Basic Science and Pathogenesis.

Background: Psychosis (broadly delusions and hallucinations) has a cumulative disease prevalence of around 40% in Alzheimer's disease (AD). The epigenomic, genomic, and neuropathological data provide powerful evidence that AD+P has a distinct neurobiological profile. Here, we used the weighted gene co-expression network analysis (WGCNA) method to investigate DNA methylation associated with AD+P in the dorsolateral prefrontal cortex of 153 post-mortem brain samples.

Basic Science and Pathogenesis.

Background: The J20 mouse is an established model of amyloid pathology, exhibiting neuropathological and behavioural symptoms reflective of human Alzheimer's disease (AD). Previous work, conducted by Castanho et al (2020), revealed transcriptomic change in the hippocampus of J20 mice to be associated with the accumulation of amyloid pathology. Here, we investigated the spatial distribution of such transcriptomic changes using novel spatial transcriptomic technology.

Clinical Manifestations.

Background: When assessed in the Mild Behavioral Impairment (MBI) framework, late-life onset psychotic like symptoms (MBI-psychosis) are associated with incident cognitive decline and dementia. One approach to examining the genetic basis of this association, is to use Polygenic Risk Scores (PRS) to determine whether genetic propensity for late-life onset psychosis is shared with other traits. We aimed to elucidate the shared genetic liability between Educational Attainment, Intelligence, Reasoning, Memory, Neuroticism, Alzheimer's Disease, Major Depression, Schizophrenia and Bipolar Disorder and Mild Behavioral Impairment (MBI)-Psychosis in later life.

Clinical Manifestations.

Background: Smell dysfunction has been one of coronavirus disease 2019 (Covid-19) symptoms. Identification of those with these symptoms are important as olfactory impairment in general has been studied to have increased mortality, poor quality of life, increased incidence of depression and risk for dementia. Smell dysfunction related to Covid-19 in older adults and its impact is lesser studied.

Clinical Manifestations.

Background: Apathy and mood symptoms are increasingly recognised as clinical important aspects of prodromal dementia; both are associated with increased risk of dementia even in cognitively normal people. The clinical overlap between apathy and low mood poses a challenge in distinguishing between the two conditions. It is crucial to differentiate between depression and apathy, along with any underlying syndromes, to facilitate the development of targeted treatments.