Life expectancy has dramatically increased over the past decades, with the global life expectancy increasing by 5 years between 2010 to 2016 (Gulland, 2016). Since age represents a key risk factor for dementia (Niu et al., 2017), it has been estimated that the global dementia prevalence will almost triple within the next 30 years (Nichols et al., 2022). Alzheimer’s disease (AD) is the most common form of dementia (Alzheimer’s Association, 2022, Barker et al., 2002) and is characterized by ß amyloid deposition, pathologic tau, and neurodegeneration in the brain (Jack et al., 2018). Surprisingly, post-mortem brain examinations revealed that about one quarter of individuals whose brains have severe AD pathology were not diagnosed with AD during their lifetime (Riley et al., 2002, Roe et al., 2007). Since dementia represents a major challenge for societies all over the world (Nichols et al., 2022), it is essential to better understand what makes some individuals resistant to the negative effects of brain pathology on clinical outcomes.

The concept that describes differential susceptibility to age- and disease-related brain pathology has been termed cognitive reserve (CR) (Stern, 2009). According to this concept, individuals with higher CR can withstand more brain pathology, such as cortical thinning, volume loss or accumulation of amyloid plaques and tau tangles, before experiencing cognitive impairment. The underlying neural mechanisms may be that individuals with higher CR have neural networks with greater efficiency and/or capacity and/or they are better in compensating for brain pathology by using alternate brain networks (Stern and Barulli, 2019). Among the best-studied factors underlying CR are high educational and occupational attainment, intelligence, as well as participation in leisure activities of intellectual or social nature (Opdebeeck et al., 2016, Tucker and Stern, 2011). To test whether a factor underlies CR, the rigorous CR-test outlined by the “Reserve and Resilience” collaboratory (https://reserveandresilience.com/) can be used. The collaboratory’s CR test states that factors associated with CR should explain variance in cognitive performance beyond the variance explained by brain status and/or moderate the brain status-cognition relationship (Stern et al., 2023, Stern et al., 2020). Since personality may influence leisure behavior, e.g., the extent to which somebody pursues intellectual or social leisure activities or takes advantage of new learning opportunities, personality may also underlie CR (Ihle et al., 2019, Trapp et al., 2019). If so, personality should explain variance in cognitive performance beyond the variance explained by brain status and/or moderate the brain status-cognition relationship.

Personality can be described by the 5 factors (BIG5) openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism (Costa and McCrae, 1992). A recent meta-analysis on personality-cognition relationships, which included data from millions of individuals from 1,976 independent samples, found that openness and some facets of conscientiousness and extraversion were positively associated with several cognitive abilities, while neuroticism was negatively associated with most cognitive abilities (Stanek and Ones, 2023). Agreeableness showed very weak associations with cognition (Stanek and Ones, 2023). Further, higher openness to experience, higher conscientiousness, lower extraversion, and lower neuroticism have been found to be related to less cognitive decline over time (Luchetti et al., 2016). Additionally, previous studies reported that individuals with AD have a distinctive personality profile compared to healthy controls, as expressed by higher scores on the neuroticism scale (D’Iorio et al., 2018, Wilson et al., 2006) and lower scores on the conscientiousness (Wilson et al., 2007), extraversion and openness scales (D’Iorio et al., 2018). However, the question whether personality is a factor underlying CR has been addressed in few studies so far (Colombo et al., 2020, Graham et al., 2021, Tautvydaitė et al., 2017, Terracciano et al., 2013). Studies on the relationship between personality and cognition provide an important basis for this question, but they do not take into account brain status. Thus, only the question of whether personality traits underlie CR can shed light on whether certain personality traits have a protective function. A protective function implies that certain personality traits can modify the effects of age- and disease-related brain pathology on cognition. Alternatively, in the absence of a modifying effect, whether personality traits have an effect on cognition that cannot be explained by brain status.

Colombo et al. (2020) investigated in 100 healthy participants aged 50 to 90 years the relationship between personality and CR and found that higher openness as well as some personality subfacets were related to higher CR. In this study, brain status was not considered as CR was assessed using the CoRe-T measurement, which consists of a self-report section on educational level, leisure activities, and occupation history, and two tasks assessing fluidity of thoughts.

In an autopsy study, Terracciano et al. (2013) investigated whether individuals with AD pathology who were asymptomatic during their lifetime differed from individuals diagnosed with AD in terms of personality. Personality was measured 1 to 30 years before death (mean (SD)=15 (7) years). They found that the asymptomatic individuals had higher conscientiousness scores and lower neuroticism scores than the individuals diagnosed with AD (Terracciano et al., 2013). This finding suggests that high conscientiousness and low neuroticism are related to high CR. Compared to the study by Colombo et al. (2020), this study has the advantage that they tested directly whether personality moderates the association between AD pathology and clinical diagnosis. However, in this study the outcome was a diagnosis of AD versus no diagnosis, which is a dichotomous rather than a continuous outcome. Using a dichotomous variable rather than a continuous outcome to classify how successfully someone has aged cognitively is an oversimplification, as individuals without a diagnosis of AD can vary widely in their cognitive performance and some individuals may also fall in the other category depending on the diagnostic criteria used.

Tautvydaitė et al. (2017) also focused on AD pathology and examined whether premorbid personality moderates the relationship between cerebrospinal fluid (CSF) markers of AD (amyloid beta1–42, phosphorylated tau, and total-tau) and global cognition or explains additional variance in cognition after correcting for these CSF AD markers. They found that premorbid conscientiousness, agreeableness, and neuroticism moderated the relationship between CSF biomarkers and cognition. Here, CSF biomarkers were almost unrelated to cognitive performance if the score for conscientiousness was high, the agreeableness score was low, or the neuroticism score was medium. Further, higher premorbid openness predicted better cognitive performance after correcting for CSF biomarkers. However, in addition to healthy controls (N=44), their study sample consisted of individuals with mild cognitive impairment (MCI) (N=57) and patients with mild AD (N=9). That is why participants’ proxies were asked to retrospectively rate participants’ personality traits at the time five years prior to onset of symptoms, which might be subject to memory bias.

Graham et al. (2021) also treated CR as a continuous variable by regressing cognitive performance onto various measures of brain pathology and then extracting the residual as a measure of CR. Like Terracciano et al. (2013), they found in their autopsy study that low neuroticism was cross-sectionally associated with higher CR and that high conscientiousness was longitudinally associated with higher CR. However, the study sample had a high mean age as participants were recruited either from retirement communities and senior housing facilities (Rush Memory and Aging Project) or from church (older nuns, priests, and brothers; Religious Orders Study). Personality is considered to be rather stable but changes in personality still occur across the adult lifespan (Wrzus and Roberts, 2017). Thus, it is unclear whether personality can also underly CR in younger age. Further, in this study a global cognition score was used, leaving the question open whether personality can account for the discrepancy between brain pathology and performance in all or only certain cognitive domains.

This project therefore uses both cross-sectional and longitudinal data to investigate whether personality represents a factor underlying CR in individuals aged 19 to 80 years who had at the time of recruitment no medical or psychiatric conditions (including MCI) that might affect cognitive performance. The inclusion of participants from a wide age range provides new insights into the question of whether personality is a factor underlying CR even at a young age. Further, screening for conditions that may affect cognition should prevent bias in personality assessment. In addition, we used a very rigorous, state-of-the-art methodology to assess whether personality traits underlie CR. To apply the CR-test proposed by the “Reserve and Resilience” collaboratory rigorously, we created brain status variables that explain the maximum amount of variance in cognitive performance. As outcome variables, we used four cognitive domain scores that have been measured on a continuous scale rather than a global dichotomous outcome. The use of four cognitive domain scores rather than a global cognition score has the added advantage of providing insight into whether personality traits can account for the discrepancy between brain pathology and performance in all or only certain cognitive domains.

Overall, this study contributes to a better understanding of which personality traits are favorable and associated with higher CR across the adult lifespan, which may also help to identify individuals at higher risk of developing dementia. Based on the findings from previous studies, we hypothesize that high openness (Colombo et al., 2020, Tautvydaitė et al., 2017), high conscientiousness (Graham et al., 2021, Tautvydaitė et al., 2017, Terracciano et al., 2013), and low neuroticism (Graham et al., 2021, Terracciano et al., 2013) underlie CR and are therefore associated with better cognitive performance and lower cognitive decline after accounting for brain status and/or moderate the brain status-cognition relationship.