With the rapid and advancing aging of the world's population, dementia has become so prevalent that 50 million people worldwide suffer from its symptoms. In order to predict and make a timely diagnosis of dementia, reliable biomarkers need to be identified, as well as modifying factors such as age and other serological or lifestyle factors. A recent study looked at how new-onset dementia was related to an array of physical and other characteristics through a prospective observational study.
Study: Walking pace, handgrip strength, age, APOE genotypes, and new-onset dementia: the UK Biobank prospective cohort study. Image Credit: Focus and Blur / Shutterstock
Introduction
Since no cure has currently been found for dementia, much interest is focused on its prevention, primarily by increasing the level of regular physical activity inherent in one's lifestyle. This is because the nervous system regulates both cognitive and physical function and because both tend to decline with age.
The current study, published in the journal Alzheimer's Research & Therapy, drew data on almost 496,000 participants from the UK Biobank Study. None had symptoms or a diagnosis of dementia at the start of the study.
Walking pace is a sound and sensitive preliminary indicator of waning health and function in older adults. Studies have demonstrated a negative association between walking pace and dementia risk. Similarly, handgrip strength reflects muscular strength overall, with a weak handgrip predicting a higher risk of adverse health outcomes.
In the current study, the scientists looked at how walking pace – slow, average or brisk – and the strength of the handgrip (objectively measured using a dynamometer) related to the risk of dementia, independently and in combination. The reason for this was that these two measures might indicate different body mechanisms on their own. It is important to note that no study has yet examined the combined effect of both factors on dementia risk.
"Grip strength is more likely a measure of contraction strength whereas walking pace integrates strength with other processes, such as balance and coordination."
Therefore, examining both together might provide a better picture of likely health outcomes than each of them individually. In fact, this has been shown to be the case with cardiovascular disease and hypertension but not with cognitive decline, where only walking pace showed a relationship.
They also examined the association of known risk factors such as age, the apolipoprotein E (apoE) profile, lifestyle factors like hypertension, physical activity, depression, and diabetes, and a family history of dementia, acted upon the risk of dementia. The results would help determine how and to what extent walking pace and/or grip strength affect dementia risk.
The participants were followed up for a median of 12 years.
What did the study show?
During this period, there was new-onset dementia from any cause in 0.8% of patients, approximately 4000. The risk was highest among those who walked slowly. At the same time, it was reduced by ~40% among those with average or brisk walking pace after adjusting for age, lifestyle factors, and socioeconomic factors, besides family history. The risk for Alzheimer's disease (AD) was reduced by 35% and by half for vascular dementia, both of new onset, with the same model.
This did not change when adjusted for APOE ε4 levels or with genetic risk scores for dementia.
Participants with stronger handgrip strength (from 2-4 quartiles) showed a negative association with new-onset dementia risk after adjusting for the other factors. Moreover, the lowest risk was observed if both average/brisk walking pace and higher handgrip strength were reported in the same patient, with a reduction in risk by 55%, compared to those who walked slowly and had low grip strength.
The dosage, or level of expression, of APOE ε4 protein significantly modified the risk elevation associated with a slow walking pace. That is, with the lowest dosage of APOE ε4, brisk walkers showed a 45% lower risk of new-onset dementia from any cause compared to slow walkers. As the dose doubled from the first category above, the risk difference lost significance.
Similarly, with increasing age, around a median age below 58 years, brisk walkers showed a reduction in risk by over 75%. The reduction was still significant but less marked, at 45%, in the group with a median age of 58 or above.
What are the implications?
The results of this study may reinforce the importance of intact walking and handgrip activity in reducing the risk of new-onset dementia. Brain areas that control these functions overlap, perhaps explaining observed associations.
"Participants with both faster walking pace and higher handgrip strength had the lowest risk of dementia, suggesting that maintaining both high handgrip strength and fast walking pace may be a more comprehensive strategy for preventing dementia risk."
While those with low or normal risk as defined by APOE ε4 dosage showed a risk reduction with brisk walking, this was not obvious in the high-risk group. This gene is linked to amyloid and neurofibrillary tangle formation in the brain, with neuronal death and neuroinflammation causing permanent loss of neuronal pathways. This could explain why brisk walking in this group failed to reduce the already high risk of dementia.
Younger patients seemed to benefit more from brisk walking, potentially emphasizing the role of age in both cognitive decline and abnormal gait. As such, older adults are already at high risk of age-related dementia and fail to show the same favorable relationship with brisk walking.
Education, physical activity, and comorbidities typically associated with a higher risk of cardiovascular diseases, such as high blood pressure and diabetes, all failed to modify these associations.
"Our findings highlight the importance of assessing combined measures of physical function, genetic profile, and age to improve the stratification of individuals at risk of dementia."
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