Background
Neuropathological hallmarks of age-related cognitive impairment, such as an accumulation of beta amyloid plaques in the brain or cerebrovascular degeneration, are well-described, but their presence does not always correlate with clinical manifestation. Given the same degree of neuropathological damage, some people show debilitating symptoms whereas others do not [
1]. The ‘cognitive reserve’ concept aims to resolve this discrepancy and suggests inter-individual differences in the ability to buffer the functional and behavioral consequences of cerebral neuropathology.
Cognitive reserve is commonly quantified by the peak level of cognitive ability in young adulthood prior to the onset of any age-related cognitive decline or dysfunction, termed ‘pre-morbid IQ’. Studies with data on pre-morbid IQ measured in young adulthood are rare, but pre-morbid IQ can additionally be approximated by vocabulary at any point throughout the lifespan, because the vocabulary domain is immune to age-related decline [
2‐
4] and remains intact even in mild to moderate dementia [
5]. Sociobehavioral measures such as self-reported educational and occupational attainment [
6], income [
7,
8], car ownership [
8] or childhood home occupancy rate [
9] or composites thereof [
10] can also serve as proxies for cognitive reserve, so that the research field is characterized by a substantial heterogeneity [
11]. Although all of these parameters are subject to an influence by societal and cultural constraints, historical context, and opportunity, introducing a noise into their statistical analysis, associations with risk of dementia [
12‐
15] and milder forms of impairment [
9,
16‐
18] are frequently found. Analyses additionally addressing several cognitive reserve parameters within the same study, which allow researchers to determine any inter-relationships among them in their associations with late-life cognition, are rarer, however. This is a relevant oversight, because unless for instance pre-morbid IQ is considered as a potential confounder in analyses of education or occupation and cognition in older age, we cannot draw conclusions as to any potential protective effects of these modifiable factors. In fact, some previous studies have reported that associations of a higher education with reduced odds of cognitive impairment or reduced rate of cognitive decline were rendered statistically non-significant or became less consistent once pre-morbid IQ was controlled for [
19‐
21], which warrants further investigation.
Here, we used a sample of older adults scheduled for surgery to determine the associations of self-reported educational and occupational attainment with their level of cognitive ability. We additionally assessed the contribution of pre-morbid IQ estimated from vocabulary to the hypothesized associations through statistical adjustment.
Discussion
In this study of older adults, we found associations of education and occupation with the level of global cognitive ability. These associations were independent of age and sex, but were attenuated when further adjusted for pre-morbid IQ and they remained statistically significant only for education. These data suggest that the association of education with cognitive ability in older persons cannot fully be explained by pre-morbid IQ.
The identification of factors that predispose or protect people from age-related cognitive impairment is gaining in importance. In this context, a higher level of education or occupation has frequently been implicated as associated with a reduced risk of cognitive impairment in epidemiological studies [
9,
16,
18], which is in line with our observation that a higher educational and occupational background were each associated with a relatively higher global cognitive ability in older age.
Considering the modifiable nature of education and occupation, a key issue approached in epidemiological research is whether or not the reported associations may reflect causality in the education/occupation-cognition direction, or whether they result from associations with confounding factors such as pre-morbid IQ. Here, we demonstrated that the associations of education and occupation with global cognitive ability in older age were substantially attenuated when adjusted for pre-morbid IQ, and remained statistically significant only for education. Thus, while the association of occupation with cognitive ability was largely explained by pre-morbid IQ, the association of education with cognitive ability was only to some extent explained by pre-morbid IQ but was additionally independently of pre-morbid IQ related to cognitive ability in older age. This finding is important, because it suggests that a higher educational attainment could potentially provide a cognitive reserve to prevent cognitive impairment in older age.
For occupation, findings similar to our own have been reported for the Lothian Birth Cohort 1936 [
48]. In that study, the effect sizes for the association of occupational complexity with cognitive ability at age 70 was reduced by 50 to 66% when IQ at age 11 was controlled for [
48]. This is a similar reduction in the variance explained by occupation as observed in our study when we adjusted for our vocabulary-based estimate of pre-morbid IQ. Overall effect sizes were larger in the Lothian Birth Cohort compared with our analysis, which may be due to the fact that the study included in-depth assessment of occupational complexity whereas we categorized into relatively coarse occupational groups. In our analysis, the association of occupation with global cognitive ability was further reduced when depression was controlled for and reduced towards null following additional adjustment for education. In addition to
g, among the six individual cognitive tests, this pattern of results was similarly observed for Trail-Making Test-B. Overall, this suggests a very limited association of occupation with late-life cognitive ability when accounting for age, sex, pre-morbid IQ, depression and education.
In contrast, pre-morbid IQ did not fully explain the association of education with cognitive ability. To some extent a higher level of education predicted later-life cognitive ability irrespectively of what people had cognitively ‘started off with’. Similar unique contributions of education to late-life cognition have previously been reported [
49,
50]. Yet, the severe attenuation of effect sizes following adjustment for pre-morbid IQ, which can be indicative of some degree if reverse causality with higher-ability individuals selecting higher education [
51], too, are representative of the research literature. For instance, a recent analysis of a US cohort found that associations of education with late-life cognition became less consistent and were weakened when cognitive function around age 20 was controlled for [
21]. Similar observations have been reported in samples of patients with Parkinson’s disease [
19] and Alzheimer’s disease [
20]. This inconsistency in the field could in part stem from relatively small effect sizes linking education to late-life cognition. Here, the association of higher education with higher late-life cognitive ability was also not confounded by depression at the time of testing and was independent of occupation. These results might suggest some (albeit relatively minor) unique contribution of education to cognitive ability in older age beyond its relationships with pre-morbid IQ, depression and occupation. Further, pairwise comparison determined that the association of education with cognitive ability was driven by highly educated individuals: the group with tertiary education had higher cognitive ability compared with the other two educational groups, whereas there was virtually no difference in cognitive ability between the two groups with primary/lower-secondary and upper secondary/post-secondary non-tertiary education in the fully adjusted model.
It may be possible that a tertiary education to some extent promoted cognitive ability and may have equipped individuals with an ability to compensate for age-related neuropathological damage, for instance through upregulation of existing and/or recruitment of novel brain networks [
7,
52]. A causal relationship is supported by results from Mendelian randomization studies utilizing genetic variants as indicators of exposures [
53] and by quasi-experimental studies on the effects of policy change. For instance, following an increase of compulsory schooling from 7 to 9 years in Norway, the IQ increased and more so than was to be expected from the naturally occurring rise in IQ since the beginning of cognitive testing [
54]. Across 11 studies of this type, a meta-analysis determined that policy change indeed influenced cognitive ability [
50]. Our observation of a beneficial role particularly of tertiary education without any difference between the lower two educational groups contrasts with those observations of effects of an increase in compulsory, i.e. primary, education, but may be due to our sample characteristics. Our lower educational groups may not be representative of the general lower-education population.
We are not in a position to determine the precise mechanisms or any potential causal relationships linking education to old-age cognitive ability in our study based on the present observational data, but our findings suggest that the associations were not fully driven by reverse causality with higher-ability individuals selecting a higher education [
51] We cannot rule out that our estimation of pre-morbid IQ around age 30 was also to some extent the result of educational attainment however. For this reason, studies with data on pre-morbid IQ obtained prior to the variation in schooling, i.e. before children enter individual educational paths (e.g., at age 11 [
55]), are key to fully characterize the relationship of education with lifespan cognition.
Interestingly, in addition to
g, education was associated with tests of verbal and non-verbal memory and with Trail-Making Test-B. Previous studies had similarly implicated memory as associated with education [
21,
56], in some even with pre-morbid IQ controlled for [
21], whereas education or cognitive reserve composite measures that include education have frequently been found not to be associated with measures of processing speed [
21,
49,
56‐
58]. These types of observations have led to the hypothesis that a longer time spent in formal education may enhance cognitive performance in areas such as memory or reasoning in older age but has no effect on more elementary abilities such as processing speed [
49]. Here, we suggest that our finding for Trail-Making Test-B may be due to its executive function component, which is a higher-order, frontal ability, rather than its processing speed component. In support of previous literature, Simple Reaction Time (a more 'pure' measure of processing speed) was indeed not associated with cognition in our analysis.
Future studies should attempt to determine the potential causality underlying observational reports such as our own. As trial studies on the effect of a modification of educational experience are difficult from an ethical and practical perspective, further Mendelian Randomization studies will prove useful in this context. Ultimately, depending on effect sizes, which may in fact be relatively small according to our and others’ cross-sectional [
21] and prospective analyses [
58], recommendations could be made on the optimal educational structure for preservation of cognitive ability into older age
. Research is also needed into any practical implications. Education is a highly individual experience dependent on preference and access, and any top-down strategies to promote education are likely complex and costly. Additionally, in ageing societies, a delay in young adults entering the workforce can be problematic and so an investigation of any differential (potentially causal) effects of earlier versus later education during the lifespan on late-life cognition could be useful. Here, we used baseline data from a sample of older adults scheduled for surgery within the next few days. Whether or not a higher education and occupation protected our patients from developing post-operative cognitive dysfunction, which at least for education previous studies appear to suggest [
59], remains to be seen.
Strengths of our study include use of a large sample size and a comprehensive cognitive test battery that covered several age-sensitive cognitive domains in addition to a composite measure of global ability. Yet some limitations need to be considered. We used a cross-sectional design and with no access to actual pre-morbid IQ obtained prior to a variation in schooling (e.g., [
55]) resorted to a vocabulary-based estimate, though previous analyses of birth cohorts comparing such estimates with measured pre-morbid IQ have validated the approach [
2]. Selection bias preferring individuals with a higher cognitive ability, education and occupation was indicated by a relatively high mean pre-morbid IQ as well as by a disproportionally high number of participants in the higher educational and occupational groups. This is a problem shared by many studies on cognitive ageing [
60]. Our results may therefore not translate to the general older population. We recruited participants from a large age range subject to cohort effects on cognitive ability [
61]. Between-test differences in terms of measurement scales will also have affected the comparison of education and occupation associations across cognitive tests. For instance, scores on Spatial Span were relatively coarse (range 0 to 9) whereas for the timed tests, measures were presented in more fine-grained scales of seconds or milliseconds. Further, participants were asked about their current occupation or their most recent occupation before retirement, which may not represent their highest level of occupational attainment. Some individuals may achieve a high level of occupation but change occupational category later in late (e.g., moving from skilled manual to skilled non-manual; or from managerial to skilled non-manual). All of these factors may have introduced noise to our analysis of occupation and may have weakened its relationship with cognitive scores. Finally, we assessed the independence of education and occupation associations with cognitive ability from pre-morbid IQ through statistical adjustment.Because pre-morbid IQ itself was associated with education and occupation, its addition to these models will have led to a lower proportion of variance being free to be accounted for by these independent variables [
62], which may have contributed to the observed reduction in effect sizes observed in this modeling step. Concurrent addition of education and occupation into a single model in our post-hoc analyses, too, was limited by their correlation.
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