Education and rates of cognitive decline in incident Alzheimer's disease
Open accessAbstract
BACKGROUND: Some (but not all) epidemiological studies have noted faster rates of progression in high education patients with Alzheimer's disease (AD), which has been attributed to harbouring/tolerating a higher pathological burden at the time of clinical dementia for subjects with higher education. We wanted to assess the relationship between education and rates of decline in AD. METHODS: During the course of a community based multiethnic prospective cohort study of individuals aged > or = 65 years living in New York, 312 patients were diagnosed with incident AD and were followed overall for 5.6 (up to 13.3) years. The subjects received an average of 3.7 (up to 9) neuropsychological assessments consisting of 12 individual tests. With the aid of a normative sample, a standardised composite cognitive score as well as individual cognitive domain scores were calculated. Generalised estimating equation models were used to examine the association between education and rates of cognitive decline. RESULTS: Composite cognitive performance declined by 9% of a standard deviation per year. Rates of decline before and after AD incidence were similar. For each additional year of education there was 0.3% standard deviation lower composite cognitive performance for each year of follow up. The association between higher education and faster decline was noted primarily in the executive speed (0.6%) and memory (0.5%) cognitive domains and was present over and above age, gender, ethnicity, differential baseline cognitive performance, depression, and vascular comorbidity. CONCLUSIONS: We conclude that higher education AD patients experience faster cognitive decline.
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TL;DR
In a multiethnic community cohort of 312 incident Alzheimer's disease patients, higher educational attainment was associated with slightly faster cognitive decline after accounting for baseline cognition and other covariates. The effect was most apparent in executive speed and memory, while pre- and post-diagnosis decline rates were similar.
Key findings
- Composite cognition declined by about 9% of a standard deviation per year (b = −0.09, p < 0.001); pre-incidence and post-incidence slopes were nearly identical (−0.09 vs −0.08 SD/year; interaction p = 0.57).
- Each additional year of education was linked to an extra 0.003 z-score-unit decline per follow-up year on the composite (p = 0.012), described in the abstract as 0.3% of an SD per year. Domain interactions were significant for executive speed (b = −0.006, p = 0.002), memory (b = −0.005, p = 0.002), and abstract reasoning (b = −0.003, p = 0.047), but not visual-spatial or language.
- At baseline, future AD patients scored 0.37 SD below matched controls about 3.8 years before diagnosis, and 0.89 SD below at the incidence visit.
- The education–decline association persisted after adjustment for age, gender, ethnicity, baseline cognition, literacy, vascular risk factors, and depression; no evidence indicated that ethnicity or literacy modified the relationship.
Methods
- Prospective community-based multiethnic cohort in northern Manhattan; 312 incident AD patients (mean age 81.6 years, mean education 7.1 years, 54% Hispanic, 33% black, 12% white) drawn mostly from WHICAP cohorts, followed on average 5.6 years (maximum 13.3) with 3.7 assessments (maximum 9) and 1159 total cognitive evaluations.
- Diagnosis used standardized clinical examination, a neuropsychological battery in English or Spanish, consensus conference, DSM-III-R and NINCDS-ADRDA criteria; composite and domain z-scores were derived from 548 cognitively healthy age-, gender-, and education-matched controls.
- Generalized estimating equation models tested education, time, and an education×time interaction, adjusted for age, gender, ethnicity, and baseline cognitive score; supplementary models examined pre/post incidence, nonlinear time, ethnicity, literacy, vascular comorbidity, and depression.
Limitations
- Stated: clinical diagnosis without biomarkers may misclassify dementia type; the standard criteria had sensitivity around 81% and specificity around 70%.
- Stated: reliance on pre-incidence data and limited post-incidence follow-up (1.8 years) may miss later disease stages; only linear and quadratic time terms were tested; education may be a proxy for unmeasured factors; years of schooling may not capture education quality.
- Evident: post-incidence analyses included only 131 of 312 patients, limiting power; the language domain had a ceiling effect and was skewed; the observational design cannot establish causality.
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Cites
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Claims the paper makes
0 of 9 cited sources checked · 0 supported · 0 flagged
- Findingown data
Higher education was associated with faster decline in the memory domain.
“The association between higher education and faster decline was noted primarily in the executive speed (0.6%) and memory (0.5%) cognitive domains and was present over and above age, gender, ethnicity, differential”
- Also stated in: § Education and rates of cognitive decline · plain
“there was an association between education and z score decline for executive speed, memory, and abstract reasoning domains”
Quote in the paperSubstantial claim - Also stated in: § Education and rates of cognitive decline · plain
- Findingown data
Ethnicity did not modify the education-decline relationship in the models.
“Additionally, there was no evidence that the relationship between education and cognitive decline varied by ethnicity: time6education6ethnicity: b = 0.03; p = 0.23.”
Quote in the paperNot a substantial claim - Findingown data
There was no association between education and the rate of visual-spatial decline.
“There was no association between education and rates of abstract reasoning (b = 20.002;p = 0.191), visual-spatial (b,20.001;p = 0.987), or language (b = 0.002; p = 0.168) decline.”
- Also stated in: § Education and rates of cognitive decline · plain
“there was no association between education and rates of visual-spatial and language decline (table 3; fig 1).”
Quote in the paperSubstantial claim - Also stated in: § Education and rates of cognitive decline · plain
- Findingown data
There was no association between education and the rate of language decline.
“There was no association between education and rates of abstract reasoning (b = 20.002;p = 0.191), visual-spatial (b,20.001;p = 0.987), or language (b = 0.002; p = 0.168) decline.”
- Also stated in: § Education and rates of cognitive decline · plain
“there was no association between education and rates of visual-spatial and language decline (table 3; fig 1).”
Quote in the paperSubstantial claim - Also stated in: § Education and rates of cognitive decline · plain
- Findingown data
There was no evidence of differential rates of cognitive decline by literacy level.
“There was no evidence of differential rates of decline for different literacy levels: b = 0.01; p = 0.43.”
Quote in the paperSubstantial claim
- Findingown data
None of the vascular variables was significantly associated with cognitive decline in the model.
“None of the vascular variables was significant in this model.”
Quote in the paperSubstantial claim - Findingown data
There was no evidence that rates of cognitive decline differed by ethnicity.
“There was no evidence of different rates of decline among ethnicities: time6ethnicity: b = 20.009;p = 0.65.”
Quote in the paperNot a substantial claim - Findingown data
After baseline cognitive performance was controlled, every extra year of schooling predicted a further 0.003 z-score unit drop in the composite score annually.
“For each additional year of education there was 0.3% standard deviation lower composite cognitive performance for each year of follow up.”
- Also stated in: § Education and rates of cognitive decline · plain
“In models adjusted for baseline cognitive performance, each additional year of education was associated with an additional decline of 0.003 z score units of the composite cognitive score per year of follow up (table 3; fig 1).”
Quote in the paperSubstantial claim - Also stated in: § Education and rates of cognitive decline · plain
- Findingown data
Literacy did not modify the association between education and cognitive decline.
“Additionally, there was no evidence that the relationship between education and cognitive decline varied by literacy: b = 20.001;p = 0.60.”
Quote in the paperNot a substantial claim - Findingown data
In this incident AD cohort, the composite cognitive score fell by 9% of a standard deviation each year.
“Composite cognitive performance declined by 9% of a standard deviation per year.”
- Also stated in: § Decline of cognition over time · hedged
“For the composite score, b was 20.09 (p,0.001),indicating a 9% decline in the score per year of follow up.”
Quote in the paperNot a substantial claim - Also stated in: § Decline of cognition over time · hedged
- Findingown data
The association between higher education and faster cognitive decline remained after adjustment for age, gender, ethnicity, baseline cognitive performance, depression, and vascular comorbidity.
“was present over and above age, gender, ethnicity, differential baseline cognitive performance, depression, and vascular comorbidity.”
- Also stated in: § Education and rates of cognitive decline · plain
“When we considered depression together with vascular risk factors, the results did not change either: time6education: b = 20.003;p = 0.017.”
Quote in the paperSubstantial claim - Also stated in: § Education and rates of cognitive decline · plain
- Findingown data
Depression at the first evaluation was not related to educational level.
“Depression at first evaluation was present for 8% of the subjects and was not related to educational level (t = 1.57; p = 0.12).”
Quote in the paperNot a substantial claim - Findingown data
Higher education was associated with faster decline in the executive speed domain.
“The association between higher education and faster decline was noted primarily in the executive speed (0.6%) and memory (0.5%) cognitive domains and was present over and above age, gender, ethnicity, differential”
- Also stated in: § Education and rates of cognitive decline · plain
“there was an association between education and z score decline for executive speed, memory, and abstract reasoning domains”
Quote in the paperSubstantial claim - Also stated in: § Education and rates of cognitive decline · plain
- Findingown data
The rate of cognitive decline was similar before and after the clinical incidence of AD.
“Rates of decline before and after AD incidence were similar.”
- Also stated in: § Decline of cognition over time · plain
“Rates of cognitive decline before and after the AD incidence visit were similar (time6pre-post incidence interaction term b = 0.007; p = 0.57).”
Quote in the paperSubstantial claim - Also stated in: § Decline of cognition over time · plain
- Findingown data
Higher education was associated with faster decline in the abstract reasoning domain.
“there was an association between education and z score decline for executive speed, memory, and abstract reasoning domains”
- Also stated in: § Education and rates of cognitive decline · plain
“significant time6education interaction for memory (b = 20.005;p = 0.002), abstract reasoning (b = 20.003;p = 0.026), and executive speed (b = 20.007;p,0.001)”
Quote in the paperSubstantial claim - Also stated in: § Education and rates of cognitive decline · plain
- Findingown data
In post-incidence visits only, there was no differential rate of decline for language by education.
“There were no differential rates of decline for the other cognitive domains: abstract reasoning (b = 20.003;p = 0.31), visual-spatial (b = 0.002; p = 0.47), and language (b = 20.002;p = 0.49).”
Quote in the paperNot a substantial claim - Findingown data
At baseline, subjects who would later be diagnosed with AD 3.8 years later already performed 0.37 SD lower than matched controls without dementia.
“there was evidence of cognitive impairment at the baseline evaluation, with subjects who were to be diagnosed with AD ,3.8 years later, already performing 0.37 SD lower than the age, gender, and education matched controls without dementia.”
Quote in the paperSubstantial claim - Findingown data
At the AD incidence visit, mean cognitive performance was 0.89 SD below that of controls.
“As expected, mean cognitive z scores were even lower at the AD incidence visit, with cognitive performance 0.89 SD below that of the controls.”
Quote in the paperNot a substantial claim - Findingown data
More educated AD patients showed higher composite cognitive scores at baseline.
“As expected, AD patients with more education had better baseline composite cognitive performance (r = 0.14, p,0.001).”
Quote in the paperNot a substantial claim - Findingown data
In post-incidence visits only, there was no differential rate of decline for visual-spatial by education.
“There were no differential rates of decline for the other cognitive domains: abstract reasoning (b = 20.003;p = 0.31), visual-spatial (b = 0.002; p = 0.47), and language (b = 20.002;p = 0.49).”
Quote in the paperNot a substantial claim - Findingown data
The association between education and cognitive decline was particularly noted in the specific domains of executive speed and memory.
“This association was particularly noted in the specific domains of executive speed and memory.”
Quote in the paperNot a substantial claim - Findingown data
In post-incidence visits only, there was no differential rate of decline for abstract reasoning by education.
“There were no differential rates of decline for the other cognitive domains: abstract reasoning (b = 20.003;p = 0.31), visual-spatial (b = 0.002; p = 0.47), and language (b = 20.002;p = 0.49).”
Quote in the paperNot a substantial claim - Findingown data
More educated AD patients had lower rates of hypertension.
“As expected, AD patients with higher education had less hypertension (t = 2.30; p = 0.022) and diabetes (t = 2.36; p = 0.019).”
Quote in the paperNot a substantial claim - Findingown data
There were significant differences in education among ethnic groups.
“There were significant education differences among ethnicities (omnibus ANOVA F = 29.1,p,0.001).”
Quote in the paperNot a substantial claim - Findingown data
Incident AD patients' cognitive performance 3.9 years before incidence was already 0.37 SD lower than that of age, gender, and education matched controls.
“Our incident AD patients' cognitive performance 3.9 years before incidence was already 0.37 SD lower than that of age, gender, and education matched controls.”
Quote in the paperSubstantial claim - Findingown data
Rates of cognitive decline were almost identical before and after incidence.
“In addition, rates of cognitive decline were almost identical before and after incidence.”
Quote in the paperSubstantial claim - Findingown data
In supplementary analyses including only post-incidence evaluations, the direction and magnitude of the coefficients were very similar despite the smaller number of patients.
“In supplementary analyses which included only the post-incidence evaluations, both the direction and the magnitude of the coefficients were very similar despite the smaller number of patients included in these analyses.”
Quote in the paperNot a substantial claim - Findingown data
In post-incidence visits only, the association between higher education and memory decline was borderline non-significant.
“The memory domain was borderline non-significant (b = 20.004;p = 0.067).”
Quote in the paperNot a substantial claim - Findingown data
There were significant differences in baseline cognitive performance among ethnic groups.
“Similarly, there were significant cognitive performance differences among ethnicities (omnibus ANOVA F = 5.47, p = 0.001).”
Quote in the paperNot a substantial claim - Findingown data
The language domain score was skewed to the left due to a ceiling effect in its constituent tests.
“The language domain score was skewed to the left because of a ceiling effect in the constituent neuropsychological measures.”
Quote in the paperNot a substantial claim - Findingown data
Hispanic subjects had significantly lower education than white and black subjects.
“In post-hoc Scheffe's tests, Hispanic subjects (mean 5.2 years of education) had significantly lower education as compared to both white subjects (mean 10.2 years of education) and black subjects (mean 8.9 years of education).”
Quote in the paperNot a substantial claim - Findingown data
More educated AD patients had lower rates of diabetes.
“As expected, AD patients with higher education had less hypertension (t = 2.30; p = 0.022) and diabetes (t = 2.36; p = 0.019).”
Quote in the paperNot a substantial claim - Findingown data
Incident AD patients with higher educational attainment had a faster rate of cognitive decline than those with lower education.
“We found a faster rate of cognitive decline in incident AD patients with higher educational attainment compared to those with lower education.”
Quote in the paperSubstantial claim - Findingown data
There was no evidence of gradual acceleration or deceleration in the rate of cognitive decline over time.
“We detected no evidence of gradual acceleration or deceleration of rates of decline.”
- Also stated in: § Decline of cognition over time · plain
“This was the case both preincidence (time 2 b = 0.001; p = 0.66) and post-incidence (time 2 b = 0.001; p = 0.75).”
Quote in the paperSubstantial claim - Also stated in: § Decline of cognition over time · plain
- Findingown data
In post-incidence visits only, higher education patients had faster decline in the executive speed domain.
“In a model with gender, age, ethnicity, time, education, and cognitive scores (at incidence), we detected faster decline for higher education patients in the executive speed domain (b = 20.007;p = 0.025).”
Quote in the paperSubstantial claim - Findingown data
Depression at any point during follow-up was not related to educational level.
“Depression at any point during the follow up was present for 32% of the subjects and was not related to educational level (t = 1.25; p = 0.21).”
Quote in the paperNot a substantial claim - Findingown data
Higher education was associated with higher baseline performance in all cognitive domains except language.
“Higher education was associated with significantly higher baseline performance in all cognitive domains except language (p = 0.08).”
Quote in the paperNot a substantial claim - Interpretationown data
In patients with incident AD, higher educational attainment is associated with faster cognitive decline.
“Conclusions: We conclude that higher education AD patients experience faster cognitive decline.”
- Also stated in: § Education and rates of cognitive decline · plain
“When we simultaneously considered all the above variables in a single GEE model, the results were unchanged: higher education patients had faster cognitive decline: b = 20.003;p = 0.017.”
Quote in the paperSubstantial claim - Also stated in: § Education and rates of cognitive decline · plain
- Study design and conductnone given
The large range and variety of education in the multiethnic population offers higher power and generalisability.
“The large range and variety of education in our multiethnic population offers the advantage of higher power and generalisability.”
Quote in the paperSubstantial claim - Interpretationown data
The results are suggestive of model B-a: the lower incidence of AD reported in previous studies may be the result of a later inflection point and not of a slower pre-incidence rate of decline for higher education AD patients.
“The results of the present analyses are suggestive of model B-a in fig 2: the lower incidence of AD reported in previous studies may be the result of a later inflection point and not of a slower preincidence rate of decline for higher education AD patients.”
Quote in the paperSubstantial claim - Study design and conductown data
Because pre-incidence data were used and post-incidence follow-up was relatively limited (1.8 years), the study may not have fully captured later stages of the disease.
“Second, because we used pre-incidence data and the postincidence follow up was relatively limited (1.8 years), it is possible that we have not fully captured the later stages of the disease.”
Quote in the paperNot a substantial claim - Interpretationown data
The authors' results do not support the alternative explanation that individuals with higher education have a younger age of onset of AD, because onset of clinical AD occurred during the evaluation period and age was included as a covariate.
“Our results do not support this since we know that the onset of clinical AD occurred during the evaluation period for these subjects and we included age as a covariate in the analyses.”
Quote in the paperSubstantial claim - Interpretationown data
The authors feel that data collected for a few years prior to AD clinical incidence reflect the effects of AD-associated pathological changes.
“We therefore feel that data collected for a few years prior to AD clinical incidence reflect the effects of AD associated pathological changes.”
Quote in the paperSubstantial claim - Premisecitation
In a Xenon study, AD patients with higher education manifested more prominent cerebral blood flow deficits when controlling for clinical severity.
“In a Xenon study, AD patients with higher education 52 manifested more prominent cerebral blood flow deficits (and hence more AD pathology) when controlling for clinical severity.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [52] 52. Stern Y, Alexander GE, Prohovnik I, et al. Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer's disease. Ann Neurol 1992;32(3):371-5.
Not checked in the free run.
- Study design and conductown data
Selecting a control sample matched additionally for ethnicity did not change the results.
“Selecting another sample of controls matched to the incident AD patients not only for age, gender, and education but also for ethnicity did not change the results.”
Quote in the paperNot a substantial claim - Premisecitation
In an MRI study of AD patients, controlling for cognitive performance, higher levels of education were associated with more severe parietal atrophy.
“In an MRI study of AD patients, controlling for cognitive performance, higher levels of education were associated with more severe parietal atrophy (an indirect measure of brain AD pathology).56”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [56] 56. Kidron D, Black SE, Stanchev P, et al. Quantitative MR volumetry in Alzheimer's disease. Topographic markers and the effects of sex and education. Neurology 1997;49(6):1504-12.
Not checked in the free run.
- Study design and conductown data
The proportion of individuals within each ethnic group and age stratum who participated did not differ significantly from the source population.
“Based on the distributions within the subsamples, the proportion of individuals within each ethnic group and age stratum who participated in the study did not differ significantly from the source population.”
Quote in the paperNot a substantial claim - Study design and conductreasoning
The current investigation was performed in a representative sample of a multiethnic community, which provides increased generalisability of the findings.
“In contrast to most previous studies which included AD patients who were self referred to clinics or university based AD research centres, the current investigation was performed in a representative sample of a multiethnic community, which provides increased generalisability of the findings.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 15
- May combine two claims. 19
- The quote only partly states this claim. 1
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataMen had slightly better baseline composite cognitive performance than women.
“Men performed slightly better than women: mean baseline composite score was -0.35 for men and -0.50 for women (p = 0.03).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataResults were similar when the language domain was analyzed as a recoded four-level categorical variable.
“The results were similar in supplementary analyses that used language domain as the outcome in the form of a recoded four level categorical variable.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataAge and baseline composite cognitive score were not associated.
“There was no association between age and education (r = 0.09, p = 0.14) or between age and baseline composite score (r = 0.10, p = 0.08).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataEducation and gender were not associated.
“There was no association between education and gender (mean years of education 7.2 for males and 7.1 for females; p = 0.86).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIncluding baseline scores as covariates in the analyses did not change the results, addressing the alternative explanation that higher education patients perform better at diagnosis and have more room for decline.
“However, we included baseline scores as covariates in the analyses and the results were unchanged.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataHispanic subjects had lower baseline cognitive performance than black subjects but similar performance to white subjects.
“In post-hoc Scheffe's tests, Hispanic subjects (mean baseline composite z score -0.57) had significantly lower baseline cognitive performance as compared to black subjects (mean baseline composite z score 20.32) but had similar baseline cognitive performance as compared to white subjects (mean baseline composite z score -0.38).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the same pre-incidence model, there were no differential rates of decline by education for abstract reasoning (b = -0.002; p = 0.33), visual-spatial (b = -0.001; p = 0.81), and language (b = -0.001; p = 0.78).
“There were no differential rates of decline for abstract reasoning (b = 20.002;p = 0.33), visual-spatial (b = 20.001;p = 0.81), and language (b = 20.001;p = 0.78).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataAge and education were not associated.
“There was no association between age and education (r = 0.09, p = 0.14) or between age and baseline composite score (r = 0.10, p = 0.08).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe composite z score and all cognitive domain scores except language were normally distributed.
“The composite z score, and all cognitive domain scores with the exception of the language domain, were normally distributed.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataEducation was not significantly linked to LDL, heart disease history, stroke, or current smoking.
“There was no significant association between education and LDL, history of heart disease, stroke, or current smoking.”
Quote in the paperNot a substantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataIn a model adjusted for all covariates, among incident AD patients, higher education was associated with faster decline in memory (b = -0.004; p = 0.037) and executive speed (b = -0.008; p = 0.006) for evaluations preceding incidence.
“There was faster decline for higher education AD patients in the memory (b = 20.004;p = 0.037) and executive speed domains (b = 20.008;p = 0.006).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe association between education and cognitive decline remained after controlling for differential cognitive performance at the initial visit and was not accounted for by literacy, vascular comorbidity, or depression.
“The association between education and cognitive decline was still noted after controlling for differential cognitive performance at the initial visit and was not accounted for by literacy, vascular comorbidity, or depression.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationResults from the Religious Order Study contested the prediction that higher education patients would have heavier brain pathological burden at clinical manifestation; the association between cognitive function and AD pathology was modified by education, with less effect of AD pathology on cognitive function for each additional year of education.
“Results from the Religious Order Study, including clinical and neuropathological data from 130 older Catholic clergy, contested this.57 The association between cognitive function and AD pathology was modified by education: there was less effect of AD pathology on cognitive function for each additional year of education.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [57] 57. Bennett DA, Wilson RS, Schneider JA, et al. Education modifies the relation of AD pathology to level of cognitive function in older persons. Neurology 2003;60(12):1909-15.
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone givenClinical diagnosis was based on uniform application of widely accepted criteria via a consensus diagnostic conference procedure.
“Clinical diagnosis was based on uniform application of widely accepted criteria via a consensus diagnostic conference procedure.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductcitationAlthough rates of decline were examined using both linear and non-linear (quadratic) terms, other types of non-linear decline may be present.
“Third, although we examined rates of decline using both linear and non-linear (quadratic) terms, it is possible that other types of non-linear decline may be present.8 9 60 61”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites 8 9 60 61
Not checked in the free run.
May combine two claims.
Study design and conductown dataThere were no differences between the 548 control subjects and the 312 incident AD patients in gender, age tertiles, or education tertiles.
“More specifically, there were no differences between the 548 subjects and the 312 incident AD patients regarding gender (x 2 = 0.19; p = 0.67), age tertiles (x 2 = 4.16 = 0.13), or education tertiles (x 2 = 1.53; p = 0.47).”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductreasoningThe design of the present study enables testing of the hypothesis during earlier stages of disease, unlike previous reports that studied more impaired AD patients.
“Previous reports studied more impaired AD patients (either prevalent cases or patients seeking medical attention) capturing the part of disease course corresponding to more advanced stages, while the design of the present study enables testing of the hypothesis during earlier stages of disease.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningAssuming that the progression of AD pathology does not differ as a function of education, the delay in clinical onset may result from differences in rate of cognitive decline, differences in the time when cognitive decline begins, or a combination of both.
“Assuming that the progression of AD pathology does not differ as a function of education, this delay in clinical onset may result from differences in rate of cognitive decline, differences in the time when cognitive decline begins (''inflection point''), or a combination of both.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The progression of AD pathology does not differ as a function of education.
Classified as probably not a substantial claim.
PremisecitationThe cognitive reserve hypothesis predicts that among AD patients with similar cognitive status, those with more CR would have or be able to tolerate more severe degrees of brain pathology.
“The CR hypothesis predicts that among AD patients with similar cognitive status, those with more CR would have (or be able to tolerate) more severe degrees of brain pathology.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites 1 2 43
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe study used a comprehensive battery of cognitive assessment, permitting evaluation of a full range of cognitive domains.
“We used a comprehensive battery of cognitive assessment, permitting evaluation of a full range of cognitive domains.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe data were examined to ensure that variables in the models met the assumption of normality.
“The data were examined to ensure that the variables included in the models met the model assumptions (that is, normality).”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductreasoningThe study is one of the largest examining this hypothesis and provided sufficient power for detection and more precise calculation of effects and ability to control for potential confounders.
“This is one of the largest studies examining this hypothesis and provided sufficient power for detection and more precise calculation of effects of interest as well as the ability to control for potential confounders.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductcitationProbable or possible AD diagnosis used NINCDS-ADRDA criteria.
“For the diagnosis of probable or possible AD, the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association 34 were used.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] 34. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34(7):939-44.
Not checked in the free run.
May combine two claims.
Study design and conductreasoningEvaluations were performed approximately every 1.5 years for an average of 5.6 years (up to 13.3), providing multiple assessments and permitting more accurate slope calculations.
“Evaluations were performed approximately every 1.5 years for an average of 5.6 (and up to 13.3) years, which provides multiple assessments of cognitive performance and therefore permits more accurate slope calculations.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationDementia diagnosis used DSM-III-R criteria.
“the criteria used for the diagnosis of dementia as required by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R).33”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] 33. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Washington, DC: American Psychiatric Association, 1987.
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).
Study design and conductnone givenYears of schooling cannot completely capture all aspects of educational experience.
“Fifth, years of schooling cannot completely capture all aspects of educational experience (that is, different quality of education in different educational systems, etc).”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningBecause AD pathology progresses independently of educational attainment or CR, when pathological burden becomes more severe and widespread, sufficient neural substrate is no longer available and a faster decline may ensue.
“However, because AD pathology progresses independently of educational attainment (or CR), when pathological burden becomes more severe and widespread, sufficient neural substrate is no londer available and a faster decline may ensue.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationMany prospective studies have suggested that higher education is associated with reduced risk of incident AD.
“Many prospective studies have suggested that higher education is associated with reduced risk of incident AD. 11 20 45-51”
Quote in the paperSubstantial claim0 of 1 sources checked- cites 11 20 45-51
Not checked in the free run.
May combine two claims.
PremisecitationThe used standard diagnostic criteria have a sensitivity of approximately 81% and a specificity of approximately 70%.
“The used standard diagnostic criteria have a sensitivity of ,81% with a specificity of ,70%.59”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [59] 59. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1143-53.
Not checked in the free run.
The paper relies on this without support.
Pathological changes of Alzheimer's disease are present in the brain many years before clinical symptoms of dementia appear.
“the pathological changes of AD are present in the brain many years before the onset of clinical symptoms of dementia”
The paper relies on this without support.
Previous studies of education and AD progression usually used clinic-referred patients, which limits generalizability to the general population.
“subjects studied in previous reports were usually clinic referred AD patients, which could limit generalisability to the population.”
The paper relies on this without support.
Previous studies of education and AD progression used prevalent AD patients recruited at various disease stages, so they could not accurately control for disease duration.
“previous studies were of prevalent AD patients who were recruited at various stages of their disease.Time of disease onset could only be estimated retrospectively or inferred by cognitive performance status.Therefore, previous studies could not accurately control for duration of disease.”
The paper relies on this without support.
Most previous investigations used limited neuropsychological measures that do not assess many cognitive domains and can suffer from floor and ceiling effects.
“most previous investigations have used limited neuropsychological measures that do not assess many cognitive domains and can suffer from floor and ceiling effects resulting in inadequately assessed cognitive performance.”
The paper relies on this without support.
Most previous reports did not adequately control for education-related differences in baseline cognitive performance.
“most previous reports did not adequately control for the potential effect on rates of cognitive decline of education related differences in baseline cognitive performance.”
The authors state this as an assumption.
The progression of AD pathology does not differ as a function of education.
“Assuming that the progression of AD pathology does not differ as a function of education”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The observation of more rapid decline in higher attainment Alzheimer's disease patients was replicated in incident Alzheimer's disease, and patients who engaged in more leisure activities prior to dementia onset also showed more rapid cognitive decline.
“We replicated this observation in patients with incident AD28 and also found more rapid decline in cognitive function in AD patients who engaged in more leisure activities prior to dementia onset29.”
From Cognitive reserve in ageing and Alzheimer's disease (2012) · cites this paper as [28]
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe rate of decline is more rapid in individuals with high reserve than those with low reserve, even when accounting for other factors that may contribute to disease course.
“The rate of decline is more rapid in individuals with high reserve than those with low reserve, even when accounting for a multitude of other factors that may contribute to disease course27, 28, 46.”
From Cognitive reserve in ageing and Alzheimer's disease (2012) · cites this paper as [28]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Post-incidence follow-up duration has conflicting values
MinorThe discussion calls post-incidence follow-up 1.8 years, while Table 1 reports a mean of 3.9 years from incidence to the last evaluation among patients with post-incidence follow-up. The table separately lists 1.8 as the mean number of post-incidence evaluations.
“the postincidence follow up was relatively limited (1.8 years)”
“| After incidence (n = 131) | | | | Years from incidence to | 3.9 (2.39) | 0.9-11.1 | | last evaluation | | |”
Visit counts do not match the reported total
MinorThe numbers of patients with two through nine evaluations imply 1,154 assessments, not the reported 1,159.
“Overall, the 312 included AD subjects had 1159 separate cognitive assessments.”
“More specifically, 110 (35%) had two evaluations, 47 (15%) had three, 60 (19%) had four, 40 (13%) had five, 37 (12%) had six, 14 (5%) had seven, three (1%) had eight, and one (0.3%) had nine.”
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Cognitive reserve in ageing and Alzheimer's disease
Stern, Y. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70191-6 · Cited by 3,557 · see citing works
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“Study 8 Scarmeas et al. (2003b) 17 youngf, 19 oldg Nonverbal serial recognition GLM Identify voxels where the change in PET”
Hertzog, C., Kramer, A. F., Wilson, R. S., & Lindenberger, U. (2008) · Psychological Science in the Public Interest · doi:10.1111/j.1539-6053.2009.01034.x · Cited by 1,495 · see citing works
“, 2000) and education (Bruandet et al., 2008; Hall et al., 2007; Scarmeas et al., 2006; Teri, McCurry, Edland, Kulkull, & Larson, 1995; Wilson, Li, et al., 2004).”
Education and cognitive functioning across the life span
Lövdén, M., Fratiglioni, L., Glymour, M. M., Lindenberger, U., & Tucker-Drob, E. M. (2020) · Psychological Science in the Public Interest · doi:10.1177/1529100620920576 · Cited by 1,224 · see citing works
Mediterranean diet and risk for Alzheimer's disease
Scarmeas, N., Stern, Y., Tang, M., Mayeux, R., & Luchsinger, J. A. (2006) · Annals of Neurology · doi:10.1002/ana.20854 · Cited by 1,103 · see citing works
“WHICAP 1999 cohort, N (%) 395 (55) 508 (55) 312 (54) 0.”
Self-citationEpidemiology of Alzheimer DiseasePreprint
Mayeux, R. P., & Stern, Y. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006239 · Cited by 1,070 · see citing works
“Similarly , higher educational or occupational attainment (Stern et al. 1999; Scarmeas et al. 2006a), increased engagement in leisure activities (Helzner et al. 2007), and greater lifetime cognitive activity (Wilson et al. 2010) have each been associated with more rapid cognitive decline in…”
InfluentialBilingualism as a protection against the onset of symptoms of dementia
Bialystok, E., Craik, F. I. M., & Freedman, M. (2007) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2006.10.009 · Cited by 967 · see citing works
“Finally, there is evidence that patients with higher education catch up with their less-educated peers by exhibiting faster rates of cognitive decline in the 5 years after diagnosis ( Scarmeas, Albert, Manly & Stern, 2006 ).”
BackgroundPhysical Activity, Diet, and Risk of Alzheimer Disease
Scarmeas, N. (2009) · JAMA · doi:10.1001/jama.2009.1144 · Cited by 916 · see citing works
Self-citationThe bilingual adaptation: How minds accommodate experience
Bialystok, E. (2017) · Psychological Bulletin · doi:10.1037/bul0000099 · Cited by 906 · see citing works
Cognitive Reserve and Alzheimer Disease
Stern, Y. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000213815.20177.19 · Cited by 838 · see citing works
Durga, J., van Boxtel, M. P., Schouten, E. G., Kok, F. J., Jolles, J., Katan, M. B., & Verhoef, P. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60109-3 · Cited by 758 · see citing works
Detecting Dementia With the Mini-Mental State Examination in Highly Educated Individuals
O’Bryant, S. E., Humphreys, J. D., Smith, G. E., Ivnik, R. J., Graff‐Radford, N. R., Petersen, R. C., & Lucas, J. A. (2008) · Archives of Neurology · doi:10.1001/archneur.65.7.963 · Cited by 653 · see citing works
“13 This literature demonstrates that oncediagnosed,patientswithprobableAlz-heimerdiseasewhohavehigherlevelsof educationtendtodemonstrateasteeper slopeofdecline 14,15 and earlier mortality rates.”
BackgroundM. Tucker, A., & Stern, Y. (2011) · Current Alzheimer Research · doi:10.2174/156720511795745320 · Cited by 561 · see citing works
“A further limitation of this model is that it cannot explain why those with higher IQ and more education decline more quickly once Alzheimer’s is diagnosed and progress to death sooner [21-27].”
BackgroundKurtz, M. M., & Gerraty, R. T. (2009) · Neuropsychology · doi:10.1037/a0016277 · Cited by 433 · see citing works
Defining Cognitive Reserve and Implications for Cognitive Aging
Pettigrew, C. A., & Soldan, A. (2019) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-019-0917-z · Cited by 437 · see citing works
Solé‐Padullés, C., Bartrés‐Faz, D., Junqué, C., Vendrell, P., Rami, L., Clemente, I. C., Bosch, B., Villar, A., Bargalló, N., Jurado, M. Á., et al. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.10.008 · Cited by 387 · see citing works
Langa, K. M., Larson, E. B., Karlawish, J. H., Cutler, D., Kabeto, M. U., Kim, S. Y. H., & Rosen, A. B. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.01.001 · Cited by 377 · see citing works
Educational attainment and cognitive decline in old age
Wilson, R. S., Hebert, L. E., Scherr, P. A., Barnes, L. L., Mendes de Leon, C. F., & Evans, D. A. (2009) · Neurology · doi:10.1212/01.wnl.0000341782.71418.6c · Cited by 354 · see citing works
Contribution of Vascular Risk Factors to the Progression in Alzheimer Disease
Helzner, E., Luchsinger, J. A., Scarmeas, N., Cosentino, S., Brickman, A. M., Glymour, M. M., & Stern, Y. (2009) · Archives of Neurology · doi:10.1001/archneur.66.3.343 · Cited by 329 · see citing works
“The z scores were averaged within cognitive domains, which were subsequently averaged to produce the composite cognitive score.(24) The outcome measure was the rate of change in the composite score from diagnosis onward.”
MethodSelf-citationMediterranean diet and Alzheimer disease mortality
Scarmeas, N., Luchsinger, J. A., Mayeux, R. P., & Stern, Y. (2007) · Neurology · doi:10.1212/01.wnl.0000277320.50685.7c · Cited by 324 · see citing works
Self-citationLong-term Cognitive and Psychological Outcomes in the Awakening and Breathing Controlled Trial
Jackson, J. C., Girard, T. D., Gordon, S. M., Thompson, J. L., Shintani, A., Thomason, J. W. W., Pun, B. T., Canonico, A. E., Dunn, J., Bernard, G. R., et al. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200903-0442oc · Cited by 255 · see citing works
“composite cognitive score, which has been employed in a variety of investigations (25-27), minimizes floor and ceiling effects and reduces the risk of type I error when multiple cognitive tests are used (28,29).”
MethodModifiable lifestyle factors and cognitive reserve: a systematic review of current evidence
Song, S., Stern, Y., & Gu, Y. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101551 · Cited by 248 · see citing works
Kemppainen, N. M., Aalto, S., Karrasch, M., Någren, K., Savisto, N., Oikonen, V., Viitanen, M., Parkkola, R., & Rinne, J. O. (2008) · Annals of Neurology · doi:10.1002/ana.21212 · Cited by 239 · see citing works
“However, after AD incident faster decline in memory and executive speed is associated with higher education.(23) The lower incidence of AD in high-educated populations has been shown in several epidemiological studies, but the protective mechanism of education against the disease is still unclear.”
BackgroundMediterranean Diet, Inflammatory and Metabolic Biomarkers, and Risk of Alzheimer's Disease
Gu, Y., Luchsinger, J. A., Stern, Y., & Scarmeas, N. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100897 · Cited by 244 · see citing works
“Cognitive performance at baseline A composite cognitive Z-score was developed to summarize cognitive performance as previously described [28–32].”
MethodSelf-citationCognitive Reserve and Alzheimer’s Disease
Xu, W., Yu, J., Tan, M., & Tan, L. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8720-y · Cited by 240 · see citing works
Sex and age differences in atrophic rates: an ADNI study with n=1368 MRI scans
Hua, X., Hibar, D. P., Lee, S., Toga, A. W., Jack, C. R., Weiner, M. W., & Thompson, P. M. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.033 · Cited by 234 · see citing works
Fotenos, A. F., Mintun, M., Snyder, A., Morris, J., & Buckner, R. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.27 · Cited by 228 · see citing works
“c 26/5 35/5 28/1 Hollingshead, mean (SD) [range] 35 (4) [29-43] 22 (3) [18-27] 13 (2) [11-15] MMSE score, mean (SD) [range] 29 (1) [25-30] 29 (1) [26-30] 29 (1) [26-30] Medications, mean (SD) [range], No.”
Incidence of Mild Cognitive Impairment: A Systematic Review
Luck, T., Luppa, M., Briel, S., & Riedel-Heller, S. G. (2010) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000272424 · Cited by 213 · see citing works
“A high level of education was also found to be associated with a decreased risk for incident Alzheimer’s disease (AD) yet with a faster cognitive decline in clinically manifest AD [”
BackgroundKim, B.-K., Noh, G. O., & Kim, K. (2021) · BMC Geriatrics · doi:10.1186/s12877-021-02109-w · Cited by 221 · see citing works
APOE ε4 allele predicts faster cognitive decline in mild Alzheimer disease
Cosentino, S., Scarmeas, N., Helzner, E., Glymour, M. M., Brandt, J., Albert, M., Blacker, D., & Stern, Y. (2008) · Neurology · doi:10.1212/01.wnl.0000304038.37421.cc · Cited by 214 · see citing works
Self-citationGildner, T. E., Liebert, M. A., Kowal, P. R., Chatterji, S., & Snodgrass, J. J. (2014) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.3782 · Cited by 217 · see citing works
“In accordance with other cognitive studies, composite z-scores were calculated to facilitate the comparison of cognitive test performance between individuals (Grodstein et al., 2003; Scarmeas et al., 2006).”
MethodSubramaniapillai, S., Almey, A., Rajah, M. N., & Einstein, G. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100879 · Cited by 204 · see citing works
Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease
Soldan, A., Pettigrew, C. A., Cai, Q., Wang, J., Wang, M., Moghekar, A., Miller, M. I., & Albert, M. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.09.002 · Cited by 206 · see citing works
“…Stern model, a number of previous studies of individuals with dementia have reported greater rates of cognitive decline (e.g., Roselli et al., 2009; Scarmeas et al., 2006; Stern et al., 1999) or functional decline (de Oliveira et al., 2015) among those with more education compared to those with…”
ResultBilingualism delays clinical manifestation of Alzheimer's disease
Woumans, E., Santens, P., Sieben, A., Versijpt, J. J., Stevens, M., & Duyck, W. (2014) · Bilingualism Language and Cognition · doi:10.1017/s136672891400087x · Cited by 190 · see citing works
“This may seem counterintuitive, but note that faster AD progression with higher education has also been reported earlier (Scarmeas et al., 2006).”
Desjardins, R., & Warnke, A. J. (2012) · OECD education working papers · doi:10.1787/5k9csvw87ckh-en · Cited by 192 · see citing works
Effects of education on cognition at older ages: Evidence from China's Great Famine
Huang, W., & Zhou, Y. (2013) · Social Science & Medicine · doi:10.1016/j.socscimed.2013.08.021 · Cited by 176 · see citing works
Dementia of the Alzheimer Type
Jalbert, J. J., Daiello, L. A., & Lapane, K. L. (2008) · Epidemiologic Reviews · doi:10.1093/epirev/mxn008 · Cited by 174 · see citing works
“If patients with higher educational levels also have a higher cognitive reserve, then, when DAT symptoms become apparent, the pathological burden will already be more severe and widespread, and, with the cognitive reserve depleted, the patient would appear to experience cognitive decline at a more rapid rate (45, 109).”
BackgroundDoes cognitive reserve shape cognitive decline?
Singh‐Manoux, A., Marmot, M. G., Glymour, M. M., Sabia, S., Mika Kivimaki, B., & Dugravot, A. (2011) · Annals of Neurology · doi:10.1002/ana.22391 · Cited by 170 · see citing works
“Clinical studies, often on a small number of subjects, assume that cognitive function declines only in the period immediately prior to the diagnosis of dementia.(24,25) However, there is now enough evidence from large scale studies to suggest a much longer period of cognitive decline.”
BackgroundHughes, M. L., Agrigoroaei, S., Jeon, M., Bruzzese, M., & Lachman, M. E. (2018) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617718000425 · Cited by 167 · see citing works
Heterogeneity of cognitive trajectories in diverse older persons.
Mungas, D., Beckett, L. A., Harvey, D. J., Farias, S. T., Reed, B., Carmichael, O. T., Olichney, J., Miller, J. W., & DeCarli, C. S. (2010) · Psychology and Aging · doi:10.1037/a0019502 · Cited by 165 · see citing works
Bosch, B., David Bartrés-faz, A., Rami, L., Arenaza‐Urquijo, E. M., Fernández‐Espejo, D., Junqué, C., Solé‐Padullés, C., Sánchez‐Valle, R., Bargalló, N., Falcón, C., et al. (2009) · Cortex · doi:10.1016/j.cortex.2009.05.006 · Cited by 153 · see citing works
“…bDepartment de Psiquiatria i Psicobiologia Clinica, Universitat de Barcelona, Catalonia, Spain cInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Catalonia, Spain dRadiology Service, Hospital Clı́nic de Barcelona, Catalonia, Spain eCIBER-BBN, Barcelona, Catalonia, Spain a r…”
BackgroundCognitive reserve and clinical progression in Alzheimer disease
van Loenhoud, A. C., van der Flier, W. M., Wink, A. M., Dicks, E., Groot, C., Twisk, J. W. R., Barkhof, F., Scheltens, P., Ossenkoppele, R., & Initiative, A. D. N. (2019) · Neurology · doi:10.1212/wnl.0000000000007821 · Cited by 149 · see citing works
Hippocampal volume varies with educational attainment across the life-span
Noble, K. G., Grieve, S. M., Korgaonkar, M. S., Engelhardt, L. E., Griffith, E. Y., Williams, L. M., & Brickman, A. M. (2012) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2012.00307 · Cited by 143 · see citing works
“ORIGINAL RESEARCH ARTICLE published: 09 November 2012 doi: 10.3389/fnhum.2012.00307 Hippocampal volume varies with educational attainment across the life-span”
BackgroundInfluentialCognitive and social lifestyle: links with neuropathology and cognition in late life
Bennett, D. A., Arnold, S. E., Valenzuela, M., Brayne, C., & Schneider, J. A. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1226-2 · Cited by 141 · see citing works
“Thus, education appears to not only delay the onset of cognitive decline but is also associated with a more rapid progression once decline commences and a greater risk of adverse health outcomes [108, 127].”
BackgroundAdam, S., Bonsang, É., Grotz, C., & Sergio, P. (2013) · Clinical Interventions in Aging · doi:10.2147/cia.s39921 · Cited by 138 · see citing works
“35 Taking into account these potential relationships with age and education, we used stochastic frontier analysis 36 to create a “frontier” corresponding to the optimum cognitive functioning that each individual is expected to achieve given age and level of education.”
Education amplifies brain atrophy effect on cognitive decline: Implications for cognitive reserve
Mungas, D., Gavett, B., Fletcher, E., Farias, S. T., Decarli, C., & Reed, B. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.04.002 · Cited by 131 · see citing works
Bialystok, E., Craik, F., Binns, M., Ossher, L., & Freedman, M. (2014) · Neuropsychology · doi:10.1037/neu0000023 · Cited by 129 · see citing works
“…rate of cognitive decline in older people, but the bulk of the evidence shows that reserve factors such as higher levels of education delay the onset of symptoms but are then followed by a faster rate of decline following diagnosis (Hall et al., 2007, 2009; Scarmeas, Albert, Manly, & Stern, 2006).”
BackgroundLANGUAGE AND DEMENTIA: NEUROPSYCHOLOGICAL ASPECTS
Kempler, D., & Goral, M. (2008) · Annual Review of Applied Linguistics · doi:10.1017/s0267190508080045 · Cited by 105 · see citing works
Perneczky, R. (2006) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.094714 · Cited by 122 · see citing works
“recently showed, for example, that the association between the Alzheimer’s disease pathology and cognitive symptoms shortly before death was attenuated by the number of years of schooling. Better educated patients had more pathology than would have been predicted from their cognitive status. Epidemiological studies th…”
BackgroundMejía-Arango, S., & Gutierrez, L. M. (2011) · Journal of Aging and Health · doi:10.1177/0898264311421199 · Cited by 125 · see citing works
Gross, A. L., Mungas, D., Crane, P. K., Gibbons, L. E., MacKay‐Brandt, A., Manly, J. J., Mukherjee, S., Romero, H., Sachs, B. C., Thomas, M., et al. (2015) · Psychology and Aging · doi:10.1037/pag0000032 · Cited by 126 · see citing works
“Level of educational attainment is strongly associated with cross-sectional cognitive test scores, explaining up to 50% of variance in some studies (Albert et al., 1995; Alley et al., 2007; Atkinson et al., 2005; Early et al., 2013; Manly et al., 2004; Mungas et al., 2000, 2005; Schaie, 1996).”
Dijk, K. R. A. V., Gerven, P. W. M. V., van Boxtel, M. P. J., der Elst, W. V., & Jolles, J. (2008) · Psychology and Aging · doi:10.1037/0882-7974.23.1.119 · Cited by 121 · see citing works
Musicco, M., Palmer, K., Salamone, G., Lupo, F., Perri, R., Mosti, S., Spalletta, G., Iulio, F. D., Pettenati, C., Cravello, L., et al. (2009) · Journal of Neurology · doi:10.1007/s00415-009-5116-4 · Cited by 118 · see citing works
“Lower education has also been found to be associated with slower progression rates in previous studies [22, 33, 36].”
ResultLesuis, S. L., Hoeijmakers, L., Kőrösi, A., de Rooij, S. R., Swaab, D. F., Kessels, H. W. H. G., Lucassen, P. J., & Krugers, H. J. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0422-7 · Cited by 120 · see citing works
Heo, J., Lee, K., Paek, S. H., Kim, M. J., Lee, J., Kim, J.-Y., Cho, S.-Y., Lim, Y. H., Kim, M.-R., Jeong, S. Y., et al. (2008) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2008.06.010 · Cited by 117 · see citing works
“Several studies reported an association between a higher level of education and a more rapid cognitive decline in Alzheimer's disease [46,47].”
Barnabé, A., Whitehead, V., Pilon, R., Arsenault‐Lapierre, G., & Chertkow, H. M. (2012) · Hippocampus · doi:10.1002/hipo.22015 · Cited by 114 · see citing works
“With regards to education, the theory predicts that higher education will delay the inception of rapid cognitive decline, but once cognitive decline has begun, it will be more accelerated in individuals with more education (Scarmeas et al., 2006; Stern, 2009).”
BackgroundRate of MMSE score change in Alzheimer's disease: Influence of education and vascular risk factors
Roselli, F., Tartaglione, B., Federico, F., Lepore, V. L., Defazio, G., & Livrea, P. (2008) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2008.10.006 · Cited by 112 · see citing works
Leisure activity and cognitive decline in incident Alzheimer disease
Helzner, E. P., Scarmeas, N., Cosentino, S., Portet, F., & Stern, Y. (2007) · Archives of Neurology · doi:10.1001/archneur.64.12.1749 · Cited by 112 · see citing works
“This was done to more fully capture the natural course of the disease, since AD-associated neuropathologic conditions and subtle cognitive decline are present many years before diagnosis.(27,28) Also, in this sample, rates of cognitive decline were similar before and after AD diagnosis.”
Self-citationAnthony, M., & Lin, F. (2018) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acx125 · Cited by 109 · see citing works
Spering, C. C., Hobson, V. L., Lucas, J. A., Menon, C. V., Hall, J. R., & O’Bryant, S. E. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls006 · Cited by 109 · see citing works
Strydom, A., Hassiotis, A., King, M., & Livingston, G. (2008) · Psychological Medicine · doi:10.1017/s0033291708003334 · Cited by 93 · see citing works
“An accelerated decline (Scarmeas et al. 2006) and higher mortality (Geerlings et al. 1999) have been noted when dementia occurs in adults with high ability or educational attainment, giving support to the idea that, in contrast to the present participants, they can tolerate some degree of pathology…”
BackgroundPhysical Activity and Alzheimer Disease Course
Scarmeas, N., Luchsinger, J. A., Brickman, A. M., Cosentino, S., Schupf, N., Xin-Tang, M., Gu, Y., & Stern, Y. (2010) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181eb00a9 · Cited by 112 · see citing works
“Higher education has been associated with faster rates of cognitive decline (25) and increased mortality (37) in AD patients.”
Self-citation‘Normal’ semantic–phonemic fluency discrepancy in Alzheimer's disease? A meta-analytic study
Laws, K. R., Duncan, A. L., & Gale, T. M. (2009) · Cortex · doi:10.1016/j.cortex.2009.04.009 · Cited by 101 · see citing works
Bessi, V., Mazzeo, S., Padiglioni, S., Piccini, C., Nacmias, B., Sorbi, S., & Bracco, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-171180 · Cited by 99 · see citing works
“These findings have been interpreted by means of the Cognitive Reserve hypothesis [35, 36].”
Noble, K. G., Korgaonkar, M. S., Grieve, S. M., & Brickman, A. M. (2013) · Developmental Science · doi:10.1111/desc.12077 · Cited by 99 · see citing works
Number of children is associated with neuropathology of Alzheimer's disease in women
Beeri, M. S., Rapp, M. A., Schmeidler, J., Reichenberg, A., Purohit, D. P., Perl, D. P., Grossman, H. T., Prohovnik, I., Haroutunian, V. H., & Silverman, J. M. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.011 · Cited by 96 · see citing works
Matallana, D., de Santacruz, C., Cano, C. A., Reyes, P. A., Samper‐Ternent, R., Markides, K. S., Ottenbacher, K. J., & Ortíz, C. (2010) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988710373597 · Cited by 96 · see citing works
Targets for the Prevention of Dementia
Middleton, L. E., & Yaffe, K. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-091657 · Cited by 94 · see citing works
“In contrast, people who are highly educated may have faster cognitive decline after the onset of AD [12,18–21], though not all studies agree [22].”
BackgroundCognitive Decline and Survival in Alzheimer’s Disease according to Education Level
Bruandet, A., Richard, F., Bombois, S., Maurage, C., Masse, I., Amouyel, P., & Pasquier, F. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000111693 · Cited by 90 · see citing works
“]; these factors may protect the brain from lesions that contribute to dementia [ , , , , ,”
BackgroundEducation Attenuates the Association between Dietary Patterns and Cognition
Akbaraly, T. N., Singh-Manoux, A., Marmot, M. G., & Brunner, E. J. (2009) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000199235 · Cited by 90 · see citing works
“Previous research shows that education is linked to dietary behavior [6, 7], the exposure being considered here and cognition [8-11], the outcome.”
BackgroundEffect of Cognitive Reserve Markers on Alzheimer Pathologic Progression
Lo, R. Y., & Jagust, W. J. (2013) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e3182900b2b · Cited by 88 · see citing works
Baldivia, B., Andrade, V. M., & Bueno, O. F. A. (2008) · Dementia & Neuropsychologia · doi:10.1590/s1980-57642009dn20300003 · Cited by 88 · see citing works
Education, cognitive function, and severity of neuropathology in Alzheimer disease
Koepsell, T. D., Kurland, B. F., Harel, O., Johnson, E. A., Zhou, X. H., & Kukull, W. A. (2008) · Neurology · doi:10.1212/01.wnl.0000284603.85621.aa · Cited by 115 · see citing works
Cespón, J., Miniussi, C., & Pellicciari, M. C. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.03.001 · Cited by 88 · see citing works
“Specifically, adherence to specific dietary habits has been associated with a lower risk of developing MCI and AD (Scarmeas et al., 2006).”
Plasma β-Amyloid and Cognitive Decline
Cosentino, S., Stern, Y., Sokolov, E., Scarmeas, N., Manly, J. J., Tang, M. X., Schupf, N., & Mayeux, R. P. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.189 · Cited by 83 · see citing works
Self-citationMantzorou, M., Vadikolias, Κ., Pavlidou, E., Serdari, A., Vasios, G. K., Tryfonos, C., & Giaginis, C. (2018) · Nutritional Neuroscience · doi:10.1080/1028415x.2018.1486940 · Cited by 82 · see citing works
Statistical Disease Progression Modeling in Alzheimer Disease
Rakêt, L. L., & Initiative, F. T. A. D. N. (2020) · Frontiers in Big Data · doi:10.3389/fdata.2020.00024 · Cited by 78 · see citing works
“It has consistently been found that higher education is associated with increased rate of cognitive decline in incident AD (Teri et al., 1995; Rasmusson et al., 1996; Wilson et al., 2004; Andel et al., 2006; Scarmeas et al., 2006; Musicco et al., 2009; Thomas et al., 2016), with several of these studies also reporting…”
ResultMazzeo, S., Padiglioni, S., Bagnoli, S., Bracco, L., Nacmias, B., Sorbi, S., & Bessi, V. (2019) · Journal of Neurology · doi:10.1007/s00415-018-9164-5 · Cited by 70 · see citing works
Trends in Psychiatry and Psychotherapy
(2020) · Trends in Psychiatry and Psychotherapy · doi:10.47626/2237-6089 · Cited by 70 · see citing works
Zahodne, L. B., Mayeda, E. R., Hohman, T. J., Fletcher, E., Racine, A. M., Gavett, B. E., Manly, J. J., Schupf, N., Mayeux, R. P., Brickman, A. M., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.08.009 · Cited by 69 · see citing works
“Current understanding of the protective effects of education on cognition is complicated by the well-replicated finding that more education is associated with better cognitive outcomes in healthy older adults, but faster cognitive decline in older adults with mild cognitive impairment (MCI) or dementia (Amieva et al.,…”
BackgroundModifiable, Non-Modifiable, and Clinical Factors Associated with Progression of Alzheimer’s Disease
Loeffler, D. A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201182 · Cited by 67 · see citing works
Identifying the Functional Brain Network of Motor Reserve in Early Parkinson's Disease
Chung, S. J., Kim, H., Jung, J. H., Lee, P. H., Jeong, Y., & Sohn, Y. H. (2020) · Movement Disorders · doi:10.1002/mds.28012 · Cited by 68 · see citing works
The cost of dementia in an unequal country: The case of Chile
Hojman, D. A., Duarte, F., Ruiz‐Tagle, J., Budnich, M., Delgado, C., & Slachevsky, A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172204 · Cited by 66 · see citing works
Gildner, T. E., Salinas‐Rodríguez, A., Manrique-Espinoza, B. S., Moreno-Tamayo, K. M., & Kowal, P. R. (2019) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2019.04.014 · Cited by 64 · see citing works
Russ, T. C., Batty, G. D., & Starr, J. M. (2011) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2795 · Cited by 62 · see citing works
“NART-IQ was significantly associated with survival in a model including age and gender—in this study, individuals with lower estimated premorbid IQ declined more rapidly after diagnosis in contrast to the cognitive reserve hypothesis (Stern et al. 1999; Scarmeas et al. 2006).”
ResultValen-Sendstad, A., Engedal, K., Stray‐Pedersen, B., Strobel, C., Barnett, L., Nurminemi, M., & Meyer, N. (2009) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181beaaf4 · Cited by 61 · see citing works
Traumatic brain injury and reserve
Bigler, E. D., & Stern, Y. (2015) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63521-1.00043-1 · Cited by 62 · see citing works
“Higher measured CR has also been associated with more rapid cognitive decline in patients with AD (Stern et al., 1999; Scarmeas et al., 2006).”
BackgroundNeural consequences of bilingualism for cortical and subcortical function
Krizman, J., & Marian, V. (2015) · Cambridge University Press eBooks · doi:10.1017/cbo9781107447257.027 · Cited by 58 · see citing works
Papaioannou, T., Voinescu, A., Petrini, K., & Fraser, D. S. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-210672 · Cited by 58 · see citing works
“…example, although people with higher education are less prone to develop dementia and MCI, when they do develop these conditions, the cognitive decline is greater than for people with lower level of education [39, 40], and therefore cognitive outcomesafterVRtrainingmaybeinfluencedbyedu-cationlevel.”
Stanley, K., Walker, Z., Koopmans, R., & Rosness, T. (2014) · International Psychogeriatrics · doi:10.1017/s1041610214001173 · Cited by 58 · see citing works
Babiloni, C., Lopez, S., Percio, C. D., Noce, G., Pascarelli, M. T., Lizio, R., Teipel, S. J., González‐Escamilla, G., Bakardjian, H., George, N., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.01.012 · Cited by 59 · see citing works
Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis
Bocancea, D. I., Svenningsson, A. L., van Loenhoud, A. C., Groot, C., Barkhof, F., Strandberg, O. T., Smith, R. A., Initiative, A. D. N., Weiner, M. W., Aisen, P., et al. (2023) · Brain · doi:10.1093/brain/awad100 · Cited by 57 · see citing works
Leoutsakos, J., Forrester, S., Corcoran, C. D., Norton, M. C., Rabins, P. V., Steinberg, M. I., Tschanz, J. T., & Lyketsos, C. G. (2014) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4221 · Cited by 56 · see citing works
“Education was associated with increased odds of membership in class 3 in the univariate analysis; this is consistent with other reports (Stern et al., 1999; Andel et al., 2006; Scarmeas et al., 2006).”
BackgroundResultEffects of education on the progression of early- versus late-stage mild cognitive impairment
Ye, B. S., Seo, S. W., Cho, H., Kim, S. Y., Lee, J., Kim, E., Lee, Y., Back, J. H., Hong, C. H., Choi, S. H., et al. (2012) · International Psychogeriatrics · doi:10.1017/s1041610212002001 · Cited by 56 · see citing works
“However, when participants with higher levels of education progressed to the stage of late-stage aMCI, they experienced more rapid cognitive decline, similar to those with AD (Teri et al., 1995; Stern et al., 1999; Amieva et al., 2005; Scarmeas et al., 2006; Bruandet et al., 2008).”
BackgroundResultInfluentialNeuroimaging modalities in the detection of Alzheimer's disease-associated biomarkers
Dang, C., Wang, Y., Li, Q., & Lu, Y. (2023) · Psychoradiology · doi:10.1093/psyrad/kkad009 · Cited by 53 · see citing works
“Epidemiological studies have reported that higher education years are associated with a reduced risk of incident AD, suggesting that education may pr ovide pr otection a gainst the on-set of AD (Cho et al. , 2015 ; Scarmeas et al. , 2006 ).”
BackgroundOffspring Educational Attainment and Older Parents' Cognition in Mexico
Ma, M., Yahirun, J., Saenz, J. L., & Sheehan, C. (2021) · Demography · doi:10.1215/00703370-8931725 · Cited by 52 · see citing works
“Indeed, re sults of pre vi ous work sug gest that the var i ance explained by one’s own ed u ca tional at tain ment may dif fer across cog ni tive di men sions (Alley et al. 2000; GuerraCarrillo 2017; Leibovici 1996; Scarmeas 2006), in clud ing in Mexico (Ardila et al. 2000).”
BackgroundNon-fluent progressive aphasia: Cerebral metabolic patterns and brain reserve
Perneczky, R., Diehl‐Schmid, J., Pohl, C., Drzezga, A. E., & Kurz, A. (2006) · Brain Research · doi:10.1016/j.brainres.2006.11.054 · Cited by 52 · see citing works
Dynamic change of cognitive reserve: associations with changes in brain, cognition, and diagnosis
Bettcher, B. M., Gross, A. L., Gavett, B. E., Widaman, K. F., Fletcher, E., Dowling, N. M., Buckley, R. F., Arenaza‐Urquijo, E. M., Zahodne, L. B., Hohman, T. J., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.08.016 · Cited by 51 · see citing works
Hu, Y., Zhang, Y., Zhang, H., Gao, S., Wang, L., Wang, T., Han, Z., Sun, B., & Liu, G. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01695-4 · Cited by 47 · see citing works
“However, other observational studies show that higher education could not protect against advanced AD [7], and even was significantly associated with increased cognitive decline rates in AD [8, 9].”
BackgroundZolochevska, O., & Taglialatela, G. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666160518142110 · Cited by 49 · see citing works
- Authors
- Scarmeas, N.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Scarmeas, N
- ORCID
- Scarmeas, N
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2005-07-26
- Volume
- 77
- Issue
- 3
- Pages
- 308-316
- ISSN
- 0022-3050 (ISSN-L)
- PMC
- PMC2077720
- OpenAlex
- W2071700556
- Cited by
- 353
- References
- 68
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 9 · 2023: 15 · 2022: 18 · 2021: 26 · 2020: 16 · 2019: 23 · 2018: 21 · 2017: 12 · 2016: 11 · 2015: 15 · 2014: 20 · 2013: 22 · 2012: 19
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- National Institute on Aging (P01AG007232, AG 07232)
- National Center for Research Resources (RR 00645, M01RR000645)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- Alzheimer's disease, educational attainment, cognitive decline, disease progression, executive function, memory, older adults
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Educational Status, Female, Follow-Up Studies, Humans, Male, Neuropsychological Tests, Prospective Studies, Psychometrics, Sick Role, Statistics as Topic, Cohort Studies, Disease Progression
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