שנת סיום: 2023
כותרת עבודת הדוקטורט: Association of Physical Activity, Sedentary Behavior, Cardiorespiratory Fitness and Body Mass Index with Brain Health
מנחים: פרופ' גלית וינשטיין ופרופ' כרם שובל
Background: Physical activity is an established modifiable risk factor for cognitive impairment and dementia. Cardiorespiratory fitness (CRF), sedentary behavior and body mass index (BMI) have also been identified as potential modifiable risk factors for cognitive health. Yet, the independent and joint associations of these risk factors with cognitive outcomes, and their underlying mechanisms, are unclear. Sedentary behavior is on the rise, and it is associated with adverse health outcomes regardless of the level of physical activity. Less is known on the relationship between sedentary behavior and cognitive health, independently and in combination with physical activity. Moreover, although physical activity plays an important preventative role, the underlying mechanisms connecting physical activity and cognitive performance have not been fully elucidated. Cardiac autonomic balance is influenced by physical activity and implicated in dementia pathogenesis. Yet, it has never been explored as a mediator of the association between physical activity and cognitive function. For dementia prevention, both lower CRF and higher BMI have been linked to increased dementia risk, but this association has not been fully established. Furthermore, despite their interrelationship, their independent and joint associations with dementia have rarely been explored.
Main Research Aims: (1) To examine the association between sedentary behavior and cognition, independent of the effect of physical activity, in both middle-aged and older adults; (2) To examine whether autonomic balance mediates the association between long term physical activity and cognition; (3) To examine the independent and joint association of midlife CRF and BMI with dementia incidence.
Methods: This study used data from two large, well-established cohort studies: the Cooper Center Longitudinal Study (CCLS) and the Coronary Artery Risk Development in Young Adults (CARDIA) study. The first part of the research included 3,780 community dwelling adults from the CCLS. Physical activity and sitting time were self-reported. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. Participants were classified based on their physical activity level as not meeting, meeting, or exceeding physical activity guidelines (500–1,000 metabolic equivalent (MET) min/week) and based on their sitting time as ≤25%, 50%, and ≥75% of time at work, school, and housework. Cognitive impairment was defined as a MoCA score<26 points. The cross-sectional independent and joint associations of sitting and physical activity with MoCA scores were assessed using multivariable logistic regression. The second part of the research included 1,939 participants from the CARDIA study. Moderate to vigorous intensity physical activity (MVPA) was obtained in seven consecutive examinations over 20 years. Cardiac autonomic balance was assessed at Year 20 via resting heart rate and heart rate variability (HRV) measurements. Group-based trajectory modeling was applied to identify homogenous MVPA trajectory groups, and formal mediation analysis was used to test whether autonomic function indices mediate the association between MVPA trajectories and cognition. The third part of the research linked data of 6,428 CCLS participants to Medicare claims files to glean information on all-cause dementia (1999–2009). Cardiorespiratory fitness and BMI were assessed twice between 1970 and 1999 as an average (i.e., baseline value) and change between the two measurements. Participants were classified into four groups: fit and normal weight, fit and overweight-obese, unfit and normal weight, and unfit and overweight-obese. Survival analysis models were used to assess the relationship of CRF and BMI with incident dementia.
Summary of main results: The first part of the research showed that overall sitting ≥75% of the time and not meeting physical activity guidelines were related to 60% and 27% higher odds for cognitive impairment, respectively. In middle-aged, but not older, adults, sitting 75% of the time was associated with higher cognitive impairment odds. The highest odds for cognitive impairment were found among those who sat ≥75% of the time while meeting or not meeting physical activity guidelines. In the second part of the research, three distinct physical activity trajectory patterns were identified: (1) Below MVPA guidelines (n=1,122; 57.9%); (2) Meeting MVPA guidelines (n=652; 33.6%); and (3) Exceeding MVPA guidelines (n=165; 8.5%). Meeting and exceeding MVPA guidelines were related to better autonomic balance overall, and to improved semantic fluency performance. Statistically, the association between higher MVPA level and verbal ability was mediated by the standard deviation of the normal-to-normal (SDNN) sinus node-initiated R-R intervals and root mean square of successive R-R interval differences (RMSSD), but not by resting heart rate (RHR). Findings from the third part of the research suggest that compared to fit participants, unfit participants had 85% higher dementia risk, and each decrement of 1 MET was related to 6% higher dementia risk after controlling for BMI and other covariates. However, BMI was not significantly associated with dementia risk independently of CRF. Participants classified as both overweight-obese and unfit had more than twice the dementia risk compared to those who were fit and normal weight. Changes in CRF and BMI between exams were not related to dementia.
Practical implications and added value: This research provides a small step towards understanding the interactive effects of modifiable risk factors for cognitive outcomes and dementia prevention. This research is among the firsts one of the first to examine the independent and combined associations of overall time spent sitting and physical activity levels on cognitive function among middle-aged and older adults. The findings suggest that by targeting both insufficient physical activity and extended sitting with behavioral interventions, particularly in middle age, we may be able to contribute to lowering the health burden related to cognitive impairment. Furthermore, the research illuminates the importance of midlife CRF level as a means of dementia prevention and suggests that it may be more important than weight status. This interactive effect of CRF and weight status has not been explored so far. Another contribution of this research is that it provides evidence that autonomic balance may play a role in mediating the effect of physical activity on cognitive outcomes. Further research is required to translate such novel findings into a simple and affordable new way of detecting individuals at high risk for cognitive impairment or as an indicator of the effectiveness of physical activity intervention.