Increased intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning hemodynamic signal IIV is limited. Cortical thinning occurs during aging and is associated with cognitive decline. Dual-task walking (DTW) performance in older adults has been related to cognition and neural integrity. We examined the hypothesis that reduced cortical thickness would be associated with greater increases in IIV in prefrontal cortex oxygenated hemoglobin (HbO2) from single tasks to DTW in healthy older adults while adjusting for behavioral performance.

Participants were 55 healthy community-dwelling older adults (mean age = 74.84, standard deviation (SD) = 4.97). Structural MRI was used to quantify cortical thickness. Functional near-infrared spectroscopy (fNIRS) was used to assess changes in prefrontal cortex HbO2 during walking. HbO2 IIV was operationalized as the SD of HbO2 observations assessed during the first 30 seconds of each task. Linear mixed models were used to examine the moderation effect of cortical thickness throughout the cortex on HbO2 IIV across task conditions.

Analyses revealed that thinner cortex in several regions was associated with greater increases in HbO2 IIV from the single tasks to DTW (ps < .02).

Consistent with neural inefficiency, reduced cortical thickness in the PFC and throughout the cerebral cortex was associated with increases in HbO2 IIV from the single tasks to DTW without behavioral benefit. Reduced cortical thickness and greater IIV of prefrontal cortex HbO2 during DTW may be further investigated as risk factors for developing mobility impairments in aging.

Preclinical Alzheimer disease (AD) has been associated with subtle changes in memory, attention, and spatial navigation abilities. The current study examined whether self- and informant-reported domain-specific cognitive changes are sensitive to AD-associated biomarkers.

Clinically normal adults aged 56–93 and their informants completed the memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the Everyday Cognition Scale (ECog). Reliability and validity of these subsections were examined using Cronbach’s alpha and confirmatory factor analysis. Logistic regression was used to examine the ability of ECog subsections to predict AD-related biomarkers (cerebrospinal fluid (CSF) ptau181/Aβ42 ratio (N = 371) or hippocampal volume (N = 313)). Hierarchical logistic regression was used to examine whether the self-reported subsections continued to predict biomarkers when controlling for depressive symptomatology if available (N = 197). Additionally, logistic regression was used to examine the ability of neuropsychological composites assessing the same or similar cognitive domains as the subsections (memory, executive function, and visuospatial abilities) to predict biomarkers to allow for comparison of the predictive ability of subjective and objective measures.

All subsections demonstrated appropriate reliability and validity. Self-reported memory (with outliers removed) was the only significant predictor of AD biomarker positivity (i.e., CSF ptau181/Aβ42 ratio; p = .018) but was not significant when examined in the subsample with depressive symptomatology available (p = .517). Self-reported memory (with outliers removed) was a significant predictor of CSF ptau181/Aβ42 ratio biomarker positivity when the objective memory composite was included in the model.

ECog subsections were not robust predictors of AD biomarker positivity.

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.

White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer’s disease (AD) risk.

The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131).

After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume.

These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.

Loneliness is a concern for patients with schizophrenia. However, the correlates of loneliness in patients with schizophrenia are unclear; thus, the aim of the study is to investigate neuro- and social cognitive mechanisms associated with loneliness in individuals with schizophrenia.

Data from clinical, neurocognitive, and social cognitive assessments were pooled from two cross-national samples (Poland/USA) to examine potential predictors of loneliness in 147 patients with schizophrenia and 103 healthy controls overall. Furthermore, the relationship between social cognition and loneliness was explored in clusters of patients with schizophrenia differing in social cognitive capacity.

Patients reported higher levels of loneliness than healthy controls. Loneliness was linked to increased negative and affective symptoms in patients. A negative association between loneliness and mentalizing and emotion recognition abilities was found in the patients with social-cognitive impairments, but not in those who performed at normative levels.

We have elucidated a novel mechanism which may explain previous inconsistent findings regarding the correlates of loneliness in individuals with schizophrenia.

To explore the relationship between age, education, sex, and ApoE4 (+) status to brain volume among a cohort with amnestic mild cognitive impairment (aMCI).

One hundred and twenty-three participants were stratified into Hispanic (n = 75) and White non-Hispanic (WNH, N = 48). Multiple linear regression analyses were conducted with age, education, sex, and ApoE4 status as predictor variables and left and right combined MRI volumes of the hippocampus, parahippocampus, and entorhinal cortex as dependent variables. Variations in head sizes were corrected by normalization with a total intracranial volume measurement.

Bonferroni-corrected results indicated that when controlling for ApoE4 status, education, and age, sex was a significant predictor of hippocampal volume among the Hispanic group (β = .000464, R2 = .196, p < .01) and the WNH group (β = .000455, R2 = .195, p < .05). Education (β = .000028, R2 = .168, p < .01) and sex (β = .000261, R2 = .168, p < .01) were significant predictors of parahippocampal volume among the Hispanic MCI group when controlling for the effects of ApoE4 status and age. One-way ANCOVAs comparing hippocampal and parahippocampal volume between males and females within groups revealed that females had significantly larger hippocampal volumes (p < .05). Hispanic females had significantly larger hippocampal (p < .001) and parahippocampal (p < .05) volume compared to males. No sex differences in parahippocampal volume were noted among WNHs.

Biological sex, rather than ApoE4 status, was a greater predictor of hippocampal volume among Hispanic and WNH females. These findings add to the mixed literature on sex differences in dementia research and highlight continued emphasis on ethnic populations to elucidate on neurodegenerative disparities.

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.

Anorexia nervosa (AN) is characterized by severe restriction of calorie intake, which persists despite serious medical and psychological sequelae of starvation. Several prior studies have identified impaired feedback learning among individuals with AN, but whether it reflects a disturbance in learning from positive feedback (i.e., reward), negative feedback (i.e., punishment), or both, and the extent to which this impairment is related to severity and duration of illness, has not been clarified.

Participants were female adolescents with AN (n = 76) and healthy teen volunteers (HC; n = 38) between the ages of 12–18 years who completed a probabilistic reinforcement learning task. A Bayesian reinforcement learning model was used to calculate separate learning rates for positive and negative feedback. Exploratory analyses examined associations between feedback learning and duration of illness, eating disorder severity, and self/parent reports of reward and punishment sensitivity.

Adolescents with AN had a significantly lower rate of learning from positive feedback relative to HC. Patients and HC did not differ in learning from negative feedback or on overall task performance measures. Feedback learning parameters were not significantly associated with duration of illness, eating disorder severity, or questionnaire-based reports of reward and punishment sensitivity.

Adolescents with AN showed a circumscribed deficit in learning from reward that was not associated with duration of illness or reported sensitivity to reward or punishment. Subsequent longitudinal research should explore whether differences in learning from positive feedback relate to course of illness in youth with AN.

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.

Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB.

The study sample included 97 participants with consensus-defined DLB from the National Alzheimer’s Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual’s performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual’s performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ).

Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores).

Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting.

This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history.

Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70–0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background.

A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

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.

Modified Mini-Mental State Examination (3MSE) is often used to screen for dementia, but little is known about psychometric validity in American Indians.

We recruited 818 American Indians aged 65–95 for 3MSE examinations in 2010–2013; 403 returned for a repeat examination in 2017–2019. Analyses included standard psychometrics inferences for interpretation, generalizability, and extrapolation: factor analysis; internal consistency-reliability; test-retest score stability; multiple indicator multiple cause structural equation models.

This cohort was mean age 73, majority female, mean 12 years education, and majority bilingual. The 4-factor and 2nd-order models fit best, with subfactors for orientation and visuo-construction (OVC), language and executive functioning (LEF), psychomotor and working memory (PMWM), verbal and episodic memory (VEM). Factor structure was supported for both research and clinical interpretation, and factor loadings were moderate to high. Scores were generally consistent over mean 7 years. Younger participants performed better in overall scores, but not in individual factors. Males performed better on OVC and LEF, females better on PMWM. Those with more education performed better on LEF and worse on OVC; the converse was true for bilinguals. All differences were significant, but small.

These findings support use of 3MSE for individual interpretation in clinic and research among American Indians, with moderate consistency, stability, reliability over time. Observed extrapolations across age, sex, education, and bilingual groups suggest some important contextual differences may exist.

To examine (1) the association between purpose in life and multiple domains of cognitive function and informant-rated cognitive decline, affect, and activities; (2) whether these associations are moderated by sociodemographic factors, cognitive impairment, or depression; (3) whether the associations are independent of other aspects of well-being and depressive symptoms.

As part of the 2016 Harmonized Cognitive Assessment Protocol from the Health and Retirement Study, participants completed a battery of cognitive tests and nominated a knowledgeable informant to rate their cognitive decline, affect, and activities. Participants with information available on their purpose in life from the 2014/2016 Leave Behind Questionnaire were included in the analytic sample (N = 2,812).

Purpose in life was associated with better performance in every cognitive domain examined (episodic memory, speed-attention, visuospatial skills, language, numeric reasoning; median β =.10, p <.001; median d =.53). Purpose was likewise associated with informant-rated cognitive decline and informant-rated affective and activity profiles beneficial for cognitive health (median β =.18, p < .001; median d =.55). There was little evidence of moderation by sociodemographic or other factors (e.g., depression). Life satisfaction, optimism, positive affect, and mastery were generally associated with cognition. When tested simultaneously with each other and depressive symptoms, most dimensions were reduced to non-significance; purpose remained a significant predictor.

Purpose in life is associated with better performance across numerous domains of cognition and with emotional and behavioral patterns beneficial for cognitive health that are observable by knowledgeable others. These associations largely generalize across demographic and clinical groups and are independent of other aspects of well-being.

The Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey’s Auditory Verbal Learning Test (AVLT).

Participants (N = 353; mean age = 71, SD = 11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years). Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (amyloid PET positive, A+, n = 125) or not (A-, n = 228), and those with biological AD (amyloid and tau PET positive, A+T+, n = 55) vs no evidence of AD pathology (A−T−, n = 195). Analyses were repeated among CU participants only.

The SLS and AVLT showed similar ability to differentiate biomarker-defined groups when comparing AUROCs (p’s > .05). In logistic regression models, SLS contributed significantly to predicting biomarker group beyond age, education, and sex, including when limited to CU participants. Medium (A− vs A+) to large (A−T− vs A+T+) unadjusted effect sizes were observed for both SLS and AVLT. Learning and delay variables were similar in terms of ability to separate biomarker groups.

Remotely administered SLS performed similarly to in-person-administered AVLT in its ability to separate biomarker-defined groups, providing evidence of criterion validity. Results suggest the SLS may be sensitive to detecting subtle objective cognitive decline in preclinical AD.

Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test – the 26-item Matrix Reasoning subtest of the WAIS-IV – might be used more efficiently if it were administered using computerized adaptive testing (CAT).

Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40).

The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3–7 items had to be administered for a large percentage of individuals.

This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS).

The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery was used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data.

For the eight domains of cognitive functioning identified (orientation, memory [immediate, delayed, and recognition], set shifting, attention/speed, language/fluency, and visuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where fit must be perfect and is not informative. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94).

The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used to operationalize notions of neurocognitive impairment, and as a starting point for prioritizing pre-statistical harmonization and evaluating configural invariance in cross-national research.

Adverse childhood experiences (ACEs) may be a risk factor for later-life cognitive disorders such as dementia; however, few studies have investigated underlying mechanisms, such as cardiovascular health and depressive symptoms, in a health disparities framework.

418 community-dwelling adults (50% nonHispanic Black, 50% nonHispanic White) aged 55+ from the Michigan Cognitive Aging Project retrospectively reported on nine ACEs. Baseline global cognition was a z-score composite of five factor scores from a comprehensive neuropsychological battery. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Cardiovascular health was operationalized through systolic blood pressure. A mediation model controlling for sociodemographics, childhood health, and childhood socioeconomic status estimated indirect effects of ACEs on global cognition via depressive symptoms and blood pressure. Racial differences were probed via t-tests and stratified models.

A negative indirect effect of ACEs on cognition was observed through depressive symptoms [β = −.040, 95% CI (−.067, −.017)], but not blood pressure, for the whole sample. Black participants reported more ACEs (Cohen’s d = .21), reported more depressive symptoms (Cohen’s d = .35), higher blood pressure (Cohen’s d = .41), and lower cognitive scores (Cohen’s d = 1.35) compared to White participants. In stratified models, there was a negative indirect effect through depressive symptoms for Black participants [β = −.074, 95% CI (−.128, −.029)] but not for White participants.

These results highlight the need to consider racially patterned contextual factors across the life course. Such factors could exacerbate the negative impact of ACEs and related mental health consequences and contribute to racial disparities in cognitive aging.

To determine whether poorer performance on the Boston Naming Test (BNT) in individuals with transactive response DNA-binding protein 43 pathology (TDP-43+) is due to greater loss of word knowledge compared to retrieval-based deficits.

Retrospective clinical-pathologic study of 282 participants with Alzheimer’s disease neuropathologic changes (ADNC) and known TDP-43 status. We evaluated item-level performance on the 60-item BNT for first and last available assessment. We fit cross-sectional negative binomial count models that assessed total number of incorrect items, number correct of responses with phonemic cue (reflecting retrieval difficulties), and number of “I don’t know” (IDK) responses (suggestive of loss of word knowledge) at both assessments. Models included TDP-43 status and adjusted for sex, age, education, years from test to death, and ADNC severity. Models that evaluated the last assessment adjusted for number of prior BNT exposures.

43% were TDP-43+. The TDP-43+ group had worse performance on BNT total score at first (p = .01) and last assessments (p = .01). At first assessment, TDP-43+ individuals had an estimated 29% (CI: 7%–56%) higher mean number of incorrect items after adjusting for covariates, and a 51% (CI: 15%–98%) higher number of IDK responses compared to TDP-43−. At last assessment, compared to TDP-43−, the TDP-43+ group on average missed 31% (CI: 6%–62%; p = .01) more items and had 33% more IDK responses (CI: 1% fewer to 78% more; p = .06).

An important component of poorer performance on the BNT in participants who are TDP-43+ is having loss of word knowledge versus retrieval difficulties.

Brain areas implicated in semantic memory can be damaged in patients with epilepsy (PWE). However, it is challenging to delineate semantic processing deficits from acoustic, linguistic, and other verbal aspects in current neuropsychological assessments. We developed a new Visual-based Semantic Association Task (ViSAT) to evaluate nonverbal semantic processing in PWE.

The ViSAT was adapted from similar predecessors (Pyramids & Palm Trees test, PPT; Camels & Cactus Test, CCT) comprised of 100 unique trials using real-life color pictures that avoid demographic, cultural, and other potential confounds. We obtained performance data from 23 PWE participants and 24 control participants (Control), along with crowdsourced normative data from 54 Amazon Mechanical Turk (Mturk) workers.

ViSAT reached a consensus >90% in 91.3% of trials compared to 83.6% in PPT and 82.9% in CCT. A deep learning model demonstrated that visual features of the stimulus images (color, shape; i.e., non-semantic) did not influence top answer choices (p = 0.577). The PWE group had lower accuracy than the Control group (p = 0.019). PWE had longer response times than the Control group in general and this was augmented for the semantic processing (trial answer) stage (both p < 0.001).

This study demonstrated performance impairments in PWE that may reflect dysfunction of nonverbal semantic memory circuits, such as seizure onset zones overlapping with key semantic regions (e.g., anterior temporal lobe). The ViSAT paradigm avoids confounds, is repeatable/longitudinal, captures behavioral data, and is open-source, thus we propose it as a strong alternative for clinical and research assessment of nonverbal semantic memory.