LAUSR

Alzheimer’s disease (AD) is characterized by progressive cognitive and functional decline. Individuals diagnosed with AD often suffer from a range of behavioral disturbances, often referred to as neuropsychiatric symptoms (NPS). The term describes heterogeneous behavioral or mood disturbances, such as aggression, agitation, anxiety, apathy, depression, psychosis, and sleep disruption. NPS are near universal among patients at all stages and etiologies of dementia, are generally multidetermined, may wax and wane, and complicate caring for patients with dementia (Porsteinsson and Antonsdottir, 2017). Extensive and reciprocal neuronal connections exist between the epicenters of emotions and cognition. This interface is convoluted as the exact mechanism of the interconnect between NPS and cognitive impairment remains obscure. Proposed mechanisms include four possible pathways: (1) etiologic pathway: where a NPS is causing pathophysiologic changes in brain tissue that is causally linked to the development of AD pathology; (2) common neuropathological pathway: NPS may be a direct non-cognitive manifestation of the Alzheimer’s neurodegenerative disease because it affects key brain areas underlying behavior, emotion, and perception; (3) psychological reaction: a person experiencing cognitive decline may develop depression, anxiety, or similar NPS because of the awareness of gradual loss of cognitive and functional abilities; and (4) interaction: a synergistic interaction between NPS and a biological factor leads to AD/mild cognitive impairment (MCI). These four mechanisms (and other possible mechanisms) are not mutually exclusive and may act in some sort of combinations (Porsteinsson and Antonsdottir, 2015). More precise neuroimaging and neurochemistry methods are leading to a clearer understanding of the relationship between the underlying AD brain disease and its clinical manifestations in the form of NPS. Furthermore, there is an increasing recognition of the overlap of neural circuits across multiple NPS that may mediate the AD pathology with behavioral manifestations of NPS (Rosenberg et al., 2015). The contribution of individual regions or activity patterns within this system is likely to be different across symptoms, which may explain the unique clinical manifestation of individual NPS domains. A thorough characterization of the shared neural circuit with the consideration of the disproportional contribution of individual regions or activity patterns to different NPS may provide a link between NPS and AD pathology. Assessment of circuit function might also play a role as a biomarker to assess or predict treatment response (Wang et al., 2019). The inability to address many important research questions despite a significant increase in funding suggests a systemic problem in the production of clinical research. Part of the solution may lie in point-of-care (POC) trials where eligible participants are identified at health care encounters, so the study population reflects the range and distribution of patients seen in clinical practice. In contrast to conventional randomized clinical trials, POC trials do not need to have study staff at each participating site to collect and enter study data into a research clinical database. Instead, the outcome data and patient characteristics are obtained from existing medical records. It introduces a new relationship between clinical care and research to address the current difficulty in which “there are too many research questions, too few investigators, and too little funding” in clinical research. Although the data of POC trials may not be as complete and clean as in clinical trials, there is an ongoing effort to improve electronic medical records (EMR) systems to facilitate their utilization for clinical research (Shih et al., 2015). In an excellent and timely study published in this issue of International Psychogeriatrics, Nowrangi et al. report on a cross-sectional, retrospective study examining the interaction between structural brain volume measures derived from clinical 3T magnetic resonance imaging (MRI) scans and the occurrence of NPS in a heterogeneous cohort seen in an outpatient memory clinic at a tertiary teaching hospital (Nowrangi et al., 2020). The patients received a clinical workup for cognitive complaints, including dementia, which includes a comprehensive cognitive, neuropsychiatric, and functional evaluation. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q), an informant International Psychogeriatrics (2021), 33:3, 199–200 © International Psychogeriatric Association 2021