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Background With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = −0.1, SE = 0.01), APOE*4 carriage (B = −0.31, SE = 0.11), depression (B = −0.11, SE = 0.06), diabetes (B = −0.23, SE = 0.10), current smoking (B = −0.20, SE = 0.08), and history of stroke (B = −0.22, SE = 0.09) were independently associated with poorer cognitive Determinants of cognition in diverse ethno-regional groups

Background Besides physical activity as a target for dementia prevention, sedentary behaviour is hypothesized to be a potential target in its own right. The rising number of persons with dementia and lack of any effective treatment highlight the urgency to better understand these modifiable risk factors. Therefore, we aimed to investigate whether higher levels of sedentary behaviour are associated with reduced global cognitive functioning and slower cognitive decline in older persons without dementia. Methods We used five population cohorts from Greece, Australia, USA, Japan, and Singapore (HELIAD, PATH, SALSA, SGS, and SLAS2) from the Cohort Studies of Memory in an International Consortium. In a coordinated analysis, we assessed the relationship between sedentary behaviour and global cognitive function with the use of linear mixed growth model analysis (mean follow-up range of 2.0-8.1 years). Results Baseline datasets combined 10,450 older adults without dementia with a mean age range between cohorts of 66.7-75.1 years. After adjusting for multiple covariates, no cross-sectional association between sedentary behaviour and cognition was found in four studies. One association was detected where more sedentary behaviour was cross-sectionally linked to higher cognition levels (SLAS2, B = 0.118 (0.075; 0.160), P < 0.001). Longitudinally, there were no associations between baseline sedentary behaviour and cognitive decline (P > 0.05). Conclusions Overall, these results do not suggest an association between total sedentary time and lower global cognition in older persons without dementia at baseline or over time. We hypothesize that specific types of sedentary behaviour may differentially influence cognition which should be investigated further. For now, it is, however, too early to establish undifferentiated sedentary time as a potential effective target for minimizing cognitive decline in older adults without dementia.

BackgroundThe purpose of this cross-sectional study was to describe the patterns and levels of sedentary time and physical activity (PA) in a general Japanese population.MethodsA total of 1,740 community-dwelling Japanese adults aged ≥40 years participated in this study. Sedentary time and PA were assessed for 7 consecutive days using a tri-axial accelerometer. Daily patterns and levels of sedentary time and PA were calculated by sex, age group (40–64, 65–74, and ≥75 years), and body mass index (BMI; <25 and ≥25 kg/m2).ResultsParticipants spent half of their waking time being sedentary, 32.7% of which was accumulated in prolonged bouts ≥30 minutes, versus only 54.4 minutes/day (7% of waking time) as moderate-to-vigorous PA (MVPA) (11.8 minutes/day in bouts ≥10 minutes). In addition to total sedentary time, men had longer prolonged sedentary bouts and fewer breaks per sedentary hour than women. Similar trends were observed in participants aged ≥75 years and those with a higher BMI (≥25 kg/m2) compared to those with a younger age and lower BMI. Moreover, participants aged ≥75 years and those with a higher BMI accumulated fewer MVPA minutes in bouts ≥10 minutes. Only 34.8% of the population met the recommended level of ≥150 minutes/week MVPA in bouts ≥10 minutes.ConclusionJapanese adults accumulated a large proportion of total sedentary time in prolonged bouts but few minutes in sustained bouts of MVPA, and few of them met the current PA guideline.

The current study examined the effect of aging and long-term wheel-running on the expression of heat shock protein (HSP), redox regulation, and endoplasmic reticulum (ER) stress markers in tibialis anterior (T.A.) and soleus muscle of mice. Male mice were divided into young (Y, 3-month-old), old-sedentary (OS, 24-month-old), and old-exercise (OE, 24-month-old) groups. The OE group started voluntary wheel-running at 3 months and continued until 24 months of age. Aging was associated with a higher thioredoxin-interacting protein (TxNiP) level, lower thioredoxin-1 (TRX-1) to TxNiP ratio—a determinant of redox regulation and increased CHOP, an indicator of ER stress-related apoptosis signaling in both muscles. Notably, GRP78, a key indicator of ER stress, was selectively elevated in T.A. Long-term exercise decreased TxNiP in T.A. and soleus muscles and increased the TRX-1/TxNiP ratio in soleus muscle of aged mice. Inducible HSP70 and constituent HSC70 were upregulated, whereas CHOP was reduced after exercise in soleus muscle. Thus, our data demonstrated that aging induced oxidative stress and activated ER stress-related apoptosis signaling in skeletal muscle, whereas long-term wheel-running improved redox regulation, ER stress adaptation and attenuated ER stress-related apoptosis signaling. These findings suggest that life-long exercise can protect against age-related cellular stress.