Baseline Neuropsychological Testing Research Articles

Cortex-to-caudate volume ratio as a predictor of cognitive decline in Alzheimer's disease and mild cognitive impairment

BackgroundBrain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or cortical volume to subcortical gray matter structure volumes are potential imaging markers for cognitive alterations in AD dementia and amnestic mild cognitive impairment (aMCI). MethodsSeventy-seven subjects diagnosed with AD dementia or aMCI underwent baseline neuropsychological testing, 2-year follow-up cognitive assessments, and high-resolution T1-weighted MRI scans. Total brain/cortical volume and subcortical gray matter structure volumes were automatically segmented and measured. Univariate and multiple linear regression analyses were conducted to determine the associations between volumetric ratios and interval changes in cognitive scores. ResultsThe ratio of cortical volume to caudate volume showed the most significant association with changes in MoCA (B = 0.132, SE = 0.042, p = 0.002), MMSE (B = 0.140, SE = 0.040, p = 0.001), and CDR-SOB (B = −0.013, SE = 0.005, p = 0.007) scores over the 2-year follow-up period. These associations remained significant after adjusting for various covariates. Similar associations were observed for the ratios of cortical volume to putamen and globus pallidum volumes. ConclusionsThe cortex-to-caudate volume ratio is significantly associated with cognitive decline in AD dementia and aMCI. This ratio may serve as a useful biomarker for monitoring disease progression and predicting cognitive outcomes. Our findings highlight the importance of considering the relative atrophy of cortical and subcortical structures in understanding AD pathology.

Neurocognitive Concussion Test Performance for Student Athletes on the Autism Spectrum.

To examine baseline neurocognitive functioning among adolescent athletes on the autism spectrum based on self-reported level of academic performance. Participants in this cross-sectional, observational study were 6,441 adolescent athletes with a self-reported diagnosis of autism who completed pre-season neurocognitive testing using Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); 4,742 reported a co-occurring learning disorder (LD), and 6,612 individuals without autism or LD were included as a control group. The majority (57%) self-reported Average Academic Performance, 39% Above Average, and 4% Below Average performance. Athletes with self-reported autism (with or without LD; 12.2%) were 2.74x (95% CI: 2.17-2.82) more likely to fall below cutoffs for ImPACT Embedded Invalidity Indicators (EVIs), with a significant interaction between self-reported Diagnosis and Academic Performance; individuals with co-occurring autism and LD who reported Below Average Academic Performance had the greatest likelihood of scoring below cutoffs (22%), followed by ASD without LD (14.8%) and Controls (14.6%) with Below Average Academic Performance. Analyses of variance (ANOVAs) revealed main effects of Diagnosis and Academic Performance on neurocognitive performance, with interactions on all ImPACT Composite Scores except Processing Speed. Athletes with self-reported ASD are more likely to fall below ImPACT EVIs and score worse on ImPACT, with greater likelihood/worse performance related to level of academic functioning. Academic performance should be considered when interpreting neurocognitive testing data, to best index neuropsychological functioning associated with concussion in this population. The current findings highlight the importance of individual participant baseline neuropsychological testing for individuals on the autism spectrum.

Differential effects of cholesterol levels on cognition according to body mass index in Parkinson’s disease

BackgroundCholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson’s disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD.MethodsThis study included 321 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging and baseline neuropsychological tests. Multivariate linear regression and Cox regression models were used to investigate the effect of TC levels on the composite score of each cognitive domain and dementia conversion after adjusting for covariates, respectively. Interaction analyses were performed to examine the interaction effect between TC levels and BMI on baseline cognition and dementia conversion.ResultsTC levels and cognition showed no significant relationship after adjusting for potential confounders. A significant interaction effect between TC levels and BMI was observed in frontal/executive function and dementia conversion. Further analyses showed that TC levels were positively associated with frontal/executive function in the under-/normal weight group (β = 0.205, p = 0.013), whereas a negative relationship existed between TC levels and frontal/executive function in the obese group (β = − 0.213, p = 0.017). Cox regression analyses also showed the differential effects of TC levels on dementia conversion according to BMI (under-/normal weight group: hazard ratio [HR] = 0.550, p = 0.013; obese group: HR = 2.085, p = 0.014).ConclusionsThis study suggests a cross-over interaction between TC levels and BMI on cognitive symptoms in PD.

A new home‐based cognitive test using phone calls in mild cognitive impairment

AbstractBackgroundMild cognitive impairment (MCI) is a risk group of dementia. Despite of plethora of hospital‐based neuropsychological tests, assessment tools that can be performed at home to detect cognitive progression are lacking. We thought that a home‐based cognitive test (HCT) is useful for regular cognitive monitoring without visiting the hospital. Our study aimed to validate the HCT by assessing relationships with existing hospital‐based neuropsychological tests scores.MethodThis pilot study was conducted in a university‐affiliated dementia clinic from July 2019 to December 2021. We had developed a new HCT that can be examined using phone calls without visiting the hospital. The newly developed HCT is composed of 20 questions (score ranges 0‐30), a higher score indicates better general cognition. Participants with MCI were enrolled and underwent regular HCT during 6 months. Brain MRI, plasma amyloid, baseline and endpoint neuropsychological tests, and assessment for clinical progression were performed. Associations between HCT scores and in‐person neuropsychological tests were investigated. We additionally assessed whether the HCT scores are correlated with Alzheimer’s disease (AD)‐related biomarkers including plasma amyloid values and regional brain volumes. To assess relevance, partial correlation coefficient adjusted by age, sex, and education was performed.ResultHCT had good intraclass correlation coefficient values (test‐retest Cronbach’s alpha 0.839 & inter‐rater reliability Cronbach’s alpha 0.627). Totally 38 participants were enrolled and 32 completed the endpoint evaluations at 6 months. Seven participants progressed to mild dementia. Baseline HCT score showed good correlations with Mini‐Mental State Examination (MMSE) score, verbal memory delayed recall scores, and stroop test scores after adjustment for age, sex, and education. However, HCT scores did not show significant associations with AD‐biomarkers. MCI with higher risk of progression (APOE4 carrier or positivity in plasma amyloid values) showed numerical trends of faster HCT declines compared with MCI with lower risk of progression, although it did not reach statistical significance (p>0.05).ConclusionWe demonstrated good reliability and correlations of the newly developed HCT with existing in‐person neuropsychological tests. It also showed good applicability on the elderly with MCI. Hence, HCT could be a promising and alternative option to monitor cognitive declines without visiting the hospital.

Associations between afternoon napping, left amygdala volume and cognitive performance in elderly with normal cognitive function

BackgroundThe relationship between afternoon napping and cognitive function in the elderly is very complex and the mechanism is unknown. MethodsIn the current study, 194 community elders with normal cognitive functions were included. All subjects completed baseline clinical assessment, baseline neuropsychological test as well as baseline structural MRI. Based on their napping status, these 194 participants were divided into the napping group (n = 88) and the non-napping group (n = 106). We then compared the differences in cognitive performance and structural magnetic resonance between the two groups. ResultsIn the intergroup analysis, we found that the nappers showed poorer cognitive performance on both overall cognitive function and domain specific cognitive function; while on the whole sample, we found a significant negative association (F = 20.27, p<0.001) between afternoon napping and left amygdala volume. However, we did not find any effect of night sleep length or napping frequency on cognitive performance or left amygdala volume. ConclusionsIn community elders with normal cognitive functions, afternoon napping is associated with cognitive performance, and left amygdala may play an important role in this process.

3 Smartphone Digital Phenotyping for Unobtrusive and Continuous Assessment of Everyday Cognition and Movement Trajectories in Older Adults

Objective:To evaluate the feasibility, usability, and preliminary validity of a digital phenotyping protocol to capture everyday cognition and activities in vivo among older adults.Participants and Methods:Eight participants (M age=69.1 + 2.6; M education=18.0 + 1.4; 50% female; 88% non-Hispanic White) with normal cognition or mild cognitive impairment used an open-source smartphone application (mindLAMP) to passively and continuously capture sensor data including global positioning system (GPS) trajectories for a 4-week study period. Baseline neuropsychological tests and measures of depression, self-reported cognitive decline and mobility patterns were collected as external validators for digital data. Participants downloaded mindLAMP onto their smartphones and resumed their daily routines for 4 weeks before removing mindLAMP and completing a debriefing questionnaire. A cognitive composite was derived by averaging T-scores across domains of attention, executive functioning, processing speed, memory, and language. GPS raw data were processed to generate monthly average and standard deviation mobility metrics for each participant, including time spent at home, distance travelled, radius of gyration, flight length, and circadian routine. Feasibility and usability findings are presented along with correlation coefficients &gt;.4 between GPS metrics and external validators.Results:100% of enrolled participants completed the 4-week study without requesting to withdraw. Usability ratings ranged from poor to excellent. 75% of participants agreed that mindLAMP was easy to use, whereas only 1 participant enjoyed using mindLAMP. 100% of participants were satisfied with the study team’s explanation of procedures, privacy safeguards, data encryption methods and risks/benefits, reflected in an average score of 98.8% on the comprehension of consent quiz. No participants reported feeling uncomfortable, suspicious, or paranoid due to the study application running on their smartphone. No participants endorsed new problems using their smartphone, though 75% reported charging it more frequently during the study period. On average each day, participants spent 1121 + 227 minutes at home, travelled 38727 + 36210 geodesic units, and had 201 + 149 minutes of missing GPS data. Overall, greater amounts of activity (monthly average) and higher variability (monthly standard deviation) in GPS metrics were associated with better outcomes. Specifically, less time spent at home, greater distance travelled, larger radius of gyration, greater flight length, and greater variability in home time, distance travelled, radius of gyration and flight length were associated with less depression, less self-reported cognitive decline, better cognition, and greater self-reported mobility (.40&lt; |r| &lt;.69). On the other hand, greater circadian routine was associated with more self-reported cognitive decline (r=.66) and less self-reported mobility (r=-.43).Conclusions:Smartphone digital phenotyping is a feasible and acceptable method to capture everyday activities in older adults. Continuous collection of data from personal devices warrants caution; however, participants denied privacy concerns and expressed an overall positive experience. High frequency GPS data collection impacts battery life and should be considered among relative risks and confounds to naturalistic assessment. Patterns of behavior from passive smartphone data show promise as an unobtrusive method to identify cognitive risk and resilience in older adults. Subsequent analyses will evaluate additional sensor metrics across a larger and more heterogeneous cohort.

2 Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes

Objective:There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer’s disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults. We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of &lt;129 across subgroups.Participants and Methods:A hierarchical cluster analysis was conducted using 11 baseline neuropsychological test scores from 365 CU participants in the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (age M=71.93 years, SD=7.51; 55.9% women; 15.6% Hispanic/Latino/a/x/e). A discriminate function analysis was then conducted to test whether the individual neuropsychological scores predicted cluster-group membership. Cox regressions examined the risk of progression to consensus diagnosis of MCI or dementia, or to DRS score &lt;129, by cluster group.Results:Cluster analysis identified 5 groups: All-Average (n=139), Low-Visuospatial (n=46), Low-Executive (n=51), Low-Memory/Language (n=83), and Low-All Domains (n=46). The discriminant function analysis using the neuropsychological measures to predict group membership into these 5 clusters correctly classified 85.2% of the participants. Subgroups had unique demographic and clinical characteristics. Relative to the All-Average group, the Low-Visuospatial (hazard ratio [HR] 2.39, 95% CI [1.03, 5.56], p=.044), Low-Memory/Language (HR 4.37, 95% CI [2.24, 8.51], p&lt;.001), and Low-All Domains (HR 7.21, 95% CI [3.59, 14.48], p&lt;.001) groups had greater risk of progression to MCI/dementia. The Low-Executive group was also twice as likely to progress to MCI/dementia compared to the AllAverage group, but did not statistically differ (HR 2.03, 95% CI [0.88,4.70], p=.096). A similar pattern of results was found for progression to DRS score &lt;129, with the Low-Executive (HR 2.82, 95% CI [1.26, 6.29], p=.012), Low-Memory/Language (HR 3.70, 95% CI [1.80, 7.56], p&lt;.001) and Low-All Domains (HR 5.79, 95% CI [2.74, 12.27], p&lt;.001) groups at greater risk of progression to a DRS score &lt;129 than the All-Average group. The Low-Visuospatial group was also twice as likely to progress to DRS &lt;129 compared to the All-Average group, but did not statistically differ (HR 2.02, 95% CI [0.80, 5.06], p=.135).Conclusions:Our results add to a growing literature documenting heterogeneity in the earliest cognitive and pathological presentations associated with Alzheimer’s disease and related disorders. Participants with subtle memory/language, executive, and visuospatial weaknesses all declined at faster rates than the All-Average group, suggesting that there are multiple pathways and/or unique subtle cognitive decline profiles that ultimately lead to a diagnosis of MCI/dementia. These results have important implications for early identification of individuals at risk for MCI/dementia. Given that the same classification approach may not be optimal for everyone, determining profiles of subtle cognitive difficulties in CU individuals and implementing neuropsychological test batteries that assess multiple cognitive domains may be a key step towards an individualized approach to early detection and fewer missed opportunities for early intervention.

Bilateral ictal EEG is associated with better memory outcome after hippocampal sclerosis surgery.

To compare memory outcomes after surgery for unilateral hippocampal sclerosis (HS)-associated epilepsy in patients with unilateral and bilateral ictal electrographic involvement. We prospectively evaluated HS patients, aged 18-55 years and IQ ≥70. Left (L) and right (R) surgical groups underwent noninvasive video-EEG monitoring and Wada test. We classified patients as Ipsilateral if ictal EEG was restricted to the HS side, or Bilateral, if at least one seizure onset occurred contralaterally to the HS, or if ictal discharge evolved to the opposite temporal region. Patients who declined surgery served as controls. Memory was evaluated on two occasions with Rey Auditory-Verbal Learning Test and Rey Visual-Design Learning Test. Baseline neuropsychological test scores were compared between groups. Pre- and postoperative scores were compared within each group. Reliable change index Z-scores (RCI) were obtained using controls as references, and compared between surgical groups. We evaluated 64 patients. Patients were classified as: L-Ipsilateral (9), L-Bilateral (15), L-Control (9), R-Ipsilateral (10), R-Bilateral (9), and R-Control (12). On preoperative evaluation, memory performance did not differ among surgical groups. Right HS patients did not present postoperative memory decline. L-Ipsilateral group presented postoperative decline on immediate (P = 0.036) and delayed verbal recall (P = 0.011), while L-Bilateral did not decline. L-Ipsilateral had lower RCI Z-scores, indicating delayed verbal memory decline compared to L-Bilateral (P = 0.012). Dominant HS patients with bilateral ictal involvement presented less pronounced postoperative verbal memory decline compared to patients with exclusive ipsilateral ictal activity. Surgery was indicated in these patients regardless of memory impairment on neuropsychological testing, since resection of the left sclerotic hippocampus could result in cessation of contralateral epileptiform activity, and, therefore, improved memory function.

A - 59 Regional Cerebral Metabolism Is Associated with Performance on the Visual Object and Space Perception Battery in those with Posterior Cortical Atrophy.

Posterior cortical atrophy (PCA) is a relatively rare clinical syndrome characterized by visuoperceptual/spatial dysfunction with relatively preserved memory, language, and insight in the early stages. Thus, PCA provides a unique population through which to evaluate structure-function relationships for commonly used neuropsychological tests. Here, we evaluated relationships between fluorodeoxyglucose (FDG) positron emission tomography (PET) and performance on the Visual Object and Space Perception (VOSP) Battery. Ten participants with an established diagnosis of PCA underwent baseline neuropsychological testing that included the VOSP, FDG-PET, and structural MRI. We used FreeSurfer to identify anatomical structures in the structural MRI scans, aligned the MRI and PET scans, and then extracted FDG signal from these same regions. Several brain regions relevant for PCA were a priori targeted. We evaluated relationships between the regional FDG values and VOSP performances using Spearman's rank correlation. Silhouettes, Dot Counting, and Number Location showed strong relationships with the superior parietal lobule bilaterally. The right superior parietal lobule showed moderate to strong relationships with Incomplete Letters and Progressive Silhouettes, whereas the left superior parietal lobule showed a strong relationship with Object Decision. Incomplete letters showed a strong relationship with the right supramarginal gyrus. Silhouettes showed a strong relationship with the left fusiform gyrus. These findings from a relatively rare and heterogeneous syndrome provide insight into the regional contributions to visuospatial functioning. Future work will evaluate network-level integrity with these tasks in order to further clarify structure-function relationships.

Predictors of Cognitive Change in Parkinson Disease: A 2-year Follow-up Study.

Mild cognitive impairment is common in Parkinson disease (PD-MCI). However, instability in this clinical diagnosis and variability in rates of progression to dementia raises questions regarding its utility for longitudinal tracking and prediction of cognitive change in PD. We examined baseline neuropsychological test and cognitive diagnosis predictors of cognitive change in PD. Persons with PD, without dementia PD (N=138) underwent comprehensive neuropsychological assessment at baseline and were followed up to 2 years. Level II Movement Disorder Society criteria for PD-MCI and PD dementia (PDD) were applied annually. Composite global and domain cognitive z -scores were calculated based on a 10-test neuropsychological battery. Baseline diagnosis of PD-MCI was not associated with a change in global cognitive z -scores. Lower baseline attention and higher executive domain z -scores were associated with greater global cognitive z -score worsening regardless of cognitive diagnosis. Worse baseline domain z -scores in the attention and language domains were associated with progression to MCI or PDD, whereas higher baseline scores in all cognitive domains except executive function were associated with clinical and psychometric reversion to "normal" cognition. Lower scores on cognitive tests of attention were predictive of worse global cognition over 2 years of follow-up in PD, and lower baseline attention and language scores were associated with progression to MCI or PDD. However, PD-MCI diagnosis per se was not predictive of cognitive decline over 2 years. The association between higher executive domain z -scores and greater global cognitive worsening is probably a spurious result.

A-53 Co-Occurring Depression and Anxiety Increases Prospective Risk for Concussion

Abstract Purpose There is limited research examining whether mental health concerns increase risk for future concussion, despite these difficulties being highly prevalent in college-age populations and student-athletes. This study investigates whether affective disturbance at baseline increases the risk for prospective concussion. We predict that athletes with co-occurring depression/ anxiety will incur the greatest risk for injury. Methods 886 collegiate athletes completed baseline neuropsychological testing and were prospectively followed as part of a sports concussion management program. Athletes were separated into 4 groups (HCs, Depression Alone, Anxiety Alone, Co-Occurring Depression/Anxiety) based on self-reported anxiety and depression at baseline. Of the 886 athletes, 96 sustained future concussion. Logistic regression was conducted with prospective concussion (yes/no) as the outcome, and affective group as the predictor. Sex and sport were examined as covariates. Results After controlling for sport, athletes in the Co-Occurring Depression/Anxiety group were more than twice as likely to sustain prospective concussion compared to HCs, p=.03, OR=2.18, 95% CI [1.10,4.33]. Though not statistically significant, athletes in the Co-Occurring Depression/Anxiety showed a 59% and 56% increased risk for prospective concussion compared to the Depression Alone and Anxiety Alone groups, respectively. Athletes in the Depression Alone and Anxiety Alone groups both showed a 31% increased risk for prospective concussion compared to HCs. Conclusions Athletes with co-occurring depression/anxiety at baseline show a notably increased risk for sustaining future concussion, even after controlling for sport. These findings highlight the importance of screening for depression and anxiety at baseline to provide treatment for these athletes, improve well-being, and reduce concussion risk.

Signatures of Neuropsychological Test Results in the Long Life Family Study: A Cluster Analysis.

Discovering patterns of cognitive domains and characterizing how these patterns associate with other risk factors and biomarkers can improve our understanding of the determinants of cognitive aging. To discover patterns of cognitive domains using neuropsychological test results in Long Life Family Study (LLFS) and characterize how these patterns associate with aging markers. 5,086 LLFS participants were administered neuropsychological tests at enrollment. We performed a cluster analysis of six baseline neuropsychological test scores and tested the association between the identified clusters and various clinical variables, biomarkers, and polygenic risk scores using generalized estimating equations and the Chi-square test. We used Cox regression to correlate the clusters with the hazard of various medical events. We investigated whether the cluster information could enhance the prediction of cognitive decline using Bayesian beta regression. We identified 12 clusters with different cognitive signatures that represent profiles of performance across multiple neuropsychological tests. These signatures significantly correlated with 26 variables including polygenic risk scores, physical and pulmonary functions, and blood biomarkers and were associated with the hazard of mortality (p < 0.01), cardiovascular disease (p = 0.03), dementia (p = 0.01), and skin cancer (p = 0.03). The identified cognitive signatures capture multiple domains simultaneously and provide a holistic vision of cognitive function, showing that different patterns of cognitive function can coexist in aging individuals. Such patterns can be used for clinical intervention and primary care.

Affective Disturbance and Neurocognitive Variability in College Athletes.

Research on the neurocognitive effects of comorbid mood/anxiety disturbance in college athletes is limited. Previous research found that athletes with comorbid depression/anxiety performed worse on measures of attention/processing speed (A/PS) at baseline compared to healthy controls. However, this work solely examined mean performance. The current study expands upon this work by examining intraindividual variability (IIV) in relation to affective disturbance. 835 (M = 624, F = 211) collegiate athletes completed baseline neuropsychological testing. Athletes were separated into four groups (Healthy Mood [n = 582], Depression Alone [n = 137], Anxiety Alone [n = 54], and Co-Occurring Depression/Anxiety [n = 62]) based on self-reported anxiety and depression. IIV was examined globally and within composites of A/PS and memory via intraindividual standard deviation, with higher scores indicating greater variability. Linear regression results revealed that the Co-Occurring Depression/Anxiety group exhibited greater variability within the memory composite compared to the Healthy Mood group, as well as the Depression Alone and Anxiety Alone groups. The Depression Alone and Anxiety Alone groups did not differ from the Healthy Mood group on memory IIV. None of the groups differed on A/PS or global IIV. Athletes with co-occurring depression/anxiety demonstrated greater variability in performance on memory tasks. Greater dispersion is predictive of greater cognitive decline following concussion; therefore, it is important that neuropsychological performance is interpreted beyond measures of central tendency. These findings also highlight the importance of having baseline data available for athletes with affective disturbance, as these factors may influence performance, place athlete at risk for poorer outcomes, and skew future post-concussion comparisons.

Enough vs. More: Neuropsychological testing is more useful than genetic testing in the baseline evaluation of Parkinson disease

In conclusion, baseline neuropsychological testing provides a vast amount of unique cognitive, psychiatric, behavioral, and psychosocial information that is useful to individuals with PD, care partners, and treatment team providers. As a baseline examination, it provides opportunities for comparison purposes in the future, a prediction of risk assessment and future treatment needs, and at the time of evaluation for clinical treatment to improve quality of life. Such information is not captured by genetic testing, although the ideal path moving forward would be to perform both neuropsychological testing and genetic testing at baseline.

Illness intrusiveness: A key part of the cognition-mood link in multiple sclerosis.

The current study attempted to expand the literature on cognition and mood in MS by determining if illness intrusiveness may potentially serve as an intermediary factor in the well-established cognition-mood relationship in people with MS. This study employed a retrospective cross-sectional design to answer this question. Baseline neuropsychological test data and mood questionnaires from 199 participants with clinically definite MS were used in this study. The sample was middle-aged (M = 48.4, SD = 11.8), highly educated (M = 14.6, SD = 2.2), majority female (76.9%) and majority White (74.5%). Assumptions for parametric statistics and ordinary least squares regression were met. Conditional process models evaluated whether illness intrusiveness mediated the relationship between cognitive functioning and psychiatric symptoms. In total, 33.2% of the sample met criteria for clinically significant anxiety, 41.7% met criteria for depression, and 27.8% of the sample met criteria for processing speed impairment, consistent with other MS samples. Illness intrusiveness was found to mediate the relationship between processing speed and depression, ab = -.07, 95% CI [-.15, -.002], processing speed and anxiety, ab = -.06, 95% CI [-.12, -.02], and processing speed and more general mood disturbance, ab = -.08, 95% CI [-.13, -.0005]. Illness intrusiveness was found to be a potential important intermediary mechanism by which the primary cognitive impairment in MS, processing speed, impacts mood in this disease population. Conclusions, treatment implications, and directions for future research in light of these findings were discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies.

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = -0.69), memory (RE model = -0.64), and executive function (RE model = -0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD.

7T amygdala and hippocampus subfields in volumetry-based associations with memory: A 3-year follow-up study of early Alzheimer’s disease

IntroductionThe hippocampus is the most prominent single region of interest (ROI) for the diagnosis and prediction of Alzheimer’s disease (AD). However, its suitability in the earliest stages of cognitive decline, i.e., subjective cognitive decline (SCD), remains uncertain which warrants the pursuit of alternative or complementary regions. The amygdala might be a promising candidate, given its implication in memory as well as other psychiatric disorders, e.g. depression and anxiety, which are prevalent in SCD. In this 7 tesla (T) magnetic resonance imaging (MRI) study, we aimed to compare the contribution of volumetric measurements of the hippocampus, the amygdala, and their respective subfields, for early diagnosis and prediction in an AD-related study population. MethodsParticipants from a longitudinal study were grouped into SCD (n = 29), mild cognitive impairment (MCI, n = 23), AD (n = 22) and healthy control (HC, n = 31). All participants underwent 7T MRI at baseline and extensive neuropsychological testing at up to three visits (baseline n = 105, 1-year n = 78, 3-year n = 39). Analysis of covariance (ANCOVA) was used to assess group differences of baseline volumes of the amygdala and the hippocampus and their subfields. Linear mixed models were used to estimate the effects of baseline volumes on yearly changes of a z-scaled memory score. All models were adjusted to age, sex and education. ResultsCompared to the HC group, individuals with SCD showed smaller amygdala ROI volumes (range across subfields −11% to −1%), but not hippocampus ROI volumes (-2% to 1%) except for the hippocampus-amygdala-transition-area (-7%). However, cross-sectional associations between baseline memory and volumes were smaller for amygdala ROIs (std. ß [95% CI] ranging between 0.16 [0.08; 0.25] and 0.46 [0.31; 0.60]) than hippocampus ROIs (between 0.32 [0.19; 0.44] and 0.53 [0.40; 0.67]). Further, the association of baseline volumes with yearly memory change in the HC and SCD groups was similarly weak for amygdala ROIs and hippocampus ROIs. In the MCI group, volumes of amygdala ROIs were associated with a relevant yearly memory decline [95% CI] ranging between −0.12 [−0.24; 0.00] and −0.26 [−0.42; −0.09] for individuals with 20% smaller volumes than the HC group. However, effects were stronger for hippocampus ROIs with a corresponding yearly memory decline ranging between −0.21 [−0.35; −0.07] and −0.31 [−0.50; −0.13]. ConclusionVolumes of amygdala ROIs, as determined by 7T MRI, might contribute to objectively and non-invasively identify patients with SCD, and thus aid early diagnosis and treatment of individuals at risk to develop dementia due to AD, however associations with other psychiatric disorders should be evaluated in further studies. The amygdala’s value in the prediction of longitudinal memory changes in the SCD group remains questionable. Primarily in patients with MCI, memory decline over 3 years appears to be more strongly associated with volumes of hippocampus ROIs than amygdala ROIs.

Comparison of Plasma‐based Biomarkers and Cognitive Assessments in predicting progression of MCI to Dementia

AbstractBackgroundWe evaluated the predictive value of phospho‐tau181 (ptau181) and neurofilament light (NfL) in predicting disease progression from amnestic mild cognitive impairment stage (aMCI) to Dementia in models including demographic data and neuropsychological test results.MethodParticipants were 248 Cognitively Normal (CN), 325 MCI, and 91 individuals with dementia due to AD confirmed with amyloid PET from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who had at least one follow‐up visit, and measures of plasma biomarkers (ptau181 and NfL) were included. We examined the separate and joint predictive value of baseline plasma biomarkers and neuropsychological tests (RAVLT: Rey Auditory Verbal Learning Test; ADAS‐Cog: Alzheimer’s Disease Assessment Scale–Cognitive Subscale; TRA‐B: Trail Making Test – Part B; FAQ: Functional Activity Questionnaire) in estimating disease progression from MCI to Dementia. Random Forests machine learning models were used for the classification. Data from CN and AD participants were used for training the models and trained models were used in MCI group to identify those more likely to progress to Dementia. Predictive performances of these models were assessed using longitudinal outcomes at 2 years.ResultParticipants were on average 71.9 yr. old (SD=6.9) and 49.6% female (Table 1). Addition of plasma biomarkers to the model with demographics and APOE4 (base model) improved predictive performance of models in prediction of conversion from MCI to dementia at 2 years (Sensitivity=53.7%, Specificity=81.5%, AUC=0.68). Models that included cognitive tests in addition to the measures in the base model had higher performance in comparison with that only included biomarkers (Sensitivity=55.6%, Specificity=91.5%, AUC=0.74). Best predictive performance was achieved when cognitive scores and plasma biomarkers were both included in the models (Sensitivity=63.0%, Specificity=91.5%, AUC=0.77, Table 2). In the MCI‐subgroup who were amyloid positive (Aβ+) at baseline, similar pattern of results was observed (Table 3).ConclusionIn persons with MCI, plasma biomarkers of ptau181and NFL can improve our ability to predict disease progression. Concurrent use of plasma biomarkers and cognitive scores improve this predictive ability. This work needs to be extended to various samples and a broader set of plasma biomarkers and neuropsychological tests.

Validation of the VE/VCO2 Slope as a Marker of Cognitive Performance in Older Adults

<h3>Research Objectives</h3> To explore the relationship between older adults' cardiorespiratory fitness and cognitive health, by evaluating the associations of maximal oxygen consumption (VO2 max) and ventilatory efficiency (VE/VCO2 slope) to global cognitive performance. <h3>Design</h3> Secondary data analysis using linear regression modeling. <h3>Setting</h3> Veterans Affairs Hospital, Palo Alto, CA. <h3>Participants</h3> Subjects included 107 community-dwelling volunteers, ages 54-88 years old (mean 71.7±8.9), recruited for their ability to fully participate in exercise and cognitive testing. Participants were screened for prior psychiatric conditions, major neurocognitive disorders, chronic or acute illnesses (including severe cardiac and respiratory disease). <h3>Interventions</h3> All participants completed a baseline neuropsychological test battery, and underwent maximal graded cardiopulmonary exercise testing (CPET) with breath-by-breath expired gas analysis. <h3>Main Outcome Measures</h3> The primary outcome was performance on a global cognition composite score, comprised from assessments of learning/memory, language fluency, attention/executive function, processing speed, and visuospatial abilities. <h3>Results</h3> At the item level, VE/VCO2 slope was significantly associated with global cognitive performance (β= -0.028, p=.007), whereas VO2 max was not (β=-0.06, p=.59). Controlling for age and education, VE/VCO2 slope accounted for 17% of the variance in outcome scores (F(3,106)=6.88, R2=.167, p<.001). Post-hoc analyses indicated that 27% of participants achieved near-maximal effort during the CPET evaluation (e.g. a Respiratory Exchange Ratio ≥1.1) to accurately reflect maximum aerobic capacity. <h3>Conclusions</h3> Findings indicate VE/VCO2 slope is a valuable marker of cognitive performance in older adults, especially when maximal exertion is not met during CPET testing. This is significant as VO2 max has been considered the criterion standard for measuring general health and fitness, and often used in studies exploring correlates of cognition. Unlike VO2 max, VE/VCO2 slope reflects the degree of ventilatory efficiency in response to exercise, and can be accurately calculated at sub-maximal thresholds. While special considerations should be made when working with older populations, this study validates the VE/VCO2 slope as an alternative exercise measure that should be utilized in future research, especially with those experiencing health or age-related physical limitations. <h3>Author(s) Disclosures</h3> The authors have no disclosures or conflicts of interest to declare.

Prevalence of invalid ImPACT baseline test results among high school athletes with invalidity and sandbagging indices

Objective: The comparison of baseline neuropsychological test results with post-concussion neuropsychological test results is a common practice to assess the aftermath of a sport-related concussion. The effectiveness of this approach is compromised when invalid baseline test performances occur. The present study was designed to assess the prevalence of invalid baseline test results of high school athletes, using the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). Method: A large sample of 8938 high school athletes’ baseline test data were examined, including the four ImPACT Composite scores and three sets of embedded invalid indices: five ImPACT Invalidity Indicators, four ImPACT sandbagging red flags, and two ImPACT sandbagging subtest flags. Results: There were 8394 (93.91%) Valid scorers, who failed no Invalidity Indicators; 544 (6.09%) Invalid scorers, who failed at least one Invalidity Indicator, 2718 (30.41%) Red Flag scorers, who had at least one Red Flag score; and 4154 (46.47%) Subtest Flag scorers, who had at least one Subtest Flag score. Of the entire sample, 4485 (54.65%) failed at least one of the invalid indices. Conclusions: As in prior studies of high school athletes, the Invalidity Indicators identified a low portion (6.09%) of the athletes with invalid baseline test results, while other invalidity measures found 30.41% to 46.48% of the athletes producing questionable test results. The high rate of invalid test findings suggested in this research calls for greater efforts to improve the accuracy of baseline test results.