Education as Proxy for Cognitive Reserve in a Large Elderly Memory Clinic: ‘Window of Benefit’

Staekenborg, Salka S.; Kelly, Naomi; Schuur, Jacqueline; Koster, Pieter; Scherder, E.J.A.; Tielkes, Caroline E.M.; Scheltens, Philip; Claus, J. J.

doi:10.3233/jad-191332

Cited by 28 publications

(32 citation statements)

References 26 publications

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“…More specifically, it has been suggested that the positive effects of education initially emerge as a function of neuropathology, plateau, and subsequently decline (Gregory et al, 2017;Staekenborg et al, 2020). For example, contrarily to our study results and prior findings (Groot et al, 2018), another recent study demonstrated that education more strongly related to cognitive performance in AD relative to SCD and MCI, although these effects diminished in the most severely affected AD patients (Staekenborg et al, 2020).…”

Section: Discussionsupporting

confidence: 73%

“…Differences in neuropathological burden across seemingly similar populations thus may influence the observed education-cognition associations, conversely contributing to discrepancies in findings across studies (Ewers, 2020;Soldan et al, 2020). More specifically, it has been suggested that the positive effects of education initially emerge as a function of neuropathology, plateau, and subsequently decline (Gregory et al, 2017;Staekenborg et al, 2020). For example, contrarily to our study results and prior findings (Groot et al, 2018), another recent study demonstrated that education more strongly related to cognitive performance in AD relative to SCD and MCI, although these effects diminished in the most severely affected AD patients (Staekenborg et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that disease state may attenuate such effects (Stern, 2012;Gregory et al, 2017;Mungas et al, 2021), and previous studies have demonstrated that the benefits of higher education become less pronounced or disappear entirely as disease severity increases (Ye et al, 2013;Soldan et al, 2015;Groot et al, 2018). In contrast, recent findings revealed stronger education-cognition associations in AD relatively to SCD and MCI (Staekenborg et al, 2020). Furthermore, neuropathological burden varies greatly within each diagnostic group (Mehta and Schneider, 2021), and the protective effects of education may consequently vary as a function of neuropathological severity (Perneczky et al, 2009;Mungas et al, 2018Mungas et al, , 2021.…”

Section: Introductionmentioning

confidence: 99%

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Positive Effects of Education on Cognitive Functioning Depend on Clinical Status and Neuropathological Severity

Jansen

Geerligs

Claassen

et al. 2021

Front. Hum. Neurosci.

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Background: Variability in cognitive functions in healthy and pathological aging is often explained by educational attainment. However, it remains unclear to which extent different disease states alter protective effects of education. We aimed to investigate whether protective effects of education on cognition depend on (1) clinical diagnosis severity, and (2) the neuropathological burden within a diagnosis in a memory clinic setting.Methods: In this cross-sectional study, we included 108 patients with subjective cognitive decline [SCD, median age 71, IQR (66–78), 43% men], 190 with mild cognitive impairment [MCI, median age 78, IQR (73–82), 44% men], and 245 with Alzheimer’s disease dementia (AD) [median age 80, IQR (76–84), 35% men]. We combined visual ratings of hippocampal atrophy, global atrophy, and white matter hyperintensities on MRI into a single neuropathology score. To investigate whether the contribution of education to cognitive performance differed across SCD, MCI, and AD, we employed several multiple linear regression models, stratified by diagnosis and adjusted for age, sex, and neurodegeneration. We re-ran each model with an additional interaction term to investigate whether these effects were influenced by neuropathological burden for each diagnostic group separately. False discovery rate (FDR) corrections for multiple comparisons were applied.Results: We observed significant positive associations between education and performance for global cognition and executive functions (all adjusted p-values < 0.05). As diagnosis became more severe, however, the strength of these associations decreased (all adjusted p-values < 0.05). Education related to episodic memory only at relatively lower levels of neuropathology in SCD (β = −0.23, uncorrected p = 0.02), whereas education related to episodic memory in those with higher levels of neuropathology in MCI (β = 0.15, uncorrected p = 0.04). However, these interaction effects did not survive FDR-corrections.Conclusions: Altogether, our results demonstrated that positive effects of education on cognitive functioning reduce with diagnosis severity, but the role of neuropathological burden within a particular diagnosis was small and warrants further investigation. Future studies may further unravel the extent to which different dimensions of an individual’s disease severity contribute to the waxing and waning of protective effects in cognitive aging.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Positive Effects of Education on Cognitive Functioning Depend on Clinical Status and Neuropathological Severity

Jansen

Geerligs

Claassen

et al. 2021

Front. Hum. Neurosci.

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“…Second, we used years of education as a proxy for CR, but this cannot capture occupational, social, or leisure experiences. However, even though there is ongoing controversy about the appropriate proxy for CR, years of education is a widely-used proxy 25 , 26 . Third, there were fewer participants in the early aMCI and moderate-to-severe ADD groups which might have led to non-significant findings in these groups.…”

Section: Discussionmentioning

confidence: 99%

Effect of education on functional network edge efficiency in Alzheimer’s disease

Kim

Seo

et al. 2021

Sci Rep

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We investigated the effect of education on the edge efficiency in resting state functional networks (RSFNs) in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease dementia (ADD). We collected the data of 57 early aMCI, 141 late aMCI, 173 mild ADD, and 39 moderate-to-severe ADD patients. We used years of education as a proxy for cognitive reserve. We measured edge efficiency for each edge in RSFNs, and performed simple slope analyses to discover their associations with education level among the four groups. In the late aMCI, a sub-network that had hub nodes in the right middle frontal gyrus and the right posterior cingulate gyrus, showed a positive association between RSFN edge efficiency and education (threshold = 2.5, p = 0.0478). There was no negative effect of education on the RSFN edge efficiency. In the early aMCI, mild ADD, and moderate-to-severe ADD, there were no sub-networks showing positive or negative correlation between education and RSFN edge efficiency. There was a positive effect of higher education on RSFN edge efficiency in the late aMCI, but not in the early aMCI or ADD. This indicates that in late aMCI, those who have higher education level have greater ability to resist collapsed functional network.

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“…Reserve was estimated by using education (total years) as a proxy ( McFall et al, 2019b ; Staekenborg et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

A Multimodal Risk Network Predicts Executive Function Trajectories in Non-demented Aging

Sapkota

McFall

Masellis

et al. 2021

Front. Aging Neurosci.

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Background: Multiple modalities of Alzheimer’s disease (AD) risk factors may operate through interacting networks to predict differential cognitive trajectories in asymptomatic aging. We test such a network in a series of three analytic steps. First, we test independent associations between three risk scores (functional-health, lifestyle-reserve, and a combined multimodal risk score) and cognitive [executive function (EF)] trajectories. Second, we test whether all three associations are moderated by the most penetrant AD genetic risk [Apolipoprotein E (APOE) ε4+ allele]. Third, we test whether a non-APOE AD genetic risk score further moderates these APOE × multimodal risk score associations.Methods: We assembled a longitudinal data set (spanning a 40-year band of aging, 53–95 years) with non-demented older adults (baseline n = 602; Mage = 70.63(8.70) years; 66% female) from the Victoria Longitudinal Study (VLS). The measures included for each modifiable risk score were: (1) functional-health [pulse pressure (PP), grip strength, and body mass index], (2) lifestyle-reserve (physical, social, cognitive-integrative, cognitive-novel activities, and education), and (3) the combination of functional-health and lifestyle-reserve risk scores. Two AD genetic risk markers included (1) APOE and (2) a combined AD-genetic risk score (AD-GRS) comprised of three single nucleotide polymorphisms (SNPs; Clusterin[rs11136000], Complement receptor 1[rs6656401], Phosphatidylinositol binding clathrin assembly protein[rs3851179]). The analytics included confirmatory factor analysis (CFA), longitudinal invariance testing, and latent growth curve modeling. Structural path analyses were deployed to test and compare prediction models for EF performance and change.Results: First, separate analyses showed that higher functional-health risk scores, lifestyle-reserve risk scores, and the combined score, predicted poorer EF performance and steeper decline. Second, APOE and AD-GRS moderated the association between functional-health risk score and the combined risk score, on EF performance and change. Specifically, only older adults in the APOEε4− group showed steeper EF decline with high risk scores on both functional-health and combined risk score. Both associations were further magnified for adults with high AD-GRS.Conclusion: The present multimodal AD risk network approach incorporated both modifiable and genetic risk scores to predict EF trajectories. The results add an additional degree of precision to risk profile calculations for asymptomatic aging populations.

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Education as Proxy for Cognitive Reserve in a Large Elderly Memory Clinic: ‘Window of Benefit’

Cited by 28 publications

References 26 publications

Positive Effects of Education on Cognitive Functioning Depend on Clinical Status and Neuropathological Severity

Positive Effects of Education on Cognitive Functioning Depend on Clinical Status and Neuropathological Severity

Effect of education on functional network edge efficiency in Alzheimer’s disease

A Multimodal Risk Network Predicts Executive Function Trajectories in Non-demented Aging

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