A purpose “driven” life: Is it potentially neuroprotective?

It may be time to ponder over the habit of setting goals and directions in life. Investigators from the Rush Memory and Aging Project administered a questionnaire that measured purpose in life to over 900 non-demented elderly persons¹. They then prospectively followed the cohort for an average of about 4 years to the outcomes of incident Alzheimer’s disease (AD), mild cognitive impairment (MCI), and time related changes in cognitive function or a censoring variable. They report that those with higher scores on the scale that measures purpose in life (> 90^th percentile vs < 10^th percentile) have a 52 % decreased risk of AD (HR, 0.48; 95% CI, 0.33–0.69; p <.001). This observation was made after adjusting for age, sex and education. The association remained significant after making additional adjustment for depressive symptoms (HR, 0.60; 95% CI, 0.39–0.92; p = .02). In elderly persons that are normal at baseline, they also observed that having purpose in life was associated with a slower rate of decline in cognitive function.

What do we learn from this study?. In order to answer this question, three issues need to be clarified: first, we need to understand what exactly is measured by using the purpose in life questionnaire which is derived from the Psychological Well-Being Scale². The Psychological Well-Being Scale operationalized various theories and philosophical views that came up with an alternative explanation to the Freudian perspective that primarily viewed the world through the lens of anxiety, conflict, neurosis, and the presence or absence of psychiatric disorders². The Psychological Well-Being Scale is a self-reported scale that measures six dimensions of well-being, one of which is purpose in life which is defined as having goals and objectives that give life meaning and direction. The remaining five dimensions are self-acceptance (the capacity to see and accept one’s strengths and weaknesses), personal growth (a feeling that one’s potentials and talents are being realized over time), positive relations with others (having close, valued connections with significant others), environmental mastery (being able to manage the demands of everyday life) and autonomy (having the strength to follow personal convictions, even if they go against conventional wisdom)². The Rush Memory and Aging Project used one of the six dimensions of well-being i.e. the purpose in life scale that has 10 questions such as “Some people wander in life aimlessly but I am not one of them”; “ I enjoy making plan for the future and working them to a reality” etc. The Rush study did not measure the hedonic construct which is defined as: 1-presence of happiness. 2- Presence of positive affect and 3- absence of negative affect³. Like all self- reported scales, recall bias is one of the key limitations of this study. However, the authors have conducted various analyses to measure and account for potential sources of bias. Additionally, the scale has a very well established reliability and validity hence, one can safely conclude that the findings of the Rush study are reasonably valid.

The second issue pertains to the interpretation of the observed associations between the exposure of interest (purpose in life) and the outcomes of interest (AD or MCI or time related changes in continuous cognitive measures). To some extent, the prospective cohort design enables one to make etiologic inferences given the occurrence of exposure prior to the outcome. One can argue that the findings might have been primarily driven by mild, undiagnosed AD cases. This question was addressed by the investigators by conducting a sensitivity analysis where in they excluded participants diagnosed with AD during the first three years of follow up. Having purpose in life remained significantly associated with a decreased risk of AD. Therefore, “reverse causality” can not explain the association between purpose in life and decreased risk of incident AD or MCI. Replication of these findings by a similar prospective study, preferably, with a longer follow up duration will strengthen the etiologic inferences that one makes from the Rush cohort study. Third, if we assume that there is an etiologic association between a purpose driven life and decreased risk of AD or MCI then we are curious to know as to how setting a goal and making a reasonable effort to implement that goal leads to actual physiological changes that prove to be ‘neuroprotective’. The Rush Memory and Aging study has not addressed mechanism of action. A cross-sectional study involving elderly women aged 75 and above indicated that higher scores on self-development and purposeful engagement are associated with lower levels of salivary cortisol, cardiovascular risk, and pro-inflammatory cytokines³. However, in a cross-sectional study, the direction of causality between an exposure of interest and an outcome of interest can not be determined. Therefore, future prospective studies need to be conducted to examine any potential etiologic association between purpose driven life and biological markers. In the absence of data, we are left with making sensible theoretical explanations. A person who derives meaning from life’s experiences and whose behavior is guided by a sense of intentionality and goal directedness may engage in health promoting activities such as regular physical exercise that could eventually prove to be neuroprotective thus leading to a decreased risk of cognitive decline⁴. Alternatively, it may be possible that a purpose driven life may be directly ‘neuroprotective’ via yet unknown physiological mechanisms³.

Regardless of the underlying mechanism of action, at an individual level, setting goals and deriving meaning from life’s experiences is not a harmful behavior. Therefore, the authors make a sensible suggestion that purpose in life is a modifiable factor that can be enhanced by engaging in goal directed behaviors. However, these findings need to be replicated by other prospective cohort studies or even clinical trials in order to recommend large scale preventive measures based on enhancing purpose driven life.