The importance of physical activity and sedentary behavior in the process of cognitive ageing.

The older adult population is increasing significantly, and with this, geriatric syndromes are becoming a great challenge for health, economy and social care. One of the major contributors to this burden is dementia, a syndrome in which cognitive function is deteriorated beyond the expected rates of ageing, and that in 2020 was estimated to affect 50 million individuals and is expected to increase to over 150 million people worldwide by 2050 (1). Dementia is considered one of the major causes of disability and dependency in older adults, given these trends, it is essential to understand the factors related with the dynamics of cognitive ageing. 

Dementia onset starts 20 years before its diagnosis (2), early detections of neurodegenerative processes that lead to a cognitive dysfunction could prevent or delay the development of dementia by modifying exposure to common risk factors (3). Mild cognitive impairment has been recognized as an intermediate stage between normal cognitive function and dementia. Previous studies have identified that people with mild cognitive impairment have 3-5 times higher risk of a progression to dementia (4-5). In this sense, the recognition of which factors have a significant impact (positive or negative) in future changes of cognitive function are of interest. Studies have found that vascular disease (hypertension, diabetes, hyperlipidemia, metabolic syndrome), tobacco and alcohol consumption, neuropsychiatric symptoms like anxiety and depression, are modifiable risk factors for the progression from mild cognitive impairment to dementia (6). As for the risk of dementia, twelve modifiable risk factors are identified: less years of education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, low social activity (social contact), excessive alcohol consumption, traumatic brain injury, and air pollution (7). Since risk factors often cluster, the unique and shared contribution of each risk factor remains unknown. This is especially the case for more recently discovered independent risk factors like air pollution and noise exposure (8-9). The Lifelines cohort study offers the unique opportunity to study all modifiable risk factors of cognitive decline jointly in a well-designed and sufficiently large population-based cohort. 

Different cognitive tests were applied to the participants of the Lifelines, among them, the Cogstate battery was administered in the second and third measurement of the study. This is a computerized cognitive screening that assesses processing speed, attention, visual learning and working memory, several studies have assessed its validity and its ability to identify cognitive changes (10). Along with this, the Ruff Figural Fluency Test (RFFT) was administered to the participants, this test has been designed specifically to examine executive function domain, it is a digital or paper-and-pencil test consisting in five trials of 60s each with different stimulus presentation, in which the participant to create unique designs with different point configurations (11). Also, the Mini Mental State Examination Test (MMSE) that assess the individuals global cognitive state was measured at baseline and in the last round of the study, it collects information of orientation, attention, memory, registration, language and visual-spatial abilities (12). 

As mentioned above, physical inactivity is one modifiable factor for dementia prevention, recently, guidelines and programs start differentiating physical inactivity from sedentary behavior, however there are gaps that need to be fulfilled. Physical inactivity is defined as “an insufficient physical activity level to meet present physical activity  recommendations” (≥150 minutes/week of moderate to vigorous physical activity), while sedentary behavior is defined as a sitting time >8hours/day or an energy expenditure <1.5 metabolic equivalent task (13). Some recent investigations have found that older adults are more prone to increase sedentary behavior, its reduction has been identified as a predictor of successful ageing independently of physical activity (14).

Several health outcomes have been associated with sedentary behavior like all-cause mortality, obesity, cardiometabolic disease, and physical function in adult population (15). Regarding the association of sedentary behavior and cognitive performance, one of the most recent meta-analyses identified that sedentary older adults had higher risk of developing dementia (Pooled RR= 1.30, 95%CI 1.12, 1.51) (16). Also, in the review and meta-analysis of Rojer M. et al were older adults with lower sedentary behavior assessed with objective measures, had better global cognitive function (β = 0.078 IQ range 0.004-0.184), however it did not reach out statistical significance (17). These results have raised the attention of researchers who have claimed that there are some activities performed in a sitting position that can be cognitive stimulating. In this extent, Lauren Yates et al identified that the incorporation of leisure cognitive activities while being in a sitting position had lower risk of cognitive impairment (Pooled HR= 0.853, 95%CI0.711-1.022), and dementia (Pooled HR= 0.584, 95%CI 0.462-0.739) than their peers who did not performed cognitive leisure activities.  However, there is a large heterogeneity between the types of activities (physical, mental or social) and how they are assessed (18).  Examples of the activities are the ones related with art, writing, board games, reading, handicrafts, crossword puzzle and learning computer skills, all of them have been associated with cognitive function, nevertheless the only way to assess them is summing the time and frequency of the activity, but other aspects like motivation, engaging, concentration and psychological characteristics may also be involved with the cognitive function (19). This increases the need for studies identifying specific types of sedentary behavior, like the mentioned above, and to create evidence regarding the association with cognitive function and whether this hypothetical association is moderated by PA.

In recent research approaches addressing the main performed activities during a day, in addition to physical activity and sedentarism, sleep is the third main component in this 24 h cycle (20). Sleep has been associated with cognitive performance through mechanisms like controlled attention, vigilance and arousal, and wake-state instability (21), however the results regarding the association of different aspects about sleeping behavior (duration, quality, latency, efficiency, etcetera) with cognitive performance, mild cognitive impairment and/or dementia are not conclusive. Furthermore, the patterns of these three activities, the time replacement by one of the other activities (e.g. replacing 30 minutes of SB with 30 minutes of sleeping), and the impact on cognitive performance has not been fully dilucidated. Hence its study in large longitudinal studies like Lifelines could help to clarify this association.

To expand this research project, one of our interests is to explore the mediating role of inflammation and sarcopenia in the association between physical activity/sedentary behavior and cognitive performance. Inflammatory biomarkers, including C-reactive protein, TNF-α and interleukins are associated with cognitive impairment (22) and it has been observed that physical activity may benefit inflammatory profile (23) while sedentary behavior seems to worsen it (24). Sarcopenia, a condition characterized with progressive and generalized loss of skeletal muscle mass, muscle strength and/or physical performance, has similar risk factors and a bidirectional association with mild cognitive impairment (25), also adults with higher sitting time have more odds of having sarcopenia (26). Thus far, this pathway has hardly been studied and can be of eminent importance for preventive strategies. 

Given that age is the main risk factor for developing cognitive impairment and dementia, modifiable factors should be deeper investigated to prevent these diseases that impair the daily living. For these reasons, our objectives are a) to investigate the determinants involved in cognitive change (5 and 10 years) in adults from Lifelines, b) to assess the longitudinal association between physical activity/sedentary behavior and cognitive performance c) to explore physical activity, sedentary behavior and sleep patterns in 24h cycle and its association with CF, and d) to explore the role of inflammation and sarcopenia in this hypothetical association.

year of approval



  • UMCG - Department of Epidemiology

primary applicant

  • Smidt, N.