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BACKGROUND AND OBJECTIVES: It is widely cited that dementia occurs in up to 80% of patients with Parkinson disease (PD), but studies reporting such high rates were published over two decades ago, had relatively small samples, and had other limitations. We aimed to determine long-term dementia risk in PD using data from two large, ongoing, prospective, observational studies. METHODS: Participants from the Parkinsons Progression Markers Initiative (PPMI), a multisite international study, and a long-standing PD research cohort at the University of Pennsylvania (Penn), a single site study at a tertiary movement disorders center, were recruited. PPMI enrolled de novo, untreated PD participants and Penn a convenience cohort from a large clinical center. For PPMI, a cognitive battery is administered annually, and a site investigator makes a cognitive diagnosis. At Penn, a comprehensive cognitive battery is administered either annually or biennially, and a cognitive diagnosis is made by expert consensus. Interval-censored survival curves were fit for time from PD diagnosis to stable dementia diagnosis for each cohort, using cognitive diagnosis of dementia as the primary end point and Montreal Cognitive Assessment (MoCA) score

INTRODUCTION: The U.S. Military Veterans aged 65 and older comprise an estimated 43% of the 22 million living Veterans in the United States. Veterans have high rates of physical, psychiatric, and social challenges, but it is not known whether Veteran status confers additional risk for cognitive or functional impairments in later life. Thus, this investigation specifically compared older Veterans with their non-Veteran peers in cognitive functioning and performance-based functional capacity. MATERIALS AND METHODS: Participants (N = 110; 29 Veterans and 81 non-Veterans) were part of a larger longitudinal study on biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. The University of California San Diego Institutional Review Board approved the study and all participants provided written informed consent. Participants provided demographic and mental health information and were administered a comprehensive neuropsychological battery. Functional capacity was assessed using the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), which uses financial and communication role-plays to assess everyday functioning skills. Neuropsychological scores were appropriately normed prior to analysis. Multivariate Analyses of Variances with post hoc t-tests and an Analysis of Covariance were used to examine neuropsychological and functional capacity differences, respectively, between Veterans and non-Veterans. RESULTS: Veterans did not differ from non-Veterans in educational attainment (16.4 years versus 15.5 years, P = 0.110), but they were significantly older (mean age 86.9 years ± 5.7, versus 81.74 years ± 6.53; P

BACKGROUND: The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. METHODS: Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. RESULTS: MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. CONCLUSION: Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

IntroductionAlthough frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.MethodsRetrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments.ResultsCommon symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations.DiscussionThis study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients.HighlightsThis project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

BackgroundTraumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.MethodsWe studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).ResultsYears of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).ConclusionsLifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores, and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation among Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression, and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate among Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. The use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology.

Both navigation abilities and gait can be affected by the atrophy in the medial temporal cortex. This study aimed to determine whether navigation abilities could differentiate seniors with and without medial temporal lobe atrophy who complained about their cognitive status. The participants, classified to either the medial temporal atrophy group (n = 23) or the control group (n = 22) underwent neuropsychological assessment and performed a spatial navigation task while their gait parameters were recorded. The study showed no significant differences between the two groups in memory, fluency, and semantic knowledge or typical measures of navigating abilities. However, gait parameters, particularly the propulsion index during certain phases of the navigation task, distinguished between seniors with and without medial temporal lobe lesions. These findings suggest that the gait parameters in the navigation task may be a valuable tool for identifying seniors with cognitive complaints and subtle medial temporal atrophy. [ABSTRACT FROM AUTHOR]

This study evaluated the measurement invariance of a neuropsychological battery across rural and urban older adults from Costa Rica. Rural and urban older adults (N = 295) from the Epidemiology and Development of Alzheimer's Disease (EDAD) study in Costa Rica were assessed. The baseline factor model for the EDAD neuropsychological measures was identified with nine neuropsychological measures and three cognitive constructs: Verbal Memory, Spatial Reasoning, and Cognitive Flexibility. Measurement and structural invariance were established, and, then, group comparisons of the latent cognitive factors were conducted to explore regional disparities. The findings showed that most of the neuropsychological tests in EDAD can be directly compared across the groups, allowing for cognitive constructs comparisons. The rural sample showed a disadvantage in the Spatial Reasoning and Cognitive Flexibility abilities. When age and education were included in the models, differences between the regions disappeared. Having more years of education was associated with higher cognitive abilities, with a larger effect for the rural group. Norms for Costa Rican older adults should consider age and education adjustments. This study contributes to the growing area of measurement invariance in neuropsychological assessment as it highlights the importance of examining the comparability of assessment measures across different cultural groups.

INTRODUCTION: The objective of this pilot study was to establish the feasibility of recruiting older Vietnamese Americans for research addressing genetic and nongenetic risk factors for Alzheimer disease (AD). METHODS: Twenty-six Vietnamese Americans were recruited from communities in San Diego. A Community Advisory Board provided cultural and linguistic advice. Bilingual/bicultural staff measured neuropsychological, neuropsychiatric, lifestyle, and medical/neurological functioning remotely. Saliva samples allowed DNA extraction. A consensus team reviewed clinical data to determine a diagnosis of normal control (NC), mild cognitive impairment (MCI), or dementia. Exploratory analyses addressed AD risk by measuring subjective cognitive complaints (SCC), depression, and vascular risk factors (VRFs). RESULTS: Twenty-five participants completed the study (mean age=73.8 y). Eighty percent chose to communicate in Vietnamese. Referrals came primarily from word of mouth within Vietnamese communities. Diagnoses included 18 NC, 3 MCI, and 4 dementia. Participants reporting SCC acknowledged more depressive symptoms and had greater objective cognitive difficulty than those without SCC. Eighty-eight percent of participants reported at least 1 VRF. DISCUSSION: This pilot study supports the feasibility of conducting community-based research in older Vietnamese Americans. Challenges included developing linguistically and culturally appropriate cognitive and neuropsychiatric assessment tools. Exploratory analyses addressing nongenetic AD risk factors suggest topics for future study.

BACKGROUND: Pathologic perivascular spaces (PVS), the fluid-filled compartments surrounding brain vasculature, may underlie cognitive decline in Parkinsons disease (PD). However, whether this impacts specific cognitive domains has not been investigated. OBJECTIVES: This study examined the relationship of PVS volume at baseline with domain-specific and global cognitive change over 2 years in PD individuals. METHODS: A total of 39 individuals with PD underwent 3T T1w magnetic resonance imaging to determine PVS volume fraction (PVS volume normalized to total regional volume) within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, and superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of cognitive domains and global cognitive function at baseline and after 2 years. RESULTS: Higher basal ganglia PVS at baseline was associated with greater decline in attention, executive function, and global cognition scores. CONCLUSIONS: While previous reports have associated elevated PVS volume in the basal ganglia with decline in global cognition in PD, our findings show such decline may affect the attention and executive function domains.

We evaluated the HIV-1 DNA reservoir in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) in people with HIV (PWH) and associations to cognitive dysfunction. Using the intact proviral DNA assay (IPDA), an emerging technique to identify provirus that may be the source of viral rebound, we assessed HIV DNA in CSF and PBMC in PWH regardless of antiretroviral therapy (ART). CSF was used as a sampling surrogate for the central nervous system (CNS) as opposed to tissue. IDPA results (3' defective, 5' defective, and intact HIV DNA) were analyzed by compartment (Wilcoxon signed rank; matched and unmatched pairs). Cognitive performance, measured via a battery of nine neuropsychological (NP) tests, were analyzed for correlation to HIV DNA (Spearman's rho). 11 CSF and 8 PBMC samples from PWH were evaluated both unmatched and matched. Total CSF HIV DNA was detectable in all participants and was significantly higher than in matched PBMCs (p ​= ​0.0039). Intact CSF HIV DNA was detected in 7/11 participants and correlated closely with those in PBMCs but tended to be higher in CSF than in PBMC. CSF HIV DNA did not correlate with global NP performance, but higher values did correlate with worse executive function (p ​= ​0.0440). Intact HIV DNA is frequently present in the CSF of PWH regardless of ART. This further supports the presence of an HIV CNS reservoir and provides a method to study CNS reservoirs during HIV cure studies. Larger studies are needed to evaluate relationships with CNS clinical outcomes.

IntroductionData-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods.MethodsCluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression.ResultsFive clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN

IntroductionDepressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear.MethodsAsian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity.ResultsHigher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function.DiscussionDepressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups.HighlightsWe examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.

The proposed symptoms for Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) were evaluated in children who participated in the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study. Children at-risk for ND-PAE (n = 204) were contrasted to children with no prenatal alcohol exposure, alcohol-related dysmorphia or growth deficits (n = 908). Symptoms were defined based on neuropsychological testing using two diagnostic threshold levels (1.0 and 1.5 STD). Individuals at risk for ND-PAE had higher endorsement rates of the self-regulation and adaptive impairments at the 1.0 threshold and of the neurocognitive and self-regulation impairments at the 1.5 threshold. Endorsement of the disorder significantly differed at the 1.0 threshold. Receiver operating characteristic curve analysis indicated that having an IQ below 70 was not predictive of the diagnosis but modifications of the IQ criterion improved predictive validity. Discrimination validity was poor without documentation of PAE which continues to be a necessity for a diagnosis of ND-PAE.

Context: Current lower-extremity return to sport testing primarily considers the physical status of an athlete; however, sport participation requires continuous cognitive dual-task engagement. Therefore, the purpose was to develop and evaluate the reliability of a visual-cognitive reactive (VCR) triple hop test that simulates the typical sport demand of combined online visual-cognitive processing and neuromuscular control to improve return to sport testing after lower-extremity injury. Design: Test–retest reliability. Methods: Twenty-one healthy college students (11 females, 23.5 [3.7] y, 1.73 [0.12] m, 73.0 [16.8] kg, Tegner Activity Scale 5.5 [1.1] points) participated. Participants performed a single-leg triple hop with and without a VCR dual task. The VCR task incorporated the FitLight system to challenge peripheral response inhibition and central working memory. Maximum hop distance, reaction time, cognitive errors, and physical errors were measured. Two identical testing visits were separated by 12 to 17 days (14 [1] d). Results: Traditional triple hop (intraclass correlation coefficients: ICC(3,1) =.96 [.91–.99]; standard error of the measurement = 16.99 cm) and the VCR triple hop (intraclass correlation coefficients(3,1) =.92 [.82–.97]; standard error of the measurement = 24.10 cm) both demonstrated excellent reliability for the maximum hop distance, and moderate reliability for the VCR triple hop reaction time (intraclass correlation coefficients(3,1) =.62 [.09–.84]; standard error of the measurement = 0.09 s). On average, the VCR triple hop resulted in a hop distance deficit of 8.17% (36.4 [5.1] cm; P <.05, d = 0.55) relative to the traditional triple hop. Conclusions: Hop distance on the VCR triple hop had excellent test–retest reliability and induced a significant physical performance deficit when compared with the traditional triple hop assessment. The VCR triple hop reaction time also demonstrated moderate reliability. [ABSTRACT FROM AUTHOR]

Background: Only 55% of anterior cruciate ligament-reconstructed (ACLR) athletes return to competitive sports. This brings into question the usefulness of current return to sport (RTS) criteria. High cognitive demand of sport environment clarifies the value of incorporating neurocognitive tests when making decisions regarding the time of RTS. This preliminary study aimed to compare the neurocognitive functions between healthy controls and ACLR male athletes who passed or failed RTS criteria. Methods: A total of 45 male football players, including 15 ACLR who passed RTS criteria, 15 ACLR who did not pass, and 15 healthy controls participated in this cross-sectional study. The Cambridge Neuropsychological Test Automated Battery was used to measure a battery of neurocognitive tasks, including speed of response, sustained attention, working memory, cognitive flexibility, and response inhibition. Results: The results revealed that compared with both the ACLR-passed and healthy groups, the ACLR-failed group showed greater values of 5-choice movement time (P =.02, P =.01, respectively) but lower values of stop signal reaction time (P =.03, P =.001, respectively) and proportion of successful stops variables (P =.02). In addition, compared with the healthy group, both the ACLR-failed and ACLR-passed groups indicated greater values in between errors (P <.001, P =.008, respectively) and reaction latency variables (P =.002, P =.01, respectively) but lower values of A′ (P <.001, P =.007, respectively), probability of hit (P <.001, P =.03, respectively), and percent correct trials variables (P =.006, P =.02, respectively). Conclusions: Our findings indicated deficits in neurocognitive functions in ACLR male athletes. In addition, poor performance in sustained attention, working memory, and cognitive flexibility measures observed in the ACLR-passed group highlighted the necessity for using a multimodal approach via implementation of neurocognitive measures in conjunction with the functional and muscular assessments when making RTS decisions. [ABSTRACT FROM AUTHOR]

BackgroundPlasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations.MethodsWe examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61-73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter.ResultsAfter adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals.ConclusionsThese results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.

BackgroundWhile obstructive sleep apnea (OSA) and insomnia symptoms in neurotypical populations are associated with Alzheimer's disease (AD), their association with dementia in adults with Down syndrome (DS) remains less clear, even though these symptoms are prevalent and treatable in DS. Understanding their associations with AD-related dementia status, cognitive impairment, and functional deterioration may lead to interventions to slow decline or disease progression in adults with DS.ObjectiveTo characterize differences in OSA and insomnia symptom expression by dementia status, and to determine which sleep factors support dementia diagnosis.MethodsMultimodal consensus conference was used to determine dementia status in 52 adults with DS (52.2 ± 6.4 years, 21 women). Cognitive impairment, adaptive behavior skills, and symptoms of OSA and insomnia were quantified using validated assessments for adults with DS and their primary informants.ResultsA sex by dementia status interaction demonstrated that older women with DS and dementia had more severe terminal insomnia but not OSA symptoms relative to older women with DS who were cognitively stable (CS). Greater insomnia symptom severity was associated with greater functional impairments in social and self-care domains adjusting for age, sex, premorbid intellectual impairment, and dementia status.ConclusionsInsomnia symptoms are more severe in women with DS with dementia than in women with DS and no dementia, and regardless of dementia status or sex, more severe insomnia symptoms are associated with greater impairment in activities of daily living. These findings underscore the potential importance of early insomnia symptom evaluation and treatment in women with DS at risk of developing AD.

BACKGROUND: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited. OBJECTIVE: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults. METHODS: We used data (n = 5,799, 45-74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms. RESULTS: Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests. CONCLUSIONS: Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults.

BACKGROUND: The Anti-Amyloid in Asymptomatic Alzheimers Disease (A4) Study failed to show a treatment benefit with solanezumab, but the longitudinal consequences of elevated amyloid were observed in study participants with objective decline on the Preclinical Alzheimer Cognitive Composite (PACC) and subjective decline on the combined Cognitive Function Index (participant + study partner CFI), during the trial period. OBJECTIVES: We sought to expand on previous findings by comparing longitudinal patterns of participant and study partner CFI separately and their associations with the PACC stratified by baseline amyloid tertile over the course of the A4 Study. DESIGN: Cognitively unimpaired older adult participants and their study partners were independently administered the CFI at screen prior to amyloid PET disclosure and then at 3 subsequent visits (week 48, week 168, week 240) of the study. PACC collected at visits concurrent with CFI administration were also examined longitudinally. SETTING: The A4 Study was conducted at 67 sites in Australia, Canada, Japan, and the United States. PARTICIPANTS: 1,147 participants with elevated amyloid based on florbetapir PET were enrolled in the A4 Study and included in these analyses. 583 were on placebo and 564 were treated with solanezumab. MEASUREMENTS: The PACC was used to assess objective cognitive performance and the CFI was used to assess change in everyday cognitive functioning by the participant and their study partner independently. Amyloid level was characterized by Centiloid tertiles (77.2 CL). Participants were aware of their elevated amyloid status, but not their CL tertile, or specific level of amyloid. Longitudinal correlations between participant and study partner CFI and PACC were examined at all visits where assessments were available. The impact of baseline amyloid tertile on CFI and PACC associations was also examined. RESULTS: Both participant and study partner CFI increased over the duration of the study indicating worsening cognitive functioning. Results did not differ by treatment group. The association between higher CFI and worse PACC for both for participant and study partner became progressively stronger over the course of the study. PACC had a significantly higher correlation with study partner CFI than with participant CFI by week 168. The stronger correlations between study partner CFI and PACC were driven by those in the highest amyloid tertile. CONCLUSION: Both participant and study partner report captured subtle changes in everyday cognitive functioning for participants with biomarker confirmed and disclosed preclinical AD. Moreover, study partner report was most highly aligned with cognitive decline, particularly among those with the highest amyloid load.

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged

BackgroundWhereas clinical experience in dementia indicates high risk for financial mismanagement, there has been little formal study of real world financial errors in dementia.ObjectiveWe aimed to compare caregiver-reported financial mistakes among people with Alzheimer's disease, behavioral variant frontotemporal dementia (bvFTD), and primary progressive aphasia (PPA).MethodsCaregivers reported whether participants with dementia had made financial mistakes within the last year; and if so, categorized these as resulting from: (a) being too trusting or gullible, (b) being wasteful or careless with money, or (c) trouble with memory. In a pre-registered analysis https://archive.org/details/osf-registrations-vupj7-v1), we examined the hypotheses that (1) financial mistakes due to impaired socioemotional function and diminished sensitivity to negative outcomes are more prevalent in bvFTD than in Alzheimer's disease, and (2) financial mistakes due to memory are more prevalent in Alzheimer's disease than in bvFTD. Exploratory analyses addressed vulnerability in PPA and brain-behavior relationships using voxel-based morphometry.ResultsConcordant with our first hypothesis, bvFTD was more strongly associated than Alzheimer's disease with mistakes due to being too trusting/gullible or wasteful/careless; contrary to our second hypothesis, both groups were similarly likely to make mistakes due to memory. No differences were found between Alzheimer's disease and PPA. Exploratory analyses indicated associations between financial errors and atrophy in right prefrontal and insular cortex.ConclusionsOur findings cohere with documented socioemotional and valuation impairments in bvFTD, and with research indicating comparable memory impairment between bvFTD and Alzheimer's disease.

ObjectiveSubjective cognitive decline (SCD) is a potential early risk marker for Alzheimer's disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status.MethodsFifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk).ResultsHigher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only.ConclusionsOur preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline.

BACKGROUND: Unsupervised online cognitive assessments have demonstrated promise as an efficient and scalable approach for evaluating cognition in aging, and Alzheimers disease and related dementias. OBJECTIVES: The aim of this study was to evaluate the feasibility, usability, and construct validity of the Paired Associates Learning task from the Cambridge Neuropsychological Test Automated Battery® in adults enrolled in the Brain Health Registry. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: The Paired Associates Learning task was administered to Brain Health Registry participants in a remote, unsupervised, online setting. In this cross-sectional analysis, we 1) evaluated construct validity by analyzing associations between Paired Associates Learning performance and additional participant registry data, including demographics, self- and study partner-reported subjective cognitive change (Everyday Cognition scale), self-reported memory concern, and depressive symptom severity (Patient Health Questionnaire-9) using multivariable linear regression models; 2) determined the predictive value of Paired Associates Learning and other registry variables for identifying participants who self-report Mild Cognitive Impairment by employing multivariable binomial logistic regressions and calculating the area under the receiver operator curve; 3) investigated feasibility by looking at task completion rates and statistically comparing characteristics of task completers and non-completers; and 4) evaluated usability in terms of participant requests for support from BHR related to the assessment. RESULTS: In terms of construct validity, in participants who took the Paired Associates Learning for the first time (N=14,528), worse performance was associated with being older, being male, lower educational attainment, higher levels of self- and study partner-reported decline, more self-reported memory concerns, greater depressive symptom severity, and self-report of Mild Cognitive Impairment. Paired Associates Learning performance and Brain Health Registry variables together identified those with self-reported Mild Cognitive Impairment with moderate accuracy (areas under the curve: 0.66-0.68). In terms of feasibility, in a sub-sample of 29,176 participants who had the opportunity to complete Paired Associates Learning for the first time in the registry, 14,417 started the task. 11,647 (80.9% of those who started) completed the task. Compared to those who did not complete the task at their first opportunity, those who completed were older, had more years of education, more likely to self-identify as White, less likely to self-identify as Latino, less likely to have a subjective memory concern, and more likely to report a family history of Alzheimers disease. In terms of usability, out of 8,395 received requests for support from BHR staff via email, 4.4% (n=374) were related to PAL. Of those, 82% were related to technical difficulties. CONCLUSIONS: Our findings support moderate feasibility, good usability, and construct validity of cross-sectional Paired Associates Learning in an unsupervised online registry, but also highlight the need to make the assessment more inclusive and accessible to individuals from ethnoculturally and socioeconomically diverse communities. A future, improved version could be a scalable, efficient method to assess cognition in many different settings, including clinical trials, observational studies, healthcare, and public health.

ObjectiveMethamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.Method423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M-/M+) and/or cannabis (C-/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.ResultsGlobally, M+C+ performed worse than M-C- but better than M+C-. M+C+ outperformed M+C- on measures of verbal fluency, information processing speed, learning, memory, and working memory. M-C+ did not display lower performance than M-C- globally or on any domain measures, and M-C+ even performed better than M-C- on measures of learning, memory, and working memory.ConclusionsOur findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.

IntroductionThis study aimed to understand whether older adults' longitudinal completion of assessments in an online Alzheimer's disease and related dementias (ADRD)-related registry is influenced by self-reported medical conditions.MethodsBrain Health Registry (BHR) is an online cognitive aging and ADRD-related research registry that includes longitudinal health and cognitive assessments. Using logistic regressions, we examined associations between longitudinal registry completion outcomes and self-reported (1) number of medical conditions and (2) eight defined medical condition groups (cardiovascular, metabolic, immune system, ADRD, current psychiatric, substance use/abuse, acquired, other specified conditions) in adults aged 55+ (N = 23,888). Longitudinal registry completion outcomes were assessed by the completion of the BHR initial questionnaire (first questionnaire participants see at each visit) at least twice and completion of a cognitive assessment (Cogstate Brief Battery) at least twice. Models included ethnocultural identity, education, age, and subjective memory concern as covariates.ResultsWe found that the likelihood of longitudinally completing the initial questionnaire was negatively associated with reporting a diagnosis of ADRD and current psychiatric conditions but was positively associated with reporting substance use/abuse and acquired medical conditions. The likelihood of longitudinally completing the cognitive assessment task was negatively associated with number of reported medical conditions, as well as with reporting cardiovascular conditions, ADRD, and current psychiatric conditions. Previously identified associations between ethnocultural identity and longitudinal assessment completion in BHR remained after accounting for the presence of medical conditions.DiscussionThis post hoc analysis provides novel, initial evidence that older adults' completion of longitudinal assessments in an online registry is associated with the number and types of participant-reported medical conditions. Our findings can inform future efforts to make online studies with longitudinal health and cognitive assessments more usable for older adults with medical conditions. The results need to be interpreted with caution due to selection biases, and the under-inclusion of minoritized communities.

BackgroundMethodsResultsConclusionsThe burden of Alzheimer’s disease and related dementias (AD/ADRD) in Costa Rica is expected to become one of the highest in the region. Early detection will help optimize resources and improve primary care interventions. The Montreal Cognitive Assessment (MoCA) has shown good sensitivity for detecting mild cognitive impairment (MCI), but specificity varies depending on the population. This motivated the analysis of different cutoffs to minimize false-positive classifications in a Costa Rican sample for its use in clinical settings.Data was analyzed from 516 memory clinic outpatients (148 cognitively normal, 260 MCI, 108 mild AD/ADRD; mean age 66.3 ± 10.8 years) who underwent complete neurological and neuropsychological assessment and were diagnosed by consensus. Optimal MoCA cutoff scores were identified using a multiple cutoff approach.Overall, a cutoff score of ≥ 23 showed better accuracy to distinguish between normal cognition (NC) and MCI (sensitivity 73%, specificity 83%). When analyzed by educational levels, a cutoff score of ≥ 21 showed better accuracy for ≤ 6 years (sensitivity 80%, specificity 76%), ≥23 for 7–12 years (sensitivity 86%, specificity 76%) and ≥ 24 for > 12 years (sensitivity 70%, specificity 85%). For distinguishing MCI from mild AD/ADRD, the optimal overall cutoff score was ≥ 15 (sensitivity 66%, specificity 85%). When stratified by years of education, cutoff scores of ≥ 14 showed better accuracy for ≤ 6 years (sensitivity 70%, specificity 88%), ≥15 for 7–12 years (sensitivity 46%, specificity 95%) and ≥ 17 for > 12 years (sensitivity 67%, specificity 93%).A MoCA cutoff score of ≥ 23 in the Costa Rican population showed better diagnostic accuracy for detecting MCI and may reduce the false positive rate. Our findings may be helpful for primary care clinical settings and further referral criteria. [ABSTRACT FROM AUTHOR]

The Test of Practical Judgment (TOP-J) has not been thoroughly investigated in terms of its incremental validity. In the current study, we explored whether the TOP-J adds unique and meaningful information to the neuropsychological assessment beyond other executive functioning tests that are often used as proxies for practical judgment. Ninety-seven older adults who were classified as cognitively unimpaired, with subjective cognitive decline, or with mild cognitive impairment completed a comprehensive neuropsychological evaluation. Incremental validity was assessed through hierarchical ordinal regression analysis by modeling the TOP-J (Forms A and B, 15-item and 9-item versions), in addition to widely used tests of executive function, with participant classification/diagnosis as the outcome. The addition of the TOP-J (both 15-item versions) added incremental validity beyond traditional executive functioning measures to predict diagnosis. Including the TOP-J within neuropsychological evaluations of older adults may enhance differentiation of preclinical dementia diagnoses and provide clinically valuable information to the exam. [ABSTRACT FROM AUTHOR]

Previous studies have reported that mode of delivery, particularly cesarean delivery (CD), is associated with neurodevelopmental outcomes in children. This study evaluates behavioral and neuropsychological test scores in children based on mode of delivery.Children enrolled in the Raine Study from Western Australia, born between 1989 and 1992 by instrumental vaginal delivery (IVD), elective CD, and non-elective CD, were compared to those with spontaneous vaginal delivery (SVD). The primary outcome was the Child Behavior Checklist (CBCL) administered at age 10. Secondary outcomes included evaluations of language, motor function, cognition, and autistic traits. Multivariable linear regression was used to evaluate score differences by mode of delivery adjusted for sociodemographic and clinical characteristics, and Poisson regression was used to evaluate for increased risk of clinical deficit.Of 2,855 children, 1770 (62.0 %) were delivered via SVD, 480 (16.8 %) via IVD, 346 (12.1 %) via elective CD, and 259 (9.1 %) via non-elective CD. Non-elective CD was associated with higher (worse) CBCL Internalizing (+2.09; 95 % CI 0.49, 3.96; p=0.01) scores, and elective CD was associated with lower (worse) McCarron Assessment of Neuromuscular Development (MAND) (−3.48; 95 % CI −5.61, −1.35; p=0.001) scores. Differences were not seen in other outcomes, and increased risk of clinical deficit was not observed with either the CBCL Internalizing or MAND scores.Differences in behavior and motor function were observed in children delivered by CD, but given that score differences were not associated with increased incidence of clinical deficit, clinical significance may be limited. [ABSTRACT FROM AUTHOR]

Introduction: Spatial construction is a complex ability involving attention, global/local visual processing, mental representation, visuo-motor coordination and, to varying extent, working memory and executive functions, and verbal abilities. In developmental neuropsychology, little attention has been paid to comprehend whether and to what extent the above cognitive processes are involved in two main spatial construction tasks, that is drawing and block building. Method: We used path analysis to test shared and specific effects of verbal and spatial working memory, spatial attention, inhibition, verbal abilities (vocabulary and naming), figure disembedding, mental rotation, and visual-motor coordination, as well as of demographics (sex, age and socio-economic status), on two classical drawing (Rey-Osterrieth Complex Figure; ROCF) and block building (Block design; BD) tasks in a sample of 195 typically developing children (age range: 7–11 years). Results: Figure disembedding and visuo-motor coordination were the only shared predictors of both spatial construction tasks. Moreover, ROCF score was directly related with spatial attention and inhibition, while BD score was directly related with sex, vocabulary, mental rotation and backward spatial working memory. Discussion: These findings distinguish between abilities involved in spatial construction regardless of the type of task and those specifically related to ROCF or Block Design, thus providing clues relevant to neuropsychological assessment and intervention in children with spatial construction disorders. [ABSTRACT FROM AUTHOR]

Area 8A has traditionally been considered to be the frontal eye field (FEF), i.e. the area for the motor production of eye movements. However, recent research has shown that the FEF lies posteriorly in premotor area 6. Research in macaque monkeys has demonstrated that, in contrast to premotor area 6, which is involved in the production of motor actions, area 8A is implicated in the cognitive allocation of attention to stimuli based on instruction cues. The aim of the present study was to elucidate the specific cognitive role of area 8A by examining a unique patient with a lesion restricted to area 8A, i.e. sparing the premotor cortex. This right‐handed male patient underwent neuropsychological assessment and testing on two conditional associative‐learning tasks: the motor hand conditional associative‐learning task (MCALT) assessing the selection of motor actions based on instruction cues and the visual conditional associative‐learning task (VCALT) assessing the selection of visual stimuli based on instruction cues. The patient's performance on the VCALT was significantly impaired compared to control subjects, but performance on the MCALT and on an Eye Movement Control Task was preserved. The present study provides evidence that area 8A is critical for the cognitive process regulating the allocation of attention to different stimuli in the environment, but not in the production of eye movements. These findings enhance understanding of the functional organization of the posterior dorsolateral frontal region in the human brain and suggest a specialized role of area 8A in high‐level cognitive processes. [ABSTRACT FROM AUTHOR]

Introduction: Endothelial dysfunction (ED) promotes the development of atherosclerosis, and studies suggest an association with age-related neurocognitive disorders. It is currently unclear whether ED is also associated with the risk of perioperative neurocognitive disorders. Method: We included 788 participants aged ≥ 65 years of the BioCog study. Patients were scheduled to undergo elective surgery with expected duration > 60 min. Blood was collected before surgery for measurement of 5 biomarkers of ED: asymmetric and symmetric dimethylarginine (ADMA; SDMA), intercellular and vascular adhesion molecule (ICAM-1, VCAM-1), and von Willebrand factor (vWF). Patients were monitored for the occurrence of postoperative delirium (POD) daily until the 7th postoperative day. 537 (68.1%) patients returned for a 3-month follow-up. Post-operative cognitive dysfunction (POCD) was defined from the change in results on a battery of 6 neuropsychological tests between baseline and 3 months, compared to the change in results of a control group during the 3-month interval. The associations of each of the 5 ED biomarkers with POD and POCD respectively were determined using multiple logistic regression analyses with adjustment for age, sex, surgery type, pre-morbid IQ, body mass index, hypertension, diabetes, HbA1C, triglyceride, total and HDL cholesterol. Results: 19.8% of 788 patients developed POD; 10.1% of 537 patients had POCD at 3 months. Concentrations of ED biomarkers were not significantly associated with a POD. A higher VCAM-1 concentration was associated with a reduced POCD risk (adjusted odds ratio 0.55; 95% CI: 0.35–0.86). No further statistically significant results were found. Conclusion: Pre-operative concentrations of ED biomarkers were not associated with POD risk. We unexpectedly found higher VCAM-1 to be associated with a reduced POCD risk. Further studies are needed to evaluate these findings. [ABSTRACT FROM AUTHOR]

White matter microvascular alterations in temporal lobe epilepsy (TLE) may be relevant to acquired neurodegenerative processes and cognitive impairments associated with this condition. We quantified microvascular changes, myelin, axonal, glial and extracellular-matrix labelling in the gyral core and deep temporal lobe white matter regions in surgical resections from 44 TLE patients with or without hippocampal sclerosis. We compared this pathology data with in vivo pre-operative MRI diffusion measurements in co-registered regions and neuropsychological measures of cognitive impairment and decline. In resections, increased arteriolosclerosis was observed in TLE compared to non-epilepsy controls (greater sclerotic index, p < 0.001), independent of age. Microvascular changes included increased vascular densities in some regions but uniformly reduced mean vascular size (quantified with collagen-4, p < 0.05–0.0001), and increased pericyte coverage of small vessels and capillaries particularly in deep white matter (quantified with platelet-derived growth factor receptorβ and smooth muscle actin, p < 0.01) which was more marked the longer the duration of epilepsy (p < 0.05). We noted increased glial numbers (Olig2, Iba1) but reduced myelin (MAG, PLP) in TLE compared to controls, particularly prominent in deep white matter. Gene expression analysis showed a greater reduction of myelination genes in HS than non-HS cases and with age and correlation with diffusion MRI alterations. Glial densities and vascular size were increased with increased MRI diffusivity and vascular density with white matter abnormality quantified using fixel-based analysis. Increased perivascular space was associated with reduced fractional anisotropy as well as age-accelerated cognitive decline prior to surgery (p < 0.05). In summary, likely acquired microangiopathic changes in TLE, including vascular sclerosis, increased pericyte coverage and reduced small vessel size, may indicate a functional alteration in contractility of small vessels and haemodynamics that could impact on tissue perfusion. These morphological features correlate with white matter diffusion MRI alterations and might explain cognitive decline in TLE. [ABSTRACT FROM AUTHOR]

Phenylketonuria, the most common inherited metabolic disease, results from a deficiency of phenylalanine hydroxylase enzyme activity that causes high blood phenylalanine levels. Most adults do not adhere to the gold standard therapy: lifelong treatment with a low‐phenylalanine diet. Elevated and fluctuating phenylalanine levels in untreated adults can cause white matter abnormalities, neurological symptoms, and cognitive dysfunction (executive function). Pegvaliase, a derivative of the phenylalanine ammonia‐lyase enzyme, metabolizes phenylalanine to trans‐cinnamic acid and ammonia, and is approved by the US Food and Drug Administration and European Medicines Agency for subcutaneous administration in adults with phenylketonuria and blood phenylalanine concentrations > 600 μmol/L. In clinical trials, it reduced blood phenylalanine, even in patients consuming an unrestricted diet. We report longitudinal results on the first three such adults, in whom phenylalanine levels were quantified monthly, starting 1 year before pegvaliase administration and continuing through achievement of a pegvaliase response (defined as six consecutive monthly blood phenylalanine concentrations < 360 μmol/L while consuming an unrestricted diet). Brain magnetic resonance imaging (MRI) and neuropsychological assessments were performed before starting therapy and after response was achieved. Our results show that all three patients had significantly reduced white matter hyperintensities on brain MRI and improved executive function on neuropsychological assessment, especially on the Paced Auditory Serial Addition Test, which is known to be very sensitive to white matter functioning. To the best of our knowledge, this is the first report of concomitant improvements in cognitive performance and white matter damage after a pharmacological intervention to normalize phenylalanine levels in adults with phenylketonuria consuming an unrestricted diet. [ABSTRACT FROM AUTHOR]

Background: Sanda, a martial art that primarily involves punching, kicking, and throwing techniques, requires athletes to maintain high levels of concentration during combat. Sanda principally involves striking the opponent to secure victory, with trauma frequently occurring to the head; however, it remains unclear whether prolonged training enhances or impairs the athletes' attentional capacities. This study aimed to investigate the impact of Sanda training on athletes' attention by employing attention network tests. Methods: A retrospective analysis was conducted on 37 professional Sanda athletes from a certain sports academy; 38 college students from the same institution majoring in physical education were recruited as the control group. Control participants had no prior experience in Sanda training, and the Sanda and control groups were matched in terms of sex, age, and education level. The Attention Network Test (ANT) was administered to both groups to compare differences in efficiency across the alerting, orienting, and executive control networks. Results: Compared to the control group, the Sanda athletes exhibited significantly higher executive control network efficiency values and executive control network efficiency ratios (P < 0.05). There were no significant differences between the Sanda group and the control group regarding the efficiency values of the alerting and orienting networks (P > 0.05). Additionally, total accuracy and total reaction time between the Sanda athletes and control participants showed no statistically significant differences (P > 0.05). Conclusion: Sanda practice has detrimental effects on attention, including a decrease in the efficiency of the executive control network and a prolongation of the total reaction time. Therefore, athletes should improve attention training and use head protection to prevent frequent head impacts during training. [ABSTRACT FROM AUTHOR]

Introduction: Research has shown that speech analysis demonstrates sensitivity in detecting early Alzheimer's disease (AD), but the relation between linguistic features and cognitive tests or biomarkers remains unclear. This study aimed to investigate how linguistic features help identify cognitive impairments in patients in the early stages of AD. Method: This study analyzed connected speech from 80 participants and categorized the participants into early-AD and normal control (NC) groups. The participants underwent amyloid-β positron emission tomography scans, brain magnetic resonance imaging, and comprehensive neuropsychological testing. Participants' speech data from a picture description task were examined. A total of 15 linguistic features were analyzed to classify groups and predict cognitive performance. Results: We found notable linguistic differences between the early-AD and NC groups in lexical diversity, syntactic complexity, and language disfluency. Using machine learning classifiers (SVM, KNN, and RF), we achieved up to 88% accuracy in distinguishing early-AD patients from normal controls, with mean length of utterance (MLU) and long pauses ratio (LPR) serving as core linguistic indicators. Moreover, the integration of linguistic indicators with biomarkers significantly improved predictive accuracy for AD. Regression analysis also highlighted crucial linguistic features, such as MLU, LPR, Type-to-Token ratio (TTR), and passive construction ratio (PCR), which were sensitive to changes in cognitive function. Conclusion: Findings support the efficacy of linguistic analysis as a screening tool for the early detection of AD and the assessment of subtle cognitive decline. Integrating linguistic features with biomarkers significantly improved diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: Detecting invalid cognitive performance is an important clinical challenge in neuropsychological assessment. The aim of this study was to explore behavior and eye-fixations responses during the performance of a computerized version of the Test of Memory Malingering (TOMM-C) under standard vs. feigning conditions. Participants and methods: TOMM-C with eye-tracking recording was performed by 60 healthy individuals (31 with standard instruction - SI; and 29 were instructed to feign memory impairment: 21 Naïve Simulators - NS and 8 Coached Simulators - CS) and 14 patients with Multiple Sclerosis (MS) and memory complaints performed. Number of correct responses, response time, number of fixations, and fixation time in old vs. new stimuli were recorded. Nonparametric tests were applied for group comparison. Results: NS produced fewer correct responses and had longer response times in comparison to SI on all three trials. SI showed more fixations and longer fixation time on previously presented stimuli (i.e., familiarity preference) specially on Trial 1, whereas NS had more fixations and longer fixation time on new stimuli (i.e., novelty preference) specially in the Retention trial. MS patients produced longer response time and had a different fixation pattern than SI subjects. No behavioral or oculomotor difference was observed between NS and CS. Conclusion: Healthy simulators have a distinct behavioral and eye-fixation response pattern, reflecting a novelty preference. Oculomotor measures may be useful to detect exaggeration or fabrication of cognitive dysfunction. Though, its application in clinical populations may be limited. [ABSTRACT FROM AUTHOR]

Between 2.5% and 28% of people infected with SARS-CoV-2 suffer long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy control subjects chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with long COVID assessed by Addenbrooke's Cognitive Examination-III screening test [overall cognitive level (OCLz) = −0.39 ± 0.12] was significantly below the infection recovered-controls (OCLz = +0.32 ± 0.16, P < 0.01). We observed that 48% of patients with long COVID had episodic memory deficit, with 27% also with impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy and higher radial diffusivity were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions. [ABSTRACT FROM AUTHOR]

Several studies suggest that a valuable tool to examine linguistic skills in communication disorders is offered by procedures of narrative discourse assessment. Following this line of research, we present an exploratory study aimed to investigate storytelling abilities of autistic children to better define the characteristics of their story production. Participants included 41 autistic children and 41 children with typical development aged between 7.02 and 11.03 years matched on age, gender, level of formal education, intelligence quotient, working memory, attention skills, theory of mind, and phonological short-term memory. Narrative production was assessed by analysing the language samples obtained through the "Nest Story" description task. A multilevel analysis including micro- and macro-linguistic variables was adopted for narrative assessment. Group differences emerged on both micro- and macro-linguistic dimensions: autistic children produced narratives with more phonological errors and semantic paraphasias (microlinguistic variables) as well as more errors of global coherence and a fewer number of visible events and inferred events (macrolinguistic variables) than the control group.This study shows that even autistic children with adequate cognitive skills display several limitations in their narrative competence and that such weaknesses affect both micro- and macrolinguistic aspects of story production. [ABSTRACT FROM AUTHOR]

Background Aims Methods & Procedures Outcomes & Results Conclusions & Implications WHAT THIS PAPER ADDS What is already known on the subject What this paper adds to the existing knowledge What are the potential or actual clinical implications of this work? Although considerable research has been conducted on post‐COVID‐19 syndrome (PCS), cognitive symptoms, particularly those related to language, are still not well understood.To provide a detailed quantitative and qualitative analysis of language performance in PCS patients using a comprehensive set of semantic and verbal production tasks.The study involved 195 PCS patients aged 26–64 years and 50 healthy controls aged 25–61 years. Participants were assessed using two semantic tasks, three naming tasks and four types of verbal fluency tasks, designed to evaluate different aspects of language processing.PCS patients demonstrated significantly poorer performance compared with controls across all verbal fluency tasks. This was evident in both the total number of words generated and their types, with patients tending to choose more easily accessible words. In naming tasks, the pattern of errors was similar in both groups, although patients showed a higher number of non‐responses and made more errors, reflecting difficulties in word retrieval. The analysis highlighted the impact of factors such as stimulus availability, educational level and cognitive reserve on performance. Notably, younger patients performed worse than older, a paradoxical trend also observed in previous research.These findings reveal significant word retrieval difficulties in PCS patients, suggesting that cognitive impairment related to language may be more pronounced than previously understood. The results underscore the need for a thorough evaluation of language functions in PCS patients and the development of more targeted and individualized language rehabilitation strategies to address these specific challenges. Studies on the cognitive characteristics of CPS have focused mainly on broad‐spectrum neuropsychological assessments covering all cognitive functions. However, there are very few studies analysing oral production with specific lexical and semantic system tasks. Furthermore, no work has specifically included tasks assessing semantic processing or conducted qualitative analyses of the psycholinguistic variables affecting performance. Such analyses could undoubtedly help clarify the nature of the language impairments in patients with PCS. This study explores in depth the evaluation and analysis of the oral production of patients with PCS using several lexical and semantic tasks. In addition, psycholinguistic variables are analysed that could undoubtedly help clarify the nature of the language impairments in patients with PCS. The study allows the identification of specific lexical–semantic deficits in the spoken language in patients with this PCS. A more detailed assessment of the oral language of these patients, keeping in mind the psycholinguistic variables that may affect the performance, will facilitate the design of more efficient and individualized rehabilitation programmes. [ABSTRACT FROM AUTHOR]

Background: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long‐term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA‐H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA‐H. Methods: The current study investigated the performance of the MoCA‐H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA‐H. Results: In a multiple regression model accounting for age, sex, and education, cultural–linguistic group accounted for 6.89% of variance in the total MoCA‐H score. Differences between languages in mean score of up to 2.6 points were observed. Conclusions: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA‐H such that optimal performance cut points for identification of cognitive impairment derived in English‐speaking populations are likely inappropriate for use in non‐English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA‐H. [ABSTRACT FROM AUTHOR]

Purpose: People with Parkinson's disease (PwP) typically experience impairments in vowel articulation; however, less is known about how this measure varies with speech task type and clinical characteristics such as cognitive impairment. We characterized vowel space in PwP with and without mild cognitive impairment (MCI) comparing performance across phonation, reading, and picture description tasks. We evaluated associations between vowel space and cognitive impairment, as well as motor symptom severity to elucidate the factors contributing to variability in this acoustic measure. Method: PwP (n = 48) and age-matched controls (n = 15) performed sustained phonation of corner vowels, a reading passage, and a picture description task (Cookie Theft picture). PwP participants were classified as with normal cognition (PD-NC) or MCI (PD-MCI), and motor symptoms were assessed using the Movement Disorders Society Unified Parkingson's Disease Rating Scale Part III (MDSUPDRS Part III). Vowel articulation index (VAI) for each task and mean difference in VAI between tasks was compared between the groups using linear mixed models adjusted for age, sex, and education. The impact of motor severity was assessed by additionally adjusting the model for MDS-UPDRS Part III score. Results: In the adjusted mixed model, mean VAI was significantly lower in the PD-MCI group compared to the PD-NC group for all tasks. Within participants, adjusted mean differences demonstrated that all groups declined in VAI when sustained phonation was compared to either reading or picture description tasks. Adjustment for MDS-UPDRS Part III did not alter the results, suggesting no major association of motor impairment with vowel space variability within or between individuals or groups. Conclusions: Variability in vowel space is impacted by cognitive impairment and speech task in PwP. These findings are relevant to the further development of speech markers in PwP and other neurogenerative diseases that impact both cognitive and motor functions. [ABSTRACT FROM AUTHOR]

Objectives To investigate the determinants of resilience phenotype in aging, operationalized as the maintenance of cognitive, physical, and psychological health in very old individuals (80+), we investigated the structure and interrelated impact of the main resilience-enhancing factors, which are usually studied in separate research fields. Methods Participants were older adults without dementia recruited for the fifth wave of the InveCe.Ab population-based cohort study (aged 83–87 years). Multidimensional evaluation comprised blood sampling, social and lifestyle survey, and geriatric and neuropsychological assessment. We classified resilient individuals as displaying normal cognition, functional independence, and mental health. First, we performed exploratory factor analysis (EFA) to examine the underlying structure of the relevant cognitive, lifestyle, physical, and psychological resilience-enhancing factors. The factors obtained were included as predictors of the resilience phenotype in the logistic regression model, controlling for sociodemographic and cumulative exposure to physical and psychosocial stressors, including COVID-19 infection. Results Among the 404 enrolled participants, 153 (38%) exhibited the resilience phenotype. EFA resulted in the identification of six factors (59% of variance): cognitive reserve, affective reserve, insecure attachment, current lifestyle, physical reserve, and avoidant attachment. Among these factors, cognitive reserve, affective reserve, and current lifestyle significantly and independently predicted resilience status, controlling for cumulative exposure to age-related stressors and COVID-19 infection. Discussion Our findings showed that, even in very old age, both early and late life modifiable factors affect individuals' ability to adapt to the aging process, thus confirming the importance of a life-course approach to improve health outcomes in the aged population. Clinical Trials Registration Number NCT01345110 [ABSTRACT FROM AUTHOR]

Few confrontation naming tests are designed for pediatric populations. The Children's Visual Naming Test (cVNT; Hamberger et al., 2018) was developed to fill this gap. No independent studies using cVNT with clinical populations have been published to date. We aimed to characterize cVNT performance in a clinical sample and analyze the relationship between cVNT and other neuropsychological tests/constructs. Retrospective data was collected from 126 consecutively referred youth, aged 6–15 years (M = 11.28, SD = 2.80), who underwent clinical neuropsychological evaluation through an academic medical center. Naming under 2 seconds (cVNT-L2) and the summary scores (cVNT-SUM) were lower compared to the normative sample (cVNT-L2: Mz =-1.30, SD = 2.17; cVNT-SUM: Mz =-1.26, SD = 2.15). cVNT was related to core verbal abilities, processing speed, and response inhibition. cVNT-L2 and cVNT-SUM, but not naming under 20 seconds, were related to overall intellectual functioning, verbal fluency, and working memory, and were associated with overall attention, processing speed, executive functions, and verbal fluency. The cVNT provides assessment of confrontation naming without downward extension in pediatric neuropsychological assessment. Importantly, cVNT offers variables of higher fidelity to the neural process of naming than previous measures. cVNT may be associated with commonly assessed neuropsychological functions, providing a rapidly effective tool for screening batteries or improving efficiency. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein E (APOE) genotypes have been suggested to influence cognitive impairment and clinical onset in presenilin-1 (PSEN1) E280A carriers for autosomal dominant Alzheimer's disease (ADAD). Less is known about their impact on the trajectory of biomarker changes. Neurofilament light chain (NfL), a marker of neurodegeneration, begins to accumulate in plasma about 20 years prior to the clinical onset of ADAD. In this study we investigated the impact of APOE ε4 and ε2 variants on age-related plasma NfL increases and cognition in PSEN1 E280A mutation carriers. Methods: We analyzed cross-sectional data from PSEN1 E280A mutation carriers and non-carriers recruited from the Alzheimer's Prevention Initiative Registry of ADAD. All participants over 18 years with available APOE genotype, plasma NfL, and neuropsychological evaluation were included in this study. APOE genotypes and plasma NfL concentrations were characterized for each participant. Cubic spline models using a Hamiltonian Markov chain Monte Carlo method were used to characterize the respective impact of at least one APOE ε4 or ε2 allele on age-related log-transformed plasma NfL increases. Linear regression models were estimated to explore the impact of APOE ε4 and ε2 variants and plasma NfL on a composite cognitive test score in the ADAD mutation carrier and non-carrier groups. Results: Analyses included 788 PSEN1 E280A mutation carriers (169 APOE ε4 + , 114 ε2 +) and 650 mutation non-carriers (165 APOE ε4 + , 80 ε2 +), aged 18–75 years. APOE ε4 allele carriers were distinguished from ε4 non-carriers by greater age-related NfL elevations in the ADAD mutation carrier group, beginning about three years after the mutation carriers' estimated median age at mild cognitive impairment onset. APOE ε2 allele carriers had lower plasma NfL concentrations than ε2 non-carriers in both the ADAD mutation carrier and non-carrier groups, unrelated to age, and an attenuated relationship between higher NfL levels on cognitive decline in the ADAD mutation carrier group. Conclusions: APOE ε4 accelerates age-related plasma NfL increases and APOE ε2 attenuates the relationship between higher plasma NfL levels and cognitive decline in ADAD. NfL may be a useful biomarker to assess clinical efficacy of APOE-modifying drugs with the potential to help in the treatment and prevention of ADAD. [ABSTRACT FROM AUTHOR]

Background: Enhancing long-term support for post-stroke cognitive impairment is a top research priority. Addressing current gaps in UK post-stroke cognitive care provision requires a pragmatic and scalable intervention that can be integrated within the existing stroke care pathway. This study aimed to develop consensus on an initial set of core features for a UK-based monitoring and psychoeducational intervention for cognitive changes after stroke. Methods: An expert panel of UK healthcare professionals and researchers participated in an online modified Delphi survey. Candidate intervention features were identified from clinical guidelines, existing literature, research team/collaborator expertise, and PPI group lived experience. Survey participants indicated whether they agreed/disagreed/had no opinion about including each candidate feature in the intervention and free-text responses were invited. We analysed responses for consensus (≥ 75% agreement) using descriptive statistics, with items not reaching consensus carried into subsequent rounds. Template analysis was used to identify similarities/differences in viewpoints for items that did not reach consensus. Results: Three survey rounds were completed by 36, 29 and 26 participants, respectively. Participants agreed reviews should include a stroke-specific cognitive screen (97% agree) and assessment of other psychological changes (low mood, anxiety, fatigue: 94%, 90%, 89% agree, respectively). They agreed stroke survivors should be offered at least one review, regardless of their cognitive profile in hospital. They agreed on the importance of various cognition-focused psychoeducation topics, and formal (100% agree) and informal (79% agree) training for those conducting reviews. Consensus was not reached on the review mode (in person/remote options: 67% agree), offering reviews one-year post-discharge to patients without acute cognitive impairments (68% disagree), or including a dementia screen (63% disagree) and/or neuropsychological assessment battery (58% disagree). However, there were similarities in participant viewpoints. For example, participants emphasised the importance of onwards referral where clinically indicated. Conclusions: The UK-based post-stroke monitoring and psychoeducation intervention was originally conceptualised as a cognitive care pathway, but expert participants agreed on the importance of simultaneously addressing related psychological changes (e.g. low mood, anxiety). There was clear consensus on a minimum set of intervention features. Recommendations outlined here may usefully inform local service improvements. [ABSTRACT FROM AUTHOR]

Background: Aging is a process inherent to the human condition that is characterized by various biological, psychological, and social changes that can lead to certain mental health problems. Objective: This study aimed to understand and characterize how biological, psychological, and social factors influence mental health symptoms and neuropsychological function in the aging process. Methods: A sample consisting of 616 participants (73.8% female) aged between 50 and 90 years, (mean [SD]: 69.6 [17.2] years). Data collection involved a neuropsychological assessment carried out by a psychologist in a clinical interview session and the self-completion of a questionnaire. Results: Regression models revealed that depressive symptoms are explained by anxiety, psychological and environmental quality of life, and sleep habits. Anxiety symptoms are explained by depression, physical quality of life, and sleep habits. Statistically significant differences were identified between participants with and without anxiety in neuropsychological terms at the level of agnosia and praxis. Statistically significant differences were identified between participants with and without depression in neuropsychological terms at the level of memory, language, agnosia and praxis, and executive function (eg, prefrontal tests). Conclusions: Depression and anxiety symptoms are associated and could negatively influence the aging process. Aging should be understood in an ecological way taking into account the action of biological, psychological, social, and environmental factors, as well as the relationship and influence between the different levels and factors. This knowledge is important for diagnosis, for clinical practice, and for the development and definition of public policies to promote healthy aging. [ABSTRACT FROM AUTHOR]

The article reviews the expanding clinical spectrum of anti-GQ1b antibody syndrome, emphasizing its association with various autoimmune peripheral neuropathies, particularly highlighting Miller Fisher syndrome (MFS). Topics discussed include the overlap of anti-GQ1b syndrome with conditions like Guillain-Barré syndrome, atypical presentations without ophthalmoplegia, and the role of intravenous immunoglobulin (IVIG) in treatment.

Background: Integrating scores from multiple cognitive tests into a single cognitive composite has been shown to improve sensitivity to detect AD-related cognitive impairment. However, existing composites have little sensitivity to amyloid-β status (Aβ +/–) in preclinical AD. Objective: Evaluate whether a data-driven approach for deriving cognitive composites can improve the sensitivity to detect Aβ status among cognitively unimpaired (CU) individuals compared to existing cognitive composites. Methods: Based on the data from the Anti-Amyloid Treatment in the Asymptomatic Alzheimer's Disease (A4) study, a novel composite, the Data-driven Preclinical Alzheimer's Cognitive Composite (D-PACC), was developed based on test scores and response durations selected using a machine learning algorithm from the Cogstate Brief Battery (CBB). The D-PACC was then compared with conventional composites in the follow-up A4 visits and in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Result: The D-PACC showed a comparable or significantly higher ability to discriminate Aβ status [median Cohen's d = 0.172] than existing composites at the A4 baseline visit, with similar results at the second visit. The D-PACC demonstrated the most consistent sensitivity to Aβ status in both A4 and ADNI datasets. Conclusions: The D-PACC showed similar or improved sensitivity when screening for Aβ+ in CU populations compared to existing composites but with higher consistency across studies. [ABSTRACT FROM AUTHOR]

Patients with spina bifida (SB), or spinal dysraphism, have several brain anomalies that influence daily life functioning. In this article we will explain how these can be investigated and what the relevance is for the care for (young) adults with SB. Predictors for problems with performance are: the level of the lesion, having hydrocephalus, having ventriculo-peritoneal draindysfunction, having seizures, and social economic status. In the daily practice you could notice that patients with SB are verbally strong, but still can get into trouble due to a lack of executive functions. Planning, handling appointments, compliance to medical advice and medication, etcetera, are more difficult for these patients. This worsens as the patient ages. It helps to offer information in a dosed manner. Use of short sentences and repetition are important. The rehabilitation team can also help, e.g. by testing neuropsychological functions and/or learning compensatory strategies. [ABSTRACT FROM AUTHOR]