To examine how executive functioning (EF) relates to academic achievement longitudinally in children with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) and whether age at baseline moderates this relationship.

Participants included 88 children with NF1 and PNs (ages 6–18 years old, M = 12.05, SD = 3.62, 50 males) enrolled in a natural history study. Neuropsychological assessments were administered three times over 6 years. EF (working memory, inhibitory control, cognitive flexibility, and attention) was assessed by performance-based (PB) and parent-reported (PR) measures. Multilevel growth modeling was used to examine how EF at baseline related to initial levels and changes in broad math, reading, and writing across time, controlling for demographic variables.

The relationship between EF and academic achievement varied across EF and academic domains. Cognitive flexibility (PB) uniquely explained more variances in initial math, reading, and writing scores; working memory (PB) uniquely explained more variances in initial levels of reading and writing. The associations between EF and academic achievement tended to remain consistent across age groups with one exception: Lower initial levels of inhibitory control (PR) were related to a greater decline in reading scores. This pattern was more evident among younger (versus older) children.

Findings emphasize the heterogeneous nature of academic development in NF1 and that EF skills could help explain the within-group variability in this population. Routine cognitive/academic monitoring via comprehensive assessments and early targeted treatments consisting of medication and/or systematic cognitive interventions are important to evaluate for improving academic performance in children with NF1 and PNs.

To compare longitudinal verbal fluency performance among Latinx Spanish speakers who develop Alzheimer’s disease to those who do not develop dementia in absolute number of words produced on each task and their ratio to combine both scores.

Participants included 833 Latinx Spanish-speaking older adults from a community-based prospective cohort in Manhattan. We performed growth curve modeling to investigate the trajectories of letter and semantic fluency, and their ratio (i.e., ‘semantic index’), between individuals who developed Alzheimer’s disease and those who did not (i.e., controls). The semantic index quantifies the proportion of words generated for semantic fluency in relation to the total verbal fluency performance.

Letter fluency performance did not decline in controls; we observed a linear decline in those who developed Alzheimer’s disease. Semantic fluency declined in both groups and showed an increased rate of change over time in the incident Alzheimer’s disease group; in comparison, the control group had a linear and slower decline. There were no group differences in the longitudinal trajectory (intercept and slope) of the semantic index.

A decline in letter fluency and a more rapid and accelerating decline over time in semantic fluency distinguished people who developed Alzheimer’s disease from controls. Using the semantic index was not a superior marker of incident Alzheimer’s disease compared to examining the two fluency scores individually. Results suggest the differential decline in verbal fluency tasks, when evaluated appropriately, may be useful for early identification of Alzheimer’s disease in Latinx Spanish speakers, a historically understudied population.

Educational attainment is a well-documented predictor of later-life cognition, but less is known about upstream contextual factors. This study aimed to identify which early-life contextual factors uniquely predict later-life global cognition and whether educational attainment mediates these relationships.

Participants were drawn from the Michigan Cognitive Aging Project (N = 485; Mage = 63.51; SDage = 3.13; 50% non-Hispanic Black). Early-life exposures included U.S. region of elementary school (Midwest, South, Northeast), average parental education, household composition (number of adults (1, 2, 3+), number of children), school racial demographics (predominantly White, predominantly Black, diverse), self-reported educational quality, and school type (public/private). Later-life global cognition was operationalized with a factor score derived from a comprehensive neuropsychological battery. Sequential mediation models controlling for sociodemographics estimated total, direct, and indirect effects of early-life contextual factors on cognition through educational attainment (years).

Higher educational quality, higher parental education, and attending a private school were each associated with better cognition; attending a predominantly Black or diverse school and reporting three or more adults in the household were associated with lower cognition. After accounting for educational attainment, associations remained for educational quality, school type, and reporting three or more adults in the household. Indirect effects through educational attainment were observed for school region, educational quality, school racial demographics, and parental education.

School factors appear to consistently predict later-life cognition more than household factors, highlighting the potential long-term benefits of school-level interventions for cognitive aging. Future research should consider additional mediators beyond educational attainment such as neighborhood resources and childhood adversity.

Alzheimer’s disease (AD) is highly comorbid with idiopathic normal pressure hydrocephalus (iNPH) and may diminish the benefits of shunting; however, findings in this area are mixed. We examined postoperative outcomes, with emphases on cognition and utilization of novel scoring procedures to enhance sensitivity.

Using participant data from an iNPH outcome study at Butler Hospital, a mixed effect model examined main and interaction effects of time since surgery (baseline, 3 months, 12 months, and 24–60 months) and AD comorbidity (20 iNPH and 11 iNPH+AD) on activities of daily living (ADLs) and iNPH symptoms. Regression modeling explored whether baseline variables predicted improvements 3 months postoperatively.

There were no group differences in gait, incontinence, and global cognition over time, and neither group showed changes in ADLs. Cognitive differences were observed postoperatively; iNPH patients showed stable improvements in working memory (p = 0.012) and response inhibition (p = 0.010), while iNPH + AD patients failed to maintain initial gains. Regarding predicting postoperative outcomes, baseline AD biomarkers did not predict shunt response at 3 months; however, older age at surgery predicted poorer cognitive outcomes (p = 0.04), and presurgical Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (p = 0.035) and Mini-Mental Status Examination (MMSE) scores (p = 0.009) predicted improvements incontinence.

iNPH + AD may be linked with greater declines in aspects of executive functioning postoperatively relative to iNPH alone. While baseline AD pathology may not prognosticate shunt response, younger age appears linked with postsurgical cognitive improvement, and utilizing both brief and comprehensive cognitive measures may help predict improved incontinence. These results illustrate the potential benefits of surgery and inform postoperative expectations for those with iNPH + AD.

Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burdensome, rely on cutoff scores that reduce information, do not examine potential variations in task engagement across a battery, and are typically not well-suited to acquisition of large cognitive datasets. Here we describe the development of novel performance validity measures that could address some of these limitations by leveraging psychometric concepts using data embedded within the Penn Computerized Neurocognitive Battery (PennCNB).

We first developed these validity measures using simulations of invalid response patterns with parameters drawn from real data. Next, we examined their application in two large, independent samples: 1) children and adolescents from the Philadelphia Neurodevelopmental Cohort (n = 9498); and 2) adult servicemembers from the Marine Resiliency Study-II (n = 1444).

Our performance validity metrics detected patterns of invalid responding in simulated data, even at subtle levels. Furthermore, a combination of these metrics significantly predicted previously established validity rules for these tests in both developmental and adult datasets. Moreover, most clinical diagnostic groups did not show reduced validity estimates.

These results provide proof-of-concept evidence for multivariate, data-driven performance validity metrics. These metrics offer a novel method for determining the performance validity for individual neurocognitive tests that is scalable, applicable across different tests, less burdensome, and dimensional. However, more research is needed into their application.

The Tower of London – Freiburg version (TOL-F) was developed in three parallel-test versions (A, B, and C) that only differ in their physical appearance by interchanged ball colors, but not in their cognitive demands. We addressed the question whether the test–retest reliability of an identical problem set differs from the parallel test–retest reliability of a structurally identical problem set with a marginally different physical appearance.

Reliabilities were assessed in two samples of young adults over a 1-week interval: In the parallel test–retest sample (n = 93; 49 female), half of the participants accomplished version A at the first session and version B at the second session, while the other half started with version B in the first session and continued with A in the second session. In the identical test–retest sample (n = 86; 48 female), half of the participants performed on version A in both the first and the second session, while the other half went through the same procedure with version B.

For overall planning accuracy, intraclass correlation coefficients for absolute agreement were r = .501 for the parallel test–retest and r = .605 for the identical test–retest sample, with Pearson correlations of r = .559 and r = .708 respectively. Greatest lower bound estimates of reliability were adequate to high in the two samples (ranging between .765 and .854) confirming previous studies.

Although the TOL-F revealed only moderate intraclass correlations for absolute agreement, it showed some of the highest psychometric indices compared to repeated assessments with other TOL tests.

To examine the association between leisure activity (LA) frequency and cognitive trajectories over 5 years across adulthood, and whether gender and age moderate these associations.

A total of 234 cognitively healthy adults (21–80 years) completed a LA questionnaire at baseline and neuropsychological measures at baseline and after 5 years. Latent change score analysis was applied to generate latent variables estimating changes in different cognitive domains. For a secondary analysis, LA components’ scores were calculated, reflecting cognitive-intellectual, social, and physical activities. Regression analysis examined the association between baseline LA and cognitive change, and potential moderation of gender and age. In addition, we tested the influence of cortical gray matter thickness on the results.

We found that higher LA engagement was associated with slower cognitive decline for reasoning, speed, and memory, as well as better vocabulary across two time points. Regarding LA components, higher Social-LA and Intellectual-LA predicted slower rates of cognitive decline across different domains, while Physical-LA was not associated with cognitive change. Gender, but not age, moderated some of the associations observed. Our results remained the same after controlling for cortical gray matter thickness.

We demonstrated a protective effect of LA engagement on cognitive trajectories over 5 years, independent from demographics and a measure of brain health. The effects were in part moderated by gender, but not age. Results should be replicated in larger and more diverse samples. Our findings support cognitive reserve hypothesis and have implications for future reserve-enhancing interventions.

Language and communication are largely understudied among youth with fetal alcohol spectrum disorders (FASD). Findings have been mixed, and have generally focused on more severely affected (i.e., children with FAS alone) or younger children. This study aimed to elucidate the profiles of language (i.e., receptive, expressive, general language) and communication (i.e., functional, social) abilities in adolescents with FASD.

Participants aged 12–17 years with (AE = 31) and without (CON = 29) prenatal alcohol exposure were included. Receptive and expressive language were measured by the Clinical Evaluation of Language Fundamentals – Fifth Edition (CELF-5). Parents or caregivers completed the Children’s Communication Checklist – Second Edition as a subjective measure of general language skills. Functional communication was measured by the Student Functional Assessment of Verbal Reasoning and Executive Strategies and parents or caregivers completed the Social Skills Improvement System Rating Scales as a measure of social communication. Multivariate analysis of variance determined the overall profiles of language and communication and whether they differed between groups.

The AE group performed significantly lower than the CON group on receptive language and parent report of general language while groups did not significantly differ on expressive language. Groups did not significantly differ on functional communication while social communication was significantly lower in the AE group.

Results of this study provide important information regarding the overall profile of basic language abilities and higher-level communication skills of adolescents with FASD. Ultimately, improving communication skills of youth with FASD may translate to better overall functioning.

There is increasing interest in the utilization of proton beam radiation therapy (PRT) to treat pediatric brain tumors based upon presumed advantages over traditional photon radiation therapy (XRT). PRT provides more conformal radiation to the tumor with reduced dose to healthy brain parenchyma. Less radiation exposure to brain tissue beyond the tumor is thought to reduce neuropsychological sequelae. This systematic review aimed to provide an overview of published studies comparing neuropsychological outcomes between PRT and XRT.

PubMed, PsychINFO, Embase, Web of Science, Scopus, and Cochrane were systematically searched for peer-reviewed published studies that compared neuropsychological outcomes between PRT and XRT in pediatric brain tumor patients.

Eight studies were included. Six of the studies utilized retrospective neuropsychological data; the majority were longitudinal studies (n = 5). XRT was found to result in lower neuropsychological functioning across time. PRT was associated with generally stable neuropsychological functioning across time, with the exception of working memory and processing speed, which showed variable outcomes across studies. However, studies inconsistently included or considered medical and sociodemographic differences between treatment groups, which may have impacted neuropsychological outcomes.

Despite methodological limitations, including limited baseline neuropsychological evaluations, temporal variability between radiation treatment and first evaluation or initial and follow-up evaluations, and heterogenous samples, there is emerging evidence of sociodemographic inequities in access to PRT. With more institutions dedicating funding towards PRT, there may be the opportunity to objectively evaluate the neuropsychological benefits of patients matched on medical and sociodemographic variables.

Computerized neglect tests could significantly deepen our disorder-specific knowledge by effortlessly providing additional behavioral markers that are hardly or not extractable from existing paper-and-pencil versions. This study investigated how testing format (paper versus digital), and screen size (small, medium, large) affect the Center of cancelation (CoC) in right-hemispheric stroke patients in the Letters and the Bells cancelation task. Our second objective was to determine whether a machine learning approach could reliably classify patients with and without neglect based on their search speed, search distance, and search strategy.

We compared the CoC measure of right hemisphere stroke patients with neglect in two cancelation tasks across different formats and display sizes. In addition, we evaluated whether three additional parameters of search behavior that became available through digitization are neglect-specific behavioral markers.

Patients’ CoC was not affected by test format or screen size. Additional search parameters demonstrated lower search speed, increased search distance, and a more strategic search for neglect patients than for control patients without neglect.

The CoC seems robust to both test digitization and display size adaptations. Machine learning classification based on the additional variables derived from computerized tests succeeded in distinguishing stroke patients with spatial neglect from those without. The investigated additional variables have the potential to aid in neglect diagnosis, in particular when the CoC cannot be validly assessed (e.g., when the test is not performed to completion).

There is limited research on the prognostic value of language tasks regarding mild cognitive impairment (MCI) and Alzheimer’s clinical syndrome (ACS) development in the cognitively normal (CN) elderly, as well as MCI to ACS conversion.

Participants were drawn from the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. Language performance was evaluated via verbal fluency [semantic (SVF) and phonemic (PVF)], confrontation naming [Boston Naming Test short form (BNTsf)], verbal comprehension, and repetition tasks. An additional language index was estimated using both verbal fluency tasks: SVF-PVF discrepancy. Cox proportional hazards analyses adjusted for important sociodemographic parameters (age, sex, education, main occupation, and socioeconomic status) and global cognitive status [Mini Mental State Examination score (MMSE)] were performed.

A total of 959 CN and 118 MCI older (>64 years) individuals had follow-up investigations after a mean of ∼3 years. Regarding the CN group, each standard deviation increase in the composite language score reduced the risk of ACS and MCI by 49% (8–72%) and 32% (8–50%), respectively; better SVF and BNTsf performance were also independently associated with reduced risk of ACS and MCI. On the other hand, using the smaller MCI participant set, no language measurement was related to the risk of MCI to ACS conversion.

Impaired language performance is associated with elevated risk of ACS and MCI development. Better SVF and BNTsf performance are associated with reduced risk of ACS and MCI in CN individuals, independent of age, sex, education, main occupation, socioeconomic status, and MMSE scores at baseline.

To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old).

Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures. We hypothesized the five-factor model (Reading, Vocabulary, Memory, Working Memory, and Executive/Speed) would have the best fit, consistent with younger populations. We assessed confirmatory and discriminant validity. We also evaluated demographic and computer use predictors of NIH TB-CB composite scores.

Findings suggest the six-factor model (Vocabulary, Reading, Memory, Working Memory, Executive, and Speed) had a better fit than alternative models. NIH TB-CB tests had good convergent and discriminant validity, though tests in the executive functioning domain had high inter-correlations with other cognitive domains. Computer use was strongly associated with higher NIH TB-CB overall and fluid cognition composite scores.

The NIH TB-CB is a valid assessment for the oldest-old samples, with relatively weak validity in the domain of executive functioning. Computer use’s impact on composite scores could be due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation. Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations.

Parkinson’s disease patients with subjective cognitive decline (PD-SCD) and mild cognitive impairment (PD-MCI) have an increased risk of dementia (PDD). Thus, the identification of early cognitive changes that can be useful predictors of PDD is a highly relevant challenge. Posterior cortically based functions, including linguistic processes, have been associated with PDD. However, investigations that have focused on linguistic functions in PD-MCI are scarce and none of them include PD-SCD patients. Our aim was to study language performance in PD-SCD and PD-MCI. Moreover, language subcomponents were considered as predictors of PDD.

Forty-six PD patients and twenty controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Language production and comprehension was assessed. Follow-up assessment was conducted to a mean of 7.5 years after the baseline.

PD-MCI patients showed a poor performance in naming (actions and nouns), action generation, anaphora resolution and sentence comprehension (with and without center-embedded relative clause). PD-SCD showed a poor performance in action naming and action generation. Deficit in action naming was an independent risk factor for PDD during the follow-up. Moreover, the combination of deficit in action words and sentence comprehension without a center-embedded relative clause was associated with a greater risk.

The results are of relevance because they suggest that a specific pattern of linguistic dysfunctions, that can be present even in the early stages of the disease, can predict future dementia, reinforcing the importance of advancing in the knowledge of linguistic dysfunctions in predementia stages of PD.

Blast related characteristics may contribute to the diversity of findings on whether mild traumatic brain injury sustained during war zone deployment has lasting cognitive effects. This study aims to evaluate whether a history of blast exposure at close proximity, defined as exposure within 30 feet, has long-term or lasting influences on cognitive outcomes among current and former military personnel.

One hundred participants were assigned to one of three groups based on a self-report history of blast exposure during combat deployments: 47 close blast, 14 non-close blast, and 39 comparison participants without blast exposure. Working memory, processing speed, verbal learning/memory, and cognitive flexibility were evaluated using standard neuropsychological tests. In addition, assessment of combat exposure and current post-concussive, posttraumatic stress, and depressive symptoms, and headache was performed via self-report measures. Variables that differed between groups were controlled as covariates.

No group differences survived Bonferroni correction for family-wise error rate; the close blast group did not differ from non-close blast and comparison groups on measures of working memory, processing speed, verbal learning/memory, or cognitive flexibility. Controlling for covariates did not alter these results.

No evidence emerged to suggest that a history of close blast exposure was associated with decreased cognitive performance when comparisons were made with the other groups. Limited characterization of blast contexts experienced, self-report of blast distance, and heterogeneity of injury severity within the groups are the main limitations of this study.

Cognitive symptoms are common in the initial weeks after mTBI, but recovery is generally expected within three months. However, there is limited information about recovery specifically in older age cohorts. Therefore, this study investigated cognitive outcome three months after mTBI in older adults (≥ 65 years) compared to trauma and community age-matched controls and explored risk factors for outcome after traumatic injury.

Older mTBI patients (n = 40) and older adults with mild traumatic injury but without head injury (n = 66) were compared to a noninjured community control group (n = 47). Cognitive assessment included neuropsychological and computerized tests. Group differences were compared on individual tasks and overall cognitive performances using composite scores. Regression analyses identified predictors of outcome for trauma patients and moderator analyses explored possible interactions of mTBI severity with age and cognition.

As well as lower performances in processing speed and memory, both trauma groups had significantly lower performance on composite neuropsychological (d = .557 and .670) and computerized tasks (d = .783 and .824) compared to noninjured controls. Age, education, and history of depression were direct predictors of cognitive performance after mild traumatic injury (with or without head injury). Further moderation analysis demonstrated that mTBI severity (Glasgow Coma Scale < 15) moderated the impact of older age on computerized assessment (β = -.138).

Three months after mild trauma (regardless of head injury), older people demonstrate lower cognition compared to noninjured peers. However, severity of mTBI (Glasgow Coma Scale < 15) can interact with older age to predict poorer cognitive outcomes.

Wiedemann-Steiner syndrome (WSS) is a rare Mendelian disorder of the epigenetic machinery caused by heterozygous pathogenic variants in KMT2A. Currently, the specific neurocognitive profile of this syndrome remains unknown. This case series provides insight into the cognitive phenotype of WSS.

This study involves a retrospective medical chart review of 10 pediatric patients, each with a molecularly confirmed diagnosis of WSS who underwent clinical neuropsychological evaluation at an academic medical center.

The majority of patients performed in the below average to very low ranges in Nonverbal Reasoning, Visual/Spatial Perception, Visuoconstruction, Visual Memory, Attention, Working Memory and Math Computation skills. In contrast, over half the sample performed within normal limits on Receptive Vocabulary, Verbal Memory, and Word Reading. Wilcoxon signed rank test showed weaker Nonverbal versus Verbal Reasoning skills (p = .005). Most caregivers reported deficits in executive functioning, most notably in emotion regulation.

Nonverbal reasoning/memory, visuospatial/construction, attention, working memory, executive functioning, and math computation skills are areas of weakness among those with WSS. These findings overlap with research on Kabuki syndrome, which is caused by variants in KMT2D, and suggest disruption in the neurogenesis of the hippocampal formation may drive shared pathogenesis of the two syndromes.

Serial position scores on verbal memory tests are sensitive to early Alzheimer’s disease (AD)-related neuropathological changes that occur in the entorhinal cortex and hippocampus. The current study examines longitudinal change in serial position scores as markers of subtle cognitive decline in older adults who may be in preclinical or at-risk states for AD.

This study uses longitudinal data from the Religious Orders Study and the Rush Memory and Aging Project. Participants (n = 141) were included if they did not have dementia at enrollment, completed follow-up assessments, and died and were classified as Braak stage I or II. Memory tests were used to calculate serial position (primacy, recency), total recall, and episodic memory composite scores. A neuropathological evaluation quantified AD, vascular, and Lewy body pathologies. Mixed effects models were used to examine change in memory scores. Neuropathologies and covariates (age, sex, education, APOE e4) were examined as moderators.

Primacy scores declined (β = −.032, p < .001), whereas recency scores increased (β = .021, p = .012). No change was observed in standard memory measures. Greater neurofibrillary tangle density and atherosclerosis explained 10.4% of the variance in primacy decline. Neuropathologies were not associated with recency change.

In older adults with hippocampal neuropathologies, primacy score decline may be a sensitive marker of early AD-related changes. Tangle density and atherosclerosis had additive effects on decline. Recency improvement may reflect a compensatory mechanism. Monitoring for changes in serial position scores may be a useful in vivo method of tracking incipient AD.

Reaction time variability (RTV) has been estimated using Gaussian, ex-Gaussian, and diffusion model (DM) indices. Rarely have studies examined interrelationships among these performance indices in childhood, and the use of reaction time (RT) computational models has been slow to take hold in the developmental psychopathology literature. Here, we extend prior work in adults by examining the interrelationships among different model parameters in the ABCD sample and demonstrate how computational models of RT can clarify mechanisms of time-on-task effects and sex differences in RTs.

This study utilized trial-level data from the stop signal task from 8916 children (9–10 years old) to examine Gaussian, ex-Gaussian, and DM indicators of RTV. In addition to describing RTV patterns, we examined interrelations among these indicators, temporal patterns, and sex differences.

There was no one-to-one correspondence between DM and ex-Gaussian parameters. Nonetheless, drift rate was most strongly associated with standard deviation of RT and tau, while nondecisional processes were most strongly associated with RT, mu, and sigma. Performance worsened across time with changes driven primarily by decreasing drift rate. Boys were faster and less variable than girls, likely attributable to girls’ wide boundary separation.

Intercorrelations among model parameters are similar in children as has been observed in adults. Computational approaches play a crucial role in understanding performance changes over time and can also clarify mechanisms of group differences. For example, standard RT models may incorrectly suggest slowed processing speed in girls that is actually attributable to other factors.

Brain reserve, cognitive reserve, and education are thought to protect against late-life cognitive decline, but these variables have not been directly compared to one another in the same model, using future cognitive and functional decline as outcomes. We sought to determine whether the influence of these protective factors on executive function (EF) and daily function decline was dependent upon Alzheimer’s disease (AD) pathology severity, as measured by the total tau to beta-amyloid (T-τ/Aβ1-42) ratio in cerebrospinal fluid (CSF).

Participants were 1201 older adult volunteers in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Brain reserve was defined using a composite index of structural brain volumes (total brain matter, hippocampus, and white matter hyperintensity). Cognitive reserve was defined as the variance in episodic memory performance not explained by brain integrity and demographics.

At higher levels of T-τ/Aβ1-42, brain and cognitive reserve predicted slower decline in EF. Only brain reserve attenuated decline at lower levels of T-τ/Aβ1-42. Education had no independent association with cognitive decline.

These results point to a hierarchy of protection against aging- and disease-associated cognitive decline. When pathology is low, only structural brain integrity predicts rate of future EF decline. The ability of cognitive reserve to predict future EF decline becomes stronger as CSF biomarker evidence of AD increases. Although education is typically thought of as a proxy for cognitive reserve, it did not show any protective effects on cognition after accounting for brain integrity and the residual cognitive reserve index.