Interplay of physical and cognitive performance using hierarchical continuous-time dynamic modelling and a dual-task training regime in Alzheimer’s patients

Background Training studies typically investigate the cumulative rather than the analytically challenging immediate effect of exercise on cognitive outcomes. Methods We investigated the dynamic interplay between single-session exercise intensity and time-locked cognition in older adults with suspected Alzheimer’s dementia (N = 17) undergoing a 24-week dual-task regime. We specified a state of the art hierarchical Bayesian continuous- time dynamic model with fully connected state variables to analyze the bidirectional effects between physical and cognitive performance over time. Results Higher physical performance was dynamically linked to improved memory recognition (-1.335, SD = 0.201, 95 BCI [-1.725, -0.954]). The effect was short-term, lasting up to five days (-0.368, SD = 0.05, 95 BCI [-0.479, -0.266]). Clinical scores supported the validity of the model and observed temporal dynamics. Conclusion Higher physical performance predicted improved memory recognition in a day- by-day manner, providing a proof-of-concept for the feasibility of linking exercise training and cognition in patients with Alzheimer’s dementia. Highlights Research in Context 1. Systematic review: Training-induced effects on cognitive outcomes in Alzheimer’s dementia and/or associated dynamic Bayesian modelling approaches were reviewed. Although studies showed exercise-induced cognitive improvements or maintenance, most of these studies fail to capture the dynamic nature of the change and interplay of physical (PP) and cognitive (COG) performance. 2. Interpretation: Using a sophisticated hierarchical Bayesian continuous-time dynamic modelling approach, a fully connected state variable model was specified. PP is dynamically linked to COG, i.e. higher PP predicted improved COG in subsequent sessions. This effect was rather short term, lasting for up to five days. 3. Future direction: Our results support exercise-induced effects on cognition. The cognitive system was still able to fluctuate and change favourably even in a sample with Alzheimer’s dementia. Further studies using dynamic modelling are necessary to replicate findings and examine other contributors to cognitive volatility in dementia. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial DRKS registration number: DRKS00019105 ### Funding Statement The project (ID: ZS/2016/05/78611) belongs to the Research Association Autonomy in old Age (AiA) funded by the European Union (ERDF-European Regional Development Fund) and the State of Saxony-Anhalt, Germany. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of the Otto-von-Guericke University, Magdeburg, Germany gave ethical approval for this work (approval number: 68/17). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors