[Dementia conditions during aging. Several risk factors in Alzheimer disease].
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Aged↗
Biomedical subjects
C G Gottfries
Publications and source records attributed to C G Gottfries.
Neuropeptides and Alzheimer's disease.
Numerous neuropeptides have been isolated from the human brain and postulated as neurotransmitter candidates. Their biochemical characteristics and anatomical distribution have been elucidated in some detail, but their possible physiological and pathophysiological roles, as well as their utility as diagnostic markers in brain disorders, have been more difficult to establish. The concentrations of several neuropeptides have been measured in postmortem human brain studies and in cerebrospinal fluid (CSF) of patients with Alzheimer's disease. Here we critically review these findings with focus on: (1) the relation between brain tissue and CSF neuropeptide alterations; (2) the specificity of neuropeptide alterations in Alzheimer's disease in relation to other degenerative brain diseases; (3) possible functional implications.
Alzheimer Disease↗
Activities of daily living ratings of elderly people using Katz' ADL Index and the GBS-M scale.
Instruments for measuring activities of daily living (ADL) are useful in estimating institutionalized elderly ill people's need of care. The aim of the present study was to investigate to what extent the GBS-M scale measures ADL status, as determined by Katz' ADL Index. Forty-two elderly patients in long-term care in a psychiatric hospital were rated independently using each of the two scales. The correlation coefficient between results of the ratings was r = 0.93, i.e., high scores on one of the scales gave high scores on the other scale. Fifty per cent of severely demented patients had maximal scores on measures of ADL.
Activities of Daily Living↗
Regulation of the hypothalamic-pituitary-adrenal axis in dementia disorders.
In 163 patients with dementia disorders, subdivided into Alzheimer's disease with early onset (AD; n = 40), senile dementia of the Alzheimer type (SDAT; n = 56), vascular dementia (VAD; n = 45) and dementia of unspecified type (NUD; n = 22) the dexamethasone suppression test (DST) was performed. The patients were rated according to the DSM-III-R criteria as having mild, moderate or severe dementia and were also assessed using the GBS scale which gives a profile of the dementia syndrome. In the total group of dementia there were significant correlations between severity of dementia and post-DST levels. The frequency of pathological DST also correlated significantly with the severity of dementia. In the subgroups of dementia a strong correlation between severity of dementia and high post-DST cortisol levels was found only in the VAD group. Between the subgroups of dementia disorders there were no significant differences in basal cortisol levels. The percentage of pathological DST was lowest in the AD group (40%). It was somewhat higher in the VAD group (49%), still higher in the SDAT group (54%) and highest in the NUD group (59%). When the relationship between post-DST cortisol levels and GBS scores was analyzed, significant correlations were found mainly in the VAD group. There intellectual impairment, anxiety, fear-panic and restlessness correlated significantly with post-DST cortisol levels. The results indicate hypothalamic overactivity in a substantial number of demented patients. In VAD and to a certain extent also in SDAT a disconnection between cortical areas, including the hippocampus, and the hypothalamus is assumed. Overactivity in the hypothalamic-pituitary-adrenal (HPA) axis is due to stress, and an insufficient feedback system leads to chronic stress adaptation failure.
Aged↗
Evidence for biochemical heterogeneity in schizophrenia: a multivariate study of monoaminergic indices in human post-mortal brain tissue.
A previously performed post-mortem study comparing monoaminergic indices in the brains of 14 schizophrenic patients and 10 patients with psychosis not diagnosed as schizophrenia, with age-matched control cases without any known neuropsychiatric illness, was re-investigated, using multivariate analysis. The monoaminergic patterns showing up in this analysis suggested the existence of at least two different forms of the disease, both of which could be distinguished from the controls as well as from each other. One of the schizophrenic groups consisted of paranoid cases, and had a relatively mild family history, whereas the other group, mainly consisting of hebephrenic cases, had a severe family history. The former group showed low levels of dopamine and high levels of serotonergic precursor and metabolite, whereas the latter group in some respects tended to show the opposite aberrations. Neuroleptic treatment did not seem to account for the different biochemical profiles, unless one assumes that this treatment can cause completely different monoaminergic aberrations in different individuals. Instead, one could argue that the different biochemical profiles found are characteristic of the disease.
Adult↗
Homocysteinemia and schizophrenia as a case of methylation deficiency.
A 27-year-old woman is described whose disorder meets the DSM-III-R criteria for a diagnosis of schizophrenia and who was found to have a significantly increased serum level of homocysteine. Repeatedly, she improved on frequent cobalamin injections and deteriorated in periods without treatment. The effects of prolonged weekly treatment appeared to diminish as time went on, suggesting that the abnormality was not wholly cobalamin-dependent. It was found that methylenetetrahydrofolate reductase (MR) activity in cultured skin fibroblasts was reduced to a magnitude that is found among people with heterozygous deficiency. A defect in MR activity indicates a deficiency in methyltetrahydrofolate (MTHF), with a consequent reduction of the remethylation of homocysteine to methionine. Thus, reduced methylation may explain the increased levels of homocysteine and the transient effects of cobalamin treatment in the patient. Theoretically, MTHF should be the optimal treatment for her. The case reported highlights the importance of assessing the serum homocysteine level in order to detect methylation deficiency in patients with schizophrenia.
Adult↗
Formulas for the quantitation of intrathecal IgG production. Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis.
There are several formulas for the quantitative determination of intrathecal IgG production: Reiber and Felgenhauer's formula (IgG(loc)), the Extended IgG index, Tourtellotte's formula (TOURT), Schuller and Sagar's formula (SCHULL), the IgG index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To evaluate the utility of these formulas in the presence of blood-brain barrier (BBB) damage, we present the results from a study of serum and cerebrospinal fluid (CSF) samples from 125 healthy individuals, 18-88 years of age; 1072 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin ratio 9.8-30); and 106 patients with definite multiple sclerosis (MS). The relation between the CSF/S albumin ratio and the CSF/S IgG ratio was remarkably linear in both healthy individuals (r = 0.95; P < 0.0001) and patients without oligoclonal bands in the CSF (r = 0.95; P < 0.0001). Therefore, IgG(loc) and the Extended IgG index, two formulas based on a nonlinear relation between the CSF/S albumin ratio and the CSF/S IgG ratio, yielded biased results (lower values) in the presence of BBB damage. TOURT and SCHULL also yielded biased (higher) values in the presence of BBB damage, probably because of incorrect constants in these formulas. There were no significant correlations between the CSF/S albumin ratio (i.e. the BBB function) and the IgG index or the Log IgG index, two dimensionless quotients for the detection of intrathecal IgG production, or between the CSF/S albumin ratio and IGGPROD, an empirical formula for the determination of intrathecal IgG production in mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Man's emotional capacity--an unexplored and unexploited possibility.
Man's mental functions have developed unevenly. Sometime during the last millennium the muscle man was superseded by the intelligent man. The human psyche, besides intellectual capacity, includes a basic function that can be called emotional capacity. This function can be studied using the same approach as in the study of intellectual capacity. The two functions are considered to be partly independent of each other. Emotional capacity depends on the individual's genetic emotional make-up (emotional genotype) and how this inherited set of qualities has been conditioned by environmental factors (emotional phenotype). Man's emotional capacity is very little differentiated: emotionally, modern man still functions almost like Stone Age man. Intellectual capacity, however, has undergone enormous development. As emotional capacity to a large extent governs man's behaviour and intellectual capacity is the instrument he uses to reach his goals, the uneven differentiation of the mental functions may have consequences that are unfavourable to the survival of our species.
Biological Evolution↗
Six-month open trial with Zimelidine in alcohol-dependent patients: reduction in days of alcohol intake.
In an open study, 14 alcohol-dependent male patients were treated with the selective serotonin reuptake inhibitor (SSRI) Zimelidine, 200 mg daily, for six months. They were given psychosocial therapy before and during the study. The number of days of alcohol intake was statistically significantly reduced from a mean of 14 days per month before to 1-5 days during drug treatment. No effect was observed on the amount of daily alcohol intake on drinking days. No tolerance to the effect of Zimelidine was observed during the study. The findings suggest an effect of combined psychosocial support with SSRI treatment that seems to be of clinical significance.
Adult↗
Ubiquitin in cerebrospinal fluid in Alzheimer's disease and vascular dementia.
Ubiquitin (Ub) was determined by a competitive enzyme-linked immunosorbent assay (ELISA) in serum (S) and cerebrospinal fluid (CSF) samples from 29 patients with 'probable Alzheimer's disease' (AD), 14 patients with vascular dementia (VAD), and 13 healthy individuals. The mean concentration of Ub in CSF (110 +/- 20 ng/mL) was about 20% of that in serum (940 +/- 120 ng/mL) in healthy controls. There was no significant correlation between S-Ub and CSF-Ub, or between the CSF/S.Ub ratio and the CSF/S albumin ratio. These findings suggest that a major portion of CSF-Ub is intrathecally produced. CSF-Ub was increased while S-Ub was decreased in both AD and VAD patients as compared with controls. As a consequence, the CSF/S Ub ratio showed good discrimination between patients and controls: 22/29 (76%) of the AD patients and 9/14 (64%) of the VAD patients had a CSF/S Ub ratio that was higher than the highest control value. No significant differences in any of the parameters were found between AD and VAD. Ub is involved in an ATP-dependent proteolytic pathway and also acts as a heatshock protein. The increase in CSF-Ub in AD and VAD may therefore be interpreted as a cytoprotective response to abnormal or damaged proteins, and CSF-Ub may have a potential as a non-disease-specific marker for cerebral degeneration.
Aged↗
Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demyelination in late-onset form (type II).
Major membrane lipids were quantified in frontal (Brodmann area 9) and temporal (Brodmann areas 21 and 22) cortices, caudate nucleus, hippocampus, and frontal white matter of 12 cases with Alzheimer's disease (AD) type I (early onset), 21 cases with AD type II (late onset), and 20 age-matched controls. The concentration of gangliosides--a marker for axodendritic arborization--was reduced to 58-70% of the control concentration in all four gray areas (p < 0.0001) and to 81% in frontal white matter (p < 0.01) of AD type I cases, whereas it was only significantly reduced in temporal cortex (p < 0.01), hippocampus (p < 0.05), and frontal white matter (p < 0.05) in AD type II cases. The concentration of phospholipids was also significantly reduced (p < 0.01-0.0001) in all four gray areas of AD type I cases but in no area of AD type II cases. The loss of cholesterol was only 50% of the corresponding phospholipid diminution in AD type I. These results suggested a pronounced loss of nerve endings in AD type I. The characteristic membrane lipid disturbance in AD type II was a loss of myelin lipids. This is the first time a fundamental biochemical difference has been shown between the two major forms of AD.
Aged↗
Hypothalamic dysfunction in dementia.
In 40 patients with Alzheimer's disease (AD) 56 patients with senile dementia of Alzheimer type (SDAT) and 45 patients with vascular dementia (VAD) degree of dementia was rated into mild, moderate and severe according to DSM-III-R and on the GBS scale. Basal cortisol levels were determined and a dexamethasone test (DST) performed. Basal cortisol levels were high in all the dementia groups. Forty percent of AD patients, 54% of SDAT patients and 49% of VAD patients were non suppressors. Significant correlations between post DST cortisol levels and rated variables were seen mainly in the VAD group. The pathological DST could hardly be explained by presence of depression. In dementia, especially those with white matter disturbances, disconnections between cortical areas (hippocampus) and hypothalamus can be assumed explaining a reduced inhibitory tone on hypothalamus. When characterizing VAD patients with pathological DST these patients were significantly more intellectually impaired, showed higher degree of anxiety, restlessness and fear-panic than VAD patients with normal DST. Some behaviourial disturbances in dementia disorders may be a consequence of HPA over activity rather than a consequence of the dementia process itself.
Aged↗
Concentration gradients for monoamine metabolites in lumbar cerebrospinal fluid.
Concentration gradients in lumbar cerebrospinal fluid (CSF) for the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were studied in 9 healthy controls and 47 neuropsychiatric patients without diseases causing disturbed CSF circulation. In a serial sampling of the first 24 ml of CSF, steep concentration gradients between the first (0-4th ml) and last (21st-24th ml) portions of CSF were found for HVA (99 +/- 59% increase; p < 0.001) and 5-HIAA (88 +/- 54% increase; p < 0.001), while the concentration gradient was slight for HMPG (11 +/- 7% increase; p < 0.001). The existence of marked concentration gradients for the monoamine metabolites HVA and 5-HIAA gives further evidence for an active transport system for these metabolites and indicates that the lumbar CSF-HVA and 5-HIAA levels reflect the dopamine and serotonin metabolism in the brain. Moreover, the existence of pronounced concentration gradients for HVA and 5-HIAA stresses the importance of making analyses on a standardized volume of CSF.
Adolescent↗
Cerebrospinal fluid monoamine metabolites in 114 healthy individuals 18-88 years of age.
Concentrations of the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 114 healthy individuals, 18-88 years of age, without histories, symptoms or signs of central nervous system dysfunction. The mean values (+/- SD) were 253 +/- 109 nmol/l for HVA, 125 +/- 54 nmol/l for 5-HIAA, 47 +/- 10 nmol/l for HMPG, and 2.10 +/- 0.52 for the HVA/5-HIAA ratio. Analyses of confounding factors revealed that all metabolites correlated negatively with body height, the values being lower in taller than in shorter individuals. This is probably attributable to a larger surface area for monoamine metabolite transport from the subarachnoid space in taller than in shorter individuals. These correlations make statistical adjustment for body height important in analyses of monoamine metabolite levels. Without considering body height, all monoamine metabolites showed a positive correlation with age, and higher levels of HVA and 5-HIAA were found in women than men. After statistical adjustment for the influence of body height, no differences in CSF monoamine metabolites levels were found between the sexes, and only 5-HIAA showed a positive correlation with age. There were no significant seasonal variations for any of the monoamine metabolites.
Adolescent↗
Low blood pressure and blood glucose levels in Alzheimer's disease. Evidence for a hypometabolic disorder?
OBJECTIVE: To test possible differences between patients with Alzheimer's disease (AD) and patients with other forms of dementia and the healthy population concerning body composition, blood pressure, metabolic data and leukoaraiosis (LA). DESIGN: Retrospective study on data collected according to a predefined protocol. SETTING: A geriatric, neuropsychiatric diagnostic unit. SUBJECTS: Seventy-one consecutive patients with dementia. MAIN OUTCOME MEASURES: Body mass index, blood pressure, metabolism and LA in AD compared to other dementia forms. RESULTS: Mean blood pressure and fasting blood glucose levels were lower in patients with AD, 94 +/- 12 mmHg and 4.3 +/- 0.5 mmol l-1, compared to patients with unspecified dementia (NUD), 100 +/- 10 mmHg and 5.5 +/- 2.5 mmol l-1 (P < 0.05) and vascular dementia (VAD), 114 +/- 12 mmHg and 5.6 +/- 1.6 mmol l-1 (P < 0.001) and the age-matched healthy population. Body mass index, serum cholesterol and cortisol were similar in all groups of dementia patients whereas triglycerides were highest in the VAD group. No cases of diabetes or treatment for hypertension were found in the AD group while the prevalence was 21% and 36% for diabetes in the NUD and VAD groups and 8% in the population from the same region. There were 16% with antihypertensive treatment in dementia NUD, 50% in VAD, and 30% in the general population. Treated or newly detected hypothyreosis was present in 11% of the AD patients, none in the other dementia groups and 2% in the general population. Smoking was least common in AD. Degree of LA correlated with blood pressure and blood glucose levels. CONCLUSIONS: AD was clearly different to other dementia patients. They had lower blood pressure, blood glucose and higher prevalence of hypothyreosis than the healthy, age-matched population. These findings may indicate that AD could be a hypometabolic disorder.
Aged↗
Protein analyses in cerebrospinal fluid. I. Influence of concentration gradients for proteins on cerebrospinal fluid/serum albumin ratio.
Concentration gradients in lumbar cerebrospinal fluid (CSF) for albumin and IgG were studied in 8 healthy individuals and 44 neuropsychiatric patients by serial sampling of 6 successive portions of CSF, each containing 4 ml, in all 24 ml. Significant and identical decreases between the first (0-4th ml) and the last (21st-24th ml) portions were found for CSF-albumin (21% decrease, p < 0.0001) and CSF-IgG (21% decrease, p < 0.0001). Therefore, the CSF/serum albumin ratio also showed a significant gradient with a 21% decrease (p < 0.0001), while no gradients were found to the IgG index. These results imply that analyses of proteins in the CSF should be performed on a standardized volume of CSF, preferably the first 12 ml, to allow comparisons of scientific results between various patient groups and controls and between different laboratories and to increase the validity of protein analyses in clinical practice.
Adolescent↗
Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age.
Analyses of the cerebrospinal fluid (CSF) to determine the blood-CSF barrier function and to detect intrathecal IgG production are used in the diagnosis of neurological and psychiatric diseases. Therefore, accurate reference values for these parameters are of utmost importance. However, current reference values are based on 'reference groups' consisting of patients with psychiatric and/or neurological symptoms but without positive clinical findings and on groups of young students. The present study presents reference values for CSF proteins in a large sample (n = 105) of healthy individuals, with a large age-span (18-88 years of age). The parameter for the determination of the blood CSF barrier function, the CSF/serum (CSF/S) albumin ratio, was found to show an increasing variability in individuals over 45 years of age, suggesting a less stable blood-CSF barrier function than in younger individuals. The upper reference limit for the CSF/S albumin ratio was 6.8 for individuals under 45 years of age and 10.2 for individuals over 45 years of age. The IgG index, a dimensionless quotient for the determination of intrathecal IgG production, showed only a minor correlation with age and had an upper reference limit of 0.63.
Adolescent↗
Protein analysis in cerebrospinal fluid. III. Relation to blood-cerebrospinal fluid barrier function for formulas for quantitative determination of intrathecal IgG production.
To examine the possible influence of the blood-CSF barrier function on mathematical formulas for estimating intrathecal IgG production (IgG index, Tourtellotte's formula [TOURT], Schuller and Sagar's formula [Schull], and Reiber and Felgenhauer's formula [IgG(loc)]), we analysed serum and CSF samples from 105 healthy individuals, aged 18-88 years, and 816 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, aged 18-91 years. In healthy individuals there was no significant correlation between the CSF/serum (S) albumin ratio (i.e. blood-CSF barrier function) and the IgG index, a dimensionless quotient for determining intrathecal IgG production, and only a small correlation (r = -0.08, p < 0.05) in patients without OCBs. However, significant dependence on the blood-CSF barrier function was found, in both healthy individuals and patients without OCBs, for the formulas determining intrathecal IgG production in milligrams (per litre CSF or per day), i.e. for TOURT, SCHULL and IgG(loc). Therefore, we propose a new formula for the quantitative determination of intrathecal IgG production in mg/l, the IGGPROD, which is calculated as: CSF-IgG -[(0.51 x CSF-Alb x S-IgG)/S-Alb]. IGGPROD is an empirical formula, based on findings in 105 healthy individuals 18-88 years of age, and does not depend on the blood CSF barrier function.
Adolescent↗