Inflammatory processes are important in the pathogenesis of Alzheimer's disease and in response to amyloid-b immunotherapy. We investigated the expression of multiple inflammatory markers in the brains of 28 non-immunized patients with Alzheimer's disease and 11 patients with Alzheimer's disease immunized against amyloid-b 42 (AN1792): microglial ionized calcium-binding adaptor Iba-1, lysosome marker CD68, macrophage scavenger receptor A, Fc receptors I (CD64) and II (CD32); and also immunoglobulin IgG, complement C1q and the T lymphocyte marker CD3 using immunohistochemistry. The data were analysed with regard to amyloid-b and phospho-tau pathology, severity of cerebral amyloid angiopathy and cortical microhaemorrhages. In non-immunized Alzheimer's disease cases, amyloid-b 42 correlated inversely with CD32 and Iba-1, whereas phospho-tau correlated directly with all microglial markers, IgG, C1q and the number of T cells. In immunized Alzheimer's disease cases, amyloid-b 42 load correlated directly with macrophage scavenger receptor A-positive clusters and inversely with C1q. The severity of cerebral amyloid angiopathy and microhaemorrhages did not relate to any of the analysed markers. Overall, the levels of CD68, macrophage scavenger receptor A, CD64, CD32 and the number of macrophage scavenger receptor A-positive plaque-related clusters were significantly lower in immunized than non-immunized cases, although there was no significant difference in Iba-1 load, number of Iba-1-positive cells, IgG load, C1q load or number of T cells. Our findings indicate that different microglial populations co-exist in the Alzheimer's disease brain, and that the local inflammatory status within the grey matter is importantly linked with tau pathology. After amyloid-b immunization, the microglial functional state is altered in association with reduced amyloid-b and tau pathology. The results suggest that, in the long term, amyloid-b immunotherapy results in downregulation of microglial activation and potentially reduces the inflammation-mediated component of the neurodegeneration of Alzheimer's disease.

BackgroundThe NHS End of Life Care Council advises that end of life (EoL) discussions should be offered to patients with chronic obstructive pulmonary disease (COPD) who have certain poor prognostic markers. EoL conversations with advanced care planning can reduce a patient's anxiety during an exacerbation, allow informed decisions about what treatment they would (or would not) like to receive in the future, reduce unnecessary or unwanted hospital admissions, and enable patients to die in their preferred place.AimsTo assess whether patients who are admitted to a respiratory ward with exacerbations of COPD, who fulfill the criteria, have been offered the opportunity to have such discussions. Secondary aims included (i) patient engagement, (ii) communication of outcomes (iii) communication of DNACPR orders.MethodsAudit of all patients admitted to a respiratory ward with an exacerbation of COPD, within a 3 month period. Specifically looking for evidence of EoL conversations during the current admission, previous admission or clinic appointments.ResultsOf 48 patients admitted with an exacerbation of COPD, 20 fulfilled the criteria to be offered EoL conversations. The 3 month mortality of these 20 patients was 25%. Three patients (15%) had documented EoL conversations. One lead to the formation of an advance directive not to return to hospital, one described a patient's wish to have no further non-invasive ventilation, and one where a patient wanted full treatment escaltion in the future. Seventeen of the 20 patients were made DNACPR, however, only 4 had this communicated to the GP.RecommendationsIdentify patients on hospital board rounds that may be suitable for end of life discussions. If patients engage with EoL discussions this should be documented in the medical notes as well as the discharge summary. Further use of an existing “Poor prognostic indicators” letter, which is sent to the GP, noting engagement in EoL discussions and decisions around DNACPR orders.

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