Görel Bråne

Alzheimer disease - effect of continuous intracerebroventricular treatment with GM1 ganglioside and a systematic activation programme.

Five patients with the early-onset form of Alzheimer disease (AD) received GM1 ganglioside by continuous injection into the frontal horns of the lateral ventricles for a period of 12 months. The optimal GM1 dose varied between 20 and 30 mg/24 h. The patients were trained twice a week for 4–5 h with an individually designed cognitive programme, which included the use of a word processor. Neurological, neuropsychological, psychiatric and neurochemical examinations were performed a week before surgery and on days 30, 90, 180, 270 and 365 after surgery. The cerebrospinal fluid levels of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased. The regional cerebral blood flow showed a tendency to increase. The progression of deterioration was stopped, and motor performance and neuropsychological assessments improved. The patients became more active and felt safer in relation to other people and performing various activities. They had improved reading comprehension and a better feeling for language. They were able to write reports and short letters on a word processor. When interviewed at the end of the study, all 5 patients stated that they felt better, and their relatives reported that they had regained integrity and their joie de vivre.

Hyperactivity in the hypothalamic-pituitary-adrenal axis in demented patients with delirium

Occurrence of delirium is known to be related to, among other things, organic brain disorder, somatic disease and old age. It has been hypothesized that delirium is also associated with stress. Disturbances of the hypothalamic-pituitary-adrenal (HPA) system have been found in delirious patients in various studies. The aim of the present study was to determine the activity in the HPA axis in demented patients to ascertain whether the stress regulating system was more disturbed in patients with delirium than in those without delirium. Demented inpatients with no acute medical illness were included in the study. Basal cortisol levels in serum were measured and dexamethasone suppression test (DST) was performed. The most important finding of the study was a strong relationship between delirium and DST pathology irrespective of age and severity of dementia. It is suggested that certain demented individuals have an impaired HPA system and a low delirium threshold and respond to stress with delirium.

Elevated CSF somatostatin concentrations in demented patients parallel improved psychomotor functions induced by integrity‐promoting care

ABSTRACT Elderly demented patients from 2 nursing homes participated in this study. An experimental group (n=17) was subjected to a 3‐month program with integrity‐promoting care resulting in emotional, intellectual and physical activation, whereas a control group (n=18) had no change from the regular ward care. Dementia rating scales and psychological tests were administered before the start of the study and at the end of the 3‐month study period. Lumbar punctures were performed at the same time for assessment of neuropeptide concentrations (somatostatin (SRIF), arginine vasopressin (AVP) and corticotropin‐releasing factor) in the cerebrospinal fluid (CSF). In the control group no significant changes were found in the ratings before and after the study. In contrast, improvements in intellectual and motor functioning were observed in the experimental group. Concomitantly, the SRIF concentrations in CSF were significantly elevated in the experimental group and not affected in the control group. The CSF AVP concentrations were reduced in both groups at the end of the study, but considerably more in the control group. It is concluded that environmental factors can improve intellectual and motor functioning in demented patients and also alter CSF biochemical measures of dementia.

Intracerebroventricular Administration of GM1 Ganglioside to Presenile Alzheimer Patients

We have conducted a preliminary study of the optimum conditions for a therapeutic effect of ganglioside GM1 in Alzheimers disease. Five patients with the early onset form of Alzheimers disease (AD type I) received the ganglioside by intracerebroventricular administration for 12 months. Bilateral stereotactic punction of the frontal horns of the ventricular system was performed, and shunt catheters were implanted and connected to a programmable pump. The optimum GM1 dose varied between 20 and 30 mg/24 h. Neurological neuropsychological, psychiatric and neurochemical examinations were performed 7 days before surgery and on days 30, 90, 180 and 360. No patient found the surgery difficult and no patient or relative regretted that they participated in the study. The patients became more active and safer in relation to others and to performance of various activities from day 90. The cerebrospinal fluid level of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased.

Effects of environmental stimulation on biochemical and psychological variables in dementia

ABSTRACT— The nursing care of a group of moderately demented patients (n= 11) in a nursing home was improved as a result of an education of the staff. Thus the patients were subjected to an increased emotional and intellectual stimulation during the ordinary daily care and participated in group sessions twice a week. In order to evaluate the effects of the treatment, psychological parameters and cerebrospinal fluid (CSF) HVA (homovanillic acid), 5‐HIAA (5‐hydroxyindole acetic acid) and HMPG (4‐hydroxy, 3‐metoxyphenylglucol) were quantified before and after a 2‐month treatment period. A group of similar patients (n= 13) in another nursing home constituted a control group. The ratings of concentration, absent mindedness and recent memory showed a more favorable development in the treatment group than in the control group where an intellectual deterioration was evident. Restlessness was rated higher in the treatment group after the treatment period, while the psychological testings showed no significant changes between the groups. CSF HVA concentrations increased in the treatment group and decreased in the control group (P < 0.05). No change was evident in 5‐HIAA or HMPG concentrations in either group. The results suggest that environmental factors influence biochemical markers of transmitter activity which thus possibly may be of etiological importance in dementia.

Regulation of the Hypothalamic‐Pituitary‐Adrenal Axis in Dementia Disorders

In 163 patients with dementia disorders, subdivided into Alzheimers 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.

Monoamine metabolites in cerebrospinal fluid and behavioral ratings in patients with early and late onset of alzheimer dementia

Patients with Alzheimer disease (AD, onset <65 years of age, n = 13) and senile dementia of the Alzheimer type (SDAT, onset ≥65 years of age, n = 28) were investigated for cerebrospinal fluid (CSF) content of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) and compared with a group of controls (n = 26). A geriatric rating scale, the Gottfries-Bråne-Steen scale, was used to assess impairment of motor performance, intellectual and emotional functioning, and symptoms common in dementia disorders. The HVA levels in CSF were significantly lower in the AD group than in the SDAT group and controls. MHPG was slightly but significantly increased in the SDAT group when compared with the controls. The HVA and 5-HIAA concentrations were correlated negatively with impairment of motor performance in the SDAT group; 5-HIAA correlated positively with impaired performance in the AD group; and 5-HIAA/HVA ratios were correlated positively with the performance variables. HVA correlated significantly and negatively with “impaired wakefulness” and “inability to increase tempo” in the SDAT group. 5-HIAA and the ratio 5-HIAA/HVA correlated significantly and positively with some items measuring intellectual and emotional impairment. In the AD group, “anxiety” and “fear-panic” correlated positively with 5-HIAA and “restlessness” with MHPG. The data indicate qualitative differences in the CSF monoamine pattern between AD and SDAT.

Long-Term Influences on Demented Patients in Different Caring Milieus, a Collective Living Unit and a Nursing Home: A Descriptive Study

Environmental influences on demented patients in a collective living (CL group, n = 5) and a nursing home (NH group, n = 5) were studied during 22 months. Intellectual functions rated by the GBS scale

Relationship between Mental Impairment and HPA Axis Activity in Dementia Disorders

In 40 patients with Alzheimers disease (AD, < 65 years), 56 patients with senile dementia of the Alzheimer type (SDAT, > or = 65 years) and 45 patients with vascular dementia (VAD), basal cortisol levels were estimated and the dexamethasone test (DST) was performed. The degree of dementia was assessed according to DSM-III-R and the GBS scale was used for quantitative measures of functional impairment. There were no significant differences in basal cortisol levels. Especially in the VAD group, scores on functional impairment correlated significantly with post-DST cortisol levels. The results indicate hypothalamic overactivity in demented patients which can be correlated to the degree of dementia. In VAD, and to a certain extent also in SDAT, there appears to be a disconnection between cortical areas, including the hippocampus and the hypothalamus.

Principal Component Analysis of the GBS Scale

Principal component analysis of the Gottfries-Brane-Steen (GBS) scale was performed. GBS ratings of 221 consecutive patients with suspected or mild to severe dementia formed the basis for the analysis