Oliveira, Fabricio Ferreira de

The brain changes of Alzheimer’s disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline. Researchers often hesitate to share DRE data, either because they are insufficiently validated or reliable for use in individuals, or there are concerns about assuring responsible use and ensuring adequate understanding of potential problems when one’s biomarker status is known. Concerns include warning people receiving DRE about situations in which they might be compelled to disclose their risk status potentially leading to discrimination or stigma. The Advisory Group on Risk Evidence Education for Dementia (AGREEDementia) welcomes all concerned with how best to share and use DRE. Supporting understanding in clinicians, stakeholders, and people with or at risk for dementia and clearly delineating risks, benefits, and gaps in knowledge is vital. This brief overview describes elements that made this group effective as a model for other health conditions where there is interest in unfettered collaboration to discuss diagnostic uncertainty and the appropriate use and communication of health-related risk information.

Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials.