Alzheimer's disease is characterized by the histopathological presence of amyloid-β plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized pathological component. The relationship between microglial activation and protein aggregation is still debated. We investigated the relationship between amyloid plaques, tau tangles and activated microglia using PET imaging. Fifty-one subjects (19 healthy controls, 16 mild cognitive impairment and 16 Alzheimer's disease subjects) participated in the study. All subjects had neuropsychometric testing, MRI, amyloid (18F-flutemetamol), and microglial (11C-PBR28) PET. All subjects with mild cognitive impairment and Alzheimer's disease and eight of the controls had tau (18F-AV1451) PET. 11C-PBR28 PET was analysed using Logan graphical analysis with an arterial plasma input function, while 18F-flutemetamol and 18F-AV1451 PET were analysed as target:cerebellar ratios to create parametric standardized uptake value ratio maps. Biological parametric mapping in the Statistical Parametric Mapping platform was used to examine correlations between uptake of tracers at a voxel-level. There were significant widespread clusters of positive correlation between levels of microglial activation and tau aggregation in both the mild cognitive impairment (amyloid-positive and amyloid-negative) and Alzheimer's disease subjects. The correlations were stronger in Alzheimer's disease than in mild cognitive impairment, suggesting that these pathologies increase together as disease progresses. Levels of microglial activation and amyloid deposition were also correlated, although in a different spatial distribution; correlations were stronger in mild cognitive impairment than Alzheimer's subjects, in line with a plateauing of amyloid load with disease progression. Clusters of positive correlations between microglial activation and protein aggregation often targeted similar areas of association cortex, indicating that all three processes are present in specific vulnerable brain areas. For the first time using PET imaging, we show that microglial activation can correlate with both tau aggregation and amyloid deposition. This confirms the complex relationship between these processes. These results suggest that preventative treatment for Alzheimer's disease should target all three processes.

New understanding in neuroscience has established that alongside the amyloid plaques, neurofibrillary tangles and atrophy, the neuroinflammation triggered by the CNS's innate immune response plays a central role in the pathogenesis of Alzheimer's disease (AD). In this review, the authors look at the roles that the cells of the immune response play in the pathogenesis of AD, the influence of genetics, the developing role for neuroimaging to detect inflammation and progress towards potential therapeutic strategies.

Aims and methodWe surveyed the views and experiences of all mental health professionals in adult community mental health teams and approved mental health professionals in 2Gether and Oxford Health NHS Foundation Trusts, regarding the use of community treatment orders (CTOs).ResultsA total of 288 surveys were completed (response rate 48%). Forty-eight (83%) psychiatrists and 142 (67%) non-psychiatrist mental health professionals were in favour of CTOs. The decision-making regarding CTOs was overwhelmingly clinically oriented for all professional groups. However, there were significant differences in views between groups regarding the effects of bureaucracy, the infringement of human rights and coercion.Clinical implicationsMultidisciplinary team involvement is crucial in decisions regarding CTOs and may protect against idiosyncratic or unhelpful practice. Further training for staff is urgently required and there may be a case for creating small local reference groups that can develop expertise and provide advice and support for clinical teams.

Structural neuroimaging is a fundamental part of a routine dementia assessment to rule out treatable causes of cognitive impairment, and to support early, accurate dementia subtype diagnosis. Dr Rayment and colleagues discuss the different types of imaging and when they should be used, as well as analysing some typical imaging findings from common dementia subtypes.

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