A new rating scale for dementia syndromes

A new scale, the GBS-scale, is constructed for rating dementia syndromes. The scale is divided into four subscales measuring motor, intellectual and emotional functions and different symptoms characteristic for dementia.The scale can be used by physicians, psychologists and registered nurses. The reliability of the scale is tested by rating 100 patients in somatic and psychogeriatric long-term care. The raters worked independently of each other and were recommended to confer with the staff about the status of the patient. The agreement between the raters was good.The validity of the scale was tested by comparing it with another geriatric rating scale. High correlations between the two scales were seen and indicated that the new scale measures dementia syndromes.The new scale measures degree of dementia and profiles of dementia syndromes. It is constructed in such a way that it can measure changes in dementia symptoms over a certain amount of time. Thus, it can be used in evaluating effect of treatment. It is not, however, meant to be a diagnostic scale.     

Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis

Summary The gene for methylenetetrahydrofolate reductase (MTHFR) has shown polymorphism in the general human population. In its homozygous form, a C677T mutation occurs in more than 5% of the grown-up population and produces a thermolabile variant which reduces the overall enzyme activity to less than 30% of normal. We investigated patients with schizophrenia-like psychosis. If hyperhomocysteinemic, their DNA-genotype for thermolabile C677T mutation was determined. Seven of 11 patients, six males and one female, were homozygous for thermolabile MTHFR. One male patient was heterozygous and all three normal homozygotes were females. In the patients who were homozygous for the C677T mutation, the homocysteine concentrations did not respond to vitamin B12 but were normalized by folate supplementation. In the normal homozygotes, however, the homocysteine concentrations were reduced by vitamin B12 alone. Our results suggest that homozygosity for thermolabile MTHFR is a risk factor for schizophrenia-like psychosis. Possibly, this risk may be reduced by folate supplementation.     

Cholecystokinin peptides and receptor binding in Alzheimer's disease

Summary Cholecystokinin (CCK) is a peptide that can be found in the cerebral cortex in high concentrations and is involved in learning and memory as well as neurodegenerative processes. Cortical brain samples from 9 patients with Alzheimer's disease and 9 matched control cases were studied with respect to the concentrations of various molecular forms of CCK and the CCK receptor binding characteristics. No differences were found between patients and controls in any of these measures. Significant correlations were found between the concentrations of CCK-8 sulphated and the three nonsulphated CCK peptides measured. In addition, the concentrations of CCK-4 and CCK-5 showed a highly significant and positive correlation.     

The role of the polymorphic genes apolipoprotein E and methylene- tetrahydrofolate reductase in the development of dementia of the Alzheimer type.

The gene for apolipoprotein E (APOE) is polymorphic, and its variant APOE4 is a major risk factor for the development of Alzheimer-type dementia (AD). Another risk factor for AD appears to be negative cobalamin balance, which is very common in elderly people. Cobalamin and folate are interdependent and essential components of the one-carbon metabolism. Another important component is methylenetetrahydrofolate reductase (MTHFR), the gene for which is also polymorphic. Thermolabile MTHFR (tMTHFR), a gene variant that reduces the activity of its enzyme, is common in the general population. In the present study, 75% of 140 AD patients had at least one APOE4 allele. The numbers of APOE4 and tMTHFR alleles correlated significantly with the serum folate levels, however, in opposite directions. The significance of this was augmented by an inverse correlation between APOE4 and tMTHFR. Thus, not only MTHFR but also APOE appears to be related to the one-carbon metabolism, suggesting that APOE4 and insufficient one-carbon metabolism may be synergistic risk factors for AD.     

THERAPY OPTIONS IN ALZHEIMER'S DISEASE

SUMMARY The aetiology of Alzheimer's disease and senile dementia of the Alzheimer type (AD/SDAT) are unknown, and primary prevention is thus infeasible. As overactivity in the hypothalamicpituitary-adrenal axis (possibly indicating maladaptation to stress) and vitamin B₁₂ deficiency are common, secondary prevention should focus on stress and dietary factors. Nerve growth factors and ganglioside GM₁ have been used to inhibit progression of the disorder, but this treatment is still at an experimental stage, as are efforts to prevent the formation of amyloid. Breakthroughs in AD/SDAT treatment have been seen in trials with supplementation of neurotransmitter deficits. Tacrine, a drug that inhibits acetylcholinesterase, has proved to have a cognitive-enhancing effect, but this is limited in time and the drug has side-effects. Selective serotonin reuptake inhibitors have a proven effect on the emotional disturbances seen in AD/SDAT.     

Reduced activity of Mg2+- and Ca2+-dependent adenosine triphosphatase in seminal fluid of patients with oligozoospermia

Mg2+- and Ca2+-dependent ATPase activity, fructose and divalent cation concentrations were determined in seminal plasmas from men with oligozoospermic ejaculates and from those with normal sperm count. The mean activity of the Mg2+- and Ca2+-stimulated ATPase from the former was 59 nmol . 0.1 ml-1 . This is significantly (p less than 0.005) lower than for men with a normal sperm count (corresponding figure is 87 nmol . 0.1m1-1 . min-1). As regards the concentrations of Mg2+, Ca2+ and Zn2+ in the seminal plasmas from these two groups there was no significant difference. The same was also valid for the fructose concentrations. The Mg2+- and Ca2+-stimulated ATPase activity as well as fructose and divalent cation concentrations were also determined in seminal plasmas from men before and after vasectomy. After vasectomy, only the ejaculates devoid of spermatozoa were included in the comparative studies. No significant difference was observed between the seminal plasmas from men before and after vasectomy. These findings support the view that the Mg2+- and Ca2+-stimulated ATPase system does not derive from the spermatozoa. Possible explanations for the significantly lowered Mg2+- and Ca2+-dependent ATPase activity from patients with oligozoospermia are given.     

Blood brain barrier function in vascular dementia

To investigate blood-brain barrier (BBB) function measured as an albumin ratio (cerebrospinal fluid/serum) in vascular dementia (VD) samples from 53 patients and 30 healthy controls were analysed. The VD group showed a higher mean albumin ratio than controls (8.5 +/- 3.8 and 5.7 +/- 2.1, respectively). The albumin ratio did not correlate significantly with age, nor with individual clinical vascular factors. The results of the present study suggest that the altered BBB might be a consequence of small vessel disorder rather than evidence of infarcts.     

Intra-blood-brain-barrier synthesis of immunoglobulins in patients with dementia of the Alzheimer type

Serum and cerebrospinal fluid (CSF) of 56 patients with dementia of the Alzheimer type (DAT) and 33 healthy controls were examined in order to investigate intra-blood-brain-barrier (intra-BBB) synthesis of immunoglobulins. Intra-BBB immunoglobulin G (IgG) synthesis was defined as an elevated IgG index (greater than 0.7) and/or presence of oligoclonal IgG in CSF but not in serum on isoelectric focusing, and intra-BBB immunoglobulin M (IgM) synthesis as an elevated IgM index (greater than 0.06). In total, 10 (18%) DAT patients displayed an intra-BBB immunoglobulin synthesis--five (9%) an IgG and five (9%) an IgM synthesis--but none among the controls. Also, the DAT patient group showed higher mean IgG and IgM indexes than the control group. These findings support the hypothesis that immunological mechanisms may play a role in the etiology and/or pathogenesis of Alzheimer disease, at least in a subgroup of patients.