John T. Lawson

Butyrylcholinesterase K variant is genetically associated with late onset Alzheimer's disease in Northern Ireland

Alzheimers disease (AD) is a progressive neurodegenerative disorder that has been associated, sometimes controversially, with polymorphisms in a number of genes. Recently the butyrylcholinesterase K variant (BCHE K) allele has been shown to act in synergy with the apolipoprotein E ε4 (APOE ε4) allele to promote risk for AD. Most subsequent replicative studies have been unable to confirm these findings. We have conducted a case-control association study using a clinically well defined group of late onset AD patients (n=175) and age and sex matched control subjects (n=187) from the relatively genetically homogeneous Northern Ireland population to test this association. The BCHE genotypes of patients were found to be significantly different from controls (χ2=23.68, df=2, p<<0.001). The frequency of the K variant allele was also found to differ significantly in cases compared to controls (χ2=16.39, df=1, p<<0.001) leading to an increased risk of AD in subjects with this allele (OR=3.50, 95% CI 2.20-6.07). This risk increased in subjects 75 years and older (OR=5.50, 95% CI 2.56-11.87). At the same time the APOE ε4 associated risk was found to decrease from 6.70 (95% CI 2.40-19.04) in 65-74 year olds to 3.05 (95% CI 1.34-6.95) in those subjects 75 years and older. However, we detected no evidence of synergy between BCHE K and APOE ε4. The results from this study suggest that possession of the BCHE K allele constitutes a significant risk for AD in the Northern Ireland population and, furthermore, this risk increases with increasing age.

Transrectal drainage of a diverticular abscess using a pigtail catheter without radiological guidance: a case report

IntroductionPercutaneous or endocavitory drainage of a diverticular abscess under radiological guidance often enables one to perform a one-staged resection and anastomosis (without stoma formation) instead of a two-staged procedure. It reduces the significant postoperative morbidity and mortality associated with the conventional emergency surgical management. However, radiological guidance is not always available due to limited resources during out-of-hours.Case presentationA 78-year-old Caucasian woman underwent transrectal drainage of a diverticular abscess performed with a pigtail catheter without radiological guidance. Technical details of the procedure are described and alternative options discussed.ConclusionIn carefully selected patients, per-rectal drainage using a pigtail catheter can be performed without radiological guidance and the procedure offers a simple and effective way of controlling sepsis.

Cathepsin D gene exon 2 polymorphism and sporadic Alzheimer's disease

It has recently been reported that a genetic polymorphism in exon 2 of the cathepsin D gene conferred increased risk for development of Alzheimers disease (AD). Because of the potential importance of this report we tested this association in a clinically well-defined group of AD patients and age and sex matched control subjects from the relatively genetically homogeneous Northern Ireland population. This study failed to confirm the reported association between the cathepsin D exon 2 polymorphism and AD. We conclude that if an association exists between this polymorphism and AD it is likely to be small.

Attention deficits in Alzheimer's disease and vascular dementia

Objective To compare the performance of patients with mild–moderate Alzheimers disease (AD) and vascular dementia (VaD) on tests of information processing and attention. Method Patients with AD (n=75) and VaD (n=46) were recruited from a memory clinic along with dementia-free participants (n=28). They underwent specific tests of attention from the Cognitive Drug Research battery, and pen and paper tests including Colour Trails A and B and Stroop. All patients had a CT brain scan that was independently scored for white-matter change/ischaemia. Results Attention was impaired in both AD and VaD patients. VaD patients had more impaired choice reaction times and were less accurate on a vigilance test measuring sustained attention. Deficits in selective and divided attention occurred in both patient groups and showed the strongest correlations with Mini Mental State Examination scores. Conclusion This study demonstrates problems with the attentional network in mild–moderate AD and VaD. The authors propose that attention should be tested routinely in a memory clinic setting.

Executive functioning in Alzheimer's disease and vascular dementia†

To compare performance of patients with mild‐moderate Alzheimers disease (AD) and vascular dementia (VaD) on tests of executive functioning and working memory.

Association of serum AACT levels and AACT signal polymorphism with late-onset Alzheimer's disease in Northern Ireland.

α1‐antichymotrypsin (AACT) is a serine protease inhibitor that has been associated with amyloid plaques in the brains of patients with Alzheimers disease (AD). It has been reported that AACT serum levels are higher in AD patients than in age and sex matched controls. In addition, polymorphisms in the signal peptide and 5′ of the AACT gene have been reported to increase the risk of developing AD. Serum AACT has also been suggested to be associated with cognitive decline in elderly subjects. Our objective was to investigate whether a relationship existed between serum AACT levels, AACT genotypes and risk for AD in a case control association study using 108 clinically well defined late onset AD cases and 108 age and sex matched controls from Northern Ireland. We also wished to determine whether higher serum AACT affected levels of cognition as had been previously reported. Serum AACT levels were found to be significantly raised in cases compared to controls (t=3.8, df=209, p<0.001). However, we detected no relationship between serum AACT levels and cognitive decline. We report allelic association of the AACT signal polymorphism with AD (χ2=3.70, df=1, p=0.04) but we failed to show any correlation between AACT serum levels and genotype. Copyright

Apolipoprotein E (ApoE) Phenotype in Alzheimer’s Disease, Vascular Dementia and Parkinson’s Disease with and Without Dementia in Northern Ireland

Apolipoprotein E (Apo E) is important in the transport of lipid to and from the liver and peripheral tissues. The three Apo E phenotypes have been shown to have different lipid transporting characteristics, E2 being the most efficient and E4 being the least efficient. E3 is the ancestral isoform and has transporting characteristics intermediate to E2 and E4 (reviewed by Mahley, 1988). Apo E also has important roles in the repair and remodelling of central neurones by facilitating the transport of lipid to damaged and repairing cells. Lipid is closely related to neurological tissue; myelin is mainly composed of lipid, and phospholipid and cholesterol are major components of neuronal membranes.