Neuropsychiatric symptoms in at-risk groups for AD dementia and their association with worry and AD biomarkers\u2014results from the DELCODE study

Lena Sannemann,Christina Rösch,Xenia Kobeleva,Nicoleta Carmen Cosma,Claudia Bartels,Alexandra Polcher,Katharina Büerger ,Klaus Fließbach ,Stefan J Teipel ,Ann‐Katrin Schild ,Boris‐Stephan Rauchmann ,Janna Rudolph,Daniel Janowitz,Josef Priller,Anja Schneider,Coraline D Metzger,Matthias H J Munk,Wenzel Glanz,Steffen Wolfsgruber,Robert Perneczky,Ruth Vukovich,Christoph Laske,Jens Wiltfang,Eike Jakob Spruth,Michael Wagner,Frederic Brosseron,Silka Dawn Freiesleben,Michael T Heneka,Oliver Peters,Emrah Duezel,Ingo Kilimann,Slawek Altenstein,Annika Spottke,Frank Jessen

doi:10.1186/s13195-020-00701-7

Abstract

BackgroundEarly identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuropsychiatric symptoms (NPS) have been proposed as potential markers for early manifestation of Alzheimer’s disease (AD). We aimed to investigate the frequency of NPS in SCD, in other at-risk groups, in healthy controls (CO), and in AD patients, and to test the association of NPS with AD biomarkers, with a particular focus on cognitively unimpaired participants with or without SCD-related worries.MethodsWe analyzed data of n = 687 participants from the German DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study, including the diagnostic groups SCD (n = 242), mild cognitive impairment (MCI, n = 115), AD (n = 77), CO (n = 209), and first-degree relatives of AD patients (REL, n = 44). The Neuropsychiatric Inventory Questionnaire (NPI-Q), Geriatric Depression Scale (GDS-15), and Geriatric Anxiety Inventory (GAI-SF) were used to assess NPS. We examined differences of NPS frequency between diagnostic groups. Logistic regression analyses were carried out to further investigate the relationship between NPS and cerebrospinal fluid (CSF) AD biomarkers, focusing on a subsample of cognitively unimpaired participants (SCD, REL, and CO), who were further differentiated based on reported worries.ResultsThe numbers of reported NPS, depression scores, and anxiety scores were significantly higher in subjects with SCD compared to CO. The quantity of reported NPS in subjects with SCD was lower compared to the MCI and AD group. In cognitively unimpaired subjects with worries, low Aß42 was associated with higher rates of reporting two or more NPS (OR 0.998, 95% CI 0.996–1.000, p < .05).ConclusionThese findings give insight into the prevalence of NPS in different diagnostic groups, including SCD and healthy controls. NPS based on informant report seem to be associated with underlying AD pathology in cognitively unimpaired participants who worry about cognitive decline.Trial registrationGerman Clinical Trials Register DRKS00007966. Registered 4 May 2015.

Highlights

In light of the growing significance of preventive interventions and clinical trials that target individuals at the very early stages of Alzheimer’s disease (AD), early detection of the disease has become a main research area
The quantity of reported neuropsychiatric symptoms (NPS) in subjects with Subjective cognitive decline (SCD) was lower compared to the mild cognitive impairment (MCI) and AD group
A study by Masters, Morris, and Roe on cognitively normal participants found that NPS appear earlier in subjects who later progress to MCI or dementia as indicated by a Clinical Dementia Rating (CDR) > 0 compared to those who remain at CDR 0 [12]

Summary

Introduction

In light of the growing significance of preventive interventions and clinical trials that target individuals at the very early stages of Alzheimer’s disease (AD), early detection of the disease has become a main research area. In cognitively normal persons of the National Alzheimer’s Coordinating Center (NACC) database who progressed to dementia over the median follow-up of 4.7 years, the most prevalent NPS were depression, irritability, sleep disturbances, appetite changes, and anxiety [5]. Recent evidence supports the idea that subtle NPS in pre-clinical stages may act as potential heralds of progression to cognitive decline [8,9,10,11] and could be used to improve early detection of the disease. Identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuropsychiatric symptoms (NPS) have been proposed as potential markers for early manifestation of Alzheimer’s disease (AD). We aimed to investigate the frequency of NPS in SCD, in other at-risk groups, in healthy controls (CO), and in AD patients, and to test the association of NPS with AD biomarkers, with a particular focus on cognitively unimpaired participants with or without SCD-related worries

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Discussion

Conclusion