Women have a greater lifetime risk of developing Alzheimer’s disease (AD) dementia than men, a sex/gender disparity that cannot be explained by female longevity alone. There is substantial evidence for sex differences in the effects of APOE £4 on risk for AD. While APOE e4 increases AD risk in both sexes, women who carry APOE e4 are disproportionately vulnerable to cognitive impairment and AD compared to their counterpart men. In contrast to APOE e4, APOE £2 is associated with slower cognitive decline and a lower risk of AD. Although a less robust literature, APOE e2 may also have sex-specific effects. Because APOE e2 is the rarest major APOE allele, well-powered studies are needed to examine sex-specific effects. The objective of the present study was to examine sex-specific associations of APOE e2 carriage with longitudinal cognitive decline in a large cohort of clinically unimpaired adults.

We used observational data from two sources: the National Alzheimer’s Coordinating Center (NACC) and the Rush Alzheimer’s Disease Center (ROS/MAP/MARS) studies. We included data from clinically unimpaired adults who were >50 years old at baseline who self-identified as non-Hispanic White (NHW) or non-Hispanic Black (NHB). Participants were categorized as APOE £2, £4, or £3/e3 carriers. APOE e2/e4 carriers were excluded. The same battery of neuropsychological tests was used to assess global cognition in participants from both data sources. Linear mixed models examined interactive associations of genotype (£2 or £4 vs. £3/£3), sex, and time on longitudinal cognition in NHW and NHB participants separately. Analyses were first performed in a pooled sample of NACC and ROS/MAP/MARS participants and if significant they were repeated separately in each data source.

Across both data sources, 9,766 NHW (mean (SD) age=73.0(9.00) years, mean (SD) education=16.3(2.83) years, n(%) women=6,344(65.0)) and 2,010 NHB participants (mean(SD) age=71.3(7.59) years, mean(SD) education=14.9(3.10) years, n(%) women=1,583(78.8)) met inclusion criteria. Sex modified the association between APOE £2 and cognitive decline in NHW (ß=0.097, 95% CI: 0.023-0.172, pint=.01) but not NHB participants (ß=-0.011, 95% CI: -0.153-0.131, pint=.9). In sex-stratified analyses of NHW participants, APOE £2 (vs. £3/£3) carriage was associated with attenuated cognitive decline in men (ß=0.096, 95% CI: 0.037-0.155, p=.001), but not women (ß=-0.001, 95% CI: -0.044-0.043, p=.97). In analyses comparing men and women APOE £2 carriers, men exhibited slower cognitive decline than women (ß=0.120, 95% CI: 0.051-0.190, p=.001). Analyses performed separately in NACC and ROS/MAP revealed the same pattern of male-specific APOE £2 protection in NHW participants in both data sources.

In light of the longstanding view that APOE £2 protects against AD and dementia, our results provide evidence that APOE £2 is associated with attenuated cognitive decline in men but not women among NHW adults. This male-specific protection may contribute to sex differences in AD-related cognitive decline. Our findings have important implications for understanding the biological drivers of sex differences in AD risk, which is crucial for developing sex-specific strategies to prevent and treat AD dementia.

Age, sex, education, memory, and the APOE e4 allele are related to Alzheimer’s disease (AD) risk. Recently it was suggested that low body mass index (BMI) contributes to the development of AD. The objective of this study was to examine how delayed recall of a word list was influenced by demographic variables, APOE and BMI in people with memory problems, and to investigate whether the impact of these variables was smaller at higher disease severity levels.

The participants were 1206 patients in the Norwegian NorCog registry diagnosed with either subjective cognitive decline (SCD) (n=274), mild cognitive impairment (MCI) (n=444), or AD (n=488). ANOVAs and hierarchical regression were applied to examine whether the delayed recall part of the 10-word test of the CERAD-WL was associated with age, sex, education, APOE (e4/non-e4) and BMI. Analyses were run separately for SCD, MCI and AD patients.

There were significant bivariate differences (p<.001) between the three patient groups for all variables; the AD patients were older, less educated, more were women, more had APOE e4 alleles, and they had lower BMI. For the SCD group, 34% of the total variance (R2) of the dependent variable was explained. All independent variables except BMI (p=.07) had a significant contribution in the prediction. For MCI, 18% of the total were explained. All variables except education and sex showed significant contribution to R2. For the AD group, R2 was 13%. Sex and BMI did not contribute significantly.

As expected, the performance on CERAD-WML was influenced by age, education and sex in the SCD group, whereas the associations between memory function and the three demographic variables were less clear among patients with MCI and AD. ApoE genotype influenced on the CERAD-WML results among all patients, whereas BMI only influenced on the results among patients with SCD and MCI. Our findings do not support that BMI is associated with delayed recall of memory in AD.

The Stricker Learning Span (SLS) is a computer-adaptive word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). Given recent evidence suggesting the prominence of learning impairment in preclinical Alzheimer’s disease (AD), the SLS places greater emphasis on learning than delayed memory compared to traditional word list memory tests (see Stricker et al., Neuropsychology in press for review and test details). The primary study aim was to establish criterion validity of the SLS by comparing the ability of the remotely-administered SLS and inperson administered Rey Auditory Verbal Learning Test (AVLT) to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.

Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11; mean education=16, SD=2; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) vs no evidence of AD pathology (A-T-, n=181). Primary neuropsychological outcome variables were sum of trials for both the SLS and AVLT. Secondary outcome variables examined comparability of learning (1-5 total) and delay performances. Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).

Both SLS and AVLT performances were worse in the biomarker positive relative to biomarker negative groups (unadjusted p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but SLS remained significant for A+ vs A- and for A+T+ vs A-T- comparisons (adjusted p’s<.05) and AVLT approached significance (p’s .05-.10). The effect sizes for the SLS were slightly better (qualitatively, no statistical comparison) for separating biomarker-defined CU groups in comparison to AVLT. For A+ vs A- and A+T+ vs A-T- comparisons, unadjusted effect sizes for SLS were -0.53 and -0.81 and for AVLT were -0.47 and -0.61, respectively; adjusted effect sizes for SLS were -0.25 and -0.42 and for AVLT were -0.19 and -0.26, respectively. In secondary analyses, learning and delay variables were similar in terms of ability to separate biomarker groups. For example, unadjusted effect sizes for SLS learning (-.80) was similar to SLS delay (.76), and AVLT learning (-.58) was similar to AVLT 30-minute delay (-.55) for the A+T+ vs AT- comparison.

Remotely administered SLS performed similarly to the in-person-administered AVLT in its ability to separate biomarker-defined groups in CU individuals, providing evidence of criterion validity. The SLS showed significantly worse performance in A+ and A+T+ groups (relative to A- and A-T-groups) in this CU sample after demographic adjustment, suggesting potential sensitivity to detecting transitional cognitive decline in preclinical AD. Measures emphasizing learning should be given equal consideration as measures of delayed memory in AD-focused studies, particularly in the preclinical phase.

Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.

This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.

The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).

Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.

Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).

This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.

Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.

The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.

The purpose of the present study was to study the clinical significance of fluctuations in cognitive impairment status in longitudinal studies of normal aging and dementia. Several prior studies have shown fluctuations in cognition in longitudinal studies is associated with greater risk of conversion to dementia. The present study defines “reverters” as participants who revert between cognitive normality and abnormality according to the Clinical Dementia Rating (CDRTM). A defining feature of the CDR at the Knight Alzheimer’s Disease Research Center (Knight ADRC) at Washington University in St. Louis is that the CDR is calculated by clinicians blinded to cognitive data and any prior assessments so that conclusions are drawn free of circularity and examiner bias. We hypothesized reverters, when compared to cognitively normal participants who remain unimpaired, would have worse cognition, abnormal biomarkers, and would eventually progress to a stable diagnosis of cognitive impairment.

From ongoing studies of aging and dementia at the Knight ADRC, we selected cognitively normal participants with at least three follow-up visits. Participants fell into three categories: stable cognitively normal (“stable CN”), converters to stable dementia (“converters”), and reverters. Cognitive scores at each visit were z-scored for comparison between groups. A subset of participants had fluid biomarker data available including cerebrospinal fluid (CSF) amyloid and phosphorylated-tau species, and plasma neurofilament light chain (NfL). Mixed effect models evaluated group relationships between biomarker status, APOE £4 status, and CDR progression.

930 participants were included in the study with an average of 5 years of follow-up (Table 1). 661 participants remained cognitively normal throughout their participation while 142 progressed to stable dementia and 127 participants had at least one instance of reversion. Compared to stable CN, reverters had more abnormal biomarkers at baseline, were more likely to carry an APOE £4 allele, and had better cognitive performance at baseline (Table 2, Figure 1). Compared to converters, reverters had less abnormal biomarkers at baseline, were less likely to carry an APOE £4 allele, and had overall better cognitive performance at baseline. In longitudinal analyses, cognitive trajectories of reverters exhibited a larger magnitude of decline compared to stable CNs but the magnitude of decline was not as steep as converters.

Our results confirm prior studies that showed reversion in cognitive status, when compared to stable cognitive normality, is associated with worse overall genetic, biomarker and cognitive outcomes. Longitudinal analyses demonstrated reverters show significantly more decline than stable participants and a higher likelihood of eventual conversion to a stable dementia diagnosis. Reverters’ cognitive trajectories appear to occupy a transitional phase in disease progression between that of cognitive stability and more rapid and consistent progression to stable dementia. Identifying participants in the preclinical phase of AD who are most likely to convert to symptomatic AD is critical for secondary prevention clinical trials. Our results suggest that examining intraindividual variability in cognitive impairment using unbiased, longitudinal CDR scores may be a good indicator of preclinical AD and predict eventual conversion to symptomatic AD.

Cognitive problems, both complaints and objective impairments, are frequent and disabling in patients with multiple sclerosis (MS) and profoundly affect daily living. However, intervention studies that focus on cognitive problems that patients experience in their daily lives are limited. This study therefore aimed to investigate the effectiveness of cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT) on patient-reported cognitive complaints in MS.

In this randomized-controlled trial, MS patients with cognitive complaints completed questionnaires and underwent neuropsychological assessments at baseline, post-treatment and 6-month follow-up. Patient-reported cognitive complaints were primarily investigated. Secondary outcomes included personalized cognitive goals and objective cognitive function. CRT and MBCT were compared to enhanced treatment as usual (ETAU) using linear mixed models.

Patients were randomized into CRT (n=37), MBCT (n=36) or ETAU (n=37), of whom 100 completed the study. Both CRT and MBCT positively affected patient-reported cognitive complaints compared to ETAU at post-treatment (p<.05), but not 6 months later. At 6-month follow-up, CRT had a positive effect on personalized cognitive goals (p=.028) and MBCT on processing speed (p=.027). Patients with less cognitive complaints at baseline benefited more from CRT on the Cognitive Failures Questionnaire (i.e. primary outcome measuring cognitive complaints) at post-treatment (p=.012-.040), and those with better processing speed at baseline benefited more from MBCT (p=.016).

Both CRT and MBCT alleviated cognitive complaints in MS patients immediately after treatment completion, but these benefits did not persist. In the long term, CRT showed benefits on personalized cognitive goals and MBCT on processing speed. These results thereby provide insight in the specific contributions of available cognitive treatments for MS patients.

Cognitive difficulties in Multiple Sclerosis (MS) are important contributors to impairment in instrumental activities of daily living. A non-randomised controlled trial was conducted to explore the effects of a cognitive rehabilitation protocol on MS patients' daily life functionality.

Seventy-five relapsing-and-remitting MS patients were recruited. Intervention Group (IG, n=31) underwent 16 individual rehabilitation sessions (1hx2/week; weeks 2-10), which included paper and pencil cognitive stimulation exercises and training memory strategies and external memory aids; and a booster session (week 37). Control Group (CG, n=44) received care as usual. These primary outcome measures were applied at baseline and at weeks 11, 36, and 62: Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ), Mental Slowness Questionnaire (MSQ), Mental Slowness Observation Test (MSOT), and Sydney Psychosocial Reintegration Scale-2 (SPRS-2). Score differences from baseline were calculated for all measures and follow-up time points except for SPRS-2, which was only applied twice (baseline and week 62). Linear regressions fitted with generalized estimating equations (GEE) were performed to verify the effects of time and group on the outcome measures. Baseline scores were included in the model as covariates for all outcome measure except SPRS-2. Chi-square and Mann-Whitney tests were applied to compare demographic and clinical characteristics of the groups.

Groups had similar demographic (i.e., sex, age, and education) and clinical (i.e., age at disease onset, disease duration, disease modifying treatments, and Expanded Disability Status Scale score) characteristics. IG's MSQ score progressively improved, whereas CG's score did not change from baseline (group x time effect: p<0.001) throughout follow-up. IG's MSNQ score improved from baseline at weeks 11 and 36, but not at week 62. CG's MSNQ score did not change from baseline throughout follow-up (group x time effect: p=0.025). Both IG's and CG's performance on the MSOT improved (time effects). Though, the IG showed greater improvement at follow-up (group effects) on MSOT score and time (both p<0.001). IG's SPRS-2 improved, whereas CG's score declined (group x time effect: p<0.001).

Combining restorative techniques with strategy-based compensatory techniques may produce significant and persistent effects on MS patients' self-reported everyday functioning and on their objective performance of instrumental tasks.

Multiple sclerosis (MS) has historically been considered a syndrome that primarily affects White persons of northern European ancestry. This has been strongly disproven in recent decades with prevalence/incidence studies showing that MS impacts individuals from diverse backgrounds. The few studies available investigating clinical characteristics of MS across diverse groups have shown that Hispanic/Latinx/e (Latinx) and non-Hispanic Black/African American (NHB) persons with MS (pwMS) have more severe disease trajectories compared to non-Hispanic Whites (NHW), including an earlier age of disease onset, greater disability, and more severe symptoms overall. Changes in brain structure have been linked outcomes and MS-itself, but what remains understudied is how brain structure differs across race/ethnicity. As such, the current study aims to investigate volumetric brain differences in a diverse sample of pwMS.

The sample (n=79) was compiled from multiple neuroimaging datasets and divided into three groups- Latinx (n=19), NHB (n=29), and NHW (n=32)- based on self-reported race/ethnicity. Participants completed demographic interviews and structural magnetic resonance imaging (MRI) scans. Neuroimaging data was visually inspected and processed in FreeSurfer (7.3.2). Volumetric measures for total gray matter, cortical gray matter, total white matter, and subcortical gray matter were used as the primary outcome measures.

A multivariate general linear model was used to examine volumetric brain differences across groups. Age and total intracranial volume were included as covariates. Results showed a significant effect of race/ethnicity (Pillai’s Trace=0.175, F(6, 148)=2.36, p=.033), indicating significant differences in volumetric brain metrics across race/ethnicity, namely for subcortical gray matter, total gray matter, and total white matter volumes. Post-hoc testing showed the Latinx group to have less subcortical gray matter, total gray matter, and total white matter than NHWs. There was a trend for the NHB versus NHW, with NHBs having less brain volume. No significant differences were observed between the Latinx and NHB groups. Lesion volume and regional gray matter volumes were also examined.

To the authors’ knowledge, this is among the first studies to investigate structural brain differences across race/ethnicity in pwMS. Results point to disparities in brain volume across racial/ethnic groups with MS. These differences may partially underlie the differing trajectories observed in clinical characteristics across race/ethnicity. Future studies should include larger samples of diverse pwMS and examine the intersection of psychosocial and systemic factors (i.e., social determinants of health) and brain metrics to better understand the divergent disease trajectories observed across groups.

PD patients commonly exhibit executive dysfunction early in the disease course which may or may not predict further cognitive decline over time. Early emergence of visuospatial and memory impairments, in contrast, are more consistent predictors of an evolving dementia syndrome. Most prior studies using fMRI have focused on mechanisms of executive dysfunction and have demonstrated that PD patients exhibit hyperactivation that is dependent on the degree of cognitive impairment, suggestive of compensatory strategies. No study has evaluated whether PD patients with normal cognition (PD-NC) and PD patients with Mild Cognitive Impairment (PD-MCI) exhibit compensatory activation patterns during visuospatial task performance.

10 PD-NC, 12 PD-MCI, and 14 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task Force, Level II assessment (comprehensive assessment). Functional magnetic resonance imaging (fMRI) was performed during a motion discrimination task that required participants to identify the direction of horizontal global coherent motion embedded within dynamic visual noise under Low and High coherence conditions. Behavioral accuracy and functional activation were evaluated using 3 * 2 analyses of covariance (ANCOVAs) (group [HC, PD-NC, PD-MCI] * Coherence [High vs. Low]) accounting for age, sex, and education. Analyses were performed in R (v4.1.2(Team, 2013)).

PD-MCI (0.702± 0.269) patients exhibited significantly lower accuracy on the motion discrimination task than HC (0.853 ± 0.241; p = 0.033) and PD-NC (0.880 ± 0.208; p =0.039). A Group * Coherence interaction was identified in which several regions, including orbitofrontal, posterior parietal and occipital cortex, showed increased activation during High relative to Low coherence trials in the PD patient groups but not in the HC group. HC showed default mode deactivation and frontal-parietal activation during Low relative to High coherence trials that was not evident in the patient groups.

PD-MCI patients exhibited worse visuospatial performance on a motion discrimination task than PD-NC and HC participants and exhibited hyperactivation of the posterior parietal and occipital regions during motion discrimination, suggesting possible compensatory activation.

Neuromelanin imaging is an emerging biomarker for PD as it captures degeneration of the midbrain, a process which is associated with the motor symptoms of the disease. Currently, it is unknown whether this degeneration also contributes to cognitive dysfunction in PD beyond dysfunction associated with fronto-subcortical systems, as quantitative examination of substantia nigra (SN) degeneration could not be studied until recently.

In the current study, we examine whether neuromelanin signal is associated with broader cognitive dysfunction in PD patients with varying degrees of cognitive impairment: PD with normal cognition (PD-NC), PD with mild cognitive impairment (PD-MCI), and healthy controls (HC).

11 PD-NC, 16 PD-MCI and 14 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task force, Level II assessment (comprehensive assessment). In addition, all participants underwent an MRI scan that included a T1-weighted sequence and a neuromelanin-sensitive (NM-MRI) sequence. Contrast-to-noise-ratio of the substantia nigra pars compacta (SNc) was calculated and a distribution-corrected z-score was used to identify the number of extrema voxels for each individual, suggestive of the number of voxels that have exhibited significant degeneration (extrema_count). An analysis of covariance (ANCOVA) was used to evaluate group differences between HC, PD-NC, and PD-MCI in the extrema_count accounting for age, sex, and education. A multiple regression for each cognitive variable with extrema_count as the dependent variable adjusting for age, sex, and education were conducted.

A significant main effect of group (F(2, 33) = 33.548 ; p < 0.001) indicated that PD-NC (21.55 ± 12.57) and PD-MCI (43.64 ± 32.84) patients exhibited significantly greater extrema_counts relative to HC (3.36 ± 3.61; both p < 0.001). Regression results indicated that higher extrema_counts were associated with worse cognitive performance across cognitive domains, including working memory (Digit Span Backward; R2 = .357, F(1,20) = 5.295, p = .032), (Hopkins Verbal Learning Test - Revised, Trials 1 to 3; R2 = .432, F(1,20) = 5.819, p = .026).

PD patients (PD-NC and PD-MCI) exhibited decreased neuromelanin in the SNc relative to healthy controls, confirming the ability of the NM-MRI sequence to differentiate PD from HC. There was no significant difference in SNc neuromelanin levels between PD-NC patients and PD-MCI patients, however, this is likely due to the small sample size. In addition, significant SNc degeneration was associated with worse cognitive performances in tasks associated with working memory and executive functioning. These results warrant further examination of the role of SN in PD patients with differing levels of cognitive impairment.

Parkinsonism and Parkinson's disease (PD) have been described as consequences of repetitive head impacts (RHI) from boxing, since 1928. Autopsy studies have shown that RHI from other contact sports can also increase risk for neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Lewy bodies. In vivo research on the relationship between American football play and PD is scarce, with small samples, and equivocal findings. This study leveraged the Fox Insight study to evaluate the association between American football and parkinsonism and/or PD Diagnosis and related clinical outcomes.

Fox Insight is an online study of people with and without PD who are 18+ years (>50,000 enrolled). Participants complete online questionnaires on motor function, cognitive function, and general health behaviors. Participants self-reported whether they "currently have a diagnosis of Parkinson's disease, or parkinsonism, by a physician or other health care professional." In November 2020, the Boston University Head Impact Exposure Assessment was launched in Fox Insight for large-scale data collection on exposure to RHI from contact sports and other sources. Data used in this abstract were obtained from the Fox Insight database https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp on 01/06/2022. The sample includes 2018 men who endorsed playing an organized sport. Because only 1.6% of football players were women, analyses are limited to men. Responses to questions regarding history of participation in organized football were examined. Other contact and/or non-contact sports served as the referent group. Outcomes included PD status (absence/presence of parkinsonism or PD) and Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) for assessment of cognitive symptoms. Binary logistic regression tested associations between history and years of football play with PD status, controlling for age, education, current heart disease or diabetes, and family history of PD. Linear regressions, controlling for these variables, were used for the PDAQ-15.

Of the 2018 men (mean age=67.67, SD=9.84; 10, 0.5% Black), 788 (39%) played football (mean years of play=4.29, SD=2.88), including 122 (16.3%) who played youth football, 494 (66.0%) played high school, 128 (17.1%) played college football, and 5 (0.7%) played at the semi-professional or professional level. 1738 (86.1%) reported being diagnosed with parkinsonism/PD, and 707 of these were football players (40.7%). History of playing any level of football was associated with increased odds of having a reported parkinsonism or PD diagnosis (OR=1.52, 95% CI=1.14-2.03, p=0.004). The OR remained similar among those age <69 (sample median age) (OR=1.45, 95% CI=0.97-2.17, p=0.07) and 69+ (OR=1.45, 95% CI=0.95-2.22, p=0.09). Among the football players, there was not a significant association between years of play and PD status (OR=1.09, 95% CI=1.00-1.20, p=0.063). History of football play was not associated with PDAQ-15 scores (n=1980) (beta=-0.78, 95% CI=-1.59-0.03, p=0.059) among the entire sample.

Among 2018 men from a data set enriched for PD, playing organized football was associated with increased odds of having a reported parkinsonism/PD diagnosis. Next steps include examination of the contribution of traumatic brain injury and other sources of RHI (e.g., soccer, military service).

Nationally and internationally, life expectancies continue to increase, and so are age-related cognitive impairment (Stough et al., 2015). As a result, the rise of consumer dietary supplement products has increased significantly in the last 20 years as older adults are inundated with media related to improving cognitive function. However, research on these nootropics and natural supplements reveals mixed efficacy (Brownie, 2009; Stough et al., 2015). Serendipitously, the COVID-19 pandemic has unveiled the necessity for increased healthy equity and screening internationally across health service disciplines (Jensen et al., 2021; Wells & Dumbrell, 2006). This poster encompasses two primary aims: (1) to highlight common international dietary supplements marketed to an older adult population. Next, (2) develop best evidenced-based practices to approach effective use of nutritional information while maintaining a neuropsychologist’s scope of care.

A literature review was conducted of peer review articles from 2006 to 2022 from the following databases PubMed and Google Scholar. Recommendations were constructed based on identifying and analyzing the emerging themes across identified articles. Keywords include neuropsychology, nootropics, natural supplement use, aging, Vitamin E, Vitamin D, Phosphatidylserine, feedback, cognition, older adults, and international.

Although supplement use and regulations may differ by country, current research suggests increased supplement use and inquiries to neuropsychologists (Armstrong & Postal, 2013; Aysin et al., 2021). Literature highlighting the benefit of taking a natural dietary supplement for older adults across the spectrum of cognitive decline has been variable (Brownie, 2009; Haider et al., 2020). Commonly explored vitamins such as Vitamin E, Vitamin D, Vitamin B 12, and Phosphatidylserine have proven to be beneficial in improvements in cognitive domains such as attention and memory for those experiencing mild cognitive impairment (Kang et al., 2022; La Fata et al., 2014; Richter et al., 2013; Van Der Shaft et al., 2013). Therefore, one alternative for defining the utility of supplement usage may be from preventive lens for those with mild or emerging cognitive concerns (Health Quality Ontario., 2013; Joshi & Practice-, 2012). Alternatively, older populations are at risk for malnutrition, which can negatively impact cognition (Well & Dumbrell, 2006).

While recognizing their clinical scope, informed neuropsychologists must be up to date on emerging literature on the efficacy of these supplements. Neuropsychologists should consider following these general guidelines when discussing recommendations for older adult clients with varying degrees of cognitive impairment. For example, neuropsychologists should approach alternative treatments as an exploration of the possible risks, costs, and benefits with evidence-based research while balancing the client’s need for hope (Armstrong & Postal, 2013). Neuropsychologists should also have increased awareness of malnutrition screening amongst this population (Gestuvo & Hung, 2012; Wells & Dumbrell, 2006). Other practices should include ongoing consultation and referral to a nutritionist or following up with their primary care physicians to assist further. With these guidelines, Neuropsychologists can be better equipped to provide ethical recommendations to facilitate clients to become informed consumers.

The prevalence of significant brain disorders and their economic burden are projected to continually increase as populations age longer. This review aims to analyze the barriers to international collaboration and propose preliminary international competency guidelines for the advancement of the neuropsychology field. Moreover, these guidelines can aid the field in advocating for international development and collaboration. Specifically, these guidelines may lead to clarity of services, culturally informed norms, cross-cultural research opportunities, and improving accessibility globally (Chan et al., 2016; Hessen et al. 2017).

Literature between 2002 and 2022 was obtained by searching the Google Scholar and PubMed databases. Keywords such as guidelines, international, and neuropsychology were used. Articles were selected on the criterion of relevance to the objective, international perspectives, and current national guidelines. The remaining articles were reviewed, and themes were clustered to identify overlapping international competencies within the literature. The findings were utilized to create preliminary competency guidelines and discuss their future implications.

Covid-19 unveiled the feasibility of health service fields collaborating internationally to solve global problems (Bump et al. 2021). The pandemic is a call to action for the neuropsychology field to improve global health equity and collaboration to address international challenges (Obschonka et al., 2021). However, one barrier is the lack of globally accepted definitions of neuropsychology and what a neuropsychologist does (Grote et al., 2016). Yet, a way to address this is for international organizations to propose international competency guidelines. This may allow countries with less developed neuropsychology fields to advocate for legislation and services (Chan et al., 2016; Hessen et al., 2017). In addition, countries reported the need for competencies to advocate for advancing current practices (Chan et al., 2016; Hokkanen et al., 2020; Janzen & Guger, 2016). Notably, by developing guidelines, public understanding and competent practices of neuropsychology can be strengthened (Grote et al., 2016; Hessen et al., 2017). Temple and colleagues (2006) discovered the two largest barriers for physicians referring to neuropsychologists were a lack of familiarity with the field and geographical limitations. Therefore, international competency guidelines present a serendipitous opportunity to benefit clients, physicians, and neuropsychologists.

Therefore, the current study presents 10 international neuropsychology practice competencies and their elements. Foundational competencies include: (1)Scientific knowledge, methods, and evidence-based practice; (2)Individual and community diversity; (3)Ethics, legal standards, and policy; (4)Interdisciplinary systems; (5)Reflective practice; (6)Therapeutic relationships. Functional competencies include: (7)Assessment; (8)Intervention; (9)Consultation; (10)Advocacy.

Although training and regulations may differ internationally, emerging literature supports the establishment of global competencies. Despite data on competencies in many countries being unavailable, the need for services in many locations suggests that using the available data to implement guidelines may allow for the growth of consistently competent neuropsychologists to serve the many underserved populations around the world (Hessen et al., 2017). Fortunately, Covid-19 exposed the need for increased health equity and mental health services globally (Jensen et al., 2021). Ultimately, the international competencies presented should be investigated further to improve international neuropsychology research, practice, advocacy, and legislation to abate global disparities.

Several studies have noted associations of higher white matter hyperintensities (WMHs) with cognitive slowing and elevated depressive symptoms in older adults. Depression is also directly associated with cognitive slowing in later life. However, the influence of WMHs on the relationship between depressive symptoms and processing speed is unclear. This interrelationship between depression, processing speed, and WMH may differ between racial groups given the well-documented evidence of racial disparities in vascular disease, WMHs, and cognitive performance, however the literature is sparse. The goal of this current study, therefore, was to investigate whether WMHs mediate the relationship between depressive symptoms and processing speed, and if this relationship differs between Black and White older adults.

A total of 171 non-Hispanic White and 111 non-Hispanic Black older adults (total sample mean age = 82.71 ± 2.74; 42.91% male) from the Healthy Brain Project (a substudy of the Health, Aging, and Body Composition Study) underwent MRI as well as a neuropsychological evaluation. Total WMH volume was quantified for each participant using an automated procedure and normalized to total brain volume. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Digit Symbol Substitution Test (DSST) served as a measure of processing speed. Causal mediation analyses were performed between CES-D and DSST scores across the total sample as well as within racial groups (Black and White), with total WMH volume as the mediator.

The direct effect of the CES-D on DSST was significant (p = 0.012) for the total sample, reflecting slower processing speed at higher levels of depressive symptoms, but the indirect effect was not (p = 0.207). When analyses were stratified by racial group, the indirect effect was significant for Black (p = 0.054; 37.17% mediated) but not White participants (p = 0.207): For Black participants, the inverse relationship between depressive symptoms and processing speed was mediated by a positive relationship between depressive symptoms and WMHs.

While these data support previous findings relating depressive symptoms to slower processing speed across racial groups, our findings also demonstrate a greater impact of WMHs on this relationship in Black older adults compared to their White counterparts. This suggests that WMHs may serve as an important risk factor for cognitive slowing in older Black adults with higher depressive symptoms. Future studies are needed to further investigate the role of WMHs on depression-related deficits in processing speed and other cognitive domains in racially diverse groups.

There is equivocal evidence that acculturation is associated with cognition. Various factors may contribute to ambiguous findings in the neuropsychology setting, including psychometric limitations of tools available for assessing acculturation as well as the frequent conflation of bilingualism with acculturation. Additionally, neuropsychological research on acculturation and cognition has largely failed to account for bidimensional models of acculturation, which have greater empirical support over unidimensional models. In response to these limitations and the theoretical literature on acculturation, we developed the Perceived Identity & Ethnicity Scales (PIES), a brief rating scale system to quickly (<2 minutes) capture an individual's perceived acculturative identity across several domains. In the current study, we sought to (1) provide initial psychometric support of the PIES and (2) examine how it relates to cognition in a culturally and linguistically diverse sample.

We recruited 242 individuals from both university and community samples (age=23.7±7.6, range 18-72; <12 Years of Education=4%; 78% Female; 58% Hispanic/Latin American; 69% middle SES; 22% educated outside the USA). In addition to demographic questionnaires, participants completed the PIES; an established measure of acculturation (the Bicultural Involvement Questionnaire, BIQ) and bilingualism (Bilingual Language Profile, BLP); measures of mood (the Depression, Anxiety, Stress Scales, DASS; Apathy Evaluation Scale, AES); and of self-reported cognitive functioning (Everyday Cognition, ECog). A subsample of Spanish speakers (n=86) also completed a cognitive battery validated for use in this population (the Spanish English Neuropsychological Assessment Scales, SENAS). For the first aim, we examined the reliability, validity, and dimensionality of the PIES in the full sample. In the Spanish-speaking subsample, we examined the relationship between the tool and both subjective and objective cognition using linear regression controlling for age, education, sex/gender, and premorbid intellectual functioning.

Measures of internal consistency and dimensionality supported a bidimensional model of acculturation; identification with culture of family origin (PIES-O) was not related to identification with US American culture (PIES-U; r=0.036, p>0.05). Cultural preference scores from the BIQ were associated with PIES-O (r=-0.322) and PIES-U (r=0.277; both ps<0.001) in the expected directions. PIES-O (r=0.350) and PIES-U (r=-0.432) were associated with the ability to speak a language other than English on the BLP (both ps<0.001). PIES-U, but not PIES-O, was also strongly associated with other BIQ and BLP scores as well as with receiving education outside of the USA at medium to large effect sizes (rs=0.3 to 0.6; all ps<0.001). In the subsample, PIES-O and PIES-U were not associated with subjective cognition as measured by the ECog (AR2=0.016, p>0.05); global cognition as measured by the Montreal Cognitive Assessment (MoCA; AR2=0.046, p>0.05); or SENAS cognitive composite scores (AR2=0.016, p>0.05) after controlling for covariates.

Findings provide strong initial psychometric support for the utility of the PIES in the assessment of acculturation. Moreover, these results further support the bidimensional model of acculturation. Acculturation as measured by the PIES was not associated with cognitive abilities in this highly educated and mainly female cross-sectional sample. Longitudinal research accounting for acculturation is needed to elucidate these relationships.

Despite the array of neuropsychological tests available, these assessments are largely made and developed for use in WEIRD (western, educated, industrialized, rich, democratic) societies (Fernandez, 2019; Ponsford, 2017). The Multicultural Neuropsychological Scale (MUNS) was developed with underrepresented groups in mind as a universally valid neuropsychological assessment which can be used across cultures and adapted to different languages. To assist with the validation of the MUNS as a cross-cultural instrument, investigators administered the MUNS to a cognitively 'healthy’ college-aged population in the United States as a means of collecting normative data. Results were compared to samples taken from an Argentine university, Universidad Catelica de Cerdoba, and combined with another American university, Marymount Loyola University. The goal of this comparison was to provide evidence supporting the validity of the MUNS as a universal, cross-cultural neuropsychological assessment battery.

Students from James Madison University (JMU) in Harrisonburg, Virginia (N = 24, Age = 20.083 1.93, Female = 87.5%) were recruited via a campus-wide email. Students who met inclusionary criteria were selected for MUNS administration. Students completed a background questionnaire and effort measure (REY-15; Rey, 1964) before completing the MUNS battery, consisting of eight subtests with four delayed trials. Descriptive statistics of the group were assessed, and one-way ANOVAs were conducted on the various subtests to determine whether differences exist between the American and Argentine samples.

No significant difference between groups was found for seven subtests. A difference existed on the Attention subtest between the American (f (1, 106) = 45.409, p < .001).

The results show support for the cross-cultural validity of the MUNS. The only significant difference was found in the Arrows (Old) subtest. This is in alignment with previous administrations of the MUNS (Fernandez et al., 2018). Further studies are needed to assess potential bias within this subtest, as well as to pursue comparison studies for the New Arrows subtest administered within this USA sample. The present findings provide further evidence that the MUNS can be applied as a neuropsychological assessment across a variety of populations.

There are approximately 1.5 million Japanese and Japanese Americans in the United States, with the Japanese population increasing steadily over the past two decades. Given the growing number of the Japanese population, it is likely that a clinical neuropsychologist may encounter a Japanese patient, particularly for neurocognitive disorder evaluations given the aging population. Literature has reported that cross-cultural bias in neuropsychological testing and cultural factors affect individuals’ test performance. In order to conduct and interpret neuropsychological assessments for this population, it is important to use normative data and consider the impact of various factors such as acculturation, language, and generation in the U.S. Availability of normative cognitive test data for Japanese-Americans is limited. Tests with most extensive use, adaptation, validation, and norming were identified. Many clinically used measures of executive functioning (EF) have been translated into Japanese and studied in multiple clinical populations. We present information on tests in this domain given their appropriateness for use in cross-linguistic and cross-cultural evaluations.

Available studies of neuropsychological tests measuring EF that have been translated and normed in the Japanese and/or Japanese-American patient population are reported. Review of the literature was conducted by authors of Japanese descent familiar with neuropsychological assessment and Japanese and Japanese-American culture. We prioritized studies published in both English and Japanese and those that included commonly utilized tests in the U.S, allowing for maximum accessibility and utility for Western-based neuropsychologists. Additionally, inclusion priority was given to studies published in English which report the clinical diagnoses, age range, and gender characteristics of the sample population. The Wisconsin card sorting test (WCST) and Trail Making Test (TMT) were reviewed.

The WCST and the TMT, with its variant, was the most normed EF cognitive test currently available. The Keio version Japanese-Trail Making Test (J-TMT) and a simplified version of the Trail Making Test (S-TMT) has been utilized in Japan, however norms are still lacking. Of the available studies, the S-TMT and J-TMT were found to be moderately correlated with the TMT. The Keio version WCST (KWCST) (Kao et al., 2012) was correlated to education level (Abe et al., 2004), appropriately differentiating severity of social anxiety disorder (Fujii et al., 2013), patients with schizophrenia (Banno et al., 2012), and cognitive impairment in Parkinson’s disease (Yoshii et al., 2019).

Information regarding translated and normed tests are presented to assist clinical neuropsychologists provide competent services to Japanese-Americans. The J-TMT and the S-TMT may be clinically useful as an evaluation of attention for the Japanese population. The KWCST has also been found to be an appropriate tool for this population. However, publicly available norms for these assessments are still sparse, and there is very limited information about administration of these tests by English-speaking neuropsychologists with the use of interpreters. Further work is needed to increase access to and awareness of linguistically and culturally appropriate versions of clinical measures to better serve the Japanese and Japanese-American population.

To establish how participant and informant reports of cognitive decline may differ between groups or remain consistent based on race and level of education in a large, national sample.

Participants were selected using the National Alzheimer’s Coordinating Center (NACC) database. Participants who were cognitively healthy at baseline and at least 65 years of age were selected. All informants either lived with the participant or visited the participant weekly (N = 9300). Participant racial groups included White American (n = 7534), Black American (n = 1453), Native American/Alaskan (n = 68), or Asian American (n = 239). Native Hawaiians were not included in this study, given the small sample size (n = 6). Participant education-levels included less than high school degree (n = 395), high school degree or GED (n = 1326), some post-secondary education (n = 1727), bachelor’s degree (n = 2184), and graduate studies (n = 3668). Pairwise comparisons examined each racial and educational attainment group by subjective reports of cognitive decline using Bayesian contingency tables to find reliable evidence to support the null or alternative hypothesis. Participant and informant reports of decline were coded to create a single variable to express no reported decline, participant reported decline, informant reported decline, or agreed decline.

Pairwise race comparisons found moderate evidence that Native Americans reliably reported cognitive decline differently than Black (BF10 = 6.973) and White Americans (BF10 = 3.634). In both cases, the Native American group reported more cases of decline than expected in all groups and reported no decline less than expected. Further analysis found very strong evidence for the null hypothesis when comparing White Americans with Black (BF01 = 60.506) and Asian Americans (BF01 = 65.72). A comparison of Black and Asian Americans found extremely strong evidence for the null hypothesis (BF01 = 199.464). No conclusive evidence was found when comparing reports of Native and Asian Americans (BF01 = 2.401). Pairwise comparisons of educational attainment with subjective reporting of cognitive decline found no evidence of reliable differences between groups. No conclusive evidence was found when comparing the reporting pattern of individuals with some post-secondary education and individuals who did not complete high school (BF01 = 1.257). Moderate evidence for the null hypothesis was found when comparing individuals with a bachelor’s degree with those who did not complete high school (BF01 = 8.57). Strong evidence for the null hypothesis was found when comparing individuals who did not complete high school with those who have studied at the graduate level (BF01 = 17.141) and those who completed high school (BF01 = 16.306). When making all other pairwise comparisons (BF01 > 100), there was extremely strong evidence for the null hypothesis.

These findings suggest that how participants and their informants report cognitive decline does not differ based upon educational attainment in almost all cases, and no evidence was found supporting differences based upon educational attainment. There is evidence that Native Americans/Native Alaskans and their informants report more cognitive decline compared to White and Black Americans. However, the findings suggest that White, Black, and Asian Americans do not differ in how participants and their informants report cognitive decline.