Slow Walking Speed May Signal Alzheimer's Risk

December 03, 2015

A slow walking speed was associated with a higher level of brain amyloid deposits in a population of older adults at a high risk of developing dementia in a new study.

The study, published online in Neurology December 2, was conducted by a team led by Natalia del Campo, PhD, University Hospital Toulouse, France.

"Our results suggest that taking into account physical parameters that are not conventionally looked at in dementia, such as walking speed, may help optimize the early identification of individuals who are at risk of Alzheimer's," Dr del Campo commented to Medscape Medical News.

"However, more evidence is needed before our data can be translated into clinical practice," she added. "There are many other causes of slow walking in older adults."

Dr del Campo explained that previous epidemiologic studies have suggested a decline in gait speed in patients with mild cognitive impairment and in healthy adults who converted to mild cognitive impairment years later. It has also been reported that Alzheimer's disease pathology on postmortem examination is associated with decline in walking speed before death. However, the neural mechanisms underlying these observations were largely unexplored.

The researchers speculated that the mechanism behind such observations may be amyloid toxicity disrupting motor circuits. They therefore conducted the current study to examine the association between amyloid deposits and walking speed in elderly individuals with high risk for dementia.

The study involved 128 people (average age, 76 years) who did not have dementia but were considered at high risk because they had concerns about their memory. They underwent positron emission tomography (PET) to measure amyloid plaques in the brain, and 48% of the group was found to have a level of amyloid often associated with dementia.

Participants also underwent cognitive testing and 46% were found to have mild cognitive impairment. Gait speed was measured by timing participants while they walked 4 meters. All but two of the participants were in the normal range of walking speed.

Results showed a significant association between slow walking speed and amyloid in several areas of the brain, including the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate (all corrected P < .05).

The researchers compared how fast people walked both with and without taking into account the amount of amyloid and found that the amyloid level accounted for up to 9% of the difference in walking speed.

The relationship between amyloid levels and walking speed did not change when researchers took into account age, education level, or cognitive function.

"Collectively, our results suggest that subtle walking disturbances in addition to subjective memory concerns may signal Alzheimer's, even in people who are fully asymptomatic and have a walking pace within the normal range," Dr del Campo said. 

But she stressed that this was a cross-sectional study; therefore, it could not prove a causal link. "It remains to be seen whether and to what extent amyloid accumulation causes a slowing of gait speed over time," she added.

She said the current results should not cause concern about slow walking speed in older people in general.

"There are many other causes of slow walking in older adults. Most subjects in our study walked at a pace considered normal according to current conventions. Also, our study sample is not representative of the general elderly population. Our subjects were at risk of developing Alzheimer's because they had some concerns about their memory, and almost half had mild cognitive impairment."

Dr del Campo noted 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, it's possible that slow gait speed may constitute a risk factor for Alzheimer's.

"We know from epidemiological studies in older people that gait speed predicts major health-related events, including future disability, hospitalization and also dementia," she said. "Slow gait speed possibly reflects an age-related reduction in physiologic reserve, which may make the brain more vulnerable to the accumulation of Alzheimer's 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 amyloid causes slow gait speed through other mechanisms implicated in Alzheimer's, such as tau deposition."

Dr del Campo said it is most likely that aspects of all three interpretations are involved in the association between amyloid and gait speed.

She added that future studies should also look at other neuropathologic processes that occur in Alzheimer's, such as the accumulation of neurofibrillary tangles, and how they relate to walking speed.  

The study was part of the Multidomain Alzheimer Preventive Trial, which was supported by the French Ministry of Health and Pierre Fabre Research Institute. The imaging was supported by Avid Radiopharmaceuticals/Eli Lilly and Company. Dr del Campo has disclosed no relevant financial relationships.

Neurology. Published online December 2, 2015. Abstract

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