Tim Whitfield1, Harriet Demnitz-King1, Fabienne Collette2,3, Miranka Wirth4, Marco Schlosser1,5, Thorsten Barnhofer6, Eric Frison7,8, Nina Coll-Padros9, Sophie Dautricourt10,11, Florence Requier2,3, Marion Delarue10, Julie Gonneaud10, Olga M Klimecki12, Antoine Lutz13, Léo Paly10, Eric Salmon2,3, Ann-Katrin Schild14, Zuzana Walker1,15, Frank Jessen14,16,17, Gaël Chételat10, Natalie L Marchant18. 1. Division of Psychiatry, University College London, 6th Floor Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK. 2. GIGA-CRC In Vivo Imaging, University of Liège, Liège, Belgium. 3. Psychology and Neuroscience of Cognition Research Unit, University of Liège, Liège, Belgium. 4. German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany. 5. Department of Psychology, Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland. 6. School of Psychology, University of Surrey, Guildford, UK. 7. Bordeaux Population Health Center, University of Bordeaux, INSERM, EUCLID/F-CRIN Clinical Trials Platform, CHU Bordeaux, F-33000, Bordeaux, France. 8. Service d'information médicale, CHU Bordeaux, Bordeaux, France. 9. Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain. 10. Normandie University, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of Neurological Disorders", Institut Blood and Brain @ Caen-Normandie, Cyceron, 14000, Caen, France. 11. Neurology Department, University Hospital, Caen, France. 12. Clinical Psychology and Behavioral Neuroscience, Faculty of Psychology, Technische Universität Dresden, Dresden, Germany. 13. Lyon Neuroscience Research Center Inserm U1028, CNRS UMR5292, Lyon 1 University, Lyon, France. 14. Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany. 15. Essex Partnership University NHS Foundation Trust, Wickford, UK. 16. Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. 17. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. 18. Division of Psychiatry, University College London, 6th Floor Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK. n.marchant@ucl.ac.uk.
Abstract
BACKGROUND: Older individuals with subjective cognitive decline (SCD) perceive that their cognition has declined but do not show objective impairment on neuropsychological tests. Individuals with SCD are at elevated risk of objective cognitive decline and incident dementia. Non-pharmacological interventions (including mindfulness-based and health self-management approaches) are a potential strategy to maintain or improve cognition in SCD, which may ultimately reduce dementia risk. METHODS: This study utilized data from the SCD-Well randomized controlled trial. One hundred forty-seven older adults with SCD (MAge = 72.7 years; 64% female) were recruited from memory clinics in four European countries and randomized to one of two group-based, 8-week interventions: a Caring Mindfulness-based Approach for Seniors (CMBAS) or a health self-management program (HSMP). Participants were assessed at baseline, post-intervention (week 8), and at 6-month follow-up (week 24) using a range of cognitive tests. From these tests, three composites were derived-an "abridged" Preclinical Alzheimer's Cognitive Composite 5 (PACC5Abridged), an attention composite, and an executive function composite. Both per-protocol and intention-to-treat analyses were performed. Linear mixed models evaluated the change in outcomes between and within arms and adjusted for covariates and cognitive retest effects. Sensitivity models repeated the per-protocol analyses for participants who attended ≥ 4 intervention sessions. RESULTS: Across all cognitive composites, there were no significant time-by-trial arm interactions and no measurable cognitive retest effects; sensitivity analyses supported these results. Improvements, however, were observed within both trial arms on the PACC5Abridged from baseline to follow-up (Δ [95% confidence interval]: CMBAS = 0.34 [0.19, 0.48]; HSMP = 0.30 [0.15, 0.44]). There was weaker evidence of an improvement in attention but no effects on executive function. CONCLUSIONS: Two non-pharmacological interventions conferred small, non-differing improvements to a global cognitive composite sensitive to amyloid-beta-related decline. There was weaker evidence of an effect on attention, and no evidence of an effect on executive function. Importantly, observed improvements were maintained beyond the end of the interventions. Improving cognition is an important step toward dementia prevention, and future research is needed to delineate the mechanisms of action of these interventions and to utilize clinical endpoints (i.e., progression to mild cognitive impairment or dementia). TRIAL REGISTRATION: ClinicalTrials.gov, NCT03005652.
BACKGROUND: Older individuals with subjective cognitive decline (SCD) perceive that their cognition has declined but do not show objective impairment on neuropsychological tests. Individuals with SCD are at elevated risk of objective cognitive decline and incident dementia. Non-pharmacological interventions (including mindfulness-based and health self-management approaches) are a potential strategy to maintain or improve cognition in SCD, which may ultimately reduce dementia risk. METHODS: This study utilized data from the SCD-Well randomized controlled trial. One hundred forty-seven older adults with SCD (MAge = 72.7 years; 64% female) were recruited from memory clinics in four European countries and randomized to one of two group-based, 8-week interventions: a Caring Mindfulness-based Approach for Seniors (CMBAS) or a health self-management program (HSMP). Participants were assessed at baseline, post-intervention (week 8), and at 6-month follow-up (week 24) using a range of cognitive tests. From these tests, three composites were derived-an "abridged" Preclinical Alzheimer's Cognitive Composite 5 (PACC5Abridged), an attention composite, and an executive function composite. Both per-protocol and intention-to-treat analyses were performed. Linear mixed models evaluated the change in outcomes between and within arms and adjusted for covariates and cognitive retest effects. Sensitivity models repeated the per-protocol analyses for participants who attended ≥ 4 intervention sessions. RESULTS: Across all cognitive composites, there were no significant time-by-trial arm interactions and no measurable cognitive retest effects; sensitivity analyses supported these results. Improvements, however, were observed within both trial arms on the PACC5Abridged from baseline to follow-up (Δ [95% confidence interval]: CMBAS = 0.34 [0.19, 0.48]; HSMP = 0.30 [0.15, 0.44]). There was weaker evidence of an improvement in attention but no effects on executive function. CONCLUSIONS: Two non-pharmacological interventions conferred small, non-differing improvements to a global cognitive composite sensitive to amyloid-beta-related decline. There was weaker evidence of an effect on attention, and no evidence of an effect on executive function. Importantly, observed improvements were maintained beyond the end of the interventions. Improving cognition is an important step toward dementia prevention, and future research is needed to delineate the mechanisms of action of these interventions and to utilize clinical endpoints (i.e., progression to mild cognitive impairment or dementia). TRIAL REGISTRATION: ClinicalTrials.gov, NCT03005652.
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