The Difference in Cognitive Profiles Between Patients With Alzheimer Dementia With and Without Psychosis: A Rapid Review.

BACKGROUND: Psychosis in Alzheimer disease (AD) is a major burden for patients and their family. Identifying the characteristics of delusions and hallucinations in the AD population is key to understanding the interconnection between the psychiatric and cognitive symptoms in neurocognitive disorders. The aim of this study is to compare the cognitive profiles of AD patients with and without psychosis. METHODS: We conducted a rapid review to explore the relationship between psychotic symptoms and cognitive performances in patients with AD. We used MEDLINE, Embase, and PsychINFO literature databases between January 2015 and January 2023. This rapid review was guided by the Cochrane Rapid Reviews Methods Group. RESULTS: We identified 2909 records from the initial searches. After reviewing the titles, abstracts, and full texts, we selected 8 cross-sectional and 5 cohort studies for the qualitative analysis. Among them, 6 studies were included in the final quantitative analysis. Most studies suggested a correlation between general cognitive decline and the risk of presenting psychotic symptoms. Three studies found an association between hallucinations and deficits in the visuocognitive domains (visuospatial, visuoperceptual, and visuoconstructive skills). Two studies found a relationship between psychotic symptoms and executive dysfunction. Two studies also found a correlation between psychotic symptoms and language. Our results are in line with previous data in the literature, especially regarding the outcome of psychosis on executive function and visuocognitive abilities. CONCLUSIONS: There appears to be an association between cognitive deficits and psychotic symptoms in AD, but the direction of causality is still unclear, and further studies using longitudinal designs would give more insight into the pathophysiological process of psychosis in AD.

Differential immune transcriptomic profiles between vaccinated and resolved HCV reinfected subjects.

Successive episodes of hepatitis C virus (HCV) infection represent a unique natural rechallenge experiment to define correlates of long-term protective immunity and inform vaccine development. We applied a systems immunology approach to characterize longitudinal changes in the peripheral blood transcriptomic signatures in eight subjects who spontaneously resolved two successive HCV infections. Furthermore, we compared these signatures with those induced by an HCV T cell-based vaccine regimen. We identified a plasma cell transcriptomic signature during early acute HCV reinfection. This signature was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in three subjects and transient increase in E2-specific neutralizing antibodies in six subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 out of 8 subjects. These results suggest a cooperative role for both antibodies and T cells in clearance of HCV reinfection and support the development of next generation HCV vaccines targeting these two arms of the immune system.

Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination.

Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine. Increased numbers of erythrocytes and the haem-induced response also correlate with poor response to the HBV vaccine. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curve≈65%) but robust signature is supported by flow cytometry and cytokine profiling. This study is the first that identifies baseline predictors and mechanisms of response to the HBV vaccine.

Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells.

Latently infected resting CD4(+) T cells are a major barrier to HIV cure. Understanding how latency is established, maintained and reversed is critical to identifying novel strategies to eliminate latently infected cells. We demonstrate here that co-culture of resting CD4(+) T cells and syngeneic myeloid dendritic cells (mDC) can dramatically increase the frequency of HIV DNA integration and latent HIV infection in non-proliferating memory, but not naïve, CD4(+) T cells. Latency was eliminated when cell-to-cell contact was prevented in the mDC-T cell co-cultures and reduced when clustering was minimised in the mDC-T cell co-cultures. Supernatants from infected mDC-T cell co-cultures did not facilitate the establishment of latency, consistent with cell-cell contact and not a soluble factor being critical for mediating latent infection of resting CD4(+) T cells. Gene expression in non-proliferating CD4(+) T cells, enriched for latent infection, showed significant changes in the expression of genes involved in cellular activation and interferon regulated pathways, including the down-regulation of genes controlling both NF-κB and cell cycle. We conclude that mDC play a key role in the establishment of HIV latency in resting memory CD4(+) T cells, which is predominantly mediated through signalling during DC-T cell contact.