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.

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.

Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects.

In the present study, a comparison was made of the fatty acid composition of the grey and white matter of the frontal, parietal and parahippocampal regions of post-mortem brains of patients who had died with Alzheimer's disease (n = 15) and control postmortem subjects (n = 10). Diagnosis of Alzheimer-type disease was based on the presence of senile plaques and neurofibrillary tangles in post-mortem sections. Several highly significant and specific differences were observed between the two groups. Adrenic acid (22:4 n-6) was three to four times higher in the grey matter but lower in the white matter in each of the three regions in the Alzheimer brains than in the control group. These alterations were compensated by reciprocal changes in 18:0 in the grey matter and 16:1 fatty acids in the white matter. There was no significant difference in the proportion of other fatty acids, including those of the n-6 and n-3 series, in either the grey or the white matter of any of the three regions of the two groups, except for a higher proportion of 22:6 n-3 in the parietal white matter in the Alzheimer patients. There was no significant relationship between the levels of the individual fatty acids and age at death. It is suggested that the alterations in the fatty acid composition observed in the brains of Alzheimer patients may be caused by an aberration in the system by which essential fatty acids are transported into the brain.

In vivo and in vitro tissue scanning studies in alcoholic brain disease.

X ray CT and MRI can identify brain lesions in organic syndromes attributed to chronic alcoholism. Cortical atrophy which improves with abstinence can also be identified. Magnetic resonance relaxation times are altered and may provide a means of monitoring improvement or deterioration in response to abstinence or continued drinking. Altered relaxation times may be due to altered free-to-bound ratios of water and may act as a marker for biochemical change in alcoholic brain disease.

Alzheimer's disease in adults with Down's syndrome: the relationship between regional cerebral blood flow equivalents and dementia.

Twenty adult patients suffering from Down's syndrome (DS) were recruited from hospitals and the community, together with 14 age- and sex-matched controls of normal intelligence. Dementia was diagnosed in patients using a structured psychiatric and physical examination as well as a carer interview and case notes. All patients and controls were imaged using single photon emission computerized tomography with 99mTc-exametazime. Four patients were clinically demented and all of them showed regional cerebral blood flow (rCBF) changes commonly found in patients with Alzheimer's disease, namely bilateral temporo-parietal deficits. These changes were also observed in about half of the patients without clinical evidence of dementia, but in none of the healthy controls. Across the group of patients, temporo-parietal rCBF deficits were associated with evidence of deterioration, but not with advancing age.

Estimation of premorbid intelligence in schizophrenia.

To determine whether the National Adult Reading Test (NART) would provide a valid estimate of premorbid intelligence in schizophrenia, two schizophrenic samples were recruited, one consisting of 35 patients resident in long-stay wards, the other of 29 patients normally resident in the community. Schizophrenic patients were individually matched for age, sex, and education with a healthy, normal subject. Both schizophrenic samples scored significantly lower on the Wechsler Adult Intelligence Scale (WAIS) than their respective control groups. NART-estimated IQ did not differ significantly between the community-resident schizophrenics and their controls, suggesting that the NART provides a valid means of estimating premorbid intelligence in such a population. NART-estimated IQ was significantly lower in the long-stay sample than in their controls. Although low NART scores in this latter sample could be a valid reflection of low premorbid IQ, the alternative explanation that NART performance was impaired by onset of the disease cannot be ruled out.

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.

Post-mortem proton magnetic resonance spectrometric measures of brain regions in patients with a pathological diagnosis of Alzheimer's disease and multi-infarct dementia.

In-vitro spectrometric measures were made of spin-lattice (T1) and spin-spin (T2) relaxation times of samples of grey and white matter from the brains of 15 patients with a pathological diagnosis of Alzheimer's disease, 5 with multi-infarct dementia, and 11 non-demented subjects. Relaxation times were significantly greater in the parietal white matter and temporal white matter of patients with Alzheimer's disease compared with that of the other subjects. This was associated with an increase in tissue water content. These findings confirm measures obtained in some imaging studies.

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.

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.

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.

Red cell caesium, lithium and selenium in abstinent alcoholics.

Using inductively coupled plasma source mass spectrometry, we have studied the red cell element concentrations of alcoholic subjects with different periods of abstinence before testing. We found consistently elevated red cell caesium concentrations and also reduced red cell selenium concentrations. These may represent persistent abnormalities in oxidation/anti-oxidation mechanisms, and red cell caesium in particular may be a long-term marker of alcohol dependence. Erythrocyte lithium, cerium and boron concentrations were also reduced in the abstinent alcoholic groups.

The clinical manifestation of mental disorder in Huntington's disease: a retrospective case record study of disease progression.

All cases (86) of Huntington's Disease presenting between 1970 and 1987 in the Grampian Health Board region were identified and a case note analysis of neurological and psychiatric syndromes carried out--the latter using the PSE syndrome check-list. The commonest syndromes were organic impairment, irritability, loss of interest and concentration and simple depression and these were often the presenting psychiatric syndromes. General anxiety, worrying and social unease occurred early, commonly before movement disorder and were associated with longer survival.

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.

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.

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.