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Biomedical subjects

C G Gottfries

Publications and source records attributed to C G Gottfries.

At least 73 records · Page 4Linked to original sources

The role of amyloid beta-protein in Alzheimer's disease.

Deposition of amyloid beta-protein in the brain has been regarded as the central event in Alzheimer's disease; however, amyloid beta-protein precursor is an endogenous protein, probably with neurotrophic functions. An alternative hypothesis is that amyloid beta-protein is involved in the disease process secondarily, as a protective reactant when brain cells are injured. Insufficiency of amyloid beta-protein precursor, whether because of a genetic defect or in relation to the action of environmental factors, then allows development of Alzheimer changes.

Alzheimer Disease↗

Brain gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) in patients with Alzheimer's disease.

Activities of Gamma-aminobutyrate aminotransferase (GABA-T) and Monoamine oxidase (MAO)-A and -B were estimated in postmortem brains from 6 control subjects without psychiatric or neurologic disorders and 8 histopathologically verified cases of patients with Alzheimer's disease and senile dementia of Alzheimer type (AD/SDAT). The enzyme activities were examined in four cortical brain regions, three nuclei in the basal ganglia, thalamus and white matter. GABA-T activities in the cortical regions (frontal, parietal, occipital and temporal cortices) and nucleus caudatus were significantly lowered in the AD/SDAT patients. The MAO-A activities were significantly increased in the occipital cortex, caudate nucleus, thalamus and white matter in the AD/SDAT patients. No significant differences were found in the other regions (frontal cortex, parietal cortex, temporal cortex, putamen and globus pallidus). The MAO-B activities in three cortical regions (frontal, parietal and occipital cortices), thalamus and white matter were significantly increased in the AD/SDAT patients, whereas no difference was apparent in the other regions. The changed activities could not be correlated with age or postmortem time. The present results are the first describing decreased GABA-T activities as well as increased MAO-A activities in brain from patients with AD/SDAT, while the results with MAO-B support previous findings. A possible connection was found between the order of magnitude of the changes in enzyme activities and the severity of the disease.

4-Aminobutyrate Transaminase↗

Dementia patients with low serum cobalamin concentration: relationship to atrophic gastritis.

Serum concentrations of group I pepsinogens (pepsinogen-I) and gastrin were determined in patients with dementia disorders in order to assess the relationship, if any, between these indices of gastric mucosal function and serum cobalamin (vitamin B12) levels. A significant positive correlation between pepsinogen-I and B12 and, as expected, an inverse relationship between gastrin and pepsinogen-I concentrations was found, indicating that vitamin B12 deficiency was mainly determined by gastric mucosal atrophy (atrophic gastritis) in this West-Swedish sample of patients with dementia disorders. Patients with low B12 but normal gastrin and pepsinogen-I concentrations should, therefore, be further evaluated for possible nutritional deficiency, as well as nongastric causes of poor B12 assimilation from the diet.

Aged↗

Slowed synthesis of DNA and methionine is a pathogenetic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease?

This is a presentation of the hypothesis of a pathogenetic mechanism common to the dementia seen in Alzheimer's disease (AD), Down's Syndrome (DS) and the acquired immunodeficiency syndrome (AIDS). As there is experimental evidence of defective DNA repair capacity in AD and DS, unrepaired damage to DNA occurs in these diseases and may lead to complete breakdown of cellular function and ultimate cell death. Cobalamin and folate are coordinated in a vulnerable key position in the synthesis of DNA and S-adenosylmethionine (SAM). Cobalamin/folate deficiency, a significant feature in senile dementia of Alzheimer type and in AIDS-related dementia complex, will result in concomitant slowed synthesis of DNA and SAM. The enzyme cystathionine-beta-synthetase (CBS) has been localized to the chromosome band 21q22.3. Owing to gene dosage, CBS activity is increased in trisomy 21. As a consequence, cobalamin/folate metabolism is inhibited, which leads to slowing of DNA and SAM synthesis in DS patients. Amyloidosis is a hallmark of AD and DS brain neuropathology and recent experimental findings support the view that amyloid or amyloid precursors stimulate DNA synthesis, which is in agreement with the hypothesis presented in this paper. In summary, demented patients with cobalamin/folate deficiency, trisomy 21 and human immunodeficiency virus (HIV) infection display a simultaneous downregulation of DNA and SAM synthesis, which may indicate a pathway common to the dementia seen in AD, DS and AIDS.

AIDS Dementia Complex↗

Dementia syndromes in nursing home patients.

Patients (n = 191) living in four comparable somatic nursing homes (NH) (nursing homes for physical illness) were studied in order to evaluate dementia syndromes. Dementia and symptoms of depressed mood occurred frequently (72% and 63%, respectively). Dementia was often undiagnosed at admittance. Neither the length of time spent in institutions, nor marital status, age, or sex seemed to be of more than minor importance to the prevalence of dementia syndromes. Concerning functional impairment, convergence of findings across the societies studied indicates that psychiatric symptoms and psychopathology are intrinsic parts of long-term care of the elderly.

Aged↗

Treatment of depression in elderly patients with and without dementia disorders.

In two inter-Nordic multicenter controlled studies the effect of Citalopram on elderly patients with depression and emotional disturbances has been studied. One investigation included 98 patients in whom Alzheimer type dementia (AD/SDAT) and vascular dementia (VD) had been diagnosed, many of whom also had emotional disturbances. After four weeks treatment with Citalopram (10-30 mg/daily) there was significant improvement in confusion, irritability, anxiety, depressed mood and restlessness. No effect was seen on the intellectual capacity or motor performance measured. In the other study, which was a six weeks trial comparing Citalopram and placebo, elderly patients with a treatment-requiring depression were treated. Demented as well as non-demented patients were included. The Hamilton Depression Scale, the Montgomery-Asberg Depression Rating Scale and The Clinical Global Impressions all recorded an effect of Citalopram superior to that of placebo. In both studies depressive symptoms as well as symptoms of agitation, anxiety, restlessness and irritability improved. Citalopram is therefore considered not only an antidepressive drug but also an emotional stabilizer. The drug was well tolerated by elderly often somatically ill patients. Side effects were few.

Aged↗

Sulfatide as a biochemical marker in cerebrospinal fluid of patients with vascular dementia.

The myelin-associated glycosphingolipid sulfatide in cerebrospinal fluid (CSF) was investigated in 20 patients with vascular dementia (VAD), 43 with Alzheimer's disease (AD) and 20 age-matched controls. The sulfatide concentration in the VAD group (307 +/- 118 nmol/l) was significantly (p less than 0.0001) higher than that in controls (145 +/- 86 nmol/l) and the AD group (178 +/- 79 nmol/l). Among the VAD patients, 8/20 had a significantly increased concentration of sulfatide (greater than mean + 2 S.D.), as compared with controls, while only 2/43 of the AD patients had a sulfatide concentration above this level. It is suggested that the elevated concentration of sulfatide in CSF from VAD patients reflects demyelination. Furthermore, sulfatide determinations, when combined with clinical findings, may be of diagnostic value, for discriminating between VAD and AD.

Aged↗

Vitamin B12 in CSF: reduced CSF/serum B12 ratio in demented men.

Vitamin B12 concentrations were determined in serum and cerebrospinal fluid (CSF) of 32 controls and 102 patients with dementia. The dementias were classified as Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). A substantial number of patients (n = 42) could not be assigned to any of these diagnostic groups, as their dementias were of non-AD/SDAT and non-MID types. They were instead assigned to a group called non ultra descriptum (NUD). CSF B12 correlated significantly with serum B12. There were no statistically significant differences in serum B12 levels between the groups. Although with considerable overlap, CSF B12 concentrations and CSF/serum B12 ratios were significantly lower in the NUD group than in the control group. The NUD group had significantly lower CSF/serum B12 ratios than the group of patients with AD/SDAT. There was significant male predominance in the group of demented patients that had low CSF/serum B12 ratios outside the bivariate reference region. CSF and serum B12 levels appear insufficient as measures of the true brain vitamin B12 status. It may be a more dynamic approach to use the CSF/serum B12 ratio as an indication of transport function across the blood brain barrier, and possibly also across the CSF brain cell barrier.

Aged↗

A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia.

A total of 149 patients in 7 centers in Denmark, Norway and Sweden entered a 6-week double-blind trial intended to assess the antidepressant effect and safety of citalopram vs placebo in depressed elderly patients (65 years of age or older) who might also suffer from somatic disorders and/or senile dementia. Results of ratings on the Hamilton Rating Scale for Depression, the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impression Scale provided consistent evidence that the citalopram-treated patients improved more than the placebo-treated patients. Results of ratings on the Gottfries-Bråne-Steen dementia rating scale indicated that both cognitive and emotional functioning improved significantly more in the citalopram-treated subgroup of patients with dementia than in the placebo-treated subgroup.

Aged↗

Differences in cerebrospinal fluid gangliosides between "probable Alzheimer's disease" and normal aging.

The four major brain gangliosides, GM1, GD1a, GD1b, and GT1b, were determined in cerebrospinal fluid (CSF) of 43 patients with "probable Alzheimer's disease (AD)" and 40 healthy controls without psychiatric or neurological disorders. The total concentration of the four gangliosides did not differ significantly between "probable AD" group (116 +/- 58 nmol/L) and controls (92 +/- 31 nmol/L), but the proportion between the gangliosides was changed. In the "probable AD" group compared with the age-matched control group, there was an increase in both the GM1 (22.6 +/- 9.3% vs 12.6 +/- 4.1%; p < 0.0001) and GD1a (32.1 +/- 9.8% vs 23.3 +/- 5.7%; p < 0.0005) proportion, and a decrease in the GD1b (20.0 +/- 6.6% vs 23.8 +/- 6.0%; p < 0.05) and GT1b (25.3 +/- 7.9 vs 40.3 +/- 9.3%; p < 0.0001) proportion. The proportion of GM1 showed a positive correlation with age in the control group (r = 0.45; p < 0.01), but a negative correlation with age in the "probable AD" group (r = -0.37; p < 0.05). Thus, although the increase in proportion GM1 in the "probable AD" group was preferentially found in younger "probable AD" patients, it was not caused by age differences. While the pathogenetic mechanism for these changes in CSF-gangliosides in "probable AD" remains to be established, it may reflect the degeneration of nerve cells and synapses.

Adolescent↗

[Reliability of the Czech version of the GBS rating scale for dementia syndromes].

By the geriatric evaluation scale GBS for syndromes of dementia in a Czech translation 31 patients of the gerontopsychiatric department were evaluated. The reliability study was implemented by two psychiatrists. The authors compared the results of their own study with results of studies made in other countries. They found a high grade of reliability of the evaluation. They consider the definition of items on the scale and their evaluation practical and suited even for less trained observers or observers with a different training.

Aged↗

Quantitative changes in the amyloid beta A4 precursor protein in Alzheimer cerebrospinal fluid.

The major three secretory isoforms of Alzheimer beta A4 amyloid precursor protein (APP) were quantified in cerebrospinal fluid (CSF) using (1) a newly developed enzyme-linked immunosorbent assay (ELISA) and (2) densitometric analysis of CSF Western blots. The protease inhibitor-containing APP751/770 isoforms represented an average of 10.5% of total APP in CSF of patients with Alzheimer's disease (AD, n = 22), multi-infarct dementia (MID, n = 5) and normal controls (n = 10). APP levels in CSF did not depend on total CSF protein. Both findings are inconsistent with a hematogeneous origin of APP in CSF and suggest an intracerebral source. Total APP, APP695 and APP751/770 were significantly decreased in the AD and in the MID groups, but were not correlated to the ages of patients or controls.

Aged↗

Gangliosides in cerebrospinal fluid in 'probable Alzheimer's disease'.

The concentrations of the four major brain gangliosides--GM1, GD1a, GD1b, and GT1b--were determined in cerebrospinal fluid from 43 patients with "probable Alzheimer's disease" and 19 healthy controls. Alzheimer's disease was divided into type I (with the memory disturbances and predominant cortical parietal symptoms that are characteristic of Alzheimer's disease) and type II (with general cognitive and mild confusional symptoms, with or without only mild parietal symptoms). The GM, concentration was significantly higher in patients with Alzheimer's disease type I than in those with Alzheimer's disease type II and age-matched controls, but did not differ significantly between patients with Alzheimer's type II and age-matched controls. As gangliosides are enriched in nerve cell membranes, preferentially in synapses, the findings suggest more severe degeneration of cortical nerve cells in patients with Alzheimer's disease type I than in those with Alzheimer's disease type II.

Aged↗

Vitamin B12-induced reduction of platelet monoamine oxidase activity in patients with dementia and pernicious anaemia.

Platelet monoamine oxidase (MAO) activity has previously been shown to be increased in patients with senile dementia of Alzheimer type (SDAT) and in patients with megaloblastic anaemia. Moreover, low serum B12 levels were found to be 4-5 times more frequent in SDAT compared with an unselected population of similar age. In the present investigation, platelet MAO activity was estimated in 14 SDAT patients with relatively low serum B12 levels and in 4 patients with pernicious anaemia. Before B12 therapy, platelet MAO activity was significantly increased in both patient groups compared with a control group. After B12 therapy, platelet MAO activity was significantly reduced in both patient groups to apparently normal levels. The present results show that B12 status is a controlling factor of platelet MAO activity and confirm that a significant connection exists between vitamin B12 deficiency and primary degenerative dementia disorders, such as SDAT.

Aged↗