ORIGINAL RESEARCH published: 28 March 2022 doi: 10.3389/fpsyg.2022.835415 Sense of Coherence Mediates the Relationship Between Cognitive Reserve and Cognition in Middle-Aged Adults Gabriele Cattaneo 1,2,3* , Javier Solana-Sánchez 1,2,3 , Kilian Abellaneda-Pérez 4,5 , Cristina Portellano-Ortiz 4,5 , Selma Delgado-Gallén 1,2,3 , Vanessa Alviarez Schulze 1,2,3,6 , Catherine Pachón-García 1,2,3 , H. Zetterberg 7,8,9,10,11 , Jose Maria Tormos 1,2,3 , Alvaro Pascual-Leone 1,12,13 and David Bartrés-Faz 1,4,5 1 Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Barcelona, Spain, 2 Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, 3 Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain, 4 Departament de Medicina, Facultat de Medicina i Ciències de la Salut i Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain, 5 Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain, 6 Departamento de Ciencias del Comportamiento, Escuela de Psicología, Universidad Metropolitana, Caracas, Venezuela, 7 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden, 8 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden, 9 Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom, 10 UK Dementia Research Institute at UCL, London, United Kingdom, 11 Hong Kong Center Edited by: for Neurodegenerative Diseases, Shatin, Hong Kong SAR, China, 12 Hinda and Arthur Marcus Institute for Aging Research Mark J. Campbell, and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA, United States, 13 Department University of Limerick, Ireland of Neurology, Harvard Medical School, Boston, MA, United States Reviewed by: Ludmila Zajac-Lamparska, In recent years, supported by new scientific evidence, the conceptualization of cognitive Kazimierz Wielki University, Poland Riccardo Manca, reserve (CR) has been progressively enriched and now encompasses not only cognitive Brunel University London, stimulating activities or educational level, but also lifestyle activities, such as leisure United Kingdom physical activity and socialization. In this context, there is increasing interest in *Correspondence: Gabriele Cattaneo understanding the role of psychological factors in brain health and cognitive functioning. gcattaneo@guttmann.com In a previous study, we have found that these factors mediated the relationship between CR and self-reported cognitive functioning. In this study, we have confirmed an Specialty section: This article was submitted to association between two important constructs included in the psychological wellbeing Cognition, and salutogenic models, “purpose in life” and “sense of coherence,” CR, as assessed a section of the journal Frontiers in Psychology using a questionnaire, and cognitive functioning, as evaluated using a comprehensive Received: 14 December 2021 neuropsychological battery. Results from 888 middle-aged healthy participants from Accepted: 02 February 2022 the Barcelona Brain Health Initiative indicate that both sense of coherence (SoC) and Published: 28 March 2022 CR were positively associated with verbal memory, reasoning and attention, working Citation: memory, and global cognition. Moreover, the relation between CR and cognitive Cattaneo G, Solana-Sánchez J, Abellaneda-Pérez K, functioning in the different domains is partially mediated by SoC. When we controlled Portellano-Ortiz C, Delgado-Gallén S, for brain integrity, introducing into the model neurofilament light chain measures, the Alviarez Schulze V, Pachón-García C, Zetterberg H, Tormos JM, mediator role of SoC was confirmed for reasoning and attention and global cognition. Pascual-Leone A and Bartrés-Faz D However, purpose in life was not associated with cognitive functioning. These results (2022) Sense of Coherence Mediates reveal the central role of the SoC construct, which mediates the association between the Relationship Between Cognitive Reserve and Cognition classic CR estimates and cognitive functions, potentially representing a modifiable target in Middle-Aged Adults. for interventions that aim to promote brain health. Front. Psychol. 13:835415. doi: 10.3389/fpsyg.2022.835415 Keywords: sense of coherence, purpose in life, cognition, cognitive reserve, brain health Frontiers in Psychology | www.frontiersin.org 1 March 2022 | Volume 13 | Article 835415 Cattaneo et al. Sense of Coherence and Cognition INTRODUCTION living are structured, predictable, and explicable; (2) the resources are available to one to meet the demands posed by these stimuli; Recent biomedical research is increasingly focused on and (3) these demands are challenges, worthy of investment and understanding why a substantial portion of individuals remain engagement” (Antonovsky, 1996). Hence, SoC has a cognitive cognitively and functionally normal throughout their lifetime, and behavioral-instrumental dimension, being considered the irrespective of the occurrence of age-related brain changes or “cognitive” component of the meaning in life theory (Martela the presence of brain pathology (Arenaza-Urquijo and Vemuri, and Steger, 2016). This cross-cultural construct represents a 2018). Parallel to experimental evidence that a large number of general orientation in promoting health by allowing individuals factors, both modifiable and non-modifiable, play a role and to actively use available internal and environmental resources to interact in determining different brain and behavioral trajectories cope with adverse events and, ultimately, to boost resilience to during the lifespan (Di Marco et al., 2014; Livingston et al., 2020), them (Antonovsky, 1990). classical theoretical models, such as cognitive reserve (CR), are Epidemiological and clinical studies have shown that SoC is an constantly evolving and expanding. important health-promoting resource, and it has been related to Among the different CR conceptualizations proposed in the the quality of life and a broad range of health-related variables, past few decades, we considered a dynamic model of reserve as well as to the prevalence of distinct pathological conditions, that includes those experiences that explain how successfully including depression, cardiovascular accidents, and mortality a person can cope with age, disease-related brain changes, or (Lundman et al., 2010; Boeckxstaens et al., 2016; Mittelmark et al., achieve better performance on cognitive tasks due to better 2016; Huang et al., 2017). brain network efficiency (Steffener and Stern, 2012). In this Sense of coherence has also been consistently associated with sense, CR is considered as “the ability to optimize or maximize classical proxies of CR, such as education (Giglio et al., 2015) performance through differential recruitment of brain networks, and leisure-time physical activity (Monma et al., 2015), and has which perhaps reflect the use of alternate cognitive strategies” been positively associated with both self-reported (Read et al., (Stern, 2002). This ability is associated with both early and 2005) and measured cognitive functioning (Boeckxstaens et al., late-life socio-behavioral experiences pertaining to a broad 2016). Interestingly, a longitudinal study in older adults observed variety of domains. a parallel decline in cognition and SoC over time (Lövheim et al., Although original conceptualizations of CR mainly 2013), supporting the role of this construct in cognition and considered the roles of education and occupation as proxy optimal functioning. variables, in combination with measures of premorbid Purpose in life, instead, represents a motivational intelligence estimations (Stern, 2012), a broad variety of psychological construct relating to the notion of having a activities through life are now being considered (Stern et al., sense of future-oriented and meaningful goals in life. It is one 2020). In this regard, the role of psychological factors, including of the six factors composing the psychological wellbeing model personality traits, coping strategies, negative thinking, and proposed by Ryff (1995), together with autonomy, personal attitude toward life, has been investigated recently as important growth, environmental mastery, positive relationships, and factors in promoting brain health and resilience (Franchow et al., self-acceptance. Higher levels of PiL could moderate the impact 2013; Ryff, 2014; Bartrés-Faz et al., 2018; Arenaza-Urquijo et al., of biological risk factors, such as inflammatory markers, and 2020; Colombo et al., 2020; Marchant et al., 2020). may be associated with a better capacity to face challenging Similarly, different variables included in the psychological conditions that could affect mental and physical health (see Ryff wellbeing construct proposed by Ryff (1995) (e.g., Purpose in et al., 2016 for a review). It has been shown that PiL is related to life, PiL), as well as dimensions included in the salutogenic a reduction in the incidence of various health-related conditions, model of Antonovsky (1993) (sense of coherence, SoC), have been such as stroke, cardiovascular accidents, disability, and other related with higher levels of mental health via stress management causes of mortality (Kim et al., 2013; Cohen et al., 2016; Kim and and self-regulation mechanisms (Durand-Bush et al., 2015; Mc Park, 2017). In the context of cognition and dementia, PiL has Gee et al., 2018). These eudaimonic dimensions, encompassing been associated with better cognitive function in healthy adults, the experience of fulfillment achieved through self-actualization reduced incidence of mild cognitive impairment (MCI) and risk and a goal-directed existence, have been consistently considered of developing Alzheimer’s disease (AD), and crucially with better as protector factors for biological markers related to the stress cognitive functioning in the presence of more AD pathology pathway, such as cortisol levels (i.e., Pressman et al., 2019) (Boyle et al., 2010, 2012; Lewis et al., 2016). and inflammatory markers (i.e., Ironson et al., 2018), and have The associations between psychological constructs and been shown to interact and moderate the relation between cognitive outcomes, as well as their consistent relation with classical proxies of CR and inflammatory processes (see Ryff, classical proxies of CR, suggest their possible role in the relation 2014 for a review). between CR and cognition. In fact, higher estimates of these Sense of coherence represents the central factor on the constructs could influence classical proxies of reserve (e.g., social salutogenic model, originally proposed by Antonovsky (1990). aspects), or be influenced by them (e.g., educational level), This construct is defined as a “global orientation that expresses modifying their relationship with cognitive functioning. the extent to which one has a pervasive, enduring though In a previous study (Bartrés-Faz et al., 2018), we already dynamic feeling of confidence that: (1) the stimuli deriving from observed that both SoC and PiL mediate the relation between one’s self internal and external environments in the course of classical proxies of CR and self-perceived cognitive functioning. Frontiers in Psychology | www.frontiersin.org 2 March 2022 | Volume 13 | Article 835415 Cattaneo et al. Sense of Coherence and Cognition In this study, we wanted to make a further step by exploring array (Simoa) NF-light Advantage Kit on an HD-X instrument the relationship between these psychological constructs, CR, as described by the kit manufacturer (Quanterix, Billerica, MA, and objective cognitive performance. This was assessed through United States). The limit of quantification was 2.7 pg/ml, and a formal neuropsychological evaluation in a large sample of the limit of detection was 0.3 pg/ml. For the quality control middle-aged and older adults (1) using objective measures (QC) sample with an 11.2 pg/ml concentration, repeatability of cognitive functioning and (2) exploring different cognitive was 3.6%, and intermediate precision was 5.0%. For a QC domains separately. sample with a 115 pg/ml concentration, repeatability was In line with the results of our previous study, we hypothesized 5.3%, and intermediate precision was 6.8%. The measurements that SoC, seen as a psychological cognitive construct related to were performed at the Clinical Neurochemistry Laboratory resources control and managing in response to environmental at the University of Gothenburg by board-certified laboratory demands, would be particularly associated with general cognitive technicians who were blinded to clinical data. functioning and executive functions, while PiL may show a weaker association with cognitive measures. To achieve Online Surveys the objectives linked to these hypotheses, we employed a Cognitive reserve was estimated using a short questionnaire “controlling” model that explores the association between proxies validated in the Spanish population and previously used in of CR and cognition, and the mediator role of two psychological studies with healthy elders and patients with AD (Rami constructs, in light of similar levels of brain status in healthy et al., 2011). The questionnaire obtained information about middle-aged adults. six main proxies of CR entailing attained level of education, occupation, musical formation, language skills, reading activity, and intellectual games. The total score (from 0 to 25) was MATERIALS AND METHODS obtained by directly adding the single response scores. Higher scores in this questionnaire correspond to higher levels of CR Participants (refer to Table 1). In the framework of the Barcelona Brain Health Initiative (BBHI) Sense of coherence was evaluated using the Spanish version of (see Cattaneo et al., 2018, 2020 for details), 888 participants (433 the orientation to life questionnaire (OLQ-13; Lizarbe-Chocarro women, mean age = 53.35, standard deviation = 7.1, range = 42– et al., 2016). This 13-item scale represented an abbreviated 67) that underwent in-person assessments participated in the version of the original 29-items tool and uses a 7-point Likert- study. Participants were selected if they accomplished a cognitive type response scale (range: 0–91). Higher scores in this scale assessment and completed an online survey on CR (Rami correspond to higher levels of SoC (refer to Table 1). et al., 2011), SoC, and PiL estimates (Díaz et al., 2006; Virués- Purpose in life was measured using the PiL subscale of the Ortega et al., 2007). Furthermore, participants did not present Spanish version of Ryff ’s wellbeing scale (van dierendonck et al., with any neurological or psychiatric diagnosis at the time of 2008) that with a Likert-type scale ranging from 1 (strongly entering the study. disagree) to 6 (strongly agree), whereby higher scores correspond to higher levels of PiL (refer to Table 1). Assessment Neuropsychological Assessment Statistical Analysis Neuropsychological testing was administered by two expert First, as performed in previous studies of our group (e.g., España- neuropsychologists (V.A. and C.P.) in a single session of Irla et al., 2021), we transformed raw scores obtained by cognitive approximately 90 min (see Cattaneo et al., 2018). Tests were tests to z-scores, then, to create composite scores of different administered in a fixed order: direct and inverse digit span cognitive domains, we ran an exploratory principal component (Peña-Casanova et al., 2012), Trail Making Test Parts A and B analysis using Oblimin rotation and fixed the acceptable level (Peña-Casanova et al., 2012), Reasoning Matrix (Weschler, 2008), of factor loading to 0.30 (Hair et al., 1998). Second, we Rey Auditory-Verbal Learning Test (Bowler, 2013), block design explored the association between SoC and PiL by running test (Weschler, 2008), letter-number sequencing (Peña-Casanova Spearman correlations. et al., 2012), digit-symbol substitution test and cancelation Finally, we ran two multivariate linear regression models, one subtests from Wechsler Adult Intelligence Scale, Fourth Edition for SoC and another for PiL, to control for collinearity due (WAIS-IV) (Weschler, 2008), and Corsi block-tapping test to the high correlation between these two measures, using the (Peña-Casanova et al., 2012). different composite cognitive scores (see below) as dependent variables and CR, age, gender, and the psychological construct Neurofilament Light Chain Measurement We collected blood samples using ethylenediaminetetra-acetic acid (EDTA) tubes during the medical assessment of the BBHI, TABLE 1 | Results of online surveys. and plasma was aliquoted and stored in a freezer at −80◦ C Survey Mean (SD) in a biobank facility following standard procedures usually employed for clinical purposes. Plasma Neurofilament light chain Cognitive reserve (CR) 19.76 (3.62) (NfL) concentration, a general marker of neurodegeneration Sense of coherence (SOC) 66.92 (12.09) (Teunissen et al., 2022), was measured using the single-molecule Purpose in life (PiL) 28.73 (6.05) Frontiers in Psychology | www.frontiersin.org 3 March 2022 | Volume 13 | Article 835415 Cattaneo et al. Sense of Coherence and Cognition estimation as regressors. Based on the results obtained, when Sense of Coherence and Purpose in Life possible, mediation analyses were undertaken using the Preacher Spearman correlations revealed a very strong positive association and Hayes’ mediation procedure (Preacher and Hayes, 2008). between SoC and PiL (ρ = 0.68, p < 0.001). Models were repeated in a subsample (N = 756) where NfL data were available. Here, NfL was used as a covariate in the analyses Sense of Coherence, Cognitive Reserve, to adjust for neurodegeneration. and Cognition All statistical analyses were carried out using the SPSS version Verbal Memory 23.0 software (Statistical Package for Social Sciences, Chicago, IL, United States), and mediation analyses were carried out using the The multivariate regression model results were statistically PROCESS macro for SPSS (Preacher and Hayes, 2008). significant (F = 45.91, p < 0.001) and explained 21% of the variance. Analyses revealed that memory was associated with age (F = 78.071, p < 0.001), gender (F = 63.851, p < 0.001), CR RESULTS (F = 61.990, p < 0.001), and SoC (F = 5.110, p = 0.024). In addition, bootstrapped mediation analysis revealed that SoC Cognitive Composite Score Calculation significantly and partially mediated the association between Neuropsychological raw data of the 888 participants (refer CR and cognitive functioning in this domain (5,000 bootstrap to Table 2) were transformed into z-scores and used in the samples, 95% CI 0.002–0.020; see Figure 1). The model explained principal component analysis. Bartlett’s test revealed a significant 19% of the variance without mediators and 20% when SoC was relationship between the factors (p < 0.001), and the Kaiser- included as a mediator. Meyer-Olkin (KMO) test confirmed that the data were suitable for factor analysis (KMO = 0.63). Reasoning and Attention The principal component analysis resulted in four In this case, the multivariate regression model results were components, the first included all measures of the Rey statistically significant (F = 69.50, p < 0.001) and explained 28% Auditory Verbal Learning Test (immediate recall = 0.88, of the variance. delayed recall = 0.91, and recognition = 0.79), indicating a Reasoning and attention were associated with age verbal memory domain. A second reasoning and attentional (F = 259.722, p < 0.001), CR (F = 82.867, p < 0.001), and component comprised the Trail Making Test A (0.77), the block SoC (F = 4.258, p = 0.039). Also, in this case, mediation analysis design test (0.74), the digit-symbol substitution test (0.70), the indicated that SoC significantly and partially mediated the WAIS-IV matrix reasoning (0.65), and the cancelation test association between CR and cognitive performance (5,000 (0.53). The third factor reflecting working memory contained bootstrap samples, 95% CI 0.002–0.024; see Figure 2). The model digit span backward (0.79), digit span forward (0.78), and the letter-number sequencing tests (0.70). Finally, set-shifting abilities were reflected in a fourth component, with the Trail Making Test Part B (0.97) and the Trail Making Test Part B-A (0.97). Based on the factorial structure obtained, we calculated composite scores of the four domains as the mean of z-scores of each neuropsychological test. Moreover, we calculated a global cognition composite as the mean of all the transformed z-scores. TABLE 2 | Results of formal neuropsychological testing of participants. FIGURE 1 | Sense of coherence (SoC) as a partial mediator of the association between CR and verbal memory. Values are B coefficients (*p < 0.05; Neuropsychological test Mean (SD) **p < 0.01); values within parentheses represent total relationship. Digit span forward 6.14 (1.21) Digit span dackward 4.92 (1.10) Letter-number sequencing 5.74 (1.04) RAVLT immediate recall 51.84 (8.65) RAVLT delayed recall 11.31 (2.68) RAVLT recognizing 14.35 (1.20) WAIS-IV logical matrices 19.97 (3.39) WAIS-IV block design 46.10 (10.44) Digit symbol substitution test 77.90 (13.41) WAIS-IV Cancelation 41.72 (8.38) FIGURE 2 | Sense of coherence as mediators of the association between CR TMT A 27.51 (8.69) and reasoning. Values are B coefficients (*p < 0.05; **p < 0.01); values within TMT B 79.14 (26.34) parentheses represent total relationship. TMT B-A 51.60 (24.64) Frontiers in Psychology | www.frontiersin.org 4 March 2022 | Volume 13 | Article 835415 Cattaneo et al. Sense of Coherence and Cognition explained 27% of the variance without mediators and 28% when and cognitive performance (5,000 bootstrap samples, 95% CI SoC was introduced as a mediator. 0.009–0.056; see Figure 4). The model explained 31% of the variance without mediators and 32% with SoC as a mediator. Working Memory Multivariate regression model results were statistically significant Neurofilament Light Chain (F = 15.43, p < 0.001) but explained only 8% of the variance. We repeated the previous analysis in a subsample (N = 756), However, working memory results were associated with age introducing NfL as a covariate to confirm our results that SoC (F = 12.571, p < 0.001), gender (F = 11.752, p < 0.001), CR exerted a modulation effect, while accounting for a measure (F = 44.183, p < 0.001), and SoC (F = 4.439, p = 0.035). Further reflecting brain status, as recommended in the operational mediation analysis indicated that SoC significantly and partially definitions of CR by Stern and collaborators (Stern et al., 2020). mediated the association between CR and cognitive functioning CR was significantly associated with all cognitive domains, while in this domain (5,000 bootstrap samples, 95% CI 0.001–0.018; SoC was associated with reasoning and attention (F = 4.328, see Figure 3). The model explained 7% of the variance without p = 0.038) and global cognition (F = 5.317, p = 0.021) and mediators and rose to 8% when SoC was included as the mediator. only partially associated with episodic memory (F = 3.045, p = 0.081) and working memory (F = 2.862, p = 0.091). When Set Shifting we ran mediation models for significantly associated domains, we The whole regression model results were statistically significant found that SoC partially mediated the relationship between CR (F = 35.83, p < 0.001) and explained 16% of the variance. and reasoning and attention (5,000 bootstrap samples, 95% CI Set shifting results were only associated with age (F = 121.658, 0.002–0.028) and global cognition (5,000 bootstrap samples, 95% p < 0.001) and CR (F = 53.326, p < 0.001) but not with SoC CI 0.007–0.061). (F = 0.001, p = 0.973). Purpose in Life, Cognitive Reserve, and Global Cognition Cognition For global cognition, the multivariate model results were Multivariate analysis revealed that PiL was not significantly statistically significant (F = 83.40, p < 0.001) and explained 32% associated with verbal memory (F = 0.326, p = 0.568), reasoning of the variance. and attention (F = 0.851, p = 0.356), working memory (F = 0.037, Global cognition results were associated with age (F = 78.071, p = 0.847), cognitive flexibility (F = 1.373, p = 0.242), or global p < 0.001), CR (F = 144.702, p < 0.001), and SoC (F = 6.995, cognition (F = 0.003, p = 0.957). Results were confirmed when we p = 0.008). Again, mediation analysis indicated that SoC introduced NfL in the model as a covariate. significantly and partially mediated the association between CR DISCUSSION In this study, we explored the relationship between two psychological constructs (SoC and PiL), CR, and cognition for different cognitive domains. We used a “controlling” model that explores the association between proxies of CR and cognition and the mediator role of two psychological constructs, in light of similar levels of brain status (Stern et al., 2020). In a first analysis, similar brain status was assumed considering the characteristics of our healthy middle-aged participants, while FIGURE 3 | Sense of coherence as a partial mediator of the association between CR and working memory. Values are B coefficients (*p < 0.05; in a second analysis realized in a subsample, we adjusted **p < 0.01); values within parentheses represent total relationship. for a neurodegeneration marker, namely NfL, to confirm the obtained results. Present findings indicated that CR was associated with all cognitive domains, while SoC was related to composite scores in verbal memory, reasoning and attention, working memory, and global cognition. Moreover, SoC exerted a mediator role on the relationship between CR and all these cognitive measures. When we corrected for a measure of brain status in a subsample, we confirmed previous results but only for reasoning and attention and global cognition. Instead, PiL did not reveal clear associations with cognitive functioning. Our findings regarding SoC add further new evidence to FIGURE 4 | Sense of coherence as a partial mediator of the association our previous study on the relationship between components between CR and global cognition. Values are B coefficients (*p < 0.05; **p < 0.01); values within parentheses represent total relationship. of meaning in life and self-reported cognitive status, cognitive complaints, and classical proxies of CR (Bartrés-Faz et al., 2018). Frontiers in Psychology | www.frontiersin.org 5 March 2022 | Volume 13 | Article 835415 Cattaneo et al. Sense of Coherence and Cognition In particular, they highlight the presence of an association role of SoC for reasoning and attention (beyond global between the psychological construct of SoC and cognitive cognition), suggesting a specific effect only on some cognitive functioning measured through formal neuropsychological domains. Therefore, beyond the potential influence of SoC on assessments, as well as its mediator role on the relation between classical proxies of CR (and vice versa) that could explain its CR and cognition. As highlighted in the introduction, SoC mediation role for specific cognitive domains, its complexity is considered a psychological construct involved in resources as a psychological construct and its relationship with a broad control and the ability to manage these resources to better variety of health-related outcomes suggest that it could act respond to environmental demands. Similarly, in its classical via independent protective mechanisms (e.g., stress reduction; formulation, CR estimations were thought to reflect mechanisms Kimhi, 2015). that allow them to manage and optimally employ available In contrast to SoC findings, PiL was not found to be resources to cope with brain changes and insults (Stern, 2009). associated with cognitive functioning in any of the domains Present results revealed that the association between these two considered. Initially, these results are contradictory to the constructs with cognitive functioning is not limited to some previous investigations that looked at the relationship between cognitive domains, but rather it seems to be spread across PiL, cognition, and cognitive decline in aging. Results from different cognitive functions. However, when we corrected for Boyle et al. (2012, 2010) indicate that individuals with higher brain status, SoC was associated with global cognition and estimations of PiL are less prone to cognitive decline, MCI, reasoning and attention, suggesting both general and specific and dementia, and they present better cognitive functioning effects on cognition of this construct. These findings parallel in the presence of more brain pathology. In contrast to these recent proposals considering that CR relates to better cognitive previous investigations, including participants affected by MCI performance in multiple areas of cognition (Stern et al., 2018; or in early or advanced stages of AD, we selected cognitive van Loenhoud et al., 2020), and it is not specifically associated spared, middle-aged individuals and did not have follow-up with executive functions, as initially proposed (Tucker and Stern, data on cognitive changes. These methodological differences 2011; Roldán-Tapia et al., 2012). may account for the observed discrepancies in results. Hence, Recently, Stern et al. (2018), using an iterative approach, albeit speculative at this stage, this more future-oriented and identified a CR neural network that included brain regions motivational construct can exert a relevant role in promoting forming parts of main large-scale networks, such as the default cognitive resilience in the presence of brain pathology and mode, the frontoparietal, and the salience networks (van less impact, or no detectable relevance on cognitive outcomes, Loenhoud et al., 2020), and was found to be involved in the when considering normally performing individuals (however, execution of different cognitive tasks. Interestingly, its expression see Merten et al., 2021, to explore the relationship between correlated with IQ, a proxy of CR, and crucially moderated psychological wellbeing composite score, including PiL, and the association between performance in some cognitive domains cognitive functioning and impairments). and other classical brain metrics, such as cortical thickness Our present findings advocate for the inclusion of the (Stern et al., 2018). construct of SoC as one of the factors potentially relevant for This evidence of a mediator role of CR on the relationship the study of CR and its relationship with cognitive functioning. between brain measures and cognitive performance (see also This is in accordance with CR being a continuously evolving, Steffener et al., 2014) clearly suggested that CR not only dynamic concept, where the relevance of psychological and acts as a mechanism that allows some individuals to better psycho-affective variables is accumulating (e.g., Marchant and tolerate brain pathology (Stern, 2002) but also facilitates healthy Howard, 2015; Marchant et al., 2020). At a practical level, the individuals to perform better in cognitive tasks, possibly incorporation of this kind of aspects in the study of the effect through promoting neural efficiency (Stern et al., 2018). To our of CR on cognition may be highly relevant, considering that knowledge, no studies have directly explored the neurobiological central concepts (such as the identification of intrinsic values substrates of SoC at the level of brain network expressions; that guide behavior, in the case of SoC) are usually amenable to the cognitive findings may suggest that SoC may promote psychological interventions (e.g., Hayes, 2016), therefore opening cognition through partial overlapping of neural underpins. In new avenues to promote reserve. this regard, literature on neurobiology of stress suggests that prefrontal brain regions involved in emotional regulation, that, in part, overlap with those included in the salience network DATA AVAILABILITY STATEMENT (Gupta et al., 2017), could be the neural substrate of SoC The raw data supporting the conclusions of this article will be (Smith, 2002), in line with the hypothesis that these act made available by the authors, without undue reservation. on the brain and mental health via stress management and self-regulation mechanisms (Mc Gee et al., 2018). The only partial mediation effect of SoC on the relationship between ETHICS STATEMENT CR and cognitive functioning, and the limited increase in the explained variance when it was included in the model The studies involving human participants were reviewed and as a mediator, suggested that the overlap between CR and approved by the Fundació Unio Catalana Hospitals (code CEIC SoC is restricted. In fact, when we adjusted analysis for a 18/07). The patients/participants provided their written informed general neurodegeneration marker, we only see a mediator consent to participate in this study. Frontiers in Psychology | www.frontiersin.org 6 March 2022 | Volume 13 | Article 835415 Cattaneo et al. Sense of Coherence and Cognition AUTHOR CONTRIBUTIONS the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical AP-L, DB-F, and JT participated in the initial conception of Research (#ALFGBG-720931), the Alzheimer’s Drug Discovery the design of the Barcelona Brain Health Initiative. GC and Foundation (ADDF), United States (#201809-2016862), the JS-S made substantial contributions to the actual design and AD Strategic Fund and the Alzheimer’s Association (#ADSF- implantation protocol. GC, JS-S, VA, and CP-G participated 21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377- actively in the data collection and analysis. HZ supervised C), the Olav Thon Foundation, the Erling-Persson Family the blood biomarker measurements. KA-P, CP-O, SD-G, JT, Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, DB-F, and AP-L contributed to the interpretation of the results. Sweden (#FO2019-0228), the European Union’s Horizon 2020 GC drafted the article. All authors made critical revisions, research and innovation program under the Marie Skłodowska- introducing important intellectual content, and final approval of Curie grant agreement no. 860197 (MIRIADE), European Union the submitted version. Joint Program for Neurodegenerative Disorders (JPND2021- 00694), and the UK Dementia Research Institute at UCL. The funders listed were not involved in the study design, collection, FUNDING analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This research was funded by grants from the La Caixa Foundation (grant agreement: LCF/PR/PR16/11110004), Institut Guttmann, and Fundació Abertis. AP-L was partly supported by the National Institutes of Health (R24AG06142 and P01 ACKNOWLEDGMENTS AG031720) and received funding from MagStim Inc. DB-F was funded by the Spanish Ministry of Science, Innovation, The authors extend their gratitude to all participants, the Universities (RTI2018-095181-B-C21) and ICREA Academia project team and research assistants, and other partners (Ad- 2019 award research grants. JT was partly supported by Salutem Institute, Sodexo, I.C.A. Informàtica y Comunicaciones Fundació Joan Ribas Araquistain_Fjra, AGAUR, Agència de Avanzadas, Neuroelectrics, Corporació Catalana de Mitjans Gestió d’Ajuts Universitaris i de Recerca (2018 PROD 00172), Audiovisuals, Club Metropolitan, Casa Ametller, and Agència Fundació La Marató De TV3 (201735.10), and the European de Qualitat i Avaluació Sanitàries de Catalunya-AQuAS) for Commission (Call H2020-SC1-2016-2017_RIA_777107). CP- their invaluable collaboration. The companies listed in the paper O and KA-P were funded by the AGAUR, Agència de were not involved in any step of the study, from design to data Gestió d’Ajuts Universitaris i de Recerca (PANDEMIES 2020). collection and analysis, data interpretation, the writing of the HZ, a Wallenberg Scholar, was supported by grants from article or the decision to submit it for publication. REFERENCES impairment in community-dwelling older persons. Arch. Gen. Psychiatry 67, 304–310. doi: 10.1001/archgenpsychiatry.2009.208 Antonovsky, A. 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Alzheimer Res. 8, 354–360. doi: 10.2174/1567205117957 Publisher’s Note: All claims expressed in this article are solely those of the authors 45320 and do not necessarily represent those of their affiliated organizations, or those of van dierendonck, D., Díaz, D., Rodriguez-Carvajal, R., Blanco, A., and Moreno- the publisher, the editors and the reviewers. Any product that may be evaluated in Jiménez, B. (2008). Ryff ’s six-factor model of psychological well-being, a this article, or claim that may be made by its manufacturer, is not guaranteed or Spanish exploration. Soc. Indic. Res. 36, 601–608. doi: 10.1007/s11205-007- endorsed by the publisher. 9174-7 van Loenhoud, A. C., Habeck, C., van der Flier, W. M., Ossenkoppele, R., Copyright © 2022 Cattaneo, Solana-Sánchez, Abellaneda-Pérez, Portellano-Ortiz, and Stern, Y. (2020). Identifying a task-invariant cognitive reserve network Delgado-Gallén, Alviarez Schulze, Pachón-García, Zetterberg, Tormos, Pascual- using task potency. NeuroImage 210, 116593. doi: 10.1016/j.neuroimage.2020.1 Leone and Bartrés-Faz. This is an open-access article distributed under the terms 16593 of the Creative Commons Attribution License (CC BY). The use, distribution or Virués-Ortega, J., Martínez-Martín, P., del Barrio, J. L., and Lozano, L. M. (2007). reproduction in other forums is permitted, provided the original author(s) and the Validación transcultural de la Escala de Sentido de Coherencia de Antonovsky copyright owner(s) are credited and that the original publication in this journal (OLQ-13) en ancianos mayores de 70 años. Med. Clín. 128, 486–492. doi: is cited, in accordance with accepted academic practice. No use, distribution or 10.1157/13100935 reproduction is permitted which does not comply with these terms. Frontiers in Psychology | www.frontiersin.org 9 March 2022 | Volume 13 | Article 835415