Biomedical subjects

B Regland

Publications and source records attributed to B Regland.

42 records · Page 3Linked to original sources

PubMedDate not supplied

Identification of cognitive impairment in the elderly: homocysteine is an early marker.

In 336 consecutive patients attending a university-affiliated memory unit, clinical and psychological findings, neuroimaging and laboratory tests were analyzed. The patients were diagnosed with early Alzheimer's disease 3%, senile dementia (SDAT) 16%, vascular dementia (VAD) 20%, other dementias 9%, minor cognitive impairment (dysmentia) 32% and subjective symptoms only 21%. Increases in vascular risk factors, serum homocysteine, ApoE4 load and neuroimaging pathology were found in dementia but also in dysmentia and in patients with subjective symptoms only. The homocysteine levels correlated inversely with cognitive performance. The increases in serum homocysteine, which were pathological in VAD, Dysmentia and SDAT, may be indicative of a disturbed cerebral one-carbon metabolism and signal-accelerated development of cognitive disease.

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PubMedDate not supplied

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.

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PubMedDate not supplied

Analogues, ageing and aberrant assimilation of vitamin B12 in Alzheimer's disease.

Vitamin B12 assimilation might be disrupted in patients with Alzheimer's disease. We therefore measured B12 carrier protein saturation and inactive B12 'analogues' in patients compared with healthy elderly individuals in a prospective case-controlled survey. Twenty-three patients, aged 60 or over, with features compatible with DSM-IV criteria for primary degenerative dementia of the Alzheimer type were recruited together with 18 cognitively intact age-matched control subjects. Total vitamin B12 (active corrinoids), holo- and apo-haptocorrin and transcobalamin were measured in serum. B12 analogues (inactive corrinoids) were estimated from the difference between R-binder-determined corrinoids and an intrinsic factor based B12 assay. Alzheimer patients had significantly lower active corrinoid than control subjects and the analogue/corrinoid ratio was significantly higher in the Alzheimer group. The inter-relationship between age, analogues and transcobalamin polarised patients into two distinct groups. Two disparate mechanisms might exist for the development of cerebral B12 deficiency in Alzheimer's disease, although both imply a disruption of selective B12 assimilation and analogue elimination in such patients.

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PubMedDate not supplied

Treatment of Alzheimer's disease with clioquinol.

As heavy metal ions may be implicated in the formation of senile plaques in Alzheimer-afflicted brains, treatment with clioquinol was tested in 20 patients with Alzheimer's disease. Clioquinol is a chelator that crosses the blood-brain barrier and has greater affinity for zinc and copper ions than for calcium and magnesium ions. Treatment was given for 21 days at doses of 20 mg/day to 10 patients and 80 mg/day to another 10 patients. The study was blind to the dosages but included no controls. Cerebrospinal fluid (CSF) investigations revealed a significant increase at day 7 and a decrease at day 21 in Tau protein and growth-associated protein (GAP43). These proteins are increased in Alzheimer's disease and considered as rather stable markers. The initial increase may indicate a temporary cytotoxicity to the brain and/or an increased release into the CSF from stores in the tissue, possibly from senile plaques where the proteins are accumulated. The levels of CSF-Tau protein correlated positively and significantly with the serum levels of copper and also with the serum copper/zinc ratio. Clinical ratings showed slight improvement after 3 weeks treatment with clioquinol in this open study.

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PubMedDate not supplied

Relationship between mental impairment and HPA axis activity in dementia disorders.

In 40 patients with Alzheimer's 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.

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PubMedDate not supplied

Apolipoprotein E in cerebrospinal fluid from patients with Alzheimer's disease and other forms of dementia is reduced but without any correlation to the apoE4 isoform.

Apolipoprotein E (apoE) has been suggested to play a role in regenerative processes in the brain after trauma, and also in the pathogenesis of Alzheimer's disease (AD). We examined cerebrospinal fluid (CSF) apoE in a material consisting of 23 patients with early-onset AD (EAD), 31 with late-onset AD (LAD), 16 with frontal-lobe dementia (FLD), 25 with vascular dementia (VAD) and 25 controls. CSF-apoE was decreased in all of EAD (1.8 +/- 1.1 mg/l; p < 0.0005), LAD (2.5 +/- 0.9 mg/l; p < 0.0005), VAD (2.3 +/- 1.4 mg/l; P < 0.0005) and FLD (3.0 +/- 1.3 mg/l; p < 0.05) compared to the control group (5.7 +/- 4.0 mg/l). Since apoE4 has been found to bind to beta/A4-amyloid, and AD patients homozygous for apoE4 to have higher number of senile plaques than apoE3 homozygotes, we also examined the relation between CSF-apoE and apoE alleles. However, CSF-apoE did not significantly differ between patients with different apoE isoforms. Our findings support that apoE is involved in the pathogenesis of dementia disorders, both degenerative and vascular, but the CSF-apoE level is not influenced by the apoE isoforms. CSF-apoE may be used as an unspecific marker for neurodegenerative disorders, but not in purpose of differential diagnostics between different dementia disorders.

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