Longevity Briefs: ‘Walk It Off’ – Exercise May Slow The Progression Of Early Alzheimer’s

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Many studies over the years have found that even small amounts of physical activity can have quite significant health benefits. Just 30 minutes of walking per day is associated with a large reduction in risk of age-related diseases and an increase in life expectancy compared to no exercise at all, with more and more exercise yielding diminishing returns (and eventually eroding some of those life expectancy gains). While this relationship seems well established, it’s worth highlighting it every time new research emerges.

In this study, researchers look at the relationship between exercise, cognitive decline and markers of Alzheimer’s disease in the brains of people who are cognitively healthy.

The discovery:

The study included 296 cognitively unimpaired older adults (meaning individuals who did not show signs of cognitive decline at the start of the study) from the Harvard Ageing Brain Study (HABS). Instead of relying on self-reported physical activity (as do many other studies), pedometer-measured step counts were used to provide an objective assessment of physical activity. The researchers also collected data on key markers of Alzheimer’s disease. The presence of amyloid-beta (Aβ) and tau protein was measured using positron emission tomography (PET) scans, and participants underwent annual cognitive assessments. Amyloid-beta is a protein that forms plaques in the brain, a hallmark of Alzheimer’s, while tau is another protein that forms tangles inside brain cells, also characteristic of the disease. Participants were followed up for a median of 9.2 years.

The researchers found that higher physical activity was associated with a slower rate of cognitive and functional decline in individuals who already had elevated levels of amyloid at the start of the study. Importantly, this protective effect did not appear to be associated with lower amyloid burden, either at the beginning of the study or over time. Instead, higher physical activity was linked to slower accumulation of tau in the inferior temporal cortex – a brain region that links visual perception to memory. This reduced tau accumulation, in turn, was associated with significantly slower cognitive decline.

The researchers also conducted dose-response analyses, and consistent with previous studies, observed diminishing returns: the benefits of physical activity on tau accumulation and cognitive decline reached a plateau between 5,001 and 7,500 steps per day. This equates to roughly an hour of brisk walking or an hour and a half of casual walking.

The implications:

The key implication of this study is that a relatively small amount of physical activity is associated with a significant reduction in cognitive decline in people who have elevated amyloid-beta levels, a marker of preclinical Alzheimer’s disease. This was associated with a reduction in tau accumulation in the brain, another marker of preclinical Alzheimer’s, though researchers did not assess actual Alzheimer’s incidence in their study. There did also appear to be a non-significant trend towards improved cognitive function with exercise in people with low amyloid-beta levels.

As already touched on, one of this study’s strengths was that it used wearable pedometers to provide a more objective assessment of physical activity. Many studies rely on participants reporting their physical activity levels, but self-reporting is often inaccurate and introduces bias into the data. While this study may have done a better job of measuring physical activity, we should remember that it’s still an observational study and can’t determine cause and effect. It’s possible that people with more rapid rates of cognitive decline did less exercise as a result, though the researchers did not find an association between cognitive function, Alzheimer’s markers and physical exercise levels at the start of the study. They also excluded participants who developed mild cognitive impairment within 2 years of the beginning of the study. These steps reduce the likelihood of reverse causation contributing to the results.