Abnormal content of n-6 and n-3 long-chain unsaturated fatty acids in the phosphoglycerides and cholesterol esters of parahippocampal cortex from Alzheimer's disease patients and its relationship to acetyl CoA content.

The long-chain fatty acid composition of cholesterol esters, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI) from parahippocampal cortex of Alzheimer's disease (AD) patients and control subjects was examined. In general the PC fraction contained less polyunsaturated long-chain fatty acids than did PE, PS or PI. Of the n-6 polyunsaturated long-chain fatty acids, PI contained the greatest incorporation of these acids followed by PE. There were significant differences between controls and AD patients in total n-6 EFAs. Arachidonic acid (C20:4n-6) was the predominant fatty acid of this family found to be present. In AD, PE and PS showed a deficit of adrenic acid (C22:4n-6) content and PE also contained less arachidonic acid. In AD subjects, the cholesterol esters contained significantly less n-3 polyunsaturated fatty acids with, specifically, a reduction in alpha-linolenic acid. Acetyl CoA content of hippocampal cortex was greater in AD patients than in control subjects indicating either an increased extent of oxidative metabolism or a failure to utilise acetyl CoA for anabolic processes. Abnormal magnitude of oxidative processes could give rise to the biosynthesis of PE and PS species containing less n-6 polyunsaturated fatty acids than occurs in control subjects.

The use of technetium-99m-HM-PAO in the assessment of patients with dementia and other neuropsychiatric conditions.

One hundred fourteen patients suffering from neuropsychiatric conditions have been studied using 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) and single photon emission computed tomography (SPECT). Ninety-one patients had a firm clinical diagnosis while 23 were examined without knowledge of the clinical diagnosis. Of the 91 patients, 51 were suffering from dementia, 25 multi-infarct type and 26 Alzheimer's disease. In 19 of the Alzheimer's patients, a characteristic pattern of decreased perfusion in the parieto-occipital regions was demonstrated while those with multi-infarct type showed varying degrees of irregular uptake in the cerebral cortex. These appearances are similar to those shown with positron emission tomography (PET) and we believe that HM-PAO will provide a widely available method for identifying patients with Alzheimer's disease. Twenty-nine patients were suffering from diseases involving the basal ganglia. Fifteen patients with Parkinson's disease showed no significant abnormality in basal ganglia uptake, while 7 or 8 patients with Huntington's disease who had full examinations showed decreased uptake in the caudate nuclei. Similarly, four of six patients with other basal ganglia diseases showed impaired uptake by basal ganglia, and it is concluded that HM-PAO may be useful for the diagnosis and management of this type of patient. Twenty-three patients received HM-PAO imaging as part of their diagnostic work-up; in 19 of them, detailed follow-up was obtained, which indicated that in 7 cases the result of the HM-PAO scan altered the clinical diagnosis and in 9 cases resulted in a change in management. In the remaining 13 cases, the study was found to be helpful in confirming the diagnosis.

Clinical features predicting dementia in idiopathic Parkinson's disease: a follow-up study.

We followed up, after 3 1/2 years, a whole population cohort of 249 patients with Parkinson's disease (PD) 1st examined in 1983 to 1984. Of the survivors, 23.6% qualified for a DSM III-R diagnosis of dementia. In univariate tests, age, certain items of the Webster scale, the Hoehn and Yahr scale, a 10-question mental status questionnaire, and a history of smoking were associated with a diagnosis of dementia 3 1/2 years later. Logistic regression with DSM III-R diagnosis (demented versus nondemented) as the dependent variable, and age and symptom scales for PD as predictor variables, revealed that PD symptoms predicted dementia even after controlling for age. We conclude that dementia is probably more common in PD patients than would be expected in the general population and is associated with the severity of PD symptoms and signs independently of age.

Regional cerebral blood flow imaging: a quantitative comparison of technetium-99m-HMPAO SPECT with C15O2 PET.

The aim of this study was to compare technetium-99m-hexamethylpropyleneamineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) with regional cerebral blood flow (rCBF) imaging using positron emission tomography (PET). As investigation of dementia is likely to be one of the main uses of routine rCBF imaging, 18 demented patients were imaged with both techniques. The PET data were compared quantitatively with three versions of the SPECT data. These were, first, data normalized to the SPECT cerebellar uptake, second, data linearly corrected using the PET cerebellar value and, finally, data Lassen corrected for washout from the high flow areas. Both the linearly-corrected (r = 0.81) and the Lassen-corrected (r = 0.79) HMPAO SPECT data showed good correlation with the PET rCBF data. The relationship between the normalized HMPAO SPECT data and the PET data was nonlinear. It is not yet possible to obtain rCBF values in absolute units from HMPAO SPECT without knowledge of the true rCBF in one reference region for each patient.

The effect of clomipramine treatment on plasma lipoproteins and high density lipoprotein subfractions in healthy subjects.

The effect of clomipramine on plasma lipoproteins, including high density lipoprotein (HDL) subfractions in five healthy males was investigated. The concentrations of total plasma cholesterol and low density lipoprotein cholesterol decreased slightly while that of total HDL-cholesterol showed a small increase, giving a decrease (p less than 0.05) in the ratio of total plasma cholesterol to HDL-cholesterol. The level of HDL2-cholesterol increased (p less than 0.01) with clomipramine treatment while there was no significant change in the concentration of HDL3-cholesterol. Gradient gel electrophoresis showed that administration of the drug was associated with an increase in the relative concentration of HDL2a as well as of HDL2b and a decrease in that of HDL3b/3c. The plasma concentration of apolipoprotein (Apo) A-I showed a small but insignificant increase. These changes in lipoprotein profile are characteristic of those associated with a decrease in coronary risk.

Intermittent alexia.

A case of intermittent alexia, sometimes accompanied by severe dysgraphia and sometimes by mild dysgraphia, which had a probable migrainous origin, is described. On some occasions the patient could write to dictation, although with many errors, while unable to read words or letters. On other occasions the patient's writing to dictation was seriously disordered in terms of content and the letters were produced clumsily. Reading of numbers, colour vision and colour naming were normal although impairments on right-left orientation and visual short term memory were present and a mild finger agnosia was apparent. Blood flow scans (SPECT) taken under normal and alexic conditions support the view that the disturbance had a vascular origin.

Relationship between observed NMR changes and brain water content following electroconvulsive stimulation in the rat.

The administration of electroconvulsive stimuli to anaesthetised rats results in changes in the relaxation times and water content of grey and white matter, but not in mid brain, hind brain or cerebellum. White matter changes occur in both T1 and T2, are biphasic in character and related to water content. Grey matter changes are confined to T1 and water content only. It is suggested that these changes are related to altered compartmentalisation of water, manifesting in a different manner in the two tissues probably due to their different cellular and biochemical composition.

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.

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.

Regional variation in rat brain proton relaxation times and water content.

Relaxation times (T1 and T2) and water content are measured in frontal cortex, amygdaloid cortex, hippocampus, mid-brain and cerebellum of rat brain. Differences are found in relaxation times, between areas containing a mixture of grey and white matter, and grey matter only. Differences were also found between certain grey matter areas. Relaxation times correlated with water content.

1H-NMR relaxation times and water content of red blood cells from chronic alcoholic patients during withdrawal.

Red blood cell proton nmr, T1 and T2 times, and water content were measured for normal control subjects and thirteen patients with chronic alcoholism during the withdrawal phase. T1 and T2 were significantly increased without significant alteration in cell water content. The relaxation times were more markedly affected in those with symptoms of delirium tremens. These findings suggest that the intracellular free:bound water states rather than water content is the more likely explanation for these changes. The results are discussed in relation to similar findings obtained from in vivo studies in man and in vitro studies in animals.

An NMR study of lithium responding manic depressive patients.

Manic depressive patients on long-term prophylactic therapy with lithium carbonate are examined by nuclear magnetic resonance imaging of the brain. Their ventricular brain ratios and cerebral grey and white matter spin lattice relaxation times (T1) are within normal limits. The implication of these findings in the light of previous studies using other techniques is discussed.

Technetium-99m HMPAO imaging in patients with basal ganglia disease.

Technetium 99m hexamethylpropylene-amine oxime (HMPAO) is trapped by cerebral grey matter and the basal ganglia on its first pass through the brain. To assess its potential for studying patients with diseases of the basal ganglia, a study of 15 normal volunteers and 32 patients with known or suspected basal ganglia disease have been investigated. Sixteen patients with idiopathic Parkinson's disease showed no abnormality of the basal ganglia and varying degrees of cerebral underperfusion consistent with their intellectual status. Eight patients with Huntington's chorea showed a characteristic pattern of reduced or absent caudate nucleus uptake. Patients with diseases affecting the basal ganglia, such as Fahr's disease, Wilson's disease and hemibalismus had varying degrees of basal ganglia underperfusion as demonstrated by an HMPAO scan. We believe that this new radiopharmaceutical for the demonstration of cerebral blood flow shows significant potential for the diagnosis and management of patients with basal ganglia disease.

Estimation of premorbid intellectual status in depression.

The validity of the NART and Vocabulary subtest of the WAIS as measures of premorbid IQ in depression was assessed by comparing a group of depressed patients (n = 39) with matched controls. The Vocabulary performance of the depressed group was significantly poorer than controls but there was no significant difference in NART performance.

The relationship between demographic variables and NART performance in normal subjects.

The relationship between NART performance and demographic variables was examined in a group of subjects free of neurologic or psychiatric disorder (n = 201). NART estimated IQ was significantly correlated with education, social class and age. The correlation between age and NART IQ was no longer significant after partialling out either education or social class. There was no evidence of a curvilinear relationship between age and NART performance. There was no significant sex difference in NART performance. Nelson's (1982) report of a high split-half reliability was confirmed.

A comparison of the WAIS and WAIS-R in matched UK samples.

A matched samples design was employed to compare WAIS and WAIS-R IQ in UK subjects. The WAIS yielded significantly higher mean Full Scale, Verbal and Performance IQs. The mean differences were 7.5, 6.4 and 7.9 IQ points respectively. The WAIS and WAIS-R samples were broadly representative of the UK adult population in terms of age, sex and social class distribution, and therefore provide tentative estimates of population mean scores for both Wechsler scales. Mean WAIS IQ was 108.6, suggesting that the WAIS yields inflated IQ scores in the contemporary UK population. Encouragingly, mean WAIS-R Full Scale IQ was 101.1, suggesting that it neither markedly underestimates nor overestimates IQ in the UK.

Estimating premorbid IQ from demographic variables: regression equations derived from a UK sample.

The purpose of the study reported here was to build regression equations for the estimation of premorbid IQ from demographic variables in a UK population. Subjects (n=151) free of neurological, psychiatric or sensory disability, were administered the Wechsler Adult Intelligence Scale (WAIS) and had their demographic details recorded (age, sex, occupation and education). WAIS Full Scale (FSIQ), Verbal (VIQ), and Performance IQ (PIQ) were regressed on the demographic variables. The regression equations generated by this procedure predicted 50, 50, and 30 percent of the variance in FSIQ, VIQ, and PIQ respectively. These equations should provide a convenient and useful supplement to psychometric estimates of premorbid IQ. Unlike psychometric estimates, demographic estimates are entirely independent of a patient's current cognitive status.

Organotin compounds in trimethyltin-treated rats and in human brain in Alzheimer's disease.

As blood tin concentrations are elevated in Alzheimer's disease and as some low molecular weight organotin compounds are neurotoxic, we have attempted to detect organotins in brain in Alzheimer's Disease. First we measured the concentration of trimethyltin (TMT) in the brains of rats which had been exposed to memory-impairing concentrations of TMT and, as the method of linking hydride generation, cryogenic trapping, gas chromotographic separation and atomic absorption spectrophotometric detection permitted the measurements of organotin compounds when the total tin was greater than 0.2 nanograms, we applied these techniques to human brain tissue, some of which showed neuropathological evidence of Alzheimer's Disease. No low molecular weight organotin compounds were detected in the human brain tissue, but it is possible that tin may be complexed with large organic molecules, the hydrides of which would not be volatile, but which could be identified by liquid chromatography.

Mortality and causes of death in idiopathic Parkinson's disease: results from the Aberdeen whole population study.

Two hundred and forty-nine patients with Parkinson's disease previously examined by Mutch et al 1,2 were followed up three and a half years after the original study. Cognitive impairment, age, some postural signs and symptoms of Parkinson's disease and high scores on the Hoehn and Yahr scale predicted premature death. Patients were more likely to die from respiratory infections than controls. Respiratory diseases as cause of death recorded on the death certificate were not related to kyphosis, posture scores or Hoehn and Yahr scores before death. The hypothesis is advanced that death of respiratory causes might be associated with signs of general autonomic dysregulation.