New research reveals that even modest daily walking can slow the buildup of Alzheimer’s-linked proteins and delay cognitive decline, giving older adults a realistic path to protect their memory and independence.
Study: Physical activity as a modifiable risk factor in preclinical Alzheimer’s disease. Image credit: candy candy/Shutterstock.com
A study led by researchers from Mass General Brigham, USA, revealed that a moderate level of physical activity can slow down the rate of cognitive and functional decline in cognitively unimpaired older adults who are at risk of developing Alzheimer’s disease. The study is published in Nature Medicine.
Why exercise matters for Alzheimer’s
Alzheimer’s disease is a progressive neurodegenerative disease, affecting over 50 million adults worldwide. Several modifiable risk factors are associated with the development and progression of this disease, including physical inactivity.
Studies using animal models suggest that regular physical activity can reduce the progression of Alzheimer’s disease. However, evidence supporting this association in humans is lacking. To consider physical activity as a clinically relevant preventive intervention, it is crucial to understand its association with cognitive and functional decline in older adults who are at the earliest stage of Alzheimer’s disease, where changes in disease biomarkers begin long before the appearance of any clinical symptoms.
Stepping exercise is an easy-to-perform physical activity that has been linked to lower risks of cognitive decline and all-cause mortality. With the increasing popularity of digital wearables, daily step count has become an easily accessible measure of physical activity.
In the current study, researchers investigated whether physical activity slows down cognitive and functional decline in cognitively unimpaired older adults, and whether the effects of physical activity on cognition depend on the brain levels of Alzheimer’s disease biomarkers.
Tracking steps and brain changes
The study included a total of 296 cognitively unimpaired older adults, who were followed for a median of 9 years (with a maximum of 14 years). Physical activity of participants was measured at baseline using a pedometer worn for seven consecutive days, and cognition and function were assessed annually using validated methods.
The brain accumulation of amyloid-beta and tau, two significant biomarkers of Alzheimer’s disease, was measured using positron emission tomography.
How activity affects tau buildup
The study analysis revealed that higher physical activity is associated with slower cognitive and functional decline in participants with elevated amyloid-beta levels at baseline (at enrollment). This beneficial association was not observed in participants with lower baseline or follow-up amyloid-beta levels.
Importantly, the study revealed that higher physical activity is associated with slower amyloid-related early tau accumulation in the inferior temporal cortex (an early neocortical region), which is the outer layer of the brain’s cerebral cortex responsible for higher-order cognitive functions. The observed beneficial impact of physical activity on cognition and function was mediated by slower amyloid-related tau accumulation in the inferior temporal cortex.
The dose-response analysis indicated that in participants with elevated amyloid-beta at baseline, even lower levels of physical activity (3,001–5,000 steps per day) are associated with significantly slower rates of tau accumulation and cognitive and functional decline.
In participants with moderate levels of physical activity (5,001–7,500 steps per day), further attenuation of tau accumulation and cognitive and functional decline was observed at similar rates to those among active participants (more than 7,501 steps per day), suggesting a plateauing of the effects.
A step toward prevention
The study highlights the importance of physical activity as a potential preventive intervention to delay cognitive and functional decline in older adults who are at high risk of developing Alzheimer’s disease.
The researchers suggest that future prevention trials should investigate physical activity, either alone or in combination with anti-amyloid-beta therapy, as an intervention to decelerate Alzheimer’s disease onset and progression.
Notably, the findings indicate that the observed association between higher physical activity and slower cognitive and functional decline is not driven by differences in amyloid-beta accumulation rates.
Instead, the study finds a new association between higher physical activity and longitudinal tau burden, which indicates that the observed benefits of physical activity are driven by reduced inferior temporal cortical tau accumulation.
According to the findings, reduced tau accumulation fully mediates the effects of cognitive decline, but only partially mediates the impact of functional decline. This observation suggests that tau-unrelated mechanisms mediate a substantial portion of the functional benefits associated with physical activity. Further research is needed to gain a more conclusive understanding of these mechanistic details.
Another notable finding of the study is that older adults with moderate activity levels can achieve similar cognitive and functional benefits as their more active peers. Furthermore, it has been observed that even a low level of physical activity is associated with a 34 % to 40 % slower cognitive and functional decline over nine years. These findings offer a more approachable goal for older sedentary individuals to maintain their neurocognitive health.
Regarding possible mechanisms, the researchers suggest that physical activity-mediated improvements in cardiorespiratory fitness and cerebral blood flow, as well as a reduction in inflammation, may potentially contribute to the observed cognitive and functional benefits.
Due to the observational design, the study was unable to determine the causality of the observed associations, highlighting the need for future randomized clinical trials. Moreover, the pedometer-measured physical activity used in the study does not include non-step-related physical activities, such as swimming and resistance training. Future studies with longitudinal daily-life physical activity data are needed for more conclusive interpretations.
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