Genetic Variation in the alpha 7 Nicotinic Acetylcholine Receptor is Associated with Delusional Symptoms in Alzheimer's Disease

Psychotic symptoms are common in Alzheimer's disease (AD) and have a negative impact oil quality of life. It is suggested that psychotic symptoms may be attributed to genetic risk factors which are revealed during neurodegeneration. CHRNA7, the gene for the alpha 7 nicotinic acetylcholine receptor, has been associated with schizophrenia in linkage and association Studies. Hence we investigated single SNPs and haplotypes in CHRNA7 in relation to AD with psychosis in a large, well-characterised and previously described cohort within the Northern Ireland population. A significant association between delusions and the T allele of rs6494223 (P = 0.014, OR = 1.63, Cl 1.22-2.17) was found. This suggests that the alpha 7 receptor may be a suitable target for the treatment of AD with psychosis.

Advanced glycation: an important pathological event in diabetic and age related ocular disease

The formation of advanced glycation end products (AGEs) is a key pathophysiological event with links to a range of important human diseases. It is now clear that AGEs may act as mediators, not only of diabetic complications(1 2) but also of widespread age related pathology such as Alzheimer's disease,(3) decreased skin elasticity,(4) (5) male erectile dysfunction,(6) (7) pulmonary fibrosis,(8) and atherosclerosis.(9 10) Since many cells and tissues of the eye are profoundly influenced by both diabetes and ageing, it is fitting that advanced glycation is now receiving considerable attention as a possible modulator in important visual disorders. An increasing number of reports confirm widespread AGE accumulation at sites of known ocular pathology and demonstrate how these products mediate crosslinking of long lived molecules in the eye. Such studies also underscore the putative pathophysiological role of advanced glycation in ocular cell dysfunction in vitro and in vivo.

Computer-assisted pathological immunohistochemistry scoring is more time-effective than conventional scoring, but provides no analytical advantage

Computer-assisted pathological immunohistochemistry scoring is more time-effective than conventional scoring, but provides no analytical advantage

Exploring the impact of depressive symptoms and medication beliefs on medication adherence in hypertension-A primary care study

Objective: This Study aimed to assess the levels of adherence in a sample of hypertensive patients being cared for in primary care in Northern Ireland and to explore the impact of depressive symptoms and medication beliefs on medication adherence.

Double blind cross-over placebo controlled study of omeprazole in the treatment of patients with reflux symptoms and physiological levels of acid reflux--the "sensitive oesophagus"

At least 10-15% of patients with reflux symptoms have a normal endoscopy and physiological levels of acid reflux on pH monitoring. Such patients with 50% or more of symptoms associated with acid reflux episodes have "a positive symptom index" (SI), and it has been proposed that this defines the "sensitive oesophagus".

Intragastric bile acid concentrations are unrelated to symptoms of flatulent dyspepsia in patients with and without gallbladder disease and postcholecystectomy

It has been proposed that duodenogastric reflux may be the basic underlying mechanism which gives rise to symptoms of flatulent dyspepsia. Fasting and postprandial gastric juice bile acid concentrations were measured in patients with flatulent dyspepsia with and without gall bladder disease and postcholecystectomy. There were 13 patients with gall bladder disease, 12 with normal gall bladders and 13 postcholecystectomy. Gastric juice was obtained by intubation. Bile acid concentrations were compared with 21 controls and 15 asymptomatic subjects with gall bladder disease. For 21 patients with gall bladder disease who underwent cholecystectomy, levels were again assessed postoperatively to allow correlation with outcome. The occurrence of reflux and the resultant gastric juice bile acids did not correlate with symptoms. Concentrations postcholecystectomy, including asymptomatic subjects were significantly higher than controls (p less than 0.01). It is concluded that limited duodenogastric reflux is common and need not be associated with symptoms even when the resultant intra-gastric concentrations are higher than normal.

A retrospective study of the behavioural and psychological symptoms of mid and late phase Alzheimer's disease

To document the behavioural and psychological symptoms in patients with a diagnosis of established Alzheimer's disease (AD) for at least 3 years.

Genome-wide association study of Alzheimer's disease with psychotic symptoms

Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWASs) to identify loci that (1) increase susceptibility to an AD and subsequent psychotic symptoms; or (2) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. In all, 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from Genetic and Environmental Risk in AD Consortium 1 (GERAD1), the National Institute on Aging Late-Onset Alzheimer's Disease (NIA-LOAD) family study and the University of Pittsburgh Alzheimer Disease Research Center (ADRC) GWASs. Unobserved genotypes were imputed to provide data on >1.8 million single-nucleotide polymorphisms (SNPs). Analyses in each data set were completed comparing (1) AD+P to AD-P cases, and (2) AD+P cases with controls (GERAD1, ADRC only). Aside from the apolipoprotein E (APOE) locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 × 10(-7); 'AD+PvControls' P=1.11 × 10(-4)). SNPs upstream of SLC2A9 (rs6834555, P=3.0 × 10(-7)) and within VSNL1 (rs4038131, P=5.9 × 10(-7)) showed strongest evidence for association with AD+P when compared with controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized.Molecular Psychiatry advance online publication, 18 October 2011; doi:10.1038/mp.2011.125.

Mood congruent psychotic symptoms and specific cognitive deficits in carriers of the novel schizophrenia risk variant at MIR-137

Objective: The Schizophrenia Psychiatric Genome-wide Association (GWAS) Consortium recently reported on five novel schizophrenia susceptibility loci. The most significant finding mapped to a micro-RNA, MIR-137, which may be involved in regulating the function of other schizophrenia and bipolar disorder susceptibility genes. Method: We genotyped 821 patients with confirmed DSM-IV diagnoses of schizophrenia, bipolar affective disorder I and schizoaffective disorder for the risk SNP (rs1625579) and investigated the clinical profiles of risk allele carriers using a within-case design. We also assessed neurocognitive performance in a subset of cases (n=399) and controls (n=171). Results: Carriers of the risk allele had lower scores for an OPCRIT-derived positive symptom factor (p=0.04) and lower scores on a lifetime measure of psychosis incongruity (p=0.017). Risk allele carriers also had more cognitive deficits involving episodic memory and attentional control. Conclusion: This is the first evidence that the MIR-137 risk variant may be associated with a specific subgroup of psychosis patients. Although the effect of this single SNP was not clinically relevant, investigation of the impact of carrying multiple risk SNPs in the MIR-137 regulatory network on diagnosis and illness profile may be warranted. © 2012 Elsevier Ireland Ltd.