Slow walking speed as indicator for Alzheimer's disease

The walking speed of the elderly may give an early indication of Alzheimer's disease.

Research published today in the journal Neurology® found an association between slow walking speed and the amount of the protein beta amyloid that has built up in the brain. Amyloid deposits have been associated with the development of Alzheimer's disease.

We spoke with study author Natalia Del Campo, post-doctoral fellow at the Gérontopôle of the Toulouse University Hospital, and the Scientific Manager of the Centre of Excellence in Neurodegeneration of Toulouse, France.

ResearchGate: What is the relationship between deposits of the protein amyloid building up in the brain and Alzheimer’s disease?

Natalia Del Campo: Alzheimer's disease (AD) leads to nerve cell death and tissue loss throughout the brain, affecting nearly all its functions over time, but scientists aren’t absolutely sure on the causes. According to the prevailing amyloid cascade hypothesis, the formation of amyloid plaques – dense deposits of the protein beta amyloid – leads to the formation of neurofibrillary tangles. Neurofibrillary tangles are aggregates of a different protein called tau. These aggregates lead to local synaptic dysfunction, neurodegeneration and neuronal loss

RG: What causes amyloid to build up in the brain?

NDC: No one knows what causes amyloid to build up in the brain. There are certain genotypes and genetic mutations that have been associated with amyloid build-up. However, these are not a necessary condition for the disease to develop. A number of lifestyle factors and certain metabolic or cardiovascular conditions have also been associated with the development of AD, but causality has not been established.

RG: What was your study about?

NDC: The goal of our study was to examine, whether there is an association between brain amyloid and gait speed in non-demented old subjects. The study involved 128 people with an average age of 76 who did not have dementia but were considered at high risk for developing it because they had some concerns about their memory. A total of 46 percent of the participants had mild cognitive impairment, which can be a precursor to the dementia that occurs in Alzheimer’s disease. The participants had positron emission tomography (PET) scans of their brains to measure amyloid plaques in the brain.

RG: What were your results?

NDC: We found an association between slow walking speed and amyloid in several areas of the brain, including the putamen, a key region involved in motor function. Most subjects in the study walked at a pace considered normal according to current conventions. We compared how fast people walked both with and without taking into account cerebral amyloid and found that the amyloid level accounted for up to 9 percent of the difference in walking speed. The association between brain amyloid and gait speed was independent of the subjects’ cognitive status. Collectively, our results suggest that subtle walking disturbances in addition to subjective memory concerns may signal AD, even in people who are fully asymptomatic and have a walking pace within the normal range.

RG: Why did you decide to focus on walking speed?

NDC: Our interest in the association between gait speed and AD pathology was partly motivated by previous epidemiological studies reporting a decline in gait speed in patients with mild cognitive impairment (MCI) and in healthy adults converting to MCI years later. The neural mechanisms underlying these observations were largely unexplored.

RG: What does this mean for future Alzheimer’s research?

More research is needed to study the relationship between brain amyloid and gait speed over time. Our study had a cross-sectional design, which allows us to look at a snapshot in time. This type of design allows you to examine associations between different events, but it does not prove causal relationships between them. In other words, our data show that there is an association between brain amyloid and gait speed, but they don’t prove that amyloid causes slowdown in walking speed. Only future longitudinal designs will help address this question.

We can however speculate about the meaning of our results, building on what we already know from the literature, and formulate hypotheses for future research to address. There are several potential interpretations to the observed relationship between amyloid and gait speed:

First, it is possible that amyloid accumulation and slow gait speed co-occur as the result of a common lifestyle factor such as a deficient diet through childhood or adulthood, low physical activity, or smoking. It may also be explained by a common underlying metabolic or cardiovascular factor, for example diabetes or hypertension. We know that these are risk factors for dementia and poor motor function, although causality has not been established.

Second, slow gait speed may constitute a risk factor for AD. We know from epidemiological studies in old individuals that gait speed predicts major health-related events, including future disability, hospitalization and also dementia. Why? Slow gait speed possibly reflects an age-related reduction in physiologic reserve, which may turn the brain more vulnerable to the accumulation of AD pathology and subsequent damage. This would be in line with evidence showing that high levels of physical activity and cardiovascular fitness, two parameters closely linked to gait speed, have protective effects against brain aging.

Finally, a third potential explanation is that amyloid in the brain causes slowing of gait speed. It is possible that amyloid exerts toxic effects on brain regions involved in motor function, thereby slowing gait speed. But it is also possible that the relationship is explained by downstream effects of amyloid plaques or other neuropathological lesions, such as tau deposition.

Most likely, a comprehensive framework of why brain amyloid is associated with gait speed will require aspects of all three explanations.

Finally, future studies should also look at other neuropathological processes that occur in AD in addition to the deposition of amyloid, such as the accumulation of neurofibrillary tangles.

RG: What impact will your results have when trying to identify those at risk of AD?

NDC: Our results suggest that taking into account physical performance parameters that are not conventionally looked at in AD, such as gait speed, may help optimize the early identification of individuals who are at risk of AD. However, more evidence is needed before our data can be translated into clinical practice. There are many other causes of slow walking in older adults.

 

The study was published in the December 2, 2015, online issue of Neurology®, the medical journal of the American Academy of Neurology and was led by Prof. Bruno Vellas, head of the Gérontopôle.

Image courtesy of Kai C. Schwarzer.