Background
Loss of motor function is a common consequence of aging and is associated with adverse health consequences[
1‐
5]. The specific motor abilities impaired in old age vary and encompass a wide spectrum including loss of muscle strength and bulk, balance, dexterity and reduced gait speed which can occur even in the absence of overt diseases[
6‐
8]. By 2030, 20% of Americans, roughly 72 million people, will be 65 years of age or older[
9], and by the age of 80 years or older, the fastest growing segment, 40% or more will have some loss of motor abilities[
10]. Identifying risk factors for age-related motor decline is an essential first step for the rational development of therapeutic interventions to reduce the growing burden of motor impairment in our rapidly aging population.
Although risk factors for common diseases known to cause motor dysfunction such as stroke are recognized, few risk factors for idiopathic motor decline in old age have been identified. While the benefits of physical activity on motor function is well-known[
11‐
14], there is increasing recognition of the importance of lifestyle and psychosocial factors for healthy aging in older persons[
15,
16]. Increased social engagement as measured by the frequency of late-life social activities in older individuals is associated with longevity and a decreased risk of dementia, while being alone is associated with disability and a more rapid rate of motor decline[
15‐
18].
Recent studies suggest that not only being alone, but also self-perceived isolation i.e., loneliness, has a detrimental effect on a wide range of physical functions including sleep, immune responses, level of physical activity, cognition and risk of Alzheimer's disease[
19‐
23]. These reports suggest that not only being alone, but also loneliness might be related to motor decline in old age. Loneliness could serve as a marker for other processes such as inflammation or cardiovascular diseases which contribute to motor decline. Alternatively, loneliness may be a causal risk factor for motor decline. For example, since loneliness is associated with poor self-regulation, it may lead to behavioral changes such as decreased exercise or changes in eating habits which could in turn cause motor decline[
24]. Furthermore, in addition to functional and structural links between social and motor behavior, social activity--like physical activity-may contribute to improved motor function by increasing neuronal plasticity and protecting against tissue damage[
25]. Despite these reports, little is currently known about whether simply feeling lonely or disconnected from others and dissatisfied with social interactions is associated with motor decline in old age[
23,
24,
26].
To test the hypothesis that feeling alone is associated with the rate of motor decline in old age, we used data from 985 older participants in the Rush Memory and Aging Project who underwent annual detailed examinations for up to 12 years[
27]. At enrollment participants underwent assessment of loneliness with a modified version of the de Jong-Gierveld Loneliness Scale. They also underwent baseline and annual detailed exam which included assessment of motor strength and performances[
18,
23]. We used linear mixed-effect models to test the hypothesis that a higher level of loneliness at study entry was associated with a more rapid rate of motor decline during the course of the study. In further analyses, we examined whether including terms for both feeling alone and being alone (based on the frequency of participation in social activities and size of social network), showed separate effects with the rate of motor decline when considered together in a single model. Finally, we examined whether the association of loneliness and motor decline was confounded when controlling for depressive symptoms, cognition, other leisure activities and chronic conditions.
Discussion
In a cohort of nearly 1000 older persons free of dementia at baseline, we found that a higher level of loneliness (i.e., self-perceived isolation) was associated with a more rapid rate of motor decline in community-dwelling elders. This association persisted even after controlling for social isolation as measured by frequency of social activities and social network size, as well as a wide range of potential confounding variables including depression, cognition, physical and cognitive activities and chronic conditions. In several sensitivity analyses, this association was unchanged after controlling for baseline disability as well as a history of stroke or Parkinson's disease.
Accumulating evidence suggests that social isolation as measured by frequency of late-life social activities or size of social network is related to adverse health outcomes such as longevity and risk of dementia, as well as the rates of cognitive and motor decline[
18,
39]. However, not only social isolation but also self-perceived isolation i.e., loneliness, has a detrimental effect on a wide range of functions including sleep, immune responses, level of physical activity, cognition and risk of AD[
19‐
23]. A prior study reported that loneliness is associated with decreased physical activity or exercise, but this report analyzed physical activity levels which were based on self-report and did not assess levels of other late-life leisure activities[
24]. The current study extends prior reports in several important ways. First we report that loneliness is related to the rate of motor decline derived from objective motor performances tested annually for up to 12 years. Second, we show that when self-perceived isolation and social engagement as measured by late-life social activities are considered together in the same model, both are relatively independent predictors of the rate of change in motor function. Third, the association between loneliness and motor decline persisted even after controlling for a wide range of leisure activities including social, physical and cognitive activities, depressive symptoms and other possible confounding covariates as well as after controlling for baseline disability or history of stroke and PD. These results have important translational implications because they suggest that public health interventions designed to maintain motor function in older adults need to consider the possible role of self-perceived isolation as a modifiable risk factor, which might increase the efficacy of other efforts implemented to decrease the burden of age-related motor decline.
The basis for the association between loneliness and motor decline is uncertain. Human social behavior is generated in the brain through interconnected brain structures which process different elements of sociocognitive and socioaffective information which are eventually integrated and translated into motor action[
40]. Loneliness and motor decline may be associated since both depend on the structural and functional integrity of neural systems underlying the initiation, planning and execution of motor action and might both be affected by common pathophysiological processes. Moreover, recent work suggests that mirror neurons are thought to play important roles not only for generating movement but also for a wide range of activities essential for social interaction including self-awareness and empathy. Further work is needed to elucidate the role of mirror neurons in human behavior, but this raises an intriguing possibility that mirror neurons might provide a structural causal linkage between self-perceived isolation i.e., loneliness and motor actions[
41]. Motor function is necessary for social behavior and is thus an integral component of one's social body. Recent work suggests that social pain may function as an aversive signal, like physical pain, signaling the need to take action against factors which can damage or harm one's social body[
42]. Thus, loneliness, as an expression of social pain, may be associated with motor decline because it serves as an aversive signal for factors which may impair motor function and the capacity for social behavior.
Loneliness may represent a true risk factor which causes motor decline. For example, loneliness is associated with poor self-regulation which may lead to behavioral changes such as decreased exercise or changes in eating habits causing motor decline[
24]. Alternatively, there may be common pathophysiological processes which affect both loneliness and motor impairment in old age. Loneliness is associated with a wide range of physiologic changes such as higher levels of cortisol, increased inflammation, immune dysfunction, increased cardiovascular disease and impaired sleep patterns which may all contribute to both loneliness and motor decline [
20,
21,
43‐
45]. In addition, to the functional and structural links between social and motor behavior, it is noteworthy that the benefits of social activity--like physical activity-may contribute to improved motor function by increasing neuronal plasticity and protecting against ischemic or neurotoxic damage[
25]. Animals subjected to social isolation show decreased dendritic arborization in the hippocampus and prefrontal cortex and down-regulation of brain-derived neurotrophic factor which may be associated with impaired plasticity degrading the ability to compensate for the accumulation of age-related pathologies[
42]. Similar findings can be seen in humans with decreased levels of physical activity which also is related to the motor decline in old age. Finally, recent work suggests that loneliness is associated with alteration in human genome-wide transcriptional activity that might account for increased inflammatory diseases in loneliness[
44,
45]. The current cohort study cannot distinguish between the existence of a pathophysiological process affecting both loneliness and motor decline or the possibility that motor decline that is caused by loneliness. Thus, further work is needed to clarify the neurobiology underlying the association between loneliness and age-related motor decline as well as the degree to which other psychosocial factors may contribute to motor decline in the elderly.
Our study has some limitations. Most importantly, inferences regarding causality must be drawn with great caution from observational studies. While the findings were robust to potential confounding variables and sensitivity analyses, the potential for reverse causality cannot be excluded. Further, it is possible that residual confounding from an unmeasured latent variable is related to both loneliness and motor decline. Other limitations include the selected nature of the cohort, the self-report measures of chronic diseases and leisure activities and that this study did not assess simultaneous change in both loneliness and motor decline.
However, several factors increase confidence in our findings. Perhaps most importantly, the study enjoys high follow-up participation reducing bias due to attrition. In addition, loneliness was assessed among persons without dementia based on a detailed clinical evaluation and motor function was evaluated as part of a uniform clinical evaluation and incorporated many widely accepted and reliable strength and motor performance measures; strength testing was done in all four extremities, and motor performances were tested in both the arms and legs. The aggregation of multiple measures of motor function into a composite measure yields a more stable measure of motor function and increases statistical power to identify associations. In addition, a relatively large number of older persons representative of the general population were studied, so that there was adequate statistical power to identify the associations of interest while controlling for several potentially confounding variables.
Acknowledgements
This work was supported by the Illinois Department of Public Health (James), the National Institute on Aging grants R01AG17917 (Bennett), R01AG24480 (Buchman), R01AG034374 (Boyle), and the Robert C. Borwell Endowment Fund (Bennett).
We thank all the participants in the Rush Memory and Aging Project. We also thank staff employed at the Rush Alzheimer's Disease Center including Traci Colvin, RN and Tracey Nowakowski, BA for project coordination; Barbara Eubeler, Mary Futrell, Karen Lowe Graham, MA and Pamela Smith, MA for participant recruitment; Liping Gu, MS for statistical programming; John Gibbons, MS and Greg Klein, BS for data management.
Competing interests
The authors (A. S. Buchman, MD, P. A. Boyle, PhD, R.S. Wilson, PhD, B. James, PhD, S. E. Leurgans, PhD, Arnold, MD and D.A. Bennett, MD) have no conflicts of interest to report.
Authors' contributions
ASB, MD had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis and affirms that everyone who contributed significantly to the work has been listed. He was involved with study concept and design, analysis and interpretation of data, and preparation of the manuscript. Drs. ASB, PAB, RSW, BDJ, SEL, SEA, and DAB were involved in study concept, acquisition of data, assisted with the analysis and interpretation of the data, and critically revised the manuscript for important intellectual content. All authors have seen and approved the final version.