Constructing a graphical model of the relationship between physical activity and cognitive function based on a systematic review of prospective evidence

Abstract

Elucidating the factors that contribute to healthy ageing is an important research goal. Physical activity (PA) has been associated with benefits for cognitive function (CF). However, most of this evidence comes from longitudinal cohort studies which, in the absence of experimental design, have limited scope to make causal inferences regarding observed relationships. This review aimed to utilise recent methodological developments allowing researchers to formulate and answer stronger causal questions using observational data, by following a best-practice method for synthesising evidence to produce a graphical causal model known as a directed acyclic graph (DAG). Following a search of 3 databases (EMBASE, MEDLINE and PsycINFO), 21 observational studies on the PA-CF relationship were reviewed and their methodological quality, characteristics, and key findings were summarised. The outcomes of interest were the covariates and modelling practices employed in each study. The reported covariates were synthesised against a set of criteria to determine their role in the DAG as confounders or mediators of the PA-CF relationship. Every included study had some areas of methodological weakness. The resulting DAG included a wide range of biopsychosocial covariates spanning the entire life-course and indicated potential intermediate pathways between PA and CF via structural brain health. Strengths, limitations and implications of this review for modelling decisions are discussed, prior to the model being taken forward to inform an empirical analysis using data from the UK Biobank cohort, separate from this review.

Estimating the effect of physical activity on cognitive function within the UK Biobank cohort

“…This pattern of results was unexpected as it does not align with most of the recent literature that was synthesized and reviewed to construct the conceptual model informing this analysis. 11 However, a minority of the synthesized studies also reported no association between PA and CF 25–28 and, in common with two of these studies, the UK Biobank sample was younger at baseline than most of the other cohorts in which protective effects have been found. Taken together, our findings may suggest that observed associations in older baseline samples reflect reverse causation, whereby some participants had preclinical cognitive decline at baseline.…”

“…The variables within the conceptual DAG model 11 were matched to the data available within UK Biobank (see Supplementary Methods , available as Supplementary data at IJE online for detail).…”

“…The covariates were identified by the graphical causal model reported in the systematic review 11 and matched to available UK Biobank data. These are described in the Supplementary Methods and listed in full in Table 1.…”

“…To address these potential shortcomings in the existing literature, we conducted a systematic review 11 using a protocol 12 for synthesizing observational evidence to produce a directed acyclic graph (DAG). This involved integrating relevant covariates identified by the review into a model by mapping the assumed structure of inter-relationships between these variables, using a set of causal criteria to guide decisions.…”

“…Previous observational studies of the PA-CF relationship may be biased because none has followed a comprehensive method to select covariates. Our study addressed this by using the DAG produced by our review 11 to inform the specification of models to estimate the total effect of PA on CF (i.e. including any effect transmitted indirectly via intermediate variables).…”