Extensive research shows that tests of executive functioning (EF) predict instrumental activities of daily living (IADLs) but are nevertheless often criticized for having poor ecological validity. The Modified Six Elements Test (MSET) is a pencil-and-paper test that was developed to mimic the demands of daily life, with the assumption that this would result in a more ecologically valid test. Although the MSET has been extensively validated in its ability to capture cognitive deficits in various populations, support for its ability to predict functioning in daily life is mixed. This study aimed to examine the MSET’s ability to predict IADLs assessed via three different modalities relative to traditional EF measures.

Participants (93 adults aged 60 – 85) completed the MSET, traditional measures of EF (Delis-Kaplan Executive Function System; D-KEFS), and self-reported and performance-based IADLs in the lab. Participants then completed three weeks of IADL tasks at home, using the Daily Assessment of Independent Living and Executive Skills (DAILIES) protocol.

The MSET predicted only IADLs completed at home, while the D-KEFS predicted IADLs across all three modalities. Further, the D-KEFS predicted home-based IADLs beyond the MSET when pitted against each other, whereas the MSET did not contribute beyond the D-KEFS.

Traditional EF tests (D-KEFS) appear to be superior to the MSET in predicting IADLs in community-dwelling older adults. The present results argue against replacing traditional measures with the MSET when addressing functional independence of generally high-functioning and cognitive healthy older adult patients.

There is limited research on neurocognitive outcome and associated risk factors in long-term, adult survivors of childhood acute lymphoblastic leukemia (ALL), without treatment of cranial radiation therapy. Moreover, the impact of fatigue severity and pain interference on neurocognition has received little attention. In this cross-sectional study, we examined neurocognitive outcome and associated factors in this population.

Intellectual abilities, verbal learning/memory, processing speed, attention, and executive functions were compared to normative means/medians with one sample t tests or Wilcoxon signed-rank tests. Associations with risk factors, fatigue severity, and pain interference were analyzed with linear regressions.

Long-term, adult survivors of childhood ALL (N = 53, 51% females, mean age = 24.4 years, SD = 4.4, mean = 14.7 years post-diagnosis, SD = 3.4) demonstrated above average intellectual abilities, but performed below average in attention, inhibition, processing speed, and shifting (p < 0.001). Executive functioning complaints were significantly higher than normative means, and positively associated with fatigue (p < 0.001). There was no interaction between sex and fatigue and no neurocognitive impairments were associated with pain interference, risk group, age at diagnosis, or sex.

Long-term, adult survivors of ALL treated without cranial radiation therapy, demonstrate domain-specific performance-based neurocognitive impairments. However, continued research on the neurocognitive outcome in this population as they age will be important in the coming years. Executive functioning complaints were frequently in the clinical range, and often accompanied by fatigue. This suggests a need for cognitive rehabilitation programs.

The Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) is well validated and commonly used to assess difficulties in everyday functioning regarding dementia. To facilitate interpretation and clinical implementation across different European countries, we aim to provide normative data and a diagnostic cutoff for dementia.

Cross-sectional data from Dutch Brain Research Registry (N = 1,064; mean (M) age = 62 ± 11 year; 69.5% female), European Medial Information Framework-Alzheimer’s Disease 90 + (N = 63; Mage = 92 ± 2 year; 52.4% female), and European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study (N = 247; Mage = 63 ± 7 year; 72.1% female) were used. The generalized additive models for location, scale, and shape framework were used to obtain normative values (Z-scores). The beta distribution was applied, and combinations of age, sex, and educational attainment were modeled. The optimal cutoff for dementia was calculated using area under receiver operating curves (AUC-ROC) and Youden Index, using data from Amsterdam Dementia Cohort (N = 2,511, Mage = 64 ± 8 year, 44.4% female).

The best normative model accounted for a cubic-like decrease of IADL performance with age that was more pronounced in low compared to medium/high educational attainment. The cutoff for dementia was 1.85 standard deviation below the population mean (AUC = 0.97; 95% CI [0.97–0.98]).

We provide regression-based norms for A-IADL-Q and a diagnostic cutoff for dementia, which help improve clinical assessment of IADL performance across European countries.

The present study aimed to develop neuropsychological norms for older Asian Americans with English as a primary or secondary language, using data from the National Alzheimer’s Coordinating Center (NACC).

A normative sample of Asian American participants was derived from the NACC database using robust criteria: participants were cognitively unimpaired at baseline (i.e., no MCI or dementia) and remained cognitively unimpaired at 1-year follow-up. Clinical and demographic characteristics were compared between Primary and Secondary English speakers using analyses of variance for continuous measures and chi-square tests for categorical variables. Linear regression models compared neuropsychological performance between the groups, adjusting for demographics (age, sex, and education). Regression models were developed for clinical application to compute demographically adjusted z-scores.

Secondary English speakers were younger than Primary English speakers (p < .001). There were significant differences between the groups on measures of mental status (Mini-Mental State Examination, p = .002), attention (Trail Making Test A, Digit Span Forward Total Score, p <.001), language (Boston Naming Test, Animal Fluency, Vegetable Fluency, p < .001), and executive function (Trail Making Test B, p = .02).

Separate normative data are needed for Primary vs. Secondary English speakers from Asian American backgrounds. We provide normative data on older Asian Americans to enable clinicians to account for English use in the interpretation of neuropsychological assessment scores.

We investigated how well a visual associative learning task discriminates Alzheimer’s disease (AD) dementia from other types of dementia and how it relates to AD pathology.

3,599 patients (63.9 ± 8.9 years old, 41% female) from the Amsterdam Dementia Cohort completed two sets of the Visual Association Test (VAT) in a single test session and underwent magnetic resonance imaging. We performed receiver operating curve analysis to investigate the VAT’s discriminatory ability between AD dementia and other diagnoses and compared it to that of other episodic memory tests. We tested associations between VAT performance and medial temporal lobe atrophy (MTA), and amyloid status (n = 2,769, 77%).

Patients with AD dementia performed worse on the VAT than all other patients. The VAT discriminated well between AD and other types of dementia (area under the curve range 0.70–0.86), better than other episodic memory tests. Six-hundred forty patients (17.8%) learned all associations on VAT-A, but not on VAT-B, and they were more likely to have higher MTA scores (odds ratios range 1.63 (MTA 0.5) through 5.13 for MTA ≥ 3, all p < .001) and to be amyloid positive (odds ratio = 3.38, 95%CI = [2.71, 4.22], p < .001) than patients who learned all associations on both sets.

Performance on the VAT, especially on a second set administered immediately after the first, discriminates AD from other types of dementia and is associated with MTA and amyloid positivity. The VAT might be a useful, simple tool to assess early episodic memory deficits in the presence of AD pathology.

Symptom clustering research provides a unique opportunity for understanding complex medical conditions. The objective of this study was to apply a variable-centered analytic approach to understand how symptoms may cluster together, within and across domains of functioning in mild cognitive impairment (MCI) and dementia, to better understand these conditions and potential etiological, prevention, and intervention considerations.

Cognitive, motor, sensory, emotional, and social measures from the NIH Toolbox were analyzed using exploratory factor analysis (EFA) from a dataset of 165 individuals with a research diagnosis of either amnestic MCI or dementia of the Alzheimer’s type.

The six-factor EFA solution described here primarily replicated the intended structure of the NIH Toolbox with a few deviations, notably sensory and motor scores loading onto factors with measures of cognition, emotional, and social health. These findings suggest the presence of cross-domain symptom clusters in these populations. In particular, negative affect, stress, loneliness, and pain formed one unique symptom cluster that bridged the NIH Toolbox domains of physical, social, and emotional health. Olfaction and dexterity formed a second unique cluster with measures of executive functioning, working memory, episodic memory, and processing speed. A third novel cluster was detected for mobility, strength, and vision, which was considered to reflect a physical functioning factor. Somewhat unexpectedly, the hearing test included did not load strongly onto any factor.

This research presents a preliminary effort to detect symptom clusters in amnestic MCI and dementia using an existing dataset of outcome measures from the NIH Toolbox.

Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer’s disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD.

Three hundred and seventy older adults (aged 75.8 +/− 5.8 years) completed a week of remote daily testing on the Ambulatory Research in Cognition (ARC) smartphone platform and also completed clinical, genetic, and conventional in-clinic cognitive assessments. RT variability was assessed in a brief (20-40 seconds) processing speed task using two different measures of variability, the Coefficient of Variation (CoV) and the Root Mean Squared Successive Difference (RMSSD) of RTs on correct trials.

Symptomatic participants showed greater variability compared to cognitively normal participants. When restricted to cognitively normal participants, APOE ε4 carriers exhibited greater variability than noncarriers. Both CoV and RMSSD showed significant, and similar, correlations with several in-clinic cognitive composites. Finally, both RT variability measures significantly mediated the relationship between APOE ε4 status and several in-clinic cognition composites.

Attentional fluctuations over 20–40 seconds assessed in daily life, are sensitive to clinical status and genetic risk for AD. RT variability appears to be an important predictor of cognitive deficits during the preclinical disease stage.

Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states.

Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded.

Mann–Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI.

FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

Normative data for older adults may be tainted by inadvertent inclusion of undiagnosed individuals at the very early stage of a neurodegenerative process. To avoid this pitfall, we developed norms for a cohort of older adults without MCI/dementia at 3-year follow-up.

A randomly selected sample of 1041 community-dwelling individuals (age ≥ 65) received a full neurological and neuropsychological examination on two occasions [mean interval = 3.1 (SD = 0.9) years].

Of these, 492 participants (Group 1; 65–87 years old) were without dementia on both evaluations (CDR=0 and MMSE ≥ 26); their baseline data were used for norms development. Group 2 (n = 202) met the aforementioned criteria only at baseline, but not at follow-up. Multiple linear regressions included demographic predictors for regression-based normative formulae and raw test scores as dependent variables for each test variable separately. Standardized scaled scores and stratified discrete norms were also calculated. Group 2 performed worse than Group 1 on most tests (p-values < .001–.021). Education was associated with all test scores, age with most, and sex effects were consistent with the literature.

We provide a model for developing sound normative data for widely used neuropsychological tests among older adults, untainted by potential early, undiagnosed cognitive impairment, reporting regression-based, scaled, and discrete norms for use in clinical settings to identify cognitive decline in older adults. Additionally, our co-norming of a variety of tests may enable intra-individual comparisons for diagnostic purposes. The present work addresses the challenge of developing robust normative data for neuropsychological tests in older adults.

Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association.

This prospective, multicenter cohort study included participants aged 5.00–17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates.

311 children (65.0% males; median age = 11.92 [IQR = 9.14–14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2 = 9.85, p = .043) and Verbal Fluency scores (χ2 = 10.48, p = .033) across time points; these associations were not moderated by sex, ps ≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores, ps ≥ .17.

Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.

Self- and informant-ratings of functional abilities are used to diagnose mild cognitive impairment (MCI) and are commonly measured in clinical trials. Ratings are assumed to be accurate, yet they are subject to biases. Biases in self-ratings have been found in individuals with dementia who are older and more depressed and in caregivers with higher distress, burden, and education. This study aimed to extend prior findings using an objective approach to identify determinants of bias in ratings.

Participants were 118 individuals with MCI and their informants. Three discrepancy variables were generated including the discrepancies between (1) self- and informant-rated functional status, (2) informant-rated functional status and objective cognition (in those with MCI), and (3) self-rated functional status and objective cognition. These variables served as dependent variables in forward linear regression models, with demographics, stress, burden, depression, and self-efficacy as predictors.

Informants with higher stress rated individuals with MCI as having worse functional abilities relative to objective cognition. Individuals with MCI with worse self-efficacy rated their functional abilities as being worse compared to objective cognition. Informant-ratings were worse than self-ratings for informants with higher stress and individuals with MCI with higher self-efficacy.

This study highlights biases in subjective ratings of functional abilities in MCI. The risk for relative underreporting of functional abilities by individuals with higher stress levels aligns with previous research. Bias in individuals with MCI with higher self-efficacy may be due to anosognosia. Findings have implications for the use of subjective ratings for diagnostic purposes and as outcome measures.

“Ecological validity” (EV) is classically defined as test’s ability to predict real-world functioning, either alone or together with test’s similarity to real-world tasks. In neuropsychological literature on assessment of executive functions (EF), EV is conceptualized inconsistently, leading to misconceptions about the utility of tests. The goal of this systematic review was to examine how EV is conceptualized in studies of EF tests described as ecologically valid.

MEDLINE and PsychINFO Databases were searched. PRISMA guidelines were observed. After applying inclusion and exclusion criteria, this search yielded 90 articles. Deductive content analysis was employed to determine how the term EV was used.

About 1/3 of the studies conceptualized EV as the test’s ability to predict functional outcomes, 1/3 as both the ability to predict functional outcome and similarity to real-world tasks, and 1/3 were either unclear about the meaning of the term or relied on notions unrelated to classical definitions (e.g., similarity to real-world tasks alone, association with other tests, or the ability to discriminate between populations).

Conceptualizations of the term EV in literature on EF assessment vary grossly, subsuming the notions of criterion, construct, and face validity, as well as sensitivity/specificity. Such inconsistency makes it difficult to interpret clinical utility of tests that are described as ecologically valid. We call on the field to require that, at minimum, the term EV be clearly defined in all publications, or replaced with more concrete terminology (e.g., criterion validity).

Numerous studies have shown a decrease in executive functions (EF) associated with aging. However, few investigations examined whether this decrease is similar between sexes throughout adulthood. The present study investigated if age-related decline in EF differs between men and women from early to late adulthood.

A total of 302 participants (181 women) aged between 18 and 78 years old completed four computer-based cognitive tasks at home: an arrow-based Flanker task, a letter-based Visual search task, the Trail Making Test, and the Corsi task. These tasks measured inhibition, attention, cognitive flexibility, and working memory, respectively. To investigate the potential effects of age, sex, and their interaction on specific EF and a global EF score, we divided the sample population into five age groups (i.e., 18–30, 31–44, 45–54, 55–64, 65–78) and conducted analyses of covariance (MANCOVA and ANCOVA) with education and pointing device as control variables.

Sex did not significantly affect EF performance across age groups. However, in every task, participants from the three youngest groups (< 55 y/o) outperformed the ones from the two oldest. Results from the global score also suggest that an EF decrease is distinctly noticeable from 55 years old onward.

Our results suggest that age-related decline in EF, including inhibition, attention, cognitive flexibility, and working memory, becomes apparent around the age of 55 and does not differ between sexes at any age. This study provides additional data regarding the effects of age and sex on EF across adulthood, filling a significant gap in the existing literature.

Although the effect of aging on episodic memory is relatively well studied, little is known about how aging influences metamemory. In addition, while executive function (EF) is known to mediate the age-related decline in episodic memory, the role of metamemory in aging-related memory differences beyond EF remains unknown. This study aimed to elucidate the effect of aging on metamemory and to clarify the role of metamemory in the age-related decline in memory.

One hundred and four adults aged 18–79 years (50 M, 54 F) performed several EF tasks, as well as a face-scene paired-associate learning task that required them to make judgments of learning, feeling-of-knowing judgments, and retrospective confidence judgments.

Aging was significantly associated with poor metamemory accuracy and increased confidence across metamemory judgment types, even after controlling for EF and memory performance. A parallel mediation analysis indicated that both confidence of learning and EF performance had significant partial mediation effects on the relationship between aging and memory, albeit in different ways. Specifically, poor EF explained the age-related decline in memory, whereas increased confidence of learning served to compensate for this memory decline.

Aging is associated with general changes (i.e., poor inferences from cues) rather than specific changes (i.e., declined activation or utilization of certain cues) in metamemory monitoring. Also, changes in confidence of learning and in EF ability contribute to the preservation and decline of memory during aging, respectively. Therefore, boosting confidence during encoding and enhancing EF skills might be complementary memory intervention strategies for older adults.

Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions causing sustained twisting movements and abnormal postures of the neck and head. Assumed affected neuronal regions are the cortico-striatal-thalamo-cortical circuits, which are also involved in cognitive functioning. Indeed, impairments in different cognitive domains have been found in CD patients. However, to date studies have only investigated a limited range of cognitive functions within the same sample. In particular, social cognition (SC) is often missing from study designs. Hence, we aimed to evaluate a broad range of cognitive functions including SC in CD patients.

In the present study 20 idiopathic CD patients and 40 age-, gender-, and IQ-matched healthy controls (HCs) were assessed with tests for non-SC (verbal memory, psychomotor speed, and executive functions) as well as for SC (emotion recognition, Theory of Mind (ToM), and empathy).

CD patients scored on average significantly lower than HC on tests for non-SC, but did not show impairments on any of the tests for SC.

The current study showed impairments in non-SC in CD, but intact social cognitive functions. These results underline the importance of recognizing non-motor symptoms in idiopathic CD patients, but emphasize a focus on identifying strengths and weaknesses in cognitive functioning as these influence daily life activities.

Previous findings suggest that time setting errors (TSEs) in the Clock Drawing Test (CDT) may be related mainly to impairments in semantic and executive function. Recent attempts to dissociate the classic stimulus-bound error (setting the time to “10 to 11” instead of “10 past 11”) from other TSEs, did not support hypotheses regarding this error being primarily executive in nature or different from other time setting errors in terms of neurocognitive correlates. This study aimed to further investigate the cognitive correlates of stimulus-bound errors and other TSEs, in order to trace possible underlying cognitive deficits.

We examined cognitive test performance of participants with preliminary diagnoses associated with mild cognitive impairment. Among 490 participants, we identified clocks with stimulus-bound errors (n = 78), other TSEs (n = 41), other errors not related to time settings (n = 176), or errorless clocks (n = 195).

No differences were found on any dependent measure between the stimulus-bound and the other TSErs groups. Group comparisons suggested TSEs in general, to be associated with lower performance on various cognitive measures, especially on semantic and working memory measures. Regression analysis further highlighted semantic and verbal working memory difficulties as being the most prominent deficits associated with these errors.

TSEs in the CDT may indicate underlying deficits in semantic function and working memory. In addition, results support previous findings related to the diagnostic value of TSEs in detecting cognitive impairment.

Facial expressions are a core component of emotions and nonverbal social communication. Therefore, hypomimia as secondary symptom of Parkinson’s disease (PD) has adverse effects like social impairment, stigmatization, under-diagnosis and under-treatment of depression, and a generally lower quality of life. Beside unspecific dopaminergic treatment, specific treatment options for hypomimia in PD are rarely investigated. This quasi-randomized controlled trial evaluated the short-term effects of facial electromyogram (EMG) based biofeedback to enhance facial expression and emotion recognition as nonverbal social communication skills in PD patients. Furthermore effects on affect are examined.

A sample of 34 in-patients with PD were allocated either to facial EMG-biofeedback as experimental group or non-facial exercises as control group. Facial expression during posing of emotions (measured via EMG), facial emotion recognition, and positive and negative affect were assessed before and after treatment. Stronger improvements were expected in the EMG-biofeedback in comparison to the control group.

The facial EMG-biofeedback group showed significantly greater improvements in overall facial expression, and especially for happiness and disgust. Also, overall facial emotion recognition abilities improved significantly stronger in the experimental group. Positive affect was significantly increased in both groups with no significant differences between them, while negative affect did not change within both groups.

The study provides promising evidence for facial EMG-biofeedback as a tool to improve facial expression and emotion recognition in PD. Embodiment theories are discussed as working mechanism.

Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer’s disease (MCI-AD), and any performance deficits which emerged with sustained effort.

We included longitudinal data on a CPT sustained attention task for 89 participants with MCI-LB or MCI-AD and 31 healthy controls, estimating ex-Gaussian response time parameters, omission and commission errors. Performance trajectories were estimated both cross-sectionally (intra-task progress from start to end) and longitudinally (change in performance over years).

While response times in successful trials were broadly similar, with slight slowing associated with clinical parkinsonism, those with MCI-LB made considerably more errors. Omission errors were more common throughout the task in MCI-LB than MCI-AD (OR 2.3, 95% CI: 1.1–4.7), while commission errors became more common after several minutes of sustained attention. Within MCI-LB, omission errors were more common in those with clinical parkinsonism (OR 1.9, 95% CI: 1.3–2.9) or cognitive fluctuations (OR 4.3, 95% CI: 2.2–8.8).

Sustained attention deficits in MCI-LB may emerge in the form of attentional lapses leading to omissions, and a breakdown in inhibitory control leading to commission errors.

Subtle changes in memory, attention, and spatial navigation abilities have been associated with preclinical Alzheimer disease (AD). The current study examined whether baseline AD biomarkers are associated with self- and informant-reported decline in memory, attention, and spatial navigation.

Clinically normal (Clinical Dementia Rating Scale (CDR®) = 0) adults aged 56–93 (N = 320) and their informants completed the memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the Everyday Cognition Scale (ECog) annually for an average of 4 years. Biomarker data was collected within (±) 2 years of baseline (i.e., cerebrospinal fluid (CSF) p-tau181/Aβ42 ratio and hippocampal volume). Clinical progression was defined as CDR > 0 at time of final available ECog.

Self- and informant-reported memory, attention, and spatial navigation significantly declined over time (ps < .001). Baseline AD biomarkers were significantly associated with self- and informant-reported decline in cognitive ability (ps < .030), with the exception of p-tau181/Aβ42 ratio and self-reported attention (p = .364). Clinical progression did not significantly moderate the relationship between AD biomarkers and decline in self- or informant-reported cognitive ability (ps > .062). Post-hoc analyses indicated that biomarker burden was also associated with self- and informant-reported decline in total ECog (ps < .002), and again clinical progression did not significantly moderate these relationships (ps > .299).

AD biomarkers at baseline may indicate risk of decline in self- and informant-reported change in memory, attention, and spatial navigation ability. As such, subjectively reported decline in these domains may have clinical utility in tracking the subtle cognitive changes associated with the earliest stages of AD.

Normative neuropsychological data are essential for interpretation of test performance in the context of demographic factors. The Mayo Normative Studies (MNS) aim to provide updated normative data for neuropsychological measures administered in the Mayo Clinic Study of Aging (MCSA), a population-based study of aging that randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. We examined demographic effects on neuropsychological measures and validated the regression-based norms in comparison to existing normative data developed in a similar sample.

The MNS includes cognitively unimpaired adults ≥30 years of age (n = 4,428) participating in the MCSA. Multivariable linear regressions were used to determine demographic effects on test performance. Regression-based normative formulas were developed by first converting raw scores to normalized scaled scores and then regressing on age, age2, sex, and education. Total and sex-stratified base rates of low scores (T < 40) were examined in an older adult validation sample and compared with Mayo’s Older Americans Normative Studies (MOANS) norms.

Independent linear regressions revealed variable patterns of linear and/or quadratic effects of age (r2 = 6–27% variance explained), sex (0–13%), and education (2–10%) across measures. MNS norms improved base rates of low performance in the older adult validation sample overall and in sex-specific patterns relative to MOANS.

Our results demonstrate the need for updated norms that consider complex demographic associations on test performance and that specifically exclude participants with mild cognitive impairment from the normative sample.