We examined the use of pupillometry as an early risk marker of Alzheimer's disease (AD). Pupil dilation during a cognitive task has been shown to be an index of cognitive effort and may provide a marker of early change in cognition even before performance begins to decline. Individuals who require more effort to successfully perform a task may be closer to decline. We previously found greater compensatory effort to perform the digit span task in individuals with amnestic mild cognitive impairment (aMCI) who may be at greater risk for AD than individuals with non-amnestic MCI (naMCI). Task evoked pupil dilation is linked to increased norepinephrine output from the locus coeruleus (LC), a structure affected early in the AD pathological process. In this study, we measured pupil dilation during verbal fluency tasks in participants with aMCI or naMCI, and cognitively normal (CN) individuals. Based on our findings using the digit span task, we hypothesized that participants with aMCI would show greater compensatory cognitive effort than the other two groups.

This study included 101 older adults without dementia recruited from the UC San Diego Shiley-Marcos Alzheimer's Disease Research Center and San Diego community (mean [SD] age = 74.7 [5.8]; education = 16.6 [2.5]; N=58 female; N=92 White); 62 CN, 20 aMCI and 19 naMCI participants. Pupillary responses (change relative to baseline at the start of each trial) were recorded at 30 Hz using a Tobii X2-30 (Tobii, Stockholm, Sweden) during semantic (animals, fruits, vegetables) and phonemic (letters F, A, S) fluency tasks. Participants generated as many words as possible in a category (semantic) or starting with a given letter (phonemic) in 60 seconds.

Repeated measures ANOVA (3 groups X 2 fluency conditions) with age, education and sex as covariates showed a significant main effect of group (F(2,95)=3.64, p=.03), but no group X condition interaction (F<1). Pairwise comparisons showed significantly greater fluency task-evoked dilation for aMCI relative to CN (p=.015) and naMCI (p=.019) participants. When controlling for performance (total letter or category words produced), pupil dilation (cognitive effort) remained significantly greater in aMCI relative to the other two groups in both fluency conditions, suggesting pupil dilation informs risk beyond information provided by task performance.

In a previous sample of community-dwelling men who were an average of 13 years younger than the present sample, we found significantly greater pupil dilation during a digit span task in aMCI relative to naMCI and CN groups. In the present study, we replicated those findings in an older sample using a different cognitive task. Significantly greater pupil dilation was found in individuals with aMCI on verbal fluency tasks, indicating greater compensatory cognitive effort to maintain performance. Pupillometry provides a promising biomarker that might be used as an inexpensive and noninvasive additional screening tool for risk of AD.

Various forms of social media have been investigated as platforms for science and health communication, with a recent growing interest in TikTok. TikTok has more than one billion active users. Sixty-two percent of TikTok users are under the age of 29, making it a platform of particular interest when considering the impact of social media content dissemination in pediatric neuropsychology. Personal communication suggests that children, adolescents, and young adults internationally reference specific information from TikToks about attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), tic disorder, and specific learning disorders in the context of clinical neuropsychological assessment. Despite the emerging prevalence of TikTok observed clinically and discussed informally among clinicians, there has yet to be a synthesis of available empirical information of TikTok as a health communication platform for discussing neurodevelopmentally relevant conditions.

A systematic review of research regarding TikTok and neurodevelopmentally relevant conditions was conducted using PRISMA guidelines. The following databases were searched: Ovid MEDLINE (to 20 July 2022), PsycINFO (to 20 July 2022), and PubMed (to 20 July 2022) using search terms TikTok AND ADHD OR autism OR tic OR learning disorder. Searches using search terms TikTok AND learning disability OR dyslexia OR dysgraphia OR dyscalculia were also conducted but were excluded as they yielded no results. Articles were eligible for inclusion if they presented original data (e.g., case series, descriptive analyses, etc.) related to information about neurodevelopmentally relevant conditions on TikTok. A final sample of 5 original papers met criteria for inclusion.

The systematic review sample included a mixture of clinical case series and empirical analyses using primary data from TikTok. Across publications, there was an emphasis on the prevalence of misinformation about disorders on TikTok, the frequency of atypical presentations of neurodevelopmental disorders on TikTok, and the potential for an iatrogenic impact on children and adolescents who view TikTok videos.

Despite the increasing frequency with which patients access TikTok for health-related information, there is a relative dearth of published research on TikTok regarding neurodevelopmentally relevant conditions. This is in contrast to other health-related areas (e.g., there are a far greater number of published articles on TikTok and COVID-19 and dermatology compared to neuropsychological disorders). These findings suggest a missed opportunity for researchers and clinicians alike to engage with TikTok. Based on clinical experience and a review of the available literature, the following recommendations are provided and will be presented in-depth:

1. 1. Clinicians should gain familiarity with virally spread information via TikTok, particularly as it relates to symptoms and presentations of neuropsychological and neurodevelopmental conditions.

2. 2. Clinicians should explicitly assess for knowledge content and source regarding neuropsychological and neurodevelopmental conditions during intake and/or feedback in order to address misinformation and myths, validate lived experiences, and develop rapport with patients.

3. 3. Clinicians and researchers should consider a strengths-based approach to TikTok usage that highlights the value of sharing resources, building community, and decreasing stigma.

4. 4. Clinicians and researchers should be aware of information shared via TikTok as a potential concern for test security.

Mild decline in independent functioning is a core diagnostic criterion for Mild Cognitive Impairment. Performance-based assessments have been considered the gold standard to identify subtle deficits in functioning. Existing assessments were largely designed using demographically homogenous samples (white, highly educated, middle class) and often assume tasks are performed similarly across populations. The current study aimed to validate the utility of the Performance Assessment of Self-Care Skills (PASS) in determining cognitive status in a sample of predominantly African American, low-income older adults.

Cognition and functional capacity were measured in n=245 older participants (aged 50+ years) who were recruited from a larger community study located in Pittsburgh, PA. Cognitive status was defined by a mean split on the Modified Mini Mental Status Examination (3MS) score (84/100). Participants above the cutoff were classified as unlikely cognitive impairment (UCI) and those below classified as potential cognitive impairment (PCI). Functional capacity was assessed using the number of cues provided on three PASS subtasks: shopping, medication management, and critical information retrieval (higher score = worse functioning). Self-reported cognitive and functional decline was assessed via the Everyday Cognition (ECog) questionnaire (higher score = greater decline). Generalized linear models compared performance scores between groups adjusting for literacy (WRAT3), age, and education. Receiver operating characteristic curve (ROC) analyses were run for select functional performance scores to assess their predictive ability in discriminating between PCI and UCI.

Compared to the UCI group (N = 179), the PCI group (N = 66) was older (68 vs. 65 years, p = 0.05), less educated (11 years vs. 12 years, p < 0.01), had lower WRAT3 z-scores (0.19 vs. -0.55, p < .01), and required more cues on the shopping (4.33 vs. 8.54, p < 0.01) and medication management PASS subtasks (2.74 vs. 6.56, p < .01). Both groups reported elevated levels of subjective cognitive complaints on the ECog (1.46 vs. 1.56, p = .09) and performed similarly on the critical information retrieval PASS subtask (0.25 vs 0.54, p = .06). When discerning between UCI and PCI groups, the PASS Shopping subtask had an optimal cut-off score of 4, sensitivity of 0.86, specificity of 0.47, positive predictive value (PPV) of 0.37, and area under the curve (AUC) of 0.71. PASS Medication Management had an optimal cut-off score of 3, sensitivity of 0.77, specificity of 0.56, PPV of 0.39, and AUC of 0.74.

Subjective functional decline and performance on the critical information retrieval subtask were not associated with cognitive groups. PASS shopping and medication management had moderately high AUCs, suggesting they can reliably distinguish between groups. However, both tasks also exhibited low PPVs, low levels of specificity, and high levels of sensitivity, making them strong “rule-out” tests but poor “rule-in” tests in this sample. Because accurate assessment of functioning is useful for MCI and critical to dementia diagnosis, it is imperative we understand how these tasks function across different populations. Future work should 1) validate measures of functional ability across different populations and 2) develop population-appropriate assessments for use in clinical and research settings.

brain white matter integrity as a result of vascular burden is associated with a form of late-life depression, known as vascular depression (VaDep). Black older adults may be particularly vulnerable to developing VaDep due to a higher prevalence of vascular conditions compared to White older adults. The current study examined whether clinical and imaging markers of vascular burden predicted depressive symptoms in an older Black sample. Based on the literature in primarily White samples, we expected greater clinical vascular burden and white matter hyperintensity (WMH) volume to predict greater depressive symptoms both cross-sectionally and over 4-year follow-up. We additionally hypothesized that participants with operationally-defined VaDep would have worse cognitive performance and slower gait speed compared to those without VaDep. Exploratory analyses examined race (Black vs. White) as an additional predictor.

This study used publicly available data from 113 Black older adults who were followed for four years in the Healthy Brain Project (a substudy of the Health, Aging, and Body Composition Study). Clinical vascular burden was defined as the number of vascular conditions (e.g., hypertension, diabetes, stroke); total WMH volume and WMH volume in the uncinate fasciculus, superior longitudinal fasciculus, and cingulum were considered imaging markers of vascular burden. Clinical and imaging-defined vascular burden were used to predict baseline depressive symptoms and average depressive symptoms over follow-up as measured by the Center for Epidemiologic Studies Depression Scale (CES-D). We then formed groups based on cutoffs for vascular burden (two or more conditions) and depressive symptoms (upper tertile of CES-D scores) to compare cognitive (Digit Symbol Substitution Test and 15-Item Executive Interview) and gait speed performance at baseline and changes over four years in VaDep, non-vascular depression, vascular only, and healthy groups. Exploratory analyses included 179 White older adults from the Healthy Brain Project dataset to examine race differences.

Total WMH volume and WMH volume in the uncinate fasciculus predicted higher depressive symptoms both cross-sectionally and longitudinally. However, no similar pattern emerged when using clinically-defined vascular burden as the predictor. The VaDep group had the slowest processing speed but the trajectory of decline over time did not differ between groups. The non-vascular depression group’s executive performance improved over time while performance by the other groups remained stable. Both VaDep and non-vascular depression groups’ gait speed declined over time. There was a stronger association between depression and uncinate fasciculus WMH in Black compared to White individuals, and the Black VaDep group had the slowest baseline processing speed of all groups.

This research supports the validity of the VaDep framework in Black older adults by showing the impact of WMH, particularly in the uncinate fasciculus, on depressive symptoms and identifying cognitive risks associated with VaDep in this population. Moreover, results suggest WMH may confer a greater risk for depression in Black compared to White older adults, and that VaDep disproportionately impacts processing speed in Black older adults. This work addresses an important gap in the VaDep literature by examining a group that has historically been underserved.

Accurately interpreting cognitive change is an essential aspect of clinical care for older adults. Several approaches to identifying 'true’ cognitive change in a single cognitive measure are available (e.g., reliable change methods, regression-based norms); however, neuropsychologists in clinical settings often rely on simple score differences rather than advanced statistics, especially since multiple scores compose a typical battery. This study sought to establish quick-reference normative criteria to help neuropsychologists identify how frequently significant change occurs across multiple measures in cognitively normal older adults.

Data were obtained from the National Alzheimer’s Coordinating Center (NACC). Participants were 845 older adults who were classified as cognitively normal at baseline and at 24-month follow-up. In NACC, these clinical classifications are made separately from the assessment of cognitive performance, including cognitive change. The sample was 34.9% female, 83.5% White, 13.1% Black 2.3% Asian, and 1.1% other race with a mean age of 70.7 years (SD=10.2). Of the sample, 95.5% identified as non-Hispanic. Mean education was 16.1 years (SD=2.8). The cognitive battery entailed: Craft Story Immediate and Delayed Recall, Benson Copy and Delayed Recall, Number Span (Forward & Backward), Category Fluency (Animals & Vegetables), Trails A&B, Multilingual Naming Test, and Verbal Fluency (F&L). Change scores between baseline performance and follow-up were calculated for each measure. The natural distribution of change scores was examined for each measure and cut points representing the 5th and 10th percentile were applied to each distribution to classify participants who exhibited substantial declines in performance on each measure. We then examined the multivariate frequency of statistically rare change scores for each individual.

As expected in a normal sample, overall cognitive performance was generally stable between baseline and 24-month follow-up. Across cognitive measures, 81.9% of participants had at least one change score fall below the 10th percentile in the distribution of change scores, and 55.7% had at least one score below the 5th percentile, 49.3% of participants had two or more change scores that fell below the 10th percentile and 21.1% with two or more below the 5th percentile. There were 26.7% participants that had three or more change scores below the 10th percentile, and 6.4% of participants had three change scores below the 5th percentile.

Among cognitively normal older adults assessed twice at a 24-month interval with a battery of 13 measures, it was not uncommon for an individual to have at least one score fall below the 10th percentile (82% of the sample) or even the 5th percentile (56%) in the natural distribution of change scores. There were 27% participants that had three or more declines in test performance below the 10th percentile; in comparison, only 6% of the sample had three or more change scores at the 5th percentile. This suggests that individuals who exhibit more multivariate changes in performance than these standards are likely experiencing an abnormal rate of cognitive decline. Our findings provide a preliminary quick-reference approach to identifying clinically significant cognitive change. Future studies will explore additional batteries and examine multivariate frequencies of change in clinical populations.

Lateralization and localization of neuropathology helps determine the extent to which eloquent cortex and diseased brain tissue share loci, important information for neurosurgical decision-making, and predicting neurocognitive outcomes. Emerging data suggest that lateralization and localization can inform specific neurorehabilitation approaches following acquired brain injury (ABI). In recent years, computerized cognitive remediation (CCR) of attention and working memory (WM) has been included among treatment guidelines to enhance cognition in post-acute recovery following ABI. Although CCR has shown promise for improving attention and executive functioning in ABI, it is unknown how treatment response may be predicted by locus of ABI. Even less is known about the effects of CCR following neurosurgery. The current study explores neurosurgical lateralization and localization as potential variables for predicting treatment response to CCR.

Adult patients with a variety of neurological diagnoses (N = 17; ∼47% women) completed a full course of Cogmed Working Memory Training (CWMT) s/p neurosurgical intervention. All participants engaged in 30 sessions of CWMT over eight weeks, as well as neuropsychological (NP) assessment at pre-training baseline, immediate post-training, and at 3-month follow-up. Objective and subjective indices of attention, working memory, executive functioning, and emotional well-being were evaluated at three time-points. Neurosurgical loci included left-hemisphere frontal, temporal, and temporoparietal lobes, as well as right-hemisphere frontal, frontotemporal, and temporal lobes.

NP data were reviewed and yielded a clinical impression of cognitive and affective functioning for a cohort of patients with heterogeneous diagnoses (e.g., brain tumor, epilepsy, NPH). Preliminary NP findings suggested that treatment response to CCR for WM was consistent with extant literature on brain-behavior relationships according to lateralization and localization of neurosurgical intervention.

Neurosurgical patients experience neurocognitive and affective dysfunction that may respond well to cognitive rehabilitation (CR) that includes CCR. Additionally, it is possible that lateralization and localization of surgical intervention may contribute to individual differences in treatment response. Further neurorehabilitation research is warranted to identify patients most likely to benefit from CCR and better tailor CR modalities to optimize recovery s/p neurological surgery.

Metamemory is a component of metacognition that includes both the knowledge of factors that affect memory (i.e., declarative metamemory) and knowledge and application of factors in one's own learning and recall performance (i.e., procedural metamemory; Kreutzer et al., 1975). Previous researchers have examined children's metamemory through interviews and found that metamemory abilities are positively associated with age and performance on memory measures (see Godfrey et al., 2022 for review). However, there is not yet a standardized measure to evaluate children's metamemory. The current study aimed to examine the psychometric characteristics of a declarative metamemory questionnaire, the Measure of Metamemory (MoM-10), for children ages 6-12 years old. Based on previous research, we hypothesized that performance on the MoM-10 would not be associated with sex but would be positively associated with age and learning and memory performance.

A total of 75 English-speaking typically developing children between the ages of 6 to 12 years old were recruited for the current study (M age=9.1+1.92; females 49%). Participants completed the MoM-10 which assessed declarative metamemory via 10 multiple choice questions (accuracy score of 0 or 1 points per question) and required participants to provide an explanation for their multiple-choice answer (explanation score of 0, 1, or 2 points per question). The metamemory questionnaire provided two outcome variables: an Accuracy score of 10 possible points, and an Explanation score of 20 possible points. Additionally, participants completed a 3-trial pictorial learning/memory task which provided an Immediate Recall score and Delayed Recall score.

As hypothesized, there were no sex differences on the MoM-10 Accuracy scores (t(73)=0.71, p=0.48) or Explanation scores (t(73)=-73, p=0.47). Consistent with our hypothesis, age was significantly associated with Accuracy (r=0.31, p<0.01) and Explanation scores (r=0.79, p<0.001). Internal consistency of the MOM-10 was moderate for the Explanation score (Cronbach's alpha=0.68) and low for the Accuracy score (KR-20=0.54). Lastly, after controlling for age, participants' MoM-10 Accuracy score was significantly associated with Immediate Recall (r=0.32, p<0.01) on the learning/memory task and the Explanation scores were significantly associated with the Immediate Recall (r=0.36, p<0.01) and Delayed Recall scores (r=0.32, p<0.01) on the learning/memory task.

The current study presents an initial review of psychometric properties of a metamemory questionnaire for children ages 6 to 12 years old. Additionally, as hypothesized, these results suggest the MOM-10 performance is significantly positively associated with participants' age and immediate and delayed recall performance on a pictorial learning/memory task. These associations provide lines of evidence for convergent validity given the expected maturation of metamemory with both age and with improvements in actual memory performance. However, based on the low internal consistency of the accuracy scores, further refinement will be explored including possibly rephrasing questions from the current item set or perhaps excluding current items in future use of the scale.

Stroke is a prevalent disease and often produces cognitive impairment. Post-stroke cognitive impairment has been associated with challenges returning to interpersonal and occupational activities. Knowing what factors are associated with cognitive impairment post-stroke can be useful for predicting outcomes and guiding rehabilitation strategies. One such factor is gender. Previous research has not led to definitive conclusions as to whether there are gender differences in cognitive outcomes following stroke. This may be because other factors, including age at stroke onset, years of education, premorbid intelligence, and lesion volume, may account for apparent gender differences in cognitive outcomes of stroke. Here, we sought to examine whether there are gender differences in general and specific cognitive functions following stroke, beyond what can be accounted for by age at stroke onset, years of education, premorbid intelligence, and lesion volume.

Participants were 237 individuals in the chronic epoch (> 3 months) following ischemic stroke. Using multivariate linear regression, we examined gender as a predictor of overall cognitive functioning and specific cognitive functions, while controlling for age at stroke onset, years of education, premorbid intelligence, and lesion volume. To quantify overall cognitive functioning, we used a measure of general cognitive ability (g) and Full Scale IQ score from the WAIS. To quantify specific cognitive functions, we used scores from 16 individual neuropsychological tests.

After controlling for demographic and lesion factors, men and women did not show any significant differences in overall cognitive functioning following stroke as measured by g (ß = -0.01, 95% CI: -0.14 - 0.12, p = .887) or Full Scale IQ (ß = -0.01, 95% CI: -2.93 - 2.27, p = .801). There were some significant gender differences on specific cognitive tests after controlling for demographic and lesion factors. Specifically, women performed better than men on the Rey Auditory Verbal Learning Test (ps < .001) and men performed better than women on the WAIS Information subtest (ß = -.65, 95% CI: -0.97 - -0.33, p < .001).

Our findings suggest that although men and women have similar overall cognitive functioning after stroke, they show some differences in specific cognitive functions even after accounting for demographic and lesion factors. Namely, women demonstrated better performance on a test of learning while men demonstrated better performance on a test of verbal knowledge/comprehension. This information is important for clinicians as they assess cognitive outcomes in patients post-stroke and plan rehabilitation strategies.

Mobile phone reminding apps can be used by people with acquired brain injury (ABI) to compensate for their memory impairments. However off-the-shelf apps may be difficult to use. ApplTree has been developed to be accessible to this group, compared to off-the-shelf reminding apps such as Google Calendar. This pilot feasibility trial aimed to establish the feasibility of running (and issues that should be addressed to complete) a randomised controlled trial comparing ApplTree to Google Calendar in an ABI community treatment setting.

Adults with self or other reported memory difficulty after an ABI were enrolled (n=39). Those who completed the baseline phase were randomised (n=29) and randomly allocated to the Google Calendar or ApplTree intervention. They were shown a 30 minute video tutorial of the app and an assessment on their ability to use it. Timely completion of everyday memory tasks were measured for a 3 week pre-intervention baseline and 3 week post-intervention follow-up phase. Participants also completed neuropsychological tests assessing memory, attention and executive function and gave qualitative feedback on the app and their experience in the trial.

Recruitment rate was 58% of the target (29 were randomised, n=50 was the target in 2 years). Retention rate was 65.5% and adherence rate was 57.9%. While the feasibility trial was not powered to calculate efficacy, there was a 13% increase in everyday memory tasks completed on time for those in the ApplTree group (n=10) compared to baseline and no change for the Google Calendar group (n=9). Feasibility results indicate 72 participants would need to fully complete a trial to detect the minimum clinically important difference (12.5% increase in successful performance of everyday memory tasks) in the efficacy of ApplTree compared to Google Calendar, should such a difference exist.

The challenges with recruitment of people receiving community care for ABI are highlighted in this trial and discussed along with the impact of the Covid-19 pandemic. Methodological considerations for researchers or clinicians looking to measure everyday memory ability are discussed. The majority (19 of 21) of participants who were given an app were capable of learning to use it during an hour-long session. This indicates it is a feasible intervention that community ABI services could offer. Participant feedback highlighted the merits of design features implemented in ApplTree that can improve the uptake and utility of reminding apps.

Alzheimer's disease (AD) is associated with the accumulation of neuropathological beta-amyloid (Ab) plaques, which is thought to be caused by an imbalance between Ab overproduction and dysfunctional Ab clearance. Both animal and human studies have shown that increased cerebrospinal fluid (CSF) levels of Ab peptides, especially Ab-38 and Ab-40 due to their high solubility, may be indicators of overall Ab dysregulation in preclinical AD, years before pathological Ab plaques begin to aggregate. This overabundance of Ab and later sequestration onto plaques eventually triggers a cascade of subsequent brain changes that may lead to cognitive decline. Indeed, alterations in gray matter integrity may play a role, as imaging studies have shown specific atrophy patterns in preclinical AD, particularly in language regions of the bilateral temporal lobes, which relate to cognitive performance. Here, we aimed to explore whether temporal lobe cortical volume is implicated in the relationship between increased CSF Ab levels and cognitive decline, as measured by confrontation naming performance -- an age-independent language task often impaired in preclinical AD -- in AD-vulnerable populations.

We selected 87 non-demented Veterans (Sex: 99% male; Age: M=68.2, SD=3.7; Education: M=15.5, SD=2.2) from the Alzheimer's Disease Neuroimaging Initiative-Department of Defense (ADNI-DOD) database based on available Boston Naming Test (BNT) scores, CSF measures of Ab-38 and Ab-40, and structural neuroimaging data. The 30-item BNT assessed confrontation naming performance. CSF Ab concentrations were measured using a 2D-UPLC-tandem mass spectrometry method outlined by ADNI-DOD. T1-weighted images were acquired on a 3T scanner and processed by ADNI to calculate cortical volumes (CVs) for regions of interest (ROIs); the present study focused on three bilateral ROIs in the temporal lobe (fusiform gyrus [FFG], inferior temporal gyrus [ITG], and middle temporal gyrus [MTG]). All CVs were adjusted (CV_adj) for intracranial volume (ICV) using the covariance formula (CV_adj = CV - b [ICV - mean(ICV)]). Linear regression models explored the relationship between CSF Ab peptides and BNT with temporal lobe ROIs as moderators using the PROCESS macro.

CV of the bilateral FFG significantly moderated the relationship between BNT performance and both CSF Ab-38 (p=.025, R2=.05, b=.0008) and Ab-40 (p=.016, R2=.06, b=.0002) levels. We then explored effects of the left and right FFG separately and found that the relationship between CSF Ab-38 and BNT was significantly moderated by the left FFG (p=.032, R2=.05, b=.0006) and nominally by the right FFG (p=.072, R2=.03, b=.0006). The relationship between CSF Ab-40 and BNT was significantly moderated by both the left (p=.032, R2=.05, b=.0001) and right (p=.038, R2=.04, b=.0001) FFG. CV of the bilateral ITG and MTG had no effect on any model (all p >.10).

Increased Ab may trigger alterations in neural gray matter integrity, specifically in the FFG of the temporal lobe, and these changes may in turn be implicated in AD-related cognitive decline, particularly in the language domain. These findings suggest that biomarker models incorporating CSF Ab and CV may aid early identification of disease and risk for cognitive decline in preclinical AD stages, which could help inform early interventions.

Among individuals with Parkinson’s Disease (PD), visual hallucinations (VH) and mild cognitive impairment (MCI) are highly prevalent and often co-occur. Atrophy in similar brain regions [e.g. cholinergic basal forebrain (BF) nuclei] as well as specific cognitive difficulties (e.g. posterior-cortical abilities such as semantic fluency and visuoperception) have been associated with the presentation of each symptom type. While there are separate lines of evidence implicating BF volume in MCI and VH, no study to date has examined BF integrity in patients with concurrent MCI and VH symptomology. Furthermore, no prior studies examining BF integrity in MCI and VH have accounted for the potential confounding effects of dopaminergic medications which are known to exacerbate both symptom types. The aims of this study were to harmonize or bridge the two bodies of literature to determine the common neural substrate of PD-VH and PD-MCI (with an emphasis on the BF), to examine the confounding effects of dopaminergic pharmacotherapy, and to examine whether nondopaminergic “posterior” cognitive abilities differ between PD-MCI with versus without VH.

This study used a clinical chart review and MRI data to examine the associations between BF volume in a large group (n=296) of advanced PD patients (∼10 years disease duration) with and without each VH and MCI, covarying the effect of dopaminergic therapy. A two-way ANCOVA was run on total and regional BF volumes (i.e., total BF volume, and four nuclei including Ch4, Ch4p, Ch1-2, Ch3) using VH and MCI as independent variables, while covarying for dopaminergic medication. Using Mann-Whitney U tests, we compared the performance of individuals with MCI-VH versus that of individuals with MCI-noVH on tasks of semantic verbal fluency and of visuoperceptual skills (e.g., judgement of line orientation, object decision, and silhouettes).

There were two major findings: (1) atrophy of the Ch4 region in the BF was associated with MCI with VH while Ch1-2 was associated with MCI regardless of VH status, and (2) patients with both MCI and VH had poorer performance than individuals with MCI without VH on tasks measuring object recognition but not on tasks of visuospatial perception or semantic verbal fluency. These results remained stable regardless of whether or not dopaminergic medication was included in the model.

PD is a heterogeneous disease with different subtypes reflecting both dopaminergic and cholinergic dysfunction. Our findings suggest further dissociations within the cholinergic system. First, atrophy in Ch4, which projects to the cortical mantle, was preferentially associated with VH symptoms and object-based visuoperception deficits. This is consistent with proposals that VH are real-world manifestations of visuoperceptual deficits. Second, Ch1-2 atrophy, which projects primarily to the hippocampus, was associated with MCI regardless of VH. Future research will extend this work to other cognitive abilities such as memory, to analyses of brain networks that implicate the BF, and to the investigation of the relationship between anti-cholinergic medications and symptom presentation in PD.

Performance validity (PVT) and symptom validity tests (SVT) have become standard practice in assessing credibility of neuropsychological profiles and symptom report. While PVTs assess cognitive task engagement, SVTs assess credibility of patient symptom report. Although prior research aimed to conceptualize the relationship between the two validity measure types, it generally focused on SVTs from the Minnesota Multiphasic Personality Inventory (MMPI-2 &RF) and the Structured Inventory of Malingered Symptoms (SIMS; Ord et al., 2021, MMPI-2; Van Dyke et al., 2013). Further studies have demonstrated mixed results, with many studies concluding that symptom and performance validity are separate but related constructs. The current study aimed to assess the relationship between PVTs and SVTs utilizing symptom validity measures from the Personality Assessment Inventory (PAI) across three samples, including neurodevelopmental, psychiatric, and traumatic brain injury groups.

Participants included 634 individuals consecutively referred for neuropsychological assessment who completed the Test of Memory Malingering (TOMM) and the PAI (mean Age = 41.7, SD = 15.7; mean Education = 13.7, SD = 2.7; 53% female; 89% Caucasian). Participants were divided into three groups based on referral, including neurodevelopmental (mean Age = SD = 10.7; mean Education = 13.4, SD = 2.5; 39% female; 79% Caucasian), psychiatric (mean Age = 44.7, SD = 15.0; mean Education = 13.8, SD = 2.8; 58% female; 90% Caucasian), and traumatic brain injury samples (mean Age = SD = 15.5; mean Education = 13.3, SD = 2.3; 50% female; 91% Caucasian). Four structural equation models (latent variable models) were constructed. The first model was fit across the entire sample while the remaining three were fit for the aforementioned subsamples. TOMM trials modeled the performance validity latent variable while SVTs from the PAI modeled the symptom validity latent variable (Positive Impression Management and Defensiveness Index modeled underreporting; Negative Impression Management, Malingering Index, and Cognitive Bias Scale modeled overreporting).

In the full sample model overreporting significantly predicted performance validity (p < 0.001, r = -0.31), indicating higher symptom overreporting related to poorer performance validity while symptom underreporting did not significantly predict performance validity (p = 0.09, r = 0.08). In the neurodevelopmental model overreporting did not significantly predict performance validity (p = 0.44, r = 0.10). Further, symptom underreporting did not significantly predict performance validity (p = 0.40, r = 0.10). Similarly, for the TBI model, overreporting did not significantly predict performance validity (p = 0.82, r = -0.02) and symptom underreporting did not significantly predict performance validity (p = 0.50, r = -0.08). For the psychiatric sample symptom underreporting did not significantly predict performance validity (p = 0.06, r = 0.11); however, symptom overreporting significantly predicted performance validity (p < 0.001, r = - 0.39).

The current study expands on prior research comparing the relationship between SVTs and PVTs in neuropsychological evaluation utilizing SVTs from the PAI. Results of the present study suggest the relationship between the SVTs and PVTs varies by referral type and further supports using both PVTs and SVTs in neuropsychological assessment.

Older age is associated with an increase in altruistic behaviors such as charitable giving. However, few studies have investigated the cognitive correlates of financial altruism in older adults. This study investigated the cognitive correlates of financial altruism measured using an altruistic choice paradigm in a community-based sample of older adults.

In the present study, a sample of older adults (N = 67; M age = 69.21, SD = 11.23; M education years = 15.97, SD = 2.51; 58.2% female; 71.6% Non-Hispanic White) completed a comprehensive neuropsychological assessment and an altruistic choice paradigm in which they made decisions about allocating money between themselves and an anonymous person.

In multiple linear regression analyses that controlled for age, education, and sex, financial altruism was negatively associated with performance on cognitive measures typically sensitive to early Alzheimer’s Disease. These included CVLT-II Short Delay Free Recall (Beta=-0.26, p=0.03); CVLT-II Long Delay Cued Recall (Beta=-0.32, p=0.04), Craft Story 21 Delayed Recall (Beta=-0.32, p=0.01), and Animal Fluency (Beta=-0.27, p=0.02). Findings held when responses were grouped according to how much was given (Gave Equally, Gave More, Gave Less) for word list memory and story memory measures.

Findings of this study point to a negative relationship between financial altruism and cognitive functioning in older adults on measures known to be sensitive to Alzheimer’s Disease (AD). Findings also point to a potential link between financial exploitation risk and AD in older age.

Diagnostic criteria for mild cognitive impairment (MCI) include a report of cognitive decline from the patient or a close informant. It is therefore important to understand the relationship between self- and informant-rated cognition and actual patient performance. Furthermore, it is unknown whether the nature of the relationship between the patient and their informant impacts accuracy of subjective reports. This study aimed to determine the association between informant report, self-report and objective cognitive performance based on relationship factors. We predicted that informant report would be more closely associated with objective performance than self-report after controlling for demographics and mood (Geriatric Depression Scale [mean= 1.4, SD=2]), especially among those who live with the participant and those who are spouses/partners.

Participants (n = 338; age= 73.5 ±6.7) of varying diagnoses and their respective informants were drawn from the longitudinal cohort of the Michigan Alzheimer’s Disease Research Center (MADRC). The majority of informants were spouses/significant others (55.6%), followed by 23.7% being other family members and 20.7% were non- family members; 58.9% of informants live with the participant. Both respondents completed the Cognitive Change Index (CCI) to rate the patient’s cognitive status (higher scores indicating worsening cognition) across three domains: memory (12 questions), language (1 question), and attention/executive functioning (7 questions). These domains were matched to objective cognitive performance measured using the MADRC neuropsychological battery. Executive functioning and attention were assessed using Number Span Test Forward and Backward (NSF, NSB) and Trail Making Test Part B and Trail- Making Test Part A and B ratio (TMTB, TMTB: A); memory was measured using Craft Story 21 (Immediate and Delayed), Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, Delayed Recall, and Benson Complex Figure (BCF) Delayed Recall; and Language was measured by the Controlled Oral Word Association Test (COWAT) and Animal fluency.

Linear regression adjusted for sex, race, and mood indicated that both patient and informant CCI ratings were significantly (p<.05) associated with objective cognitive performance. For every one unit increase on executive CCI items, there was a significant decline in executive functioning (NSF patient and informant ß= -0.09, NSB: [ßP= -.14; ßp-0.13]) and TMTB [ßP= 3.85; ß= 3.10 [% change]). Memory performance also declined per unit increase on CCI memory items: (Craft Story 21 Immediate [ßP=-0.32; ß= -0.37] and Delayed [ßP=-.40; ßp -.47], HVLT-R Total Recall [ßP= -.31; ßI=-.37] and Delayed Recall [ßP= -.16; ß=-.20], and BCF Delayed Recall [ßP= -.18; ß= -.23]. Similarly, one unit increase on the single CCI language item was associated with a decline in COWAT (ßP= -2.27; ß= -4.61) and Animal fluency (ßP= -1.88; ß= -3.03). Effect modification by participant-informant relationship type or participant-informant cohabitation was not significant.

Patient and informant ratings are associated with objective measures of cognition regardless of the relationship between informant and patient or if they live together. This study was limited by a well-educated sample (mean= 16.1 years of education, SD= 2.4 years) with relatively limited diversity among participant-informant relationships. Future studies should replicate analyses across a larger and more diverse sample.

Growing evidence demonstrates that subtle changes in spontaneous speech can be used to distinguish older adults with and without cognitive impairment, including those with Alzheimer's disease (AD). Recent work suggests that quantification of the meaningful connectedness of speech - termed semantic coherence - may be sensitive to cognitive dysfunction. The current study compared global coherence (GC; the degree to which individual utterances relate to the overall topic being discussed) and local coherence (LC; the degree to which adjoining utterances relate meaningfully to each other) in persons with AD and healthy controls.

Speech transcripts from 81 individuals with probable AD (Mage = 72.7 years, SD = 8.8, 70.3% female) and 61 healthy controls (HC) (Mage = 63.9 years, SD = 8.5, 62.2% female) from Dementia Bank were analyzed. All participants completed the Cookie Theft and MMSE as part of that larger project. Machine learning analyses of GC and LC were conducted and models evaluated classification accuracy (i.e., AD vs HC) as well as ROC-AUC. Relationships between coherence indices and MMSE performance were also quantified.

Though no significant group differences emerged in LC (Estimate = 0.012, p = 0.32), persons with AD differed from healthy controls in GC (Estimate = 0.03, p = 0.006) and produced less semantically coherent speech. GC indices predicted AD diagnoses with 65% accuracy. Interestingly, coherence indices showed only modest correlation with MMSE scores (r = .19).

GC metrics of spontaneous speech differentiated between persons with AD and controls, but did not strongly correlate with MMSE performance. Such findings support the notion that many aspects of language are impacted in persons with AD. In addition to replication, future work should evaluate whether GC is also disrupted in persons with pre-clinical AD and its potential to assist with early detection.

Translatability of preclinical results remains a major obstacle in neuropsychiatric research. Even when cognitive tests in preclinical models show translational validity for human testing, with sensitivity to clinical deficits, there remains the issue of heterogeneity among human participants. Norming of performance on cognitive tasks enable corrections for any differences in performance that may arise from the influence of socioeconomic factors, and thus a more direct comparison with preclinical testing results. The 5-choice continuous performance task (5C-CPT) is a test sensitive to changes in sustained attention and cognitive control in rodent manipulations and clinical populations, including schizophrenia and bipolar disorder. Herein, we present normed results of 5C-CPT data from a cohort of human participants, enabling greater comparison to future clinical and rodent testing.

5C-CPT data were generated from a range of participants from the Translational Methamphetamine AIDS Research Center (n=82) and a study of bipolar disorder (n=45). Participant demographics were as follows: Age M=38.5, SD=16.7, Education: M=14.5, SD=1.9, 45% female, 10% Asian, 17% African American, 27% Hispanic, and 46% non-Hispanic White. We used the test2norm R-package to create norms for each of the major outcomes from the 5C-CPT. Non-normally distributed raw scores were transformed to generate more normally distributed data needed for the norming process. Raw scores were first converted into uniform scaled scores that range from 0-20 where a higher score indicated better performance. We then generated T-score formulas, which are standardized residuals and scaled to have a mean of 50 and standard deviation of 10. The residuals are obtained from regressions, modeled using multiple fractional polynomial method (MFP), which regresses scaled scores on demographic variables, which a user wishes to control for (gender, age, education, ethnicity, etc.). MFP models allow to fit non-linear effects for numeric demographic factors (e.g., age), if such effects exist.

New, demographically corrected T-score formulas were calculated for each major outcome of the 5C-CPT: reaction time (MCL), reaction time variability (VarRT), dprime, hit rate (HR) and false-alarm rate (FAR). MFP models showed that age had a significant effect on MCL, VarRT, dprime, and HR (all p<0.01), while gender only showed a significant effect for MCL and VarRT (all p<0.05). Interestingly, education and ethnicity did not show a significant effect for any MFP model and none of the demographic factors (age, education, gender, ethnicity) were significant in the model for FAR. As defined in the test2norm package, all scaled scores had a mean of 10 and SD of 3 and all T-scores had a mean of 50 and SD of 10.

The 5C-CPT is a test of attention and cognitive control available for human testing, reverse-translated from rodent studies. The normative data generated here will enable future comparisons of data without the need for additional control studies. Furthermore, comparing these normative data to manipulations will enable further comparisons to rodent testing, with manipulations relative to baseline becoming more meaningful. Thus, the 5C-CPT is a viable tool for conducting cross-species translational research toward developing novel therapeutics that treat dysfunctional attentional and cognitive control.

Word finding or “naming” difficulty is a symptom of multiple neurological disorders; therefore, naming assessment is an integral component of neuropsychological evaluation. Prior work has found weaker second-language naming in healthy proficient bilingual youth than monolingual youth, and similar findings have been shown in adults with epilepsy. Considering the potential influences of both early onset epilepsy and bilingualism on brain development, we compared naming in English second language (ESL) and monolingual youth with epilepsy. To assess the impact of bilingualism independent of the known effects of seizure laterality (i.e., poor naming in those with left, dominant-hemisphere seizures), we excluded patients with left language dominance and unilateral seizures. We hypothesized that like other groups, naming would be weaker in ESL than in monolingual youth with epilepsy.

Participants included 84 children with seizures that could not be lateralized clinically (n=36), bilateral seizures (n=20), centrotemporal spikes (n=3), and those with unilateral seizures and atypical language dominance (n=25), ages 6-15 years old: 66 monolingual, English (mean age: 10.87 ± 2.70 years) and 18 ESL (mean age: 10.78 ± 2.88 years). Those with FSIQ < 70 and vocabulary SS < 6 were excluded to ensure English proficiency. Independent samples t-tests, multivariate ANOVA, and chi-square tests compared groups on demographic factors and test performance. All measures (FSIQ, WISC/WASI Vocabulary, letter and category fluency, Children’s Auditory (AN) and Visual Naming (VN) Tests) were administered in English.

Monolingual and ESL groups did not differ in: age, sex, SES, seizure type (i.e., non-lateralized, bilateral, centrotemporal spikes, or atypical language dominance), epilepsy onset age, or number of AEDs. Comparisons also showed no differences in FSIQ, vocabulary, letter fluency, or category fluency (all ps > 0.05). By contrast, auditory and visual naming performances were weaker among ESL patients than monolingual patients: AN accuracy, F(1,81) = 10.89, p = 0.001; AN tip-of-the-tongues (TOTs), F(1,81) = 6.35, p = 0.014; AN Summary Scores (SS), F(1,81) = 6.17, p = 0.015; VN accuracy, F(1,81) = 4.66, p = 0.034; VN SS, F(1,81) = 4.87, p = 0.030, with the exception of VN TOTs, which approached significance, F(1,81) = 3.55, p = 0.063.

Consistent with findings in bilingual healthy youth and ESL adults with epilepsy, naming in ESL youth with epilepsy was weaker than in monolingual children. The groups did not differ on other aspects of language. Thus, unlike other expressive verbal functions, naming is adversely affected in the second language of bilingual people with epilepsy across the age span. These results suggest that poor naming in ESL patients cannot be used to infer a naming deficit, and/or left (dominant) temporal lobe dysfunction.

People with HIV (PWH) are at an increased risk for cognitive impairment as they age compared to their HIV-negative counterparts. Lifestyle factors can have protective effects on cognitive outcomes among PWH. However, little work has examined diet quality and cognitive function in PWH. Examining the association between diet quality and cognitive function among PWH is particularly important given this population’s increased risk for both poor diet quality and cognitive impairment. The purpose of this study was to examine the relationship between diet and cognitive function in aging PWH.

This cross-sectional study was conducted in Birmingham, Alabama and Cleveland, Ohio. Eighty-six PWH (mean age 56 years) completed standard triple-pass 24-hour diet recalls and a neurocognitive assessment. Partial Pearson’s correlations were conducted between diet variables and global neurocognitive function T scores, adjusting for total calories, sex, and education level.

Overall diet quality of the sample was poor. The overall sample presented with low Healthy Eating Index (HEI)-2015 scores, high glycemic index, twice the goal amount for saturated fatty acids (SFAs), and inadequate consumption of several nutrients typically associated with cognitive health including omega-3 fatty acids, dietary protein, fiber, Vitamin D, Zinc, and several B-vitamins. Greater total calories per day (r=0.28, p<0.05), greater percentage of total calories of SFAs (r=0.26, p<0.01), and lower glycemic index (r=-0.24, p<0.05) were associated with better cognition. Higher intake of several individual fatty acids, particularly SFAs, were associated with better cognition (correlations ranging from 0.23 to 0.31). Higher intakes of phosphorus (r=0.29, p<0.01), magnesium (r=0.25, p<0.05), and potassium (r=0.22, p<0.05) were associated with better cognition. Higher grams/day of several amino acids were associated with better cognition (correlations ranging from 0.22 to 0.27).

In a sample with overall poor diet quality not meeting recommended guidelines, findings suggest that being nourished in itself is associated with better cognitive function. Associations with several individual nutrients may inform potential intervention targets to protect brain health in PWH. Further, targeting food insecurity in interventions may have downstream effects on cognition in PWH.

Stress is well known to increase the severity of somatization and insomnia. A recent major stressor that could have influenced the severity of these presentations was world-wide COVID-19 Pandemic. Somatization is the physical expression of stress and emotional distress that can manifest itself throughout various corporal domains and can be a comorbidity to insomnia. Headaches represent some of the most common complaints associated with brain injuries and neurological disorders but are common in somaticized disorders as well. In large survey study we examined whether exercise was associated with severity of somatization and headaches. We hypothesized that both healthy individuals and those with insomnia who exercised during the pandemic would report less severe somatic symptoms and headaches than those who did not.

A large survey was sent out to 4,073 individuals to measure their experience in numerous domains during the COVID-19 pandemic. This survey included a short symptom questionnaire used to measure somatization and the Insomnia Scale Index to measure insomnia. These questionnaires were administered along with a “yes or no” question on whether the participants exercised regularly in that period. A univariate ANOVA was performed to analyze the data to determine if exercise during the pandemic was beneficial in the reduction of somatic symptoms and headache severity. Furthermore, these tests were run to determine if the effect was greater on those with insomnia.

The effect of insomnia and exercise on total somatic symptoms were significant at F(1, 3445)=650.5, p<0.001 and F(1, 3445)=26.1, p<0.001, respectively. For reported headache severity, there was a significant effect of exercise F(1, 4073)=14.5, p<0.001 and insomnia F(1, 4073)=160.5, p<0.001; therefore, those who exercised reported less severe headaches and those who suffered from insomnia reported more severe somatic symptoms. This meant that those who exercised reported less severe somatization and headaches than those who didn’t and those with insomnia reported more severe somatization and headaches than healthy individuals. However, the interaction between exercise and insomnia on overall somatization severity was not significant at F(1, 3445)=3.4, p=0.066 nor for reported headache severity F(1, 4073)=0.81, p=0.370. Despite there not being a significant interaction, the benefit of exercise was slightly greater on healthy individuals than those with insomnia.

Those with insomnia reported more severe headaches and overall somatic symptoms than non-insomniacs regardless of whether they exercised or not. Exercise did make a difference on the reported severity of headaches and somatization in both groups; however, the benefit of exercise on headaches and somatization was greater in individuals who do not suffer from insomnia. Thus, exercise was noted to be beneficial to those in the general population and those suffering from insomnia as it can potentially reduce the severity of somatization and headaches. Of course, this research was cross sectional and correlational, so the directionality of the effects cannot be inferred. For future research, it would be instrumental to use experimental methods to help determine the duration and type of exercise that may optimize its potential benefits on headaches and somatic symptoms.

Higher educational attainment is associated with reduced risk for Alzheimer's disease (AD) dementia, and its protective effect may act through alterations in cerebral blood flow (CBF) that allow for better coping with accumulating neuropathology. Additionally, there are sex differences in both the risk of developing AD as well as the potential protective effects of education. We therefore sought to investigate whether education moderates the association of hippocampal CBF and memory in cognitively unimpaired older adults, and to examine if these interactions were moderated by sex.

Cognitively unimpaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 51 men, 50 women) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify bilateral hippocampal CBF. Sex was defined as sex at birth. Multiple linear regressions assessed (1) the independent associations among education, CBF, and memory performance separately in men and women and (2) the three-way interactions among CBF, sex, and education, followed by sex-stratified analyses. Three outcome measures were examined: Logical Memory Story A immediate and delayed recall, and Rey Auditory Verbal Learning Test (RAVLT) intrusions. All models adjusted for age and APOE epsilon-4 allele frequency, and all models with CBF additionally adjusted for cerebral metabolism (baseline FDG-PET composite) and pulse pressure.

CBF was not associated with education or memory in either women or men. There was a positive association between education and delayed memory in women (ß=0.14, t=2.64, p=0.008) as well as trending, positive associations between education and immediate memory in women (ß=0.09, t=1.79, p=0.074) and education and delayed memory in men (ß=0.09, t=1.94, p=0.054). Three-way interactions among sex, CBF, and education were significant on immediate recall (ß=2.55, t=2.53, p=0.013), delayed recall (ß=2.56, t=2.44, p=0.017), and RAVLT intrusions (ß=-2.28, t=-2.27, p=0.026). In women, there were interactions between education and hippocampal CBF on both immediate (ß=2.49, t=2.90, p=0.006) and delayed recall (ß=2.30, t=2.78, p=0.009), such that as education increased, the strength of the association between CBF and immediate memory increased. There was also an interaction between education and hippocampal CBF on RAVLT intrusions in women (ß=-2.42, t=-3.05, p=0.004), such that as education increased, the strength of the association between CBF and number of intrusions decreased; there was a main effect where in women with lower education, as CBF increased, the number of intrusions increased (ß=0.76, t=2.59, p=0.032); in women with higher education, there was no association between CBF and intrusions. In men, none of these two-way interactions were significant.

These results suggest that, in cognitively unimpaired older women, the relationship between hippocampal CBF and memory is moderated by education level, even when adjusting for several other factors. Specifically, higher education may serve as a protective factor in the hippocampal CBF-memory relationship, and this relationship was sex-dependent, occurring in women only. Further research is needed to examine these relationships longitudinally across the clinical continuum of AD. Additionally, this work needs to be conducted in more diverse samples to allow for analyses investigating the impact of education on the intersection of race/ethnicity and sex/gender.