Age and gender both appear to affect the relationship between state fatigue and brain activation


To study the relationship between age and fatigue, Kessler Foundation researchers conducted a novel study using neuroimaging and self-report data.

Their findings were published online on May 9, 2022, in Frontiers in Human Neuroscience.

The authors are Glenn Wylie, DPhil, Amanda Pra Sisto, Helen M. Genova, Ph.D., and John DeLuca, Ph.D., of Kessler Foundation. All have faculty appointments at Rutgers New Jersey Medical School. Dr. Wylie is also a research scientist at The Department of Veterans’ Affairs War-related Injury and Illness Study Center at the New Jersey Healthcare System.

Their study is the first to report the effects of gender and age on both ‘state’ and ‘trait’ fatigue, and the first to report fatigue-related differences in brain activation across the lifespan and across gender during a cognitively fatiguing task.

“State” measure of fatigue assesses a subject’s instantaneous experience of fatigue at the time of testing; “trait” measure of fatigue assesses how much fatigue a subject experienced over a longer period of time, such as the previous four weeks.

Researchers collected data on trait fatigue and state fatigue from 43 healthy men and women aged 20 to 63 years. State fatigue was measured during fMRI scans while participants performed a cognitively challenging task.

The study was conducted at the Rocco Ortenzio Neuroimaging Center at Kessler Foundation, a specialized facility dedicated solely to rehabilitation research. They found that older individuals reported less state fatigue.

Dr. Wylie, director of the Ortenzio Center, commented: “Our neuroimaging data show that the role of middle frontal areas of the brain changes with age. Younger individuals may use these areas to combat fatigue, but this is not the case with older individuals. Moreover, these results suggest that women show greater resilience when faced with a fatiguing task.”

“This study is an important first step toward explaining some of the differences reported in the literature of fatigue, by showing that state and trait measures of fatigue measure different aspects of fatigue, and that age and gender both appear to affect the relationship between state fatigue and brain activation,” Dr. Wyle concluded.

While some qualities improve as we grow older (e.g., wisdom), other physical and mental abilities tend to decline later in life. For example, physical strength and processing speed both begin to wane as we pass middle age. Because sleep quality is another factor that commonly deteriorates with age (Åkerstedt et al., 2018), it might seem intuitive to expect fatigue to increase as age advances past middle age, but surprisingly the literature is mixed. Some studies have reported a greater prevalence of fatigue in the aged than in the young (Soyeur and Senol, 2011), while others have shown a decrease in fatigue with greater age (Åkerstedt et al., 2018).

While there is no clear, universally accepted definition of fatigue, it is widely agreed that fatigue is a state that is caused by exertion that results in changes in strategy or resource use (Kluger et al., 2013; Phillips, 2015). Fatigue also has several different subtypes, including cognitive or mental fatigue, psychological fatigue, and physical fatigue. The study described here is aimed at better understanding cognitive fatigue. Additionally, fatigue can be thought of as a trait—conceptualized as the extent to which one is prone to fatigue—or a state—the instantaneous experience of fatigue. While terms such as “fatigability” have been proposed to describe one’s propensity to become fatigued (Zijdewind et al., 2016), we prefer the state vs. trait distinction, given the long history of state and trait measures in the neuropsychological literature [e.g., Spielberger et al. (1970), Endler and Parker (1990), and Chiappelli et al. (2014)].

Fatigue is a troubling symptom in neurological disorders such as Multiple Sclerosis, but it is also widespread in the general population, with a prevalence of up to 45% in healthy individuals (Junghaenel et al., 2011; Galland-Decker et al., 2019). Much of the existing literature on fatigue points to fatigue differentially affecting younger vs. older populations, as well as males vs. females. Sleep problems and fatigue are often linked, such that those who get less sleep experience greater fatigue (Avlund, 2010). Several studies point to quality of sleep decreasing with age (Sivertsen et al., 2009; Mander et al., 2017), which suggests that fatigue may increase with age. However, fatigue and sleep are distinct constructs, and fatigue has not been found to consistently increase with age in the literature. One potential explanation for mixed findings in the literature examining age and fatigue is that different studies have used different fatigue assessments. For instance, Åkerstedt et al. (2018) used a “state” measure of fatigue (assessing subjects’ instantaneous experience of fatigue at the time of testing) and found that fatigue declined with age, even despite age-related increases in sleep problems. Conversely, Soyeur and Senol (2011) used a “trait” measure of fatigue (assessing subjects’ assessment of how much fatigue they had experienced over the previous four weeks) and discovered a high prevalence of fatigue in elderly people living in a rest home. Furthermore, in a study looking at fatigue in both cancer survivors and general populations using a trait fatigue measure, older participants (>64) reported greater fatigue than younger participants (Butt et al., 2010).

Another potential source of variance in the literature is gender. A few studies have found women to report greater trait levels of fatigue than men (Butt et al., 2010; Engberg et al., 2017). Biological factors, including menstruation and pregnancy, compounded with social context (e.g., taking care of young children), may result in elevated fatigue in females as opposed to males (Bensing et al., 1999). Avlund (2010) used trait measures to show that women reported more fatigue than men, but only when they were 70 years old or older. This suggests that age may interact with gender such that men and women show different propensities to trait fatigue across the lifespan. However, whether this also is found with state fatigue measures is currently unknown.

Here, we investigated the effects of age on both state and trait measures of fatigue, while also looking at the effects of gender. To study state fatigue, we induced cognitive fatigue by asking participants to repeatedly perform a demanding working memory paradigm (the 2-back condition of the N-back paradigm). We have used this approach to induce fatigue in healthy and clinical populations in previous work (Wylie et al., 2017a,2019; Chen et al., 2020b). We also included neuroimaging metrics—acquired during the fatigue induction task—because we have found these metrics to be important indexes of fatigue in other work (Wylie et al., 2017b,2020, 2021). Based on pre-existing literature, we hypothesized that trait measures of fatigue would show increased fatigue with age, while state measures would result in decreasing fatigue with age. We also hypothesized that women would report more fatigue than men on both state and trait fatigue measures. While there is evidence to suggest that older adults and younger adults may rely on different brain regions when performing a cognitive task (Crowell et al., 2020), there are no neuroimaging studies to our knowledge that have looked at the relationship between cognitive fatigue and brain activity across different ages.

The ventromedial prefrontal cortex, the dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, and the anterior insula are regions that have been linked to cognitive fatigue [e.g., Wylie et al. (2019, 2020) and Chen et al. (2020a,b)], so we expected differences in activation in these areas between younger and older individuals, as well as between males and females. In order to better understand the neural substrates of age and gender on fatigue, we investigated where in the brain increasing levels of fatigue correlated with brain activation, accounting for age and gender.

Original Research: Open access.
Fatigue Across the Lifespan in Men and Women: State vs. Trait” by Glenn R. Wylie et al. Frontiers in Human Neuroscience


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