Symptomatic clusters related to amyloid positivity in cognitively unimpaired individuals
Author:
Sannemann Lena1, Bartels Claudia2, Brosseron Frederic3, Buerger Katharina4, Fliessbach Klaus3, Freiesleben Silka Dawn5, Frommann Ingo3, Glanz Wenzel6, Heneka Michael T.7, Janowitz Daniel8, Kilimann Ingo9, Kleineidam Luca3, Lammerding Dominik10, Laske Christoph11, Munk Matthias H. J.11, Perneczky Robert4, Peters Oliver5, Priller Josef5, Rauchmann Boris-Stephan12, Rostamzadeh Ayda1, Roy-Kluth Nina3, Schild Ann-Katrin1, Schneider Anja3, Schneider Luisa-Sophie10, Spottke Annika3, Spruth Eike Jakob5, Teipel Stefan9, Wagner Michael3, Wiltfang Jens2, Wolfsgruber Steffen3, Duezel Emrah6, Jessen Frank1
Affiliation:
1. Department of Psychiatry, University of Cologne, Medical Faculty, Cologne 2. Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen 3. German Center for Neurodegenerative Diseases (DNZE), Bonn 4. German Center for Neurodegenerative Diseases (DZNE), Munich 5. German Center for Neurodegenerative Diseases (DNZE), Berlin 6. German Center for Neurodegenerative Diseases (DNZE), Magdeburg 7. Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg 8. Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich 9. German Center for Neurodegenerative Diseases (DZNE), Rostock 10. Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin - Department of Psychiatry and Neurosciences, Berlin 11. German Center for Neurodegenerative Diseases (DZNE), Tuebingen 12. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich
Abstract
Abstract
Background: The NIA-AA Research Framework on Alzheimer’s Disease (AD) proposes a transitional stage (stage 2) between the fully asymptomatic stage 1 and mild cognitive impairment (stage 3) in the evolution of symptoms over the disease course. Proposed features of stage 2 include subtle cognitive dysfunction, subjective cognitive decline (SCD) and mild neurobehavioral symptoms. Here, we aimed to identify specific clusters of participants based on these features and assess the association with amyloid positivity in cognitively unimpaired individuals.
Methods: We used baseline data of n=338 participants from the German DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study without objective evidence of cognitive impairment and with available data on cerebrospinal fluid biomarkers for AD. Specifically, healthy controls (n=90), participants with SCD (n=202) and first-degree relatives of AD patients (n=46) were included. Classification into the Alzheimer’s continuum (i.e., amyloid positivity, A+) was based on Aß42/40 status. Neuropsychological test data were used to assess subtle objective cognitive dysfunction (OBJ), the subjective cognitive decline interview (SCD-I) was used to detect SCD, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess neurobehavioral changes (NPS). A two-step cluster analysis was carried out and differences in AD biomarkers between clusters were analysed.
Results: We identified three distinct participant clusters based on presented symptoms. The highest rate of A+ participants (47.6%) was found in a cluster characterized by both OBJ and SCD. A cluster of participants that presented with SCD and NPS (A+:26.6%) and a cluster of participants with overall few symptoms (A+:19.7%) showed amyloid positivity in a range that was not higher than the expected A+ rate for the age group. Across the full sample, participants with a combination of SCD and OBJ in the memory domain showed a lower Aß42/ptau181 ratio compared to those with neither SCD nor OBJ.
Conclusion: In this study, we identified three distinct clusters of participants based on symptoms associated with the NIA-AA stage 2. The cluster characterized by OBJ and concomitant SCD was associated with an increased A+ frequency, suggesting that this combination is enriched for stage 2 of the Alzheimer’s continuum.
Trial registration
German Clinical Trials Register DRKS00007966. Registered 4 May 2015.
Publisher
Research Square Platform LLC
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