It has been established that purpose in life is related to cognitive function and predicts cognitive decline in elderly individuals in analyses based on almost 1000 persons with up to 12 follow-up assessments of cognition.21–24
Here, we sought to examine the neurobiologic basis of this association. In a cohort of almost 250 older persons with detailed cognitive testing and autopsy data, we found that higher levels of purpose in life reduced the deleterious effects of AD pathologic changes on cognitive function. This protective effect was observed for a global measure of the changes as well as a more molecularly specific measure of tangle pathologic changes. In addition, the protective effect of purpose in life on cognition persisted after controlling for various potentially confounding variables. Moreover, higher levels of purpose in life reduced the deleterious effect of AD pathologic changes on the rate of cognitive decline. These findings suggest that purpose in life provides neural reserve by protecting against the harmful effects of AD pathologic changes on cognitive function in elderly persons.
The concept of reserve applies to many physiological systems; that is, most systems can sustain extensive organ damage before clinical manifestation of deficits. The brain also can tolerate the accumulation of pathologic changes without expressing them clinically. This is evident from numerous clinicopathologic and, more recently, neuroimaging studies1,9,36,39–45
that have demonstrated the nearly ubiquitous accumulation of AD pathology even among older persons without overt cognitive deficits. Identifying determinants of neural reserve has proved to be challenging, in part because reserve is multifactorial and few studies have the specimen data needed to directly test neurobiologic hypotheses. However, recent evidence6–10,37
suggests that psychosocial variables, such as educational level and social networks, may provide reserve by reducing the deleterious effects of AD pathologic changes on cognition. It is now widely recognized that AD has a long preclinical phase during which the pathologic changes accumulate and cognitive function declines, and the identification of factors that protect against the deleterious effects of this process may help combat the large and rapidly increasing public health challenge posed by AD.46
Purpose in life, an indicator of human thriving, has long been hypothesized to be an important determinant of health outcomes.11,15,20,30
In recent years, prospective studies19,21
have shown that purpose in life and related aspects of well-being are associated with a substantially reduced risk of adverse cognitive health outcomes, including the risk of AD and its precursor, mild cognitive impairment, as well as a slower rate of cognitive decline even among older persons without AD or mild cognitive impairment. Furthermore, purpose in life is associated with a reduced risk of incident disability and death.22,23
Initial evidence suggests that purpose in life may also be modifiable, rendering it a potential treatment target.47
To date, however, we are not aware of any study that has examined the neurobiologic basis of the protective effect of purpose in life.
Purpose in life is a complex and multifaceted trait like construct, and it is likely that purpose in life works via complex mechanisms to provide reserve. The ability to find meaning in life’s experiences and develop a sense of direction and intentionality requires self-reflection, synthesis of diverse experiences into a narrative, awareness of one’s role and potential within the broader context, establishment of goals and priorities, and focus. Furthermore, having a sense of purpose is thought to generate motivation to behave in ways consistent with one’s purpose and work toward goals.11,48,49
Purpose in life is related to aspects of psychological health, including happiness, satisfaction, personal growth, and better sleep,14,17,18,50
and associations between purpose in life and aspects of personality (ie, neuroticism, extraversion, and conscientiousness), as well as depressive symptoms, have been reported.23,48,50
Although few studies have examined the extent to which purpose is related to engagement in health-promoting behaviors, results of a meta-analysis48
showed that a higher level of purpose in life was associated with better health, everyday competence, social integration, participation in the labor force, and socioeconomic status among middle-aged and older persons. Purpose in life also is associated with better treatment outcomes for persons with addiction.51
Taken together, the available data suggest that persons with higher levels of purpose tend to be goal-oriented and resilient, and their active pursuit of goals likely enhances the strength and efficiency of neural systems. Furthermore, although purpose in life may be most beneficial in aging (when cognitive and other resources are diminishing), elderly persons who report higher levels may have acquired over their lifespan an expanded repertoire of behaviors that facilitate neurocognitive development.21
Although one could speculate from this that purpose in life may somehow prevent the accumulation of AD pathologic changes, we did not find evidence of a direct association with the changes. This may indicate that, instead of preventing the accumulation of pathologic changes, purpose in life contributes to the development of efficient neural systems that allow one to maintain cognition even in the face of accumulating characteristics of AD.
Another possibility is that purpose in life may reduce the association of AD pathologic features with cognition by helping to invoke compensatory processes in the face of accumulating damage. The current study was motivated in part by a clinicopathologic study10
that showed that social networks modified the association of AD pathologic characteristics with cognition. Given that the development of social networks includes brain regions not involved in traditional aspects of cognition, such findings may indicate that social cognitive brain regions are brought online to maintain cognition in the face of accumulating AD pathologic changes in regions that support traditional cognitive abilities.52,53
It is noteworthy that higher levels of purpose in life are associated with less negative affect, more positive social relations, and better sleep and other health outcomes.15,17,47
Although controlling for covariates such as neuroticism, social networks, and depressive symptoms did not affect our findings, it seems intuitive that the noncognitive abilities that allow some people to readily derive meaning from life’s experiences and persist through challenging events might also provide reserve by increasing the availability of social cognitive or other noncognitive neural networks that can help preserve cognition even as AD pathologic changes accumulate.
Notably, the beneficial effect of purpose in life was most evident in analyses with tangles as compared with amyloid. Previous studies54
have shown that tangles are more strongly associated with cognitive function than amyloid. This generally was true in our data, and the modifying effects may have been most evident in analyses with tangles because of their relatively stronger association with cognition. Similar differential effects were reported in 2 studies; one of these55
showed that processing resources protected against the deleterious effects of AD pathologic changes on other cognitive systems, particularly in analyses of tangles, and the other10
showed a similar effect with social networks. These findings likely suggest that tangles are a major driver of cognitive impairment in old age and that the association of tangles with cognition is the predominant beneficiary of factors that provide reserve.
Our study has several strengths, including the ability to relate purpose in life to several alternative and highly specific measures of AD pathologic characteristics and detailed assessments of cognition conducted annually and proximate to death in a single cohort with very high rates of follow-up and brain autopsy; this allowed for testing of specific hypotheses about reserve with a high degree of internal validity. Furthermore, uniform structured procedures were followed, with blinding to previously collected data and of personnel collecting postmortem data to clinical data. The study also has limitations; in particular, data from observational studies do not allow for determination of causal effects. Further studies are needed to determine whether purpose in life may be useful as a target for interventions aimed to reduce the public health burden of cognitive decline in aging and AD.