Lower Executive Function Scores Research Articles

The Relationship Between Executive Functioning and Narrative Language Abilities in Aphasia.

Although individuals with aphasia commonly exhibit challenges in executive functioning (EF) and spoken discourse, there is limited research exploring connections between these abilities within this specific population. Therefore, this study investigated the relationship between verbal and nonverbal EF and narrative productions in aphasia using a multilevel linguistic approach. Participants included 22 persons with aphasia (PWA) and 24 age- and education-matched, neurologically healthy controls (NHC). All participants completed assessments for EF and a story retelling task. Narrative samples were analyzed for microlinguistic (productivity, lexical and syntactic features, semantic content, word and sentence errors) and macrolinguistic (coherence, informational content, organization, and language use) characteristics. Correlational analyses were employed to explore the relationships among narrative variables. EF factors, extracted from principal component analysis, were used as predictive variables in hierarchical stepwise regression analyses to evaluate their role in predicting narrative performances of PWA and NHC. Relative to NHC, PWA exhibited impaired narrative performance affecting both microlinguistic and macrolinguistic levels. Breakdowns at the structural level (i.e., reduced productivity, syntax, lexical retrieval, and diversity) correlated with impaired story completeness, organization, and connectedness; this relationship was more prominent for PWA. Three EF factors representing (1) verbal EF, (2) verbal and nonverbal fluency, and (3) nonverbal EF were extracted. Factors 1 and 2 largely predicted narrative performance, whereas Factor 3 (i.e., nonverbal EF) contributed prominently to predicting macrolinguistic discourse performance in both groups although accounting for less variance in the data. Overall, lower EF scores, particularly verbal EF variables, predicted poor narrative performance in both groups. Our results indicate that both linguistic and extralinguistic cognitive abilities play a role in story retelling performances among PWA. Notably, both verbal and nonverbal EF skills were found to be correlated with narrative abilities. However, the extent of their contributions varied depending on the discourse levels assessed. These findings provide a significant contribution to our understanding of the cognitive factors associated with breakdowns in discourse among PWA and highlight the importance of comprehensive assessment of EF and discourse within this population. https://doi.org/10.23641/asha.26485627.

Enlarged perivascular space burden predicts declines in cognitive and functional performance

IntroductionWe evaluated the relationship between baseline enlarged perivascular space (ePVS) burden and later cognitive decline. Methods83 community-dwelling, older adults (aged 56–86) completed three annual cognitive assessments that included the Clinical Dementia Rating (CDR®) Dementia Staging Instrument Sum of Boxes (CDR-SB) and composite measures of executive function and episodic memory. An MRI scan at baseline was used to count ePVS in the basal ganglia and centrum semiovale. Mixed effects models were run with ePVS as the predictor variable and cognitive measures as the dependent variable. Covariates included age, sex, education, cerebral small vessel disease (cSVD) risk factors, and cSVD neuroimaging biomarkers. ResultsAt baseline, high basal ganglia ePVS counts were associated with lower executive function scores and episodic memory scores. Moreover, baseline basal ganglia ePVS predicted worse longitudinal CDR-SB scores over the study period. DiscussionBasal ganglia ePVS burden is a promising biomarker for cSVD-related cognitive and functional decline.

Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease

Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population. To investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience. This single-center, population-based case-control study was conducted at the University Children's Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023. Patients with cCHD who underwent infant open heart surgery. Physiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire. The study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (β, 0.28 [95% CI, 0.12 to 0.43]; P < .001) and lower EF scores (β, -0.36 [95% CI, -0.49 to -0.23]; P < .001) than controls. There was no group difference in self-reported resilience (β, -0.04 [95% CI, -0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (β, -0.65 [95% CI, -1.15 to -0.15]; P = .01). The contrast effects were not significant in patients (β, -0.21 [95% CI, -0.43 to -0.00]; P = .06) and controls (β, 0.09 [95% CI, -0.11 to 0.30]; P = .38). This case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment.

637-P: Sex-Specific Associations between Fatty Acid–Derived Oxylipins and Executive Function in T2DM

T2DM increases the risk of cognitive decline, especially in women. Sex-specific associations between lipids and cognition have been reported, though underlying mechanisms remain unclear. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been linked to both T2DM and cognitive dysfunction. CYP450s convert long-chain polyunsaturated fatty acids into epoxides which are anti-inflammatory and help resolve inflammation, however sEH metabolizes these into inactive or cytotoxic diols, limiting their benefits. We hypothesized that oxylipin epoxides and diols of arachidonic acid (AA) and docosahexaenoic acid (DHA) would be associated with cognition in people with T2DM, particularly in women. Women and men with T2DM were recruited as part of the study. Twenty-two fasting serum free oxylipins were quantified by ultra-high performance liquid chromatography tandem mass spectrometry. Executive function was assessed using a composite z-score from the following tests: Stroop Colour-Word Interference Victoria Version, FAS Verbal Fluency, Digit Symbol Substitution, and Trails Making Test Part B. All analyses controlled for age, sex, BMI, HbA1c and years of education. Among 72 individuals with T2DM (mean age 61.8±9.2, mean HbA1c 7.4±0.1%, 53% women), demographic characteristics, oxylipin concentrations and cognitive performance did not differ between women and men. Some CYP450-derived epoxides of DHA and AA were associated with lower executive function scores in women, but with higher scores in men. Epoxide × sex interactions were found for 3 of 4 DHA epoxides (16(17) [F=20.2, p&amp;lt;0.001]; 13(14) [F=8.5, p=0.005]; and 10(11) [F=7.4, p=0.009]), and for the 14(15) AA epoxide [F=3.9, p&amp;lt;0.05]). Circulating concentrations of the corresponding diols were not associated with executive function. These associations between epoxides and executive function suggest a sex difference in the relevance of the CYP450 pathway to cognitive performance in T2DM. Disclosure S.Ryoo: None. B.R.Shah: None. J.Gilbert: Speaker's Bureau; Abbott, AstraZeneca, Amgen Canada, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Sanofi, Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Novo Nordisk Canada Inc. A.Assal: None. I.Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd./Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk. A.Taha: None. W.Swardfager: None. N.Z.Anita: None. C.Major-orfao: None. W.Lin: None. S.Noor: None. F.Kwan: None. K.L.Lanctôt: Consultant; Exciva, GW Pharmaceuticals, ICG Farma, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sumitomo Pharma Co. Ltd., Other Relationship; BioXcel, Cerevel Therapeutics, H Lundbeck A/S. N.Herrmann: None. P.Oh: Advisory Panel; Novartis Canada. Funding Canadian Institutes of Health Research; Banting &amp; Best Diabetes Centre; National Institute of Diabetes and Digestive and Kidney Diseases

Validation of the European Cross-Cultural Neuropsychological Test Battery (CNTB) for the assessment of mild cognitive impairment due to Alzheimer's disease and Parkinson's disease.

The Cross-Cultural Neuropsychological Test Battery (CNTB) is a novel test battery specifically designed to reduce the impact of multiculturality in cognitive assessment. We aimed to validate the CNTB in Spaniards in patients with Alzheimer's disease (AD), including patients at mild cognitive impairment (MCI) and mild dementia stages, and Parkinson's disease with MCI (PD-MCI). Thirty patients with AD-MCI, 30 with AD-dementia (AD-D), and 30 with PD-MCI were recruited. Each clinical group was compared against a healthy control group (HC) with no differences in sex, age, or years of education. Intergroup comparisons, ROC analysis, and cut-off scores were calculated. AD-MCI scored lower than HC in those subtests associated with episodic memory and verbal fluency. AD-D also showed lower scores in executive functions and visuospatial tests. Effect sizes for all the subtests were large. PD-MCI showed lower performance than HC in memory and executive functions, particularly on error scores, with large effect sizes. Comparing AD-MCI and PD-MCI, AD-MCI had lower memory scores, while PD-MCI showed the worst performance in executive functions. CNTB showed appropriate convergent validity with standardized neuropsychological tests measuring the same cognitive domains. We obtained similar cut-off scores to previous studies performed in other populations. The CNTB showed appropriate diagnostic properties in AD and PD, including those stages with mild cognitive impairment. This supports the utility of the CNTB for the early detection of cognitive impairment in AD and PD.

Age at first exposure to antibiotics and neurodevelopmental outcomes in childhood

RationaleViral illnesses in children are common and are frequently treated with antibiotic medication. Antibiotics reduce the diversity and composition of the gut microbiota, leading to poor developmental outcomes.ObjectivesTo investigate the relationship between age at first exposure to antibiotics and cognitive and behavioural development at 4.5 years while controlling for multiple confounders, including otitis media.MethodsStudy participants were 5589 children enrolled in the broadly generalisable Growing Up in New Zealand cohort study, with antibiotic exposure data, maternal antenatal information, and age 4.5-year behaviour and cognitive outcome data. Children were categorised as first exposed to antibiotics according to the following mutually exclusive ages: 0–2 months; 3–5 months; 6–8 months; 9–11 months; 12–54 months or not exposed by 54 months. Developmental outcome measures included the Strengths and Difficulties Questionnaire, Luria hand clap task, and the Peabody Picture Vocabulary Test-III.ResultsIn univariate analysis, there was an evident dose–response relationship where earlier exposure to antibiotics in the first year of life was associated with behavioural difficulties, lower executive function scores, and lower receptive language ability. After adjusting for confounders, pairwise comparisons showed that first antibiotic exposure between birth and 3 months or between 6 and 9 months was associated with lower receptive vocabulary. Antibiotic exposure at any age prior to 12 months was associated with increases in behavioural difficulties scores at 4.5 years.ConclusionsFollowing adjustment for socioeconomic factors and otitis media, there is evidence that antibiotic exposure during potentially sensitive windows of development is associated with receptive language and behaviour later in childhood.

THE EFFECT OF ACTIGRAPHY MEASURED PHYSICAL ACTIVITY ON EXECUTIVE FUNCTION IN OLDER ADULTS

Abstract Executive function (i.e., decision making, self-control, planning) is important for facilitating independent living in older adults. Physical activity may preserve executive function, but previous research has demonstrated sex differences in both physical activity and executive function among older adults. Few studies have investigated sex differences in the association between the two. We examined associations between objectively measured physical activity and executive function with attention to sex differences. We recruited N = 204 participants (Mage =71, SD=6.36; 57% women) with (n=47) and without (n=157) Alzheimer’s disease from the University of Kansas Alzheimer’s Disease Research Center. We used wrist-worn accelerometers (Actigraph GT9X) to measure physical activity 24 hours a day for 7 days in a free-living environment. We categorized physical activity as moderate to vigorous (MVPA) based on the Montoye (2020) Adult Vector Magnitude cut-points. We evaluated sex differences in the association between executive function and MVPA using multiple regression with an interaction term, adjusting for age, education, and dementia status. We used a composite score to combine tests of executive function (Digit Symbol Substitution, Stroop Interference, Trail making Part B, and Verbal Fluency). Results indicated, older age and lower education were associated with lower executive function scores (β=-2.12, p &amp;lt; 0.001; B=2.13, p &amp;lt; .05). In contrast to previous research, we did not find evidence for sex differences in the MVPA, executive function, nor the association between the two in our sample. Future research should investigate whether individualized exercise-based interventions and treatment between men and women may differentially benefit cognitive function.

Videofluoroscopic Swallowing Study Features and Resting-State Functional MRI Brain Activity for Assessing Swallowing Differences in Patients with Mild Cognitive Impairment and Risk of Dysphagia.

To examine the swallowing characteristics in patients with mild cognitive impairment (MCI) and dysphagia risk and explore brain activity changes using regional homogeneity (ReHo) with resting-state functional magnetic resonance imaging (rs-fMRI). We included 28 patients with MCI and dysphagia risk and 17 age-matched older adults. All participants underwent neurological, cognitive examinations, and a videofluoroscopic swallowing study (VFSS). We quantitatively analyzed the VFSS temporal and kinetic parameters of the 5- and 10-mL swallows. The participants underwent rs-fMRI, and the ReHo values were calculated. Differences in the swallowing physiology and rs-fMRI findings between participants with MCI and controls were analyzed. Correlation analyses were also conducted. Compared to the control group, patients with MCI and dysphagia risk had lower global cognition scores, longer 10-mL oral transit times (OTTs), and lower executive function scores. ReHo in the bilateral inferior occipital lobes (IOLs) and left prefrontal lobe decreased in patients with MCI and dysphagia risk compared to participants in the control group. In patients with MCI, the 10-mL OTT was negatively correlated with the Montreal Cognitive Assessment (MoCA) score, and the ReHo values were positive correlated with quantitative temporal swallowing measurements using canonical correlation analysis. Mediation analysis revealed that the ReHo values of the left and right IOL acted as significant mediators between the MoCA score and the 10-mL OTT. We found that individuals with MCI and dysphagia risk, verified by reduced MoCA scores, demonstrated prolonged OTTs when swallowing larger boluses compared with age-matched controls. There was a negative correlation between the MoCA score and 10-mL OTT, which was partially mediated by the left and right IOL ReHo values, suggesting that functional changes in the IOLs and left prefrontal lobe associated with oral swallowing status and cognitive level in individuals with MCI and dysphagia risk.

Retinal microvascular impairment in Parkinson's disease with cognitive dysfunction

BackgroundParkinson's disease (PD) is associated with structural alterations of the retina. However, it remains unknown whether these changes are present in PD with mild cognitive impairment (MCI). The purpose of the study was to evaluate the retinal microvasculature using optical coherence tomography angiography (OCTA) to assess possible retinal microvascular impairments associated with PD and PD with MCI. MethodsThis study included 83 eyes of 45 PD patients and 83 eyes of 42 healthy controls. All subjects underwent complete neurological and ophthalmological examinations before measurements. Cognitive function was also measured in PD patients. Retinal microvasculature was evaluated with OCTA. Vessel density in the superficial capillary plexus (SRCP), deep capillary plexus (DRCP), and radial peripapillary capillaries (RPC) and intraretinal layer thickness in the peripapillary retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) were analysed. Correlations between vessel density and cognitive function were analysed in the PD group. ResultsParafoveal vessel density in the SRCP and DRCP were lower in the eyes of PD patients than healthy controls (P < 0.05). However, there were no significant differences in the RPC (P = 0.120), RNFL (P = 0.303) or GCC (P = 0.375) between PD patients and healthy controls. Lower executive function scores were associated with lower vessel density in the DRCP of PD patients (P < 0.05, 95% CI [0.133,1.342]). ConclusionOCTA revealed lower macular microvascular density in PD patients and microvascular impairments in the deep retinal capillary layer in PD patients with executive dysfunction. These parameters might have potential utility as early disease diagnostic biomarkers.

Association Between Late-Life Neuropsychiatric Symptoms and Cognitive Decline in Relation to White Matter Hyperintensities and Amyloid Burden.

Neuropsychiatric symptoms (NPS) among cognitively normal older adults are increasingly recognized as risk factors for cognitive decline and impairment. However, the underlying mechanisms remain unclear. To examine whether biomarkers of Alzheimer's disease (amyloid burden) and cerebrovascular disease (white matter hyperintensity (WMH) volume) modify the association between NPS and cognitive decline among cognitively unimpaired older adults. Analyses included 193 cognitively unimpaired participants (M age = 70 years) from the BIOCARD study, including 148 with PET amyloid and WMH biomarker data. NPS were measured with Neuropsychiatric Inventory and Geriatric Depression Scale scores. Linear mixed effects models were used to examine the association between baseline NPS and longitudinal cognitive trajectories (M follow-up = 3.05 years), using separate models for global, episodic memory, and executive function cognitive composite scores. In a subset of individuals with biomarker data, we evaluated whether WMH or cortical amyloid burden modified the relationship between NPS and cognitive change (as indicated by the NPS×biomarker×time interactions). Higher baseline NPS were associated with lower executive function scores, but not a faster rate of decline in executive function. NPS symptoms were unrelated to the global or episodic memory composite scores, and there was little evidence of a relationship between NPS symptoms and cognitive change over time. The associations between NPS and cognitive decline did not differ by amyloid or WMH burden, and NPS were unrelated to amyloid and WMH burden. These results suggest that the effect of neuropsychiatric symptoms on executive dysfunction may occur through mechanisms outside of amyloid and cerebrovascular disease.

MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium.

To evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function. Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years). Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values<0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p=0.0026). mFW is a sensitive biomarker of cognitive decline, providing a strong clinical rational for its use as a marker of white matter (WM) injury in multi-site observational studies and clinical trials of vascular cognitive impairment and dementia (VCID).

Developmental Consequences of Early Life Stress on Risk for Psychopathology: Longitudinal Associations with Children's Multisystem Physiological Regulation and Executive Functioning.

The etiology of psychopathology is multifaceted and warrants consideration of factors at multiple levels and across developmental time. Although experiences of adversity in early life have been associated with increased risk of developing psychopathology, pathways toward maladaptation or resilience are complex and depend upon a variety of factors, including individuals' physiological regulation and cognitive functioning. Therefore, in a longitudinal cohort of 113 mother-child dyads, we explored associations from early adverse experiences to physiological co-regulation across multiple systems and subsequent variations in executive functioning. Latent profile analysis derived multisystem profiles based on children's heart rate, respiratory sinus arrhythmia, pre-ejection period, and cortisol measured during periods of rest and reactivity throughout a developmentally challenging protocol. Three distinct profiles of multisystem regulation emerged: heightened multisystem baseline activity (Anticipatory Arousal/ANS Responder), typically adaptive patterns across all systems (Active Copers/Mobilizers) and heightened HPA axis activity (HPA Axis Responders). Path models revealed that children exposed to adversity before 18-months were more likely to evidence an Anticipatory Arousal/ANS Responders response at 36-months, and children in this profile had lower executive functioning scores than the Active Copers/Mobilizers. In sum, these findings provide important information about potential physiological associations linking early adversity to variations in children's task-based executive functioning.

Lower White Matter Volume and Worse Executive Functioning Reflected in Higher Levels of Plasma GFAP among Older Adults with and Without Cognitive Impairment.

There are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer's dementia. We studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates. Higher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = -0.33, p = .002; Cohort 2: β = -0.36, p = .03) and parietal ROIs (Cohort 1: β = -0.31, p = .01; Cohort 2: β = -0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = -0.38, p = .01; Cohort 2: β = -0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP. Plasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.

Associations Between Neonatal Brain Structure, the Home Environment, and Childhood Outcomes Following Very Preterm Birth

BackgroundVery preterm birth is associated with an increased risk of childhood psychopathology and cognitive deficits. However, the extent to which these developmental problems associated with preterm birth are amenable to environmental factors or determined by neurobiology at birth remains unclear. MethodsWe derived neonatal brain structural covariance networks using non-negative matrix factorization in 384 very preterm infants (median gestational age [range], 30.29 [23.57–32.86] weeks) who underwent magnetic resonance imaging at term-equivalent age (median postmenstrual age, 42.57 [37.86–44.86] weeks). Principal component analysis was performed on 32 behavioral and cognitive measures assessed at preschool age (n = 206; median age, 4.65 [4.19–7.17] years) to identify components of childhood psychopathology and cognition. The Cognitively Stimulating Parenting Scale assessed the level of cognitively stimulating experiences available to the child at home. ResultsCognitively stimulating parenting was associated with reduced expression of a component reflecting developmental psychopathology and executive dysfunction consistent with the preterm phenotype (inattention-hyperactivity, autism spectrum behaviors, and lower executive function scores). In contrast, a component reflecting better general cognitive abilities was associated with larger neonatal gray matter volume in regions centered on key nodes of the salience network, but not with cognitively stimulating parenting. ConclusionsOur results suggest that while neonatal brain structure likely influences cognitive abilities in very preterm children, the severity of behavioral symptoms that are typically observed in these children is sensitive to a cognitively stimulating home environment. Very preterm children may derive meaningful mental health benefits from access to cognitively stimulating experiences during childhood.

Generation and age of immigration on later life cognitive performance in KHANDLE.

We examined the association of generational status and age at immigration with later life cognitive outcomes in a diverse sample of Latinos and Asian Americans. Baseline data were obtained from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, and a prospective cohort is initiated in 2017. Older adults in Northern California. Our cohort consisted of Asians (n = 411) and Latinos (n = 340) who were on average 76 years old (SD = 6.8). We used multivariable linear regression models to estimate associations between generational status and age at immigration (collapsed into one five-level variable) with measures of verbal episodic memory, semantic memory, and executive function, adjusting for age, gender, race and ethnicity, and own- and parental education. Generational status and age at immigration were associated with cognitive outcomes in a graded manner. Compared to third-generation or higher immigrants, first-generation immigration in adulthood was associated with lower semantic memory (β = -0.96; 95% CI: -1.12, -0.81) than immigration in adolescence (β = -0.68; 95% CI: -0.96, -0.41) or childhood (β = -0.28; 95% CI: -0.49, -0.06). Moreover, immigration in adulthood was associated with lower executive function (β = -0.63; 95% CI: -0.78, -0.48) than immigration in adolescence (β = -0.49; 95% CI: -0.75, -0.23). Similarly, compared to third-generation individuals, first-generation immigrants had lower executive functioning scores. Our study supports the notion that sociocontextual influences in early life impact later life cognitive scores. Longitudinal studies are needed to further clarify how immigration characteristics affect cognitive decline.

Poor sleep correlates with biomarkers of neurodegeneration in mild traumatic brain injury patients: a CENC study.

Sleep disorders affect over half of mild traumatic brain injury (mTBI) patients. Despite evidence linking sleep and neurodegeneration, longitudinal TBI-related dementia studies have not considered sleep. We hypothesized that poor sleepers with mTBI would have elevated markers of neurodegeneration and lower cognitive function compared to mTBI good sleepers and controls. Our objective was to compare biomarkers of neurodegeneration and cognitive function with sleep quality in warfighters with chronic mTBI. In an observational warfighters cohort (n = 138 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with plasma biomarkers of neurodegeneration and cognitive scores collected an average of 8 years after injury. In the mTBI cohort, poor sleepers (PSQI ≥ 10, n = 86) had elevated plasma neurofilament light (NfL, x̅ = 11.86 vs 7.91 pg/mL, p = 0.0007, d = 0.63) and lower executive function scores by the categorical fluency (x̅ = 18.0 vs 21.0, p = 0.0005, d = -0.65) and stop-go tests (x̅ = 30.1 vs 31.1, p = 0.024, d = -0.37). These findings were not observed in controls (n = 44). PSQI predicted NfL (beta = 0.22, p = 0.00002) and tau (beta = 0.14, p = 0.007), but not amyloid β42. Poor sleepers showed higher obstructive sleep apnea (OSA) risk by STOP-BANG scores (x̅ = 3.8 vs 2.7, p = 0.0005), raising the possibility that the PSQI might be partly secondary to OSA. Poor sleep is linked to neurodegeneration and select measures of executive function in mTBI patients. This supports implementation of validated sleep measures in longitudinal studies investigating pathobiological mechanisms of TBI related neurodegeneration, which could have therapeutic implications.

Relative contribution of white matter hyperintensity to amyloid and neurodegeneration in cognitive decline over time or clinical diagnoses in a diverse, community‐based cohort of older adults

AbstractBackgroundThe 2018 NIA‐AA Alzheimer’s disease (AD) research framework moves towards a multiple biomarker approach to explain AD development and progression more fully. This research framework has the flexibility to incorporate various biomarkers into a full or partial amyloid‐tau‐neurodegeneration (A/T/N) profile. The objective of this study was to determine the relative contribution of white matter hyperintensities (WMH) to amyloid and neurodegeneration on cognition in a diverse, community‐based cohort of older adults.MethodA subset of cognitively healthy participants (n=155; age=69‐99yrs; 65% women, 30%/44%/26% Non‐Hispanic White/Non‐Hispanic Black/Hispanic) from the Washington Heights‐Inwood Columbia Aging Project underwent baseline Florbetaben PET (amyloid SUVR), T1‐weighted (cortical thickness[mm]) and T2‐weighted FLAIR MRI (WMH volume[cm3]), as well as subsequent neuropsychological assessments and consensus diagnoses every 1.5 years (up to 6 visits). Linear mixed effects models were used to test for change over time in language, memory, executive function, and visuospatial ability, while cox proportional hazard models were used to test for risk of developing MCI or AD. Biomarkers of interest included amyloid, cortical thickness, and WMH, adjusted for demographics (sex/gender, race/ethnicity, education). Interactions between biomarkers and time (e.g., slope differences) were evaluated as significant below 0.1.ResultIn A/N/V models, higher amyloid was associated with faster rates of decline in language (B [95%CI]: ‐0.08 [‐0.13, ‐0.02]), memory (‐0.13 [‐0.21, ‐0.05]), and visuospatial ability (‐0.05 [‐0.12, 0.01]), higher WMH was associated with faster rates of decline in executive function (‐0.05 [‐0.11, 0.009]) and visuospatial ability (‐0.02 [‐0.05, 0.005]), and lower cortical thickness was associated with lower executive function scores (1.6 [0.10, 3.0]). Individuals were more likely to develop MCI or AD with higher amyloid (Hazard Ratio=4.2, [1.1, 15.9]), but not with higher WMH (1.2 [0.83, 1.7]) or lower cortical thickness (0.03 [4E‐4, 2]).ConclusionIn this imaging subsample of older community‐dwelling adults, cognitive decline is differentially associated by domain with amyloid or vascular burden, while broader, multi‐domain cognitive impairment necessary for MCI or AD diagnoses is associated with amyloid, one of the hallmark AD pathologies. Results support the use of complementary information from biomarker profiles, including traditional AD, vascular, and neurodegenerative biomarkers, to investigate AD and related dementias.

Mild behavioral impairment associates with Alzheimer’s disease biomarkers and greater risk of incident dementia in patients with MCI

AbstractBackgroundMild behavioral impairment (MBI) is characterized by later life onset of sustained neuropsychiatric symptoms (NPS) as an at‐risk state for incident cognitive decline and dementia. Here we assess differences in sustained NPS versus transient NPS versus no NPS, on neuroimaging markers and cognitive scores, and the risk of progression to dementia.MethodData from 764 individuals with MCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed. NPI‐Q items were transformed to MBI domains using a published algorithm. MBI requires sustained NPS for 6 months, thus we grouped individuals based on two visits 6‐months apart as sustained (present at both visits, n=258), transient (present at one visit, n=346), and no NPS (present at neither visit, n=160). For the cross‐sectional analyses, outcomes of interest were matched to the clinical visits assessing NPS. We investigated differences in brain metabolic activity by [18F] fluorodeoxyglucose (FDG)‐PET, and composite scores of executive functioning and memory in these groups using multiple linear regression adjusted for age, sex and education. Time‐varying cox regression models were constructed, adjusting for age, sex, and education to assess if time to dementia is associated with MBI.ResultIn these participants with MCI, compared to individuals with no NPS, sustained NPS was associated with reduced [18F] FDG uptake [Adjusted‐=‐0.06 (SE=0.02); p value=0.003], lower executive functioning scores [Adjusted‐=‐0.28 (SE=0.08); p value=0.001], and memory impairment [Adjusted‐=‐0.38 (SE=0.08); p value=&lt;.001]. Compared to individuals with transient NPS, sustained NPS was also associated with reduced glucose metabolism [Adjusted‐=‐0.03 (SE=0.01); p value=0.018], and lower memory scores [Adjusted‐=‐0.17 (SE=0.06); p value=0.007], but not executive functioning. Compared to no or transient NPS, the risk for incident dementia was highest in the sustained NPS group (HR 1.87, 95% CI 1.50 to 2.34).ConclusionIn a cohort of individuals with MCI, baseline NPS are associated with biomarkers of dementia risk and predict progression to dementia. MBI, as operationalized here by sustained NPS, was associated with worse memory, lower glucose metabolism, and higher risk of incident dementia compared to transient NPS. There is diagnostic and prognostic utility in determining if NPS are sustained or transient, further validating the MBI construct.

Changes in Cerebral Volume and White Matter Integrity in Adults on Hemodialysis and Relationship to Cognitive Function

Introduction: Patients on hemodialysis (HD) have a significant burden of cognitive impairment. Characterizing the cerebral structural changes in HD patients compared to healthy controls and evaluating the relationship of cerebral structural integrity with cognitive performance in HD patients can help clarify the pathophysiology of the cognitive impairment in HD patients. Methods: In this cross-sectional study, in-center HD patients ≥50 years of age underwent brain structural and diffusion MRIs and cognitive assessment using the NIH Toolbox cognition battery. The cerebral imaging measures of the HD participants were compared to imaging from age-matched controls. Gray matter volume, white matter volume, and white matter integrity determined by diffusion tensor imaging parameters (including fractional anisotropy [FA]) were measured in both cohorts to determine differences in the cerebral structure between HD participants and healthy controls. The association between cognitive performance on the NIH Toolbox cognition battery and cerebral structural integrity was evaluated using multiple linear regression models. Results: We compared imaging measures form 23 HD participants and 15 age-matched controls. The HD participants had decreased gray matter volumes (526.8 vs. 589.5 cm³, p < 0.01) and worsened white matter integrity overall (FA values of 0.2864 vs. 0.3441, p < 0.01) within major white matter tracts compared to healthy controls. Decreases in white matter integrity in the left superior longitudinal fasciculus was associated with lower executive function scores (r² = 0.24, p = 0.02) and inferior longitudinal fasciculus with lower memory scores (r = 0.25 and p = 0.03 for left and r² = 0.21 and p = 0.03 for right). Conclusions: HD patients have a pattern of decreased white matter integrity and gray matter atrophy compared to controls. Decreases in white matter integrity were associated with decreased cognitive performance in the HD population.

Cognition Predicts Mobility Change in Lower Extremity Amputees Between Discharge From Rehabilitation and 4-Month Follow-up: A Prospective Cohort Study

ObjectivesTo assess (1) the effect of task (single and dual task), time (discharge and 4mo), and their interaction for mobility; (2) task prioritization during dual-task testing; and (3) the association between cognition on change in mobility between discharge from rehabilitation and 4 months’ follow-up. DesignProspective cohort study. SettingRehabilitation hospital. ParticipantsPeople with lower extremity amputations (N=22) were consecutively recruited at discharge from an inpatient prosthetic rehabilitation program. InterventionsNot applicable. Main Outcome MeasuresGait velocity and the L Test of Functional Mobility, single and dual task (serial subtractions by 3), were the primary outcomes. Montreal Cognitive Assessment and Trail Making Test quantified cognition as secondary outcomes. Repeated measures analysis of variance evaluated the effects of task (single task and dual task) and time (at discharge and 4 months’ follow-up) and their interaction on each outcome. A performance-resource operating characteristic graph evaluated gait and cognitive task prioritization. Multivariable linear regression evaluated the association between cognition and change in mobility over time. ResultsNo significant interactions between task and time were found (all P>.121) for L Test and gait velocity. The L Test single task (P=.001) and dual task (P=.004) improved over time. Gait velocity improved over time for both single task and dual task (P<.001). Dual-task performance was slower than single-task performances at each time point. The Trail Making Test B was independently associated with the change in dual-task L Test (P=.012), and single-task (P=.003) and dual-task (P=.006) gait velocity at follow-up. ConclusionsGait velocity and L Test single and dual task improved over time. No significant interactions indicated that cognitive task did not differentially affect performance over time. Lower executive function scores at discharge were independently associated with lower gains in all gait velocity and dual-task L Test outcomes at follow-up.