23 Sep 2022

Have you hit your 10,000 steps today? If not, consider lacing up those sneakers in the name of dementia prevention. In the September 6 JAMA Neurology, researchers led by Borja del Pozo Cruz, University of Southern Denmark, reported that middle-aged and older adults who took 9,800 steps per day were half as likely to develop dementia within seven years as were their sedentary peers. Likewise, 30 minutes of moderate-intensity walking daily reduced dementia risk by 62 percent. “Such a goal is likely much more attainable for a larger slice of the adult population than the customary ‘10,000 steps a day’ mantra,” wrote Elizabeth Planalp and Ozioma Okonkwo, University of Wisconsin School of Medicine, Madison (comment below).

The more steps a person took, the lower his or her risk of developing dementia.
Walking 9,800 steps a day halved dementia risk.
Striding at 112 steps per minute for 30 minutes daily reduced risk by 60 percent.

The mantra is supported by physical activity guidelines set by the World Health Organization and other government agencies (see O’Connell et al., 2016; Tudor-Locke et al., 2011). “This study confirms the well-known hypothesis that being physically active reduces your dementia risk, [but shows that] even walking has this positive effect, not just strenuous activities such as aerobic exercise,” wrote Robert Perneczky of Ludwig-Maximilians University in Munich (full comment below).

While the brain-preserving benefits of exercise are well-documented, the effects of simply walking are unknown (Aug 2019 news; Jul 2019 conference news; Jan 2019 news). First author del Pozo Cruz analyzed step count and intensity, as measured by cadence, from 78,430 UK Biobank participants. They ranged from 40 to 79 years old, with an average age of 61. Half were women, most were Caucasian. Volunteers wore a wrist accelerometer all day for an average of seven days.

Del Pozo Cruz scoured their medical records over the subsequent seven years, finding that 866 had been diagnosed with all-cause dementia. Active participants who had spent 30 minutes per day pressing on at the brisk cadence of 112 steps per minute had a 62 percent lower risk than people who strolled at 30 steps per minute (see image below). “This finding aligns with many randomized controlled trials of moderate-intensity exercise on cognitive function,” Teresa Liu-Ambrose, University of British Columbia, wrote to Alzforum (full comment below).

A half-hour of such power walking would carry the average person about 1.6 miles. Is this feasible for a 70- or 80-year-old? Yes, del Pozo Cruz said. “The key is 30 minutes of walking at your best effort, regardless of your step rate.” While 112 steps per minute delivered the highest reduction in dementia risk, any fast-paced walking speed was beneficial. Also, these active minutes don’t have to be clocked consecutively. Even participants who made up the 30 mins with shorter intervals of walking throughout the day saw the same protection, highlighting the benefit of even a few minutes of exercise here and there.

By the Numbers. Sweet spots for lowering dementia risk were 10,000 steps per day (left) and 30 minutes at 112 steps per minute (right). [Courtesy of del Pozo Cruz et al., JAMA Neurology, 2022.]

What about the total daily step count? The ideal number in this study was 9,800 (see image above). People who walked these 4.6 miles slashed their dementia risk in half compared to those who walked just 1,000 steps per day. Even less-active participants who clocked 3,800 daily steps reduced their dementia risk by 25 percent. “Every step counts,” said del Pozo Cruz.

Curiously, among people who walked more, the risk for dementia seemed to rise again, but there were too few of them to make the associations statistically significant. Researchers led by Ahmad Aziz, German Center for Neurodegenerative Diseases, Bonn, also found that the brain benefits of exercise peaked in people who did mostly light to moderate activities rather than high-intensity ones (Fox et al., 2022). Aziz noted that they saw the greatest increase in brain volume, gray-matter density, and cortical thickness at the lower end of the physical activity spectrum.

The risk reductions seen around 10,000 steps were dramatic. Perneczky thinks this might be because the cohort was too young and the follow-up too short to accurately capture dementia risk. Many participants in this cohort fell outside the typical age range for dementia. Planalp and Okonkwo agreed. “For example, a 50-year-old followed up to age 57 may have remained cognitively intact at that point only to develop dementia in their next decade of life,” they wrote in a JAMA Neurology editorial. Johnathan Cooper-Knock, University of Sheffield, U.K., noted that most UK Biobank volunteers are relatively healthy compared to the general population. “It is possible that study participants are enriched for higher levels of daily exercise and lower levels of dementia without there being a causal link between the two,” he wrote (full comment below).

Still, Planalp and Okonkwo noted that other studies have found that being physically active in midlife leads to a lower incidence of dementia later in life, suggesting the authors may be on to something (Mar 2018 news).

Del Pozo Cruz plans to follow up with these UK Biobank participants after they’ve aged a few more years, and to analyze other cohorts that capture accelerometer and dementia data.—Chelsea Weidman Burke

Comments

- Elizabeth Planalp
  University of Wisconsin-Madison
- Ozioma Okonkwo
  University of Wisconsin, Madison
- Posted: 23 Sep 2022
In this article, we really were struck by the possibility that walking pace is perhaps more impactful for dementia prevention than the volume of steps taken; essentially, quality over quantity! Specifically, by walking for 30 minutes at a slightly more brisk pace (112 steps/minute), one could lessen their risk for dementia by more than 60 percent. This was particularly exciting because such a goal is likely much more attainable for a larger slice of the adult population than the customary “10,000 steps a day” mantra!

Admittedly, the cohort studied had a wide age range, and the follow-up was relatively short (mean seven years). However, it is important to highlight that 1) the brain changes that ultimately manifest as dementia begin a few decades prior to symptom onset and 2) studies have shown that adopting and sticking with a physically active lifestyle, even as “early” as midlife, leads to an appreciable reduction in the incidence of dementia in later life. This is a valuable insight that we hope stimulates scientific efforts to launch rigorous interventional and observational studies, in multi-ethnic cohorts, that will shed greater light on the role of lifestyle factors for mitigating the onset of dementia in an increasingly aging population.

View all comments by Elizabeth Planalp View all comments by Ozioma Okonkwo

- Robert Perneczky
  Ludwig-Maximilians-Universität München
- Posted: 23 Sep 2022
The study confirms the well-known hypothesis that being physically active reduces your dementia risk (and also your mortality, etc.). The important message of this study is that even walking shows this positive effect, not only more strenuous activities such as aerobic exercise. Other interesting findings are that apparently fewer steps than usually recommended are sufficient to reduce risk for dementia by 25 percent, and that not only the number, but also the intensity of steps matters.

I was surprised that even walking only 3,800 steps per day reduced dementia risk by 25 percent, and that the effect of walking 9,800 steps per day was this large (50 percent dementia reduction). This makes me wonder if the findings are somewhat biased by the relatively short follow-up time and the inclusion of younger individuals. Some stratification by age, sex, type of dementia, etc. would have been helpful to clarify in which groups the effects are largest.

The findings of this study will be helpful for defining the optimal “dose” of physical activity required for dementia prevention, both for future prevention studies and for developing better recommendations for maintaining lifestyles that support healthy brain aging.

Having said that, the study provides no new insight into the neurobiological mechanisms of the protective effects of physical activity, and should not be used to establish any causal links between healthy lifestyle choices and neurodegeneration/dementia. The young age of some participants together with the relatively short follow-up period of seven years also somewhat limits the value of the study, since many participants would not have been in the typical age range for dementia.

View all comments by Robert Perneczky

- Teresa Liu-Ambrose
  University of British Columbia
- Posted: 23 Sep 2022
It was nice to see the finding regarding intensity of physical activity. One hundred and twelve steps per minutes would be considered moderate, and this finding aligns with many randomized controlled trials of exercise that have focused on the effect of moderate-intensity exercise on both cognitive function and brain outcomes.

It was also nice to see that a lower dose than 10,000 is protective. Other research has shown this to a degree. For example, Kirk Erickson using the HABC data showed that walking a minimum of just 72 city blocks (which would translate to just under 1 km per day, which is 1,200 to 1,400 steps) could be neuroprotective 13 years later (Erickson et al., 2010).

One limitation is reverse causality. The authors aimed to minimize this by excluding those who developed dementia within two years in their sensitivity analysis. Nevertheless, results from the Whitehall Cohort Study previously showed that there is a decline in PA levels in the preclinical phase of dementia—nine years prior to diagnosis (Sabia et al., 2017).

In addition, prior research shows that walking speed significantly slows up to 10-12 years prior to mild cognitive impairment (Buracchio et al., 2010).

References:

Erickson KI, Raji CA, Lopez OL, Becker JT, Rosano C, Newman AB, Gach HM, Thompson PM, Ho AJ, Kuller LH. Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study. Neurology. 2010 Oct 19;75(16):1415-22. PubMed.

Sabia S, Dugravot A, Dartigues JF, Abell J, Elbaz A, Kivimäki M, Singh-Manoux A. Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study. BMJ. 2017 Jun 22;357:j2709. PubMed.

Buracchio T, Dodge HH, Howieson D, Wasserman D, Kaye J. The trajectory of gait speed preceding mild cognitive impairment. Arch Neurol. 2010 Aug;67(8):980-6. PubMed.

View all comments by Teresa Liu-Ambrose

- Johnathan Cooper-Knock
  University of Sheffield
- Posted: 23 Sep 2022
Borja del Pozo Cruz and colleagues have used UK Biobank accelerometer data to assess the relationship between measured daily "steps" and the incidence of all-cause dementia; they find evidence for a protective effect suggesting that a dose of ~9,800 steps optimally reduced risk of dementia (HR=0.49) without additional benefit from higher step counts.

One issue with the UK Biobank is a "healthy volunteer" selection bias (Fry et al., 2017). Therefore it is possible that study participants overall are enriched for higher levels of daily exercise and lower levels of dementia, without a causal link between the two. This would be optimally addressed by a population-scale cohort, such as already exists in Iceland and is increasingly being produced elsewhere. In the absence of such a cohort, the authors have used a dose-response relationship to infer causality rather than association.

What the UK Biobank cohort does have is large size. The authors used this to great effect, along with longitudinal clinical data, to perform what was in effect a prospective study: All of the participants were dementia-free at baseline, but 866 individuals developed dementia over just 6.7 years of follow-up.

The authors suggest an optimal dose of ~9,800 steps per day to reduce dementia, but they also note that their data for higher "doses" of steps was limited by lack of information. Indeed, the data as presented suggests that higher numbers of steps may be paradoxically associated with increased risk for dementia.

This study has many strengths, but to exactly define the relationship between daily step counts and dementia we await future studies, perhaps using population-based cohorts, perhaps meta-analyses across multiple cohorts, perhaps with more dementia cases across an older age group.

References:

Fry A, Littlejohns TJ, Sudlow C, Doherty N, Adamska L, Sprosen T, Collins R, Allen NE. Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population. Am J Epidemiol. 2017 Nov 1;186(9):1026-1034. PubMed.

View all comments by Johnathan Cooper-Knock

- N. Ahmad Aziz
  Population & Clinical Neuroepidemiology, German Center for Neurodegenerative Diseases (DZNE) & Dept. of Neurology, Bonn University Hospital
- Posted: 26 Sep 2022
Using data derived from a large subcohort of the UK Biobank study, Borja del Pozo Cruz and colleagues investigated the relation between wrist accelerometry-derived estimates of step count and intensity with incident dementia. The key finding of the study—that both higher step count and intensity of activity were associated with decreased risk of dementia—is well in line with our recent study, in which we found that physical activity dose and intensity are both independently associated with larger brain volumes, gray-matter density, and cortical thickness of several brain regions in participants of the Rhineland Study, a large prospective cohort study in Bonn, Germany (Fox et al., 2022).

I find it particularly interesting that the study by del Pozo Cruz et al. also found a non-linear association between physical activity and risk of incident dementia, with the greatest relative risk reduction seen at the lower end of the physical activity spectrum (del Pozo Cruz et al., 2022). This finding also mirrors our results, in that the greatest relative gains of physical activity dose and intensity with respect to markers of brain health were observed in this range (Fox et al., 2022). Together these findings thus indicate that, from a public health perspective, strategies to mobilize “couch potatoes” will be more efficient than promotion of physical activity in individuals who are already relatively active.

The main strengths of this paper are the relatively large sample size of 78,430 individuals whose data were included in the analyses, as well as the availability of follow-up data (median of 6.9 follow-up years) and additional information on a range of relevant covariates, including age, sex, body weight, diet, and many other cardiovascular risk factors. Moreover, through sensitivity analyses, the authors addressed the issues of residual confounding and reverse causation, which usually plague observational studies of this kind.

Nevertheless, with regard to the latter, exclusion of the first two years of follow-up may not have been sufficient as the prodromal stages of dementia are likely to last much longer. Furthermore, given the relatively young age of the participants, the follow-up period of about seven years appears quite short, as the risk of dementia increases exponentially with age. However, I suspect that a longer follow-up period may have shown an even stronger association between physical activity and dementia onset, as it is to be expected that a relatively larger proportion of young inactive individuals will develop dementia as compared to their more active counterparts. Longer follow-up studies are required to appropriately settle this issue.

The authors are to be commended for their timely and relevant work. Nevertheless, they could have made the paper even more interesting by addressing some key biological mechanisms. For example, did the effect estimates differ between the sexes? Were the effects similar for different forms of dementia, especially Alzheimer's disease and vascular dementia? What were the effects on longitudinal imaging-derived brain phenotypes? How much of the protective effects of physical activity was mediated through metabolic and cardiovascular risk factors?

Despite our increasing understanding of the beneficial effects of physical activity on brain health, many relevant questions remain to be addressed, but the results of this paper also underscore that for your brain, every step counts (Gogniat and Hvid, 2022).

References:

Fox FA, Diers K, Lee H, Mayr A, Reuter M, Breteler MM, Aziz NA. Association Between Accelerometer-Derived Physical Activity Measurements and Brain Structure: A Population-Based Cohort Study. Neurology. 2022 Sep 13;99(11):e1202-e1215. Epub 2022 Aug 2 PubMed.

Gogniat MA, Hvid LG. The Case for Light Physical Activity and Brain Health: Every Move Counts. Neurology. 2022 Sep 13;99(11):455-456. Epub 2022 Aug 2 PubMed.

View all comments by N. Ahmad Aziz