinemia and causes a significant deterioration in memory tests, probably due to a reduction in regional cerebral perfusion. The model of simulating the metabolic effects of an upper gastrointestinal bleed in patients with cirrhosis of the liver seems to be useful in studying the metabolism of hepatic encephalopathy.
Regional cerebral blood flow in IDDM patients: effects of diabetes and of recurrent severe hypoglycaemia.
Chronic hyperglycaemia and recurrent severe hypoglycaemia have both been implicated as causing cerebral damage in patients with diabetes. Although cognitive dysfunction and intellectual impairment have been demonstrated in patients with recurrent severe hypoglycaemia, structural correlates have not been described, and it is not known whether specific functional changes occur in the brains of affected patients. Regional cerebral blood flow was estimated by SPECT with 99mTechnetium Exametazime in 20 patients with IDDM. Ten patients had never experienced severe hypoglycaemia and 10 had a history of recurrent severe hypoglycaemia. Patient results were compared with 20 age- and sex-matched healthy volunteers. We observed differences between the two patient groups and the control group. Tracer uptake was greater in diabetic patients in the superior pre-frontal cortex. This effect was particularly pronounced in the group who had a history of previous severe hypoglycaemia. Patients with a history of recurrent hypoglycaemia also had a relative reduction in tracer uptake to the calcarine cortex. This suggests an alteration in the pattern of baseline regional cerebral blood flow in diabetic patients with frontal excess and relative posterior reduction in cerebral blood flow.
The effects of progressive abstinence from alcohol on red blood cell proton NMR relaxation times and water content.
Red blood cell proton relaxation times T1 and T2 were measured in samples from chronic alcoholic patients abstinent for varying periods from 1 week to over 6 months. T1 and T2 were elevated in the early stages of abstinence and declined to the values of controls after 8 weeks. Changes in the water content of the red blood cells and the mean corpuscular volume paralleled these changes but were more closely associated with T2. It is suggested that T1 and T2 may reflect different aspects in water content and free-to-bound ratio of water. The significance of these findings is discussed in the context of changes previously observed in the brains of alcoholic patients, and in rats fed a diet supplemented with alcohol for 6 months.
Clonidine infusion increases uptake of 99mTc-Exametazime in anterior cingulate cortex in Korsakoff's psychosis.
The effects upon regional brain function of infusing either saline or clonidine (1.5 microgram/kg) has been examined in 18 patients with alcoholic Korsakoff's psychosis using 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO or 99mTc-Exametazime) and Single Photon Emission Tomography (SPET or SPECT). The hypothesis tested was that frontal lobe function would be increased by adrenoceptor stimulation. This was confirmed by an increase in the uptake of 99mTc-Exametazime into anterior cingulate regions of the frontal lobes. Patients were scanned before and after saline or clonidine infusion during performance of a verbal fluency task. There was a significantly increased performance of verbal fluency in patients given clonidine. This effect was variable and could not be unequivocably distinguished from increases in performance in the saline treated group. Nevertheless, the increase in neuropsychological performance was also correlated with increased function in left dorsolateral frontal cortex within the clonidine treated group. An exploratory examination of other brain areas suggested that relative increases in posterior cingulate cortex and changes in the symmetry of function within the thalamus may also be produced by acute infusion of clonidine in Korsakoff patients. The findings support the idea that adrenergic mechanisms may modulate cognitive performance by actions on attentional systems within the brain. These appear to be located primarily within limbic cortex. It is, of course, notable that this can occur in patients with profound and disabling amnesia.
Methodological considerations in measurement of the P300 component of the auditory oddball ERP in schizophrenia.
Twenty-three schizophrenic patients and 26 age-matched control subjects were studied using the P300 recorded during the auditory oddball task, with counting. Our aim was to assess the most suitable method of measurement and analysis of P300 amplitude and latency for use in clinical studies of schizophrenia. The effect of high-pass filtering, peak definition method and recording electrode site were all investigated. We have developed a technique, based on a least-mean-squares approximation to data, which seems particularly well suited to dealing with multi-peak P300 complexes. We have also investigated the spectral composition of the P300 and have found some evidence to support a proposed 2-frequency model of the P300 complex.
The differentiation of major depression from dementia of the Alzheimer type using within-subject neuropsychological discrepancy analysis.
The method of comparing premorbid versus current intellectual ability has become established clinical practice in the differential diagnosis of dementia versus depression. Recently, Schlosser & Ivison (1989) suggested that the comparison of premorbid ability versus current memory function may offer a more sensitive method of assessing early dementia. In the present study, a variety of within-subject discrepancy analyses comparing premorbid estimates with current measures of memory and intellectual functioning were compared across three groups: patients with dementia of the Alzheimer type, patients with major depression and healthy controls. The results revealed that, while mean group differences were easily demonstrated, the overlap between Alzheimer and depressed patients was large. It is concluded that none of the simple neuropsychological discrepancy analyses examined in the present study can be recommended for use in clinical practice for the differential diagnosis of dementia from major depression.
Dementia in idiopathic Parkinson's disease: prevalence and relationship with symptoms and signs of parkinsonism.
A whole population cohort of 157 patients with idiopathic Parkinsonism, most of whom had previously been clinically examined by Mutch (1986a), were assessed to determine prevalence figures for dementia and examine the relationship between dementia, cognitive impairment and Parkinsonian signs. Dementia according to DSM-III-R criteria was diagnosed in 23.3% of all patients (95% confidence interval: 17.1 to 32.4%). Dementia and cognitive impairment were associated with overall measures of Parkinsonian impairment and rigidity, but not tremor, even after controlling for age, sex and education.
Red blood cell NMR proton relaxation times in ill and recovered patients with unipolar and bipolar affective disorders.
Red blood cell NMR relaxation times T1 and T2 and water content were measured in ill and recovered patients with mania, unipolar depressed phase, bipolar depressed phase and control subjects. The results suggest that relaxation times are elevated in ill bipolar manic and ill unipolar depressed patients but are normal in both groups in the recovered phase and in ill bipolar depressed patients. Relaxation times therefore seem to be state-dependent but behave differently in unipolar and bipolar patients.