Moorgreen Hospital

About: Moorgreen Hospital is a healthcare organization based out in Southampton, United Kingdom. It is known for research contribution in the topics: Dementia & Donepezil. The organization has 74 authors who have published 116 publications receiving 11488 citations.

Neuroinflammation in Alzheimer's disease

Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report.

Abstract: Amyloid-beta peptide (Abeta) has a key role in the pathogenesis of Alzheimer disease (AD). Immunization with Abeta in a transgenic mouse model of AD reduces both age-related accumulation of Abeta in the brain and associated cognitive impairment. Here we present the first analysis of human neuropathology after immunization with Abeta (AN-1792). Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few Abeta plaques; (ii) those areas of cortex that were devoid of Abeta plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, Abeta-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages. Findings (i)-(iii) strongly resemble the changes seen after Abeta immunotherapy in mouse models of AD and suggest that the immune response generated against the peptide elicited clearance of Abeta plaques in this patient. The T-lymphocyte meningoencephalitis is likely to correspond to the side effect seen in some other patients who received AN-1792 (refs. 7-9).

Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study

Abstract: Summary Background Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand 123 I-2β-carbometoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ( 123 I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included. Methods We did a phase III study in which we used a 123 I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0·80) and specificity (0·85) targets and prespecified lower thresholds (sensitivity 0·65, specificity 0·73) using one-sided binomial tests with a significance level of α=0·025. Findings Abnormal scans had a mean sensitivity of 77·7% for detecting clinical probable DLB, with specificity of 90·4% for excluding non-DLB dementia, which was predominantly due to Alzheimer's disease. A mean value of 85·7% was achieved for overall diagnostic accuracy, 82·4% for positive predictive value, and 87·5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's κ=0·87). The procedure was well tolerated with few adverse events. Interpretation A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with 123 I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.

Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies.

Abstract: BACKGROUND Following the success of the NINCDS-ADRDA criteria for Alzheimer's disease, groups interested in vascular dementia and dementia with Lewy bodies have now adopted similar criteria. AIMS To assess whether the validity of these criteria are influenced by the prevalence of mixed pathologies or by the prevalence rate. METHOD A community based post-mortem study. RESULTS Mixed pathologies were common (33.8%). The high specificities obtained for the CDLB and NINDS-AIREN criteria (1.00 and 0.95, respectively) were associated with low sensitivities (0.22 and 0.43, respectively). Low prevalence and the presence of mixed pathologies had a deleterious effect on positive predictive values. CONCLUSIONS Current clinical diagnostic criteria are good at detecting pathology per se but not at detecting pure pathology. A large proportion of subjects from the general population fulfilling probable CDLB, probable NINCDS-ADRDA or probable NINDS-AIREN will have mixed pathologies.