Research shows that exercise can slow Alzheimer's disease, but there is a catch

A new study found that staying active can help slow brain changes associated with Alzheimer's disease. Until the tau level reaches a turning point. Can exercise be key to slowing down cognitive decline?

study: Associations with moderate to intense physical activity, P-TAU181, and cognition in healthy elderly with memory complaints: a secondary analysis from MAPT. Image credits: Roman Samborskyi / Shutterstock

A recent study published in the journal Healthy longevity in the lancetresearchers evaluated the association between phosphorylation (P)-TAU181 levels, moderate to intense physical activity (MVPA), and cognition in older adults.

Tau proteins are abundant in neurons, where they regulate and stabilize axonal microtubule activity, and Cell signaling. Aggregation of p-TAU181 in dysfunction in the brain is associated with aging-related cognitive decline, and represents a characteristic of Alzheimer's disease (AD) pathology.

Therefore, it is important to determine whether and how these accumulations (P-TAU181) can be prevented through non-pharmaceutical approaches such as physical activity. Cross-sectional analyses of the association between tau levels and physical activity produce different results, with some studies revealing opposite associations, and others showing no associations. Previous studies have found little significant effects of MVPA on P-TAU accumulation, making this new study particularly important.

About the research

This study investigated the longitudinal and cross-sectional associations between MVPA, P-TAU181 levels, and cognition. They used data from the Multidomain Alzheimer's Disease Prevention Trial (MAPT), which recruited more than 70 dementia-free adults from memory centres in Monaco and France.

Eligible participants had self-reported memory complaints, limited tool activities in daily life, or low walking speeds. However, individuals were excluded if diagnosed with a dementia condition, a Mini Mental Status Test (MMSE) score of less than 24, a limitation of basic activities in daily life, or if an omega-3 supplement had already been taken prior to enrollment. This study included MAPT participants with P-TAU181 measurements at baseline, 3 years, or both time points. They were randomized to receive one of four interventions: 1) multidomain interventions and placebo, 2) multidomain interventions and omega-3 supplementation, 3) omega-3 supplementation only, or 4) placebo alone.

The multidomain intervention consisted of cognitive training and counseling on physical activity and nutrition. Blood samples were analyzed at the Institute of Clinical Neurochemistry at the University of Gothenburg using an in-house SIMOA-based method. Physical activity was assessed at baseline, 6 months, 1 year, 2 years, and 3 years using the Minnesota Leisure Time Activity Survey.

At these time points, cognition was assessed using category naming tests, digit symbol replacement tests, 10 MMSE directional items, and free and cue selective remind tests. Combined cognitive scores were calculated from the scores for these (4) tests. Mixed effects models were used to investigate the association between MVPA and P-TAU181 levels and assessed the non-mitigation but mediation role of p-TAU181 levels between cognitive and MVPA.

Survey results

In total, MAPT registered 1,679 individuals from May 30, 2008 to February 24, 2011. Of these, 558 (33%) had P-TAU181 measurements, with median baseline age of 74 years. Furthermore, MVPA levels were low at 47% of participants and high at 45%. Forty-one subjects (7%) were inactive. At baseline, the median level of MVPA was 1,099 metabolic equivalence tasks (MET)-minutes, with median P-TAU181 concentrations of 8.9 pg/mL (range 0.4 to 31.7 pg/mL).

The median baseline MMSE score was 28. There was no association between baseline MVPA and baseline P-TAU181 levels. Nevertheless, there was a significant longitudinal association associated with the slow increase in P-TAU181 levels over time. However, this association was only significant when comparing inactive individuals with active individuals. No differences were found between low and high levels of MVPA.

Furthermore, there was no mediation effect at p-TAU181 level on the association between MVPA and changes in compound cognitive scores. Furthermore, there was no effect of MVPA on changes in composite cognitive scores.

In moderation analysis, P-TAU181 levels significantly influenced the association between MVPA and combined cognitive scores. Higher P-TAU181 levels attenuated the positive association between MVPA and cognition. In particular, when P-TAU181 levels exceed 9.36 pg/ml in cross section and 3.5 pg/mL in length, the effect of MVPA is no longer significant, suggesting that high tau burden may reduce or eliminate the benefits of exercise.

Conclusion

Findings revealed that MVPA was not associated with P-TAU181 levels at baseline, but higher MVPA levels were associated with slower increases in P-TAU181 levels over time. However, these findings contrast to previous studies, and no effect of MVPA on P-TAU accumulation was observed. This suggests that long-term follow-up, rather than cross-sectional studies, may be required to detect these associations.

Moreover, higher baseline P-TAU181 levels attenuated the positive association between MVPA and cognition. P-TAU181 levels did not mediate the association between MVPA and cognitive.

Limitations of this study include the usefulness of subjective tools for physical activity assessment. Furthermore, light intensity physical activity and sedentary time are not considered and may affect outcomes. MAPT subjects received interventions that may have influenced the observed associations. Furthermore, researchers analyzed APOE-ε4 status, which did not affect the outcome and showed that the effects of MVPA on P-TAU181 levels and cognition are independent of genetic Alzheimer's pathogenesis. Further analysis is needed to support these findings.