Are neuropsychiatric symptoms in dementia linked to CSF biomarkers of synaptic and axonal degeneration?

© 2020, The Author(s). Background: The underlying disease mechanism of neuropsychiatric symptoms (NPS) in dementia remains unclear. Cerebrospinal fluid (CSF) biomarkers for synaptic and axonal degeneration may provide novel neuropathological information for their occurrence. The aim was to investigate the relationship between NPS and CSF biomarkers for synaptic (neurogranin [Ng], growth-associated protein 43 [GAP-43]) and axonal (neurofilament light [NFL]) injury in patients with dementia. Methods: A total of 151 patients (mean age ± SD, 73.5 ± 11.0, females n = 92 [61%]) were included, of which 64 had Alzheimer’s disease (AD) (34 with high NPS, i.e., Neuropsychiatric Inventory (NPI) score > 10 and 30 with low levels of NPS) and 18 were diagnosed with vascular dementia (VaD), 27 with mixed dementia (MIX), 12 with mild cognitive impairment (MCI), and 30 with subjective cognitive impairment (SCI). NPS were primarily assessed using the NPI. CSF samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) for T-tau, P-tau, Aβ1–42, Ng, NFL, and GAP-43. Results: No significant differences were seen in the CSF levels of Ng, GAP-43, and NFL between AD patients with high vs low levels of NPS (but almost significantly decreased for Ng in AD patients < 70 years with high NPS, p = 0.06). No significant associations between NPS and CSF biomarkers were seen in AD patients. In VaD (n = 17), negative correlations were found between GAP-43, Ng, NFL, and NPS. Conclusion: Our results could suggest that low levels of Ng may be associated with higher severity of NPS early in the AD continuum (age < 70). Furthermore, our data may indicate a potential relationship between the presence of NPS and synaptic as well as axonal degeneration in the setting of VaD pathology

Agitation and impulsivity in mid and late life as possible risk markers for incident dementia

To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre-dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre-dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre-dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Daniel Bateman receives support from the Indiana University Richard M. Fairbanks Chair of Aging Research, the Indiana University Cornelius and Yvonne Pettinga Chair of Medicine, and funding from the National Institute on Aging (NIA) grants K23AG059914 and P30AF10133. Sascha Gill receives funding from a University of Calgary Graduate Student Research Award. Sophie Hu receives funding from a Cana dian Institute of Health Research (CIHR) Master’s Research Award. Erin Foster: none. Myuri Ruthirakuhan receives funding from a CIHR Doctoral Research Award. Allis Sellek receives funding from Alzheimer Foundation of Costa Rica. Moyra Mortby receives support from the Australian National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) Dementia Research Development Fellowship #1102028. Veronika Matušková receives support from MH CZ – DRO, Motol University Hospital, Prague, Czech Republic 00064203 and Czech Ministry of Health grant 16-27611A. Kok Pin Ng: none. Rawan Tarawneh receives support from the Ohio State University Chronic Brain Injury Discovery Themes. Yvonne Freund-Levi:none. Sanjeev Kumar receives research support from Brain and Behavior Foundation, National institute on Ageing, BrightFocus Foundation, Brain Canada, Canadian Institute of Health Research, Centre for Ageing and Brain Health Innovation, Weston Brain Institute, and Centre for Mental Health and Addiction Foundation and University of Toronto. Serge Gauthier receives support from the CIHR, Weston, and the National Institutes of Health (NIH). Paul Rosenberg receives funding from the National Institute on Aging (NIA) grants R01AG049872 and R01 AG054771. Fabricio Ferreira de Oliveira has a grant from FAPESP - The State of São Paulo Research Foundation (grant #2015/10109-5). Devangere Devanand: none. Clive Ballard: none. Zahinoor Ismail has received funding from Alzheimer’s Society of Calgary via the Hotchkiss Brain Institute.published version, accepted version (12 month embargo), submitted versio