Worse Performance In Executive Functions Research Articles

Effects of Type 2 Diabetes on the Neuropsychological Profile in Mild Cognitive Impairment.

Diabetes is one of the main risk factors for developing mild cognitive impairment (MCI) and Alzheimer's disease. Most studies have demonstrated a worse performance in executive function, verbal fluency, and information processing speed in patients with diabetes. To assess the cognitive functioning of persons with type 2 diabetes and amnesic mild cognitive impairment (aMCI-T2DM) compared to persons with aMCI without diabetes and persons without diabetes or aMCI as controls, to understand the role of diabetes in the neuropsychological profile. Cross-sectional study involving a sample of 83 patients, ranging in age from 61 to 85 years and divided into three groups: aMCI-T2DM (27 patients), aMCI (29 patients), Controls (27 individuals). All the participants undertook an exhaustive neuropsychological assessment (auditory-verbal and visual memory, attention, information processing speed, language, executive function, and depression). Both groups of aMCI patients performed significantly worse than the controls in all the neuropsychological tests. A significant linear tendency (p trend < 0.05) was found between groups, with the aMCI-T2DM group presenting worse results in global cognition assessed by the Mini-Mental State Examination and Montreal Cognitive Assessment; Rey-Osterrieth Complex Figure Test; Auditory Verbal Learning Test; Trail Making Test A and B, Verbal Fluency Test, and Hamilton Depression Rating Scale. aMCI patients with or without diabetes showed worse cognitive function compared to persons without diabetes or aMCI. Additionally, aMCI patients without T2DM presented a different cognitive profile than aMCI patients with T2DM, which tended towards presenting worse cognitive functions such as global cognition, memory, attention, executive function, and language.

Slow-wave brain connectivity predicts executive functioning and group belonging in socially vulnerable individuals

Important efforts have been made to describe the neural and cognitive features of healthy and clinical populations. However, the neural and cognitive features of socially vulnerable individuals remain largely unexplored, despite their proneness to developing neurocognitive disorders. Socially vulnerable individuals can be characterised as socially deprived, having a low socioeconomic status, suffering from chronic social stress, and exhibiting poor social adaptation. While it is known that such individuals are likely to perform worse than their peers on executive function tasks, studies on healthy but socially vulnerable groups are lacking. In the current study, we explore whether neural power and connectivity signatures can characterise executive function performance in healthy but socially vulnerable individuals, shedding light on the impairing effects that chronic stress and social disadvantages have on cognition. We measured resting-state electroencephalography and executive functioning in 38 socially vulnerable participants and 38 matched control participants. Our findings indicate that while neural power was uninformative, lower delta and theta phase synchrony are associated with worse executive function performance in all participants, whereas delta phase synchrony is higher in the socially vulnerable group compared to the control group. Finally, we found that delta phase synchrony and years of schooling are the best predictors for belonging to the socially vulnerable group. Overall, these findings suggest that exposure to chronic stress due to socioeconomic factors and a lack of education are associated with changes in slow-wave neural connectivity and executive functioning.

Cognitive and Behavioral Features of Patients With Amyotrophic Lateral Sclerosis Who Are Carriers of the TARDBP Pathogenic Variant.

TARDBP patients are considered particularly prone to cognitive involvement, but no systematic studies of cognitive impairment in TARDBP patients are available. The aim of this article was to depict in depth the cognitive-behavioral characteristics of a cohort of patients with amyotrophic lateral sclerosis (ALS) carrying TARDBP pathogenetic variants followed by an ALS referral center. We enrolled all patients with ALS seen at the Turin ALS expert center in the 2009-2021 period who underwent extensive genetic testing and a neuropsychological battery encompassing executive function, verbal memory, language, visual memory, visuoconstructive abilities, attention/working memory, psychomotor speed, nonverbal intelligence, cognitive flexibility, social cognition, and behavior. Tests were compared with the Mann-Whitney U test on age-corrected, sex-corrected, and education-corrected scores. Cognition was classified as normal (ALS-CN); isolated cognitive impairment (ALSci), that is, evidence of executive and/or language dysfunction; isolated behavioral impairment (ALSbi), that is, identification of apathy; cognitive and behavioral impairment (ALScbi), that is, evidence meeting the criteria for both ALSci and ALSbi; and frontotemporal dementia (ALS-FTD). This study includes 33 patients with TARDBP pathogenetic variants (TARDBP-ALS) (median age 61 years [interquartile range (IQR) 53-67], 8 female [24.2%]) and 928 patients with ALS not carrying the pathogenic variant (WT-ALS) (median age 67 years [IQR 59-74], 386 female [41.6%]). TARDBP-ALS cases were also compared with 129 matched controls (median age 66 years [IQR 57.5-71.5], 55 female [42.6%]). TARDBP-ALS and WT-ALS patients were cognitively classified as ALS-CN (54% vs 58.8%, respectively), ALSci (21.2% vs 18.3%), ALSci (9.1% vs 9.5%), ALScbi (6.1% vs 6.0%), and ALS-FTD (9.1 vs 6.7%), with no significant difference (p = 0.623). Compared with controls, TARDBP-ALS had a worse performance in executive functions, visual memory, visuoconstructive abilities, verbal fluency, and the apathy behavioral component of FrSBe. The scores of performed tests, including all Edinburgh Cognitive and Behavioral ALS Screen subdomains, were similar in TARDBP-ALS and WT-ALS. TARDBP-ALS patients were significantly more impaired than controls in most examined domains but do not show any specific pattern of cognitive impairment compared with WT-ALS. Our findings are relevant both clinically, considering the effect of cognitive impairment on patients' decision-making and caregivers' burden, and in designing clinical trials for the treatment of patients carrying TARDBP pathogenetic variants.

Deficits in specific executive functions manifest by severity in major depressive disorder: a comparison of antidepressant naïve inpatient, outpatient, subclinical, and healthy control groups.

Previous research has highlighted the executive function (EF) deficits present in depressed patients; however, conflicting results exist regarding the impact of depression severity on the size of these deficits. This study aimed to compare deficits in EF between antidepressant naïve inpatient and outpatient depressed, a group with subclinical depression symptoms, and a healthy control group while controlling for education, sex, and age. In cross-sectional research, 245 antidepressant naive participants (46 inpatient, 68 outpatient, 65 subclinical, and 67 healthy control individuals) were recruited by convenience sampling. The Structured Clinical Interview for DSM-5 Disorders (SCID-5) and Beck Depression Inventory-II (BDI-II) were used to assess depression. EF was measured using several neuropsychological tests, including the Stroop Color-Word Test, the Wisconsin Card Sorting Test, and the N-back Test, which assessed the components of Inhibition, Shifting, and Updating, respectively. Multivariate analysis of covariance revealed a significant difference between the groups in EF components (p < 0.001). Pairwise comparisons further showed that inpatient and outpatient patients had more depressive symptoms and worse EF performance than subclinical and healthy control groups (p < 0.05). In the analysis of EF measures, a significant difference was found among the four groups, with post-hoc tests revealing variations in specific EF components. Overall, patients with more severe depressive symptoms show more deficits in EF. Additionally, correlations between clinical characteristics and EF measures varied across patient groups, but many correlations became non-significant after adjusting for the false discovery rate (FDR). This study emphasizes the impact of depression severity on deficits in the EF of depressed patients and at-risk populations. Consequently, it is important to consider executive dysfunctions as an underlying vulnerability in the development and persistence of depressive disorder.

Lowered Delta Activity in Post-COVID-19 Patients with Fatigue and Cognitive Impairment.

In post-COVID-19 syndrome (PCS), neurocognitive symptoms and fatigue are often associated with alterations in electroencephalographic (EEG) activity. The present study investigates the brain source activity at rest in PCS patients (PCS-pts) perceiving cognitive deficits and fatigue. A total of 18 PCS-pts and 18 healthy controls (HCs) were enrolled. A Montreal Cognitive Assessment (MoCA), Perceived Cognitive Difficulties Scale (PDCS) and Fatigue Severity Scale (FSS) were administered for assessing the symptoms' severity. Brain activity at rest, both with open (OE) and closed eyes (CE), was recorded by high-density EEG (Hd-EEG) and localized by source estimation. Compared to HCs, PCS-pts exhibited worse performance in executive functions, language and memory, and reported higher levels of fatigue. At resting OE state, PCS-pts showed lower delta source activity over brain regions known to be associated with executive processes, and these changes were negatively associated with PDCS scores. Consistent with recent literature data, our findings could indicate a dysfunction in the neuronal networks involved in executive functions in PCS-pts complaining of fatigue and cognitive impairment.

Accelerated brain age and associated neurocognitive impairments in adult survivors of childhood cancer.

10028 Background: Structural brain aging assessed from routine clinical MRI exams is associated with neurologic and neurocognitive impairments in older non-cancer populations yet is unexplored in childhood cancer survivors. Methods: Neurocognitive assessments and clinical 3-D T1 MRI whole brain images were obtained on 253 childhood cancer survivors (acute lymphoblastic leukemia = 118; brain tumor = 49; Hodgkin lymphoma = 86) and 43 community controls. Brain age was estimated using open-source Gaussian process regression software (BrainAgeR) on visually inspected, segmented, and normalized MRI scans. Benjamin-Hochberg adjusted T-tests were used to compare age-adjusted neurocognitive z-scores between controls and survivors. Linear regression tested associations between brain age acceleration (brain age-chronological age) and treatment (multivariable), and neurocognitive outcomes (univariable). Results: Survivors (mean(SD) age 31.2[8.9]) had poorer executive function (Trails B survivors -0.72 vs controls 0.32, p &lt; 0.0001), processing speed (Grooved Peg Board -0.77 vs 0.05, p &lt; 0.0001), memory (visual selection -0.73 vs -0.10, p = 0.0010; digit backward span -0.45 vs 0.08, p = 0.0304), vocabulary (WASI vocabulary -0.43 vs 0.14, p = 0.0007), and reading (WJ letter word -0.43 vs -0.05, p = 0.0006) compared to controls. In survivors, mean[95%CI] brain age was 7.5[6.4 to 8.6] years older than chronologic age; 0.65[-1.0 to 2.3] years for controls. Compared to males without cranial radiation, for females age≥10 years at cancer diagnosis treated with ≥40Gy cranial radiation, brain age acceleration was 13.35 years (p &lt; 0.001), which worsened by an additional 9.81 years (p = 0.017) for those diagnosed &lt; 10 years. Greater brain age acceleration was associated with a worse performance in executive function (β = -1.73, p &lt; 0.001), processing speed (β = -2.18, p &lt; 0.001), memory (β = -2.07, p &lt; 0.001; β = -1.78, p &lt; 0.029), vocabulary (β = -2.04, p &lt; 0.001), and reading (β = -3.77,p &lt; 0.001). Conclusions: Survivors of childhood cancer experience significant brain age acceleration that is associated with impairments in neurocognitive function. In non-cancer populations, accelerated brain age has been shown to predict late morbidities and mortalities. BrainAge is a promising surrogate biomarker that could predict cognitive decline and improve early detection of dementia risk. Finally, it highlights the risk of cranial radiation in &lt; 10-year-old female cancer survivors.

Role of Thalamus and Thalamic Nuclei in Mediating Post-Treatment Cognitive Changes in Primary Brain Tumor Patients

<h3>Purpose/Objective(s)</h3> Growing evidence suggests that the thalamus plays a central role in neurocognition. The thalamus is comprised of several nuclei, each with different anatomic connectivity and functional properties. We sought to understand the impact of microstructural injury to the thalamus and thalamic nuclei on neurocognition following RT in primary brain tumor patients, using quantitative neuroimaging biomarkers. <h3>Materials/Methods</h3> On a prospective trial, 63 primary brain tumor patients receiving fractionated RT underwent high resolution volumetric and diffusion brain MRI along with prospective neurocognitive assessments (Wechsler Adult Intelligence Scale [WAIS IV], Hopkins Verbal Learning Test [HVLT], Brief Visuospatial Memory Test [BVMT], and Delis-Kaplan Executive Function System [D-KEFS]) at baseline (pre-RT) and 3, 6, and 12 months post-RT. Validated autosegmentation was performed, generating bilateral (R/L) thalami and individual thalamic nuclei. Nuclei were grouped by anatomical region (anterior, lateral, ventral, intralaminar, medial, posterior) into subfields. Tumor, surgical bed and edema were censored to avoid confounding. Quantitative neuroimaging biomarkers were analyzed: volume, fractional anisotropy (FA; decreases with injury) and mean diffusivity (MD; increases with injury). Linear mixed-effects models assessed change in biomarkers with time and dose, and as longitudinal predictors of cognitive function, controlling for time and subject-specific effects. <h3>Results</h3> We found significant atrophy over time after RT in the L/R-anterior (p=0.038, p=0.016), L/R-lateral (p=0.022, p=0.033), R-ventral (p=0.032), R-intralaminar (p<0.001), R-medial (p=0.036), and R-posterior (p<0.001) thalamic subfields. Increased dose was associated with decreased volume (p=0.006) in the lateral geniculate nucleus (LGN) of the L-posterior field and increased MD (p=0.006, p=0.014) in the LGN of the L/R posterior fields. Increased dose was associated with decreased FA (p=0.043) in the R-ventral field. Decreased volume in the L/R-anterior (p=0.011, p=0.033), L/R-ventral (p=0.0125, p=0.012), L/R-intralaminar (p=0.006, p=0.046), L/R-medial (p<0.001, p=0.027), and L-posterior fields (p=0.013) was associated with worse performance on WAIS-IV Digit Span Forward Test. Decreased FA in L/R-anterior fields predicted worse performance on DKEFS Letter Fluency Test (p=0.048, p=0.013). Increased MD in L/R thalamus (p=0.004, p=0.021) and L/R-posterior fields (p=0.022, p=0.011) was associated with worse performance on BVMT Total Recall Test. <h3>Conclusion</h3> Microstructural injury to the thalamus and thalamic nuclei is dose-dependent and progressive over time. Injury to these regions is associated with worse performance in executive function, visuospatial memory, and auditory attention. Dose avoidance efforts in these regions should be explored.

Metabolite changes in prefrontal lobes and the anterior cingulate cortex correlate with processing speed and executive function in Parkinson disease patients.

BackgroundProcessing speed and executive function can be impaired in patients with Parkinson disease (PD). However, the neural factors related to the slowdown in processing speed and dysexecutive function in PD are not completely understood. The objective of this study is to investigate the metabolic changes of the frontal and anterior cingulate cortex (ACC) through the use of 1H magnetic resonance spectroscopy and to explore the association between cognitive function and metabolic ratios.MethodsIn this retrospective case-control study, we conducted neuropsychological assessments of executive function and information processing speed in healthy controls (HCs) and in patients with PD. Chemical information was obtained for the of N-acetyl-aspartate (NAA):creatine (Cr) ratio and the choline-containing compounds (Cho):Cr ratio within the bilateral prefrontal cortex and ACC. Using hierarchical multiple regression analysis, we analyzed the relationship between cognitive function and metabolic ratios in the bilateral prefrontal lobe and ACC in patients with PD.ResultsIn all, 59 patients with PD and 30 HCs were recruited. Patients with PD showed worse performance in executive function and processing speed compared with HCs (P<0.001). In patients with PD, the Cho:Cr ratios in the ACC (Z=2.20, P=0.028) and the right prefrontal cortex (t=2.16, P=0.034) were significantly increased. The hierarchical multiple regressions in patients with PD showed that the NAA:Cr ratio in the ACC correlated with the Stroop A completion times (P<0.05) and that the NAA:Cr ratio of the right prefrontal cortex correlated with the scores of the Wechsler Adult Intelligence Scale (WAIS)-Digit symbol test (P<0.05).ConclusionsInformation processing speed and executive function are impaired in patients with PD. Neuronal integrity and membrane turnover in the ACC and the right prefrontal cortex may be important factors in the slowdown of the information processing speed in patients with PD.

An Integrated Analysis of Clinical, Genomic, and Imaging Features Reveals Predictors of Neurocognitive Outcomes in a Longitudinal Cohort of Pediatric Cancer Survivors, Enriched with CNS Tumors (Rad ART Pro).

BackgroundNeurocognitive deficits in pediatric cancer survivors occur frequently; however, individual outcomes are unpredictable. We investigate clinical, genetic, and imaging predictors of neurocognition in pediatric cancer survivors, with a focus on survivors of central nervous system (CNS) tumors exposed to radiation.MethodsOne hundred eighteen patients with benign or malignant cancers (median diagnosis age: 7; 32% embryonal CNS tumors) were selected from an existing multi-institutional cohort (RadART Pro) if they had: 1) neurocognitive evaluation; 2) available DNA; 3) standard imaging. Utilizing RadART Pro, we collected clinical history, genomic sequencing, CNS imaging, and neurocognitive outcomes. We performed single nucleotide polymorphism (SNP) genotyping for candidate genes associated with neurocognition: COMT, BDNF, KIBRA, APOE, KLOTHO. Longitudinal neurocognitive testing were performed using validated computer-based CogState batteries. The imaging cohort was made of patients with available iron-sensitive (n = 28) and/or T2 FLAIR (n = 41) sequences. Cerebral microbleeds (CMB) were identified using a semi-automated algorithm. Volume of T2 FLAIR white matter lesions (WML) was measured using an automated method based on a convolutional neural network. Summary statistics were performed for patient characteristics, neurocognitive assessments, and imaging. Linear mixed effects and hierarchical models assessed patient characteristics and SNP relationship with neurocognition over time. Nested case-control analysis was performed to compare candidate gene carriers to non-carriers.ResultsCMB presence at baseline correlated with worse performance in 3 of 7 domains, including executive function. Higher baseline WML volumes correlated with worse performance in executive function and verbal learning. No candidate gene reliably predicted neurocognitive outcomes; however, APOE ϵ4 carriers trended toward worse neurocognitive function over time compared to other candidate genes and carried the highest odds of low neurocognitive performance across all domains (odds ratio 2.85, P=0.002). Hydrocephalus and seizures at diagnosis were the clinical characteristics most frequently associated with worse performance in neurocognitive domains (5 of 7 domains). Overall, executive function and verbal learning were the most frequently negatively impacted neurocognitive domains.ConclusionPresence of CMB, APOE ϵ4 carrier status, hydrocephalus, and seizures correlate with worse neurocognitive outcomes in pediatric cancer survivors, enriched with CNS tumors exposed to radiation. Ongoing research is underway to verify trends in larger cohorts.

High-density EEG sleep correlates of cognitive and affective impairment at 12-month follow-up after COVID-19

ObjectiveTo disentangle the pathophysiology of cognitive/affective impairment in Coronavirus Disease-2019 (COVID-19), we studied long-term cognitive and affective sequelae and sleep high-density electroencephalography (EEG) at 12-month follow-up in people with a previous hospital admission for acute COVID-19. MethodsPeople discharged from an intensive care unit (ICU) and a sub-intensive ward (nonICU) between March and May 2020 were contacted between March and June 2021. Participants underwent cognitive, psychological, and sleep assessment. High-density EEG recording was acquired during a nap. Slow and fast spindles density/amplitude/frequency and source reconstruction in brain gray matter were extracted. The relationship between psychological and cognitive findings was explored with Pearson correlation. ResultsWe enrolled 33 participants ( 17 nonICU) and 12 controls. We observed a lower Physical Quality of Life index, higher post-traumatic stress disorder (PTSD) score, and a worse executive function performance in nonICU participants. Higher PTSD and Beck Depression Inventory scores correlated with lower executive performance. The same group showed a reorganization of spindle cortical generators. ConclusionsOur results show executive and psycho-affective deficits and spindle alterations in COVID-19 survivors – especially in nonICU participants – after 12 months from discharge. SignificanceThese findings may be suggestive of a crucial contribution of stress experienced during hospital admission on long-term cognitive functioning.

Disentangling brain heterogeneity via semi‐supervised deep‐learning and MRI: Application to dimensional representations of Alzheimer’s disease

AbstractBackgroundHeterogeneity of neurodegenerative diseases, including Alzheimer’s disease (AD), has hampered precision diagnosis and prognosis. Machine learning methods are able to dissect neuroanatomical heterogeneity and enable identification of disease subtypes via their imaging signatures.MethodWe apply a novel semi‐supervised deep‐learning clustering method to derive dimensions of neurodegeneration, and investigate longitudinal paths in this dimensional system. Analyses used structural MRIs (from the Alzheimer’s Disease Neuroimaging Initiative and the Baltimore Longitudinal Study of Aging; total 2,832 participants; 8,146 scans) including controls and patients with Mild Cognitive Impairment (MCI) and AD.ResultSmile‐GAN identified 4 neurodegenerative patterns/axes (Figure 1): P1, normal anatomy; P2, mild/diffuse atrophy; P3, focal medial temporal atrophy; P4, advanced neurodegeneration. Further application to longitudinal data revealed two distinct progression pathways: P1→P2→P4 and P1→P3→P4. Clinically, P2 participants showed worse performance in executive function than P3 participants (median ADNI‐EF= ‐0.29 vs. ‐0.1, with p=0.038) but had better memory (ADNI‐MEM= ‐0.13 vs. ‐0.39, with p=0.003) (Figure 2). Progression to P4 occurred more rapidly from P3 than P2, with median survival time to progression of 4.5 years and 3.2 years for P2 and P3 MCI/Dementia participants, respectively. Baseline expression of these patterns predicted the pathway and rate of future neurodegeneration, with high accuracy for determining whether P1 participants would progress and whether they would progress to P2 or P3 (Cox‐proportional‐hazard model average concordance index (CI) on the validation set of 0.8±0.02). Pattern expression offered better performance (CI=0.72±0.02) in predicting clinical conversion from MCI to Dementia compared to amyloid/tau (CI=0.69±0.02), with all three together showing modest improvement over pattern performance (CI=0.76±0.02). A composite risk score comprised of pattern probabilities, Abeta, pTau, presence of APOE E4, and ADAS‐cog score was able to predict survival time with an average concordance index, 0.78±0.02 on randomly split validation sets. (Figure 3).ConclusionFour reproducible volumetric patterns, and 2 major longitudinal pathways were revealed using deep learning, which can be determined on an individual patient basis and has implications for rate of future decline. These pattern‐based biomarkers can enrich the N‐dimension of the A/T/N framework which may inform on clinical trial enrollment and monitoring outcomes in a more personalized manner.

Executive functions and emotion regulation in substance use disorder

ABSTRACT Objective The executive functions (EF) and emotion regulation (ER) and their relationship with the substance use disorder (SUD) were analyzed. Methods A cross-sectional design was used. The sample consisted of 130 volunteers divided into three groups: group 01 (n = 60), composed of participants who did not meet the diagnostic criteria for any type of SUD; group 02 (n = 51), with users with alcohol and/or tobacco use disorder; group 03 (n = 19), with users with multiple substance use disorder, including at least one illicit substance. Results Group 02 presented worse performance in EF and ER when compared to group 01, and showed a significant correlation between the working memory and the use of maladaptive ER. Group 03 showed great losses in EF and ER when compared to the other groups. Conclusion This study supports the idea that EF, ER and SUD are related. In addition, it was observed that people with SUD had worse performance in EF and ER when compared to people without SUD, greater damage being observed in people with SUD of polysubstances.

White matter network damage mediates association between cerebrovascular disease and cognition

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores. Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers. Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.

Lower average daily step count is associated with poorer executive function and rurality in a veteran cohort

AbstractBackgroundAn active lifestyle is associated with better cognitive health in older individuals. This relationship is understudied in U.S. Veterans, a population at risk of cognitive impairment due to the high prevalence of associated risk factors and comorbidities. Passive monitoring of daily activities provides objective measures of activity that may serve as a sensitive index of day‐to‐day function and dementia risk.MethodParticipants (age &gt; 57) were enrolled as part of Collaborative Aging Research using Technology (CART), a multi‐site study examining the feasibility of unobtrusive remote sensing and monitoring of physical, cognitive, and health‐related activities. The Veteran cohort consists of volunteers living in largely rural communities in the Pacific Northwest, self‐identified as being a Veteran, and included their cohabitant, if applicable. Daily step counts were acquired using a wrist‐worn device. Baseline one‐month averages were compared with rurality and cognitive function.Result114 nondemented participants residing in 67 homes underwent neuropsychological assessment and passive monitoring of daily activities (55% male, age 70.7, MOCA 23.4). 70% resided in a rural area (rural‐urban commuting area (RUCA) score &gt; 4 ) and 29% had &gt; three vascular risk factors. Participants with 14+ days of gait activity measured within a one‐month period near baseline cognitive assessments not using a walker in the home were included (n = 107). Average daily step count obtained over an average of 27.7 days was 3,065 (median 2,515) and was greater in large rural towns compared with small‐isolated rural (p = 0.07) or urban (p = 0.04) towns. After adjusting for potential confounders, lower average daily steps were associated with worse performance in executive function, a relationship observed in Veterans in large rural, but not urban or small rural towns.ConclusionIn a cohort comprised primarily of rural Veteran’s and their spouses, lower average number of steps per day is associated with poorer executive function and this relationship varied by rurality. Real‐world monitoring of daily activities may identify those at greatest risk of cognitive decline for interventional studies aimed at dementia prevention in older individuals, and is of particular relevance in rural settings, where access to specialty care is limited.

White matter hyperintensities across the adult lifespan: relation to age, A\u03b2 load, and cognition

BackgroundWhite matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults.MethodsOne hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aβ. The relationships of total and regional WMH to age, vascular risk factors, cortical Aβ, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old).ResultsWMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aβ, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aβ load in the models did not alter the results, and there was no interaction between WMH and Aβ on cognition.ConclusionWMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aβ load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH.

Differentiating Symptoms of ADHD in Preschoolers: The Role of Emotion Regulation and Executive Function

Objective: This study examined the extent to which individual differences in executive function (EF) and emotion regulation (ER) were uniquely associated with inattention and hyperactivity symptoms of ADHD, respectively. Method: Participants included 249 preschool children with at-risk or clinically elevated levels of externalizing behavior problems (EBPs). Results: Regression analyses were conducted examining the association between EF and ER—as reported by parents/teachers and assessed via child task performance—and hyperactivity and inattention. Even after accounting for IQ, age, sex, and severity of oppositional defiant disorder, greater levels of parent/teacher-reported EF problems and worse EF performance were associated with greater inattention. In addition, better observed ER was associated with lower inattention. Conversely, greater levels of parent/teacher-reported EF problems and worse parent/teacher-reported ER were associated with greater hyperactivity. Conclusion: Our findings suggest that underlying deficits in EF and ER do differentially relate to ADHD symptoms.

Molecular Senescence Is Associated With White Matter Microstructural Damage in Late-Life Depression

ObjectivesThe authors aim to investigate the association between white matter integrity and accelerated brain aging in late-life depression. MethodsThe authors measured senescence-associated secretory phenotype (SASP) index proteins, cognitive performance, and MRI diffusion tensor imaging (DTI) measures of fractional anisotropy and mean diffusivity-based indices of white matter microstructure measures in 56 older adults with remitted late-life depression. ResultsHigher SASP index was significantly correlated with older age (r = 0.42, p = 0.001) and worse executive function performance (r = −0.27, p = 0.04). After controlling for the effect of age, overall cognitive performance, and white matter hyperintensities, the association between SASP and left and right cingulate bundle mean diffusivity remained statistically significant. ConclusionsOur data suggest that, in the context of late-life depression, SASP proteins are associated with microstructural abnormalities in white matter tracts in brain and worse executive function performance.

Type 2 diabetes and cognitive impairment in an older population with overweight or obesity and metabolic syndrome: baseline cross-sectional analysis of the PREDIMED-plus study

This study cross-sectionally examines in the elderly population: (a) the association of type 2 diabetes with executive function (EF); (b) the effect of BMI on both type 2 diabetes and EF; (c) the association between glycaemia control and EF in type 2 diabetes. 6823 older individuals with overweight/obesity and metabolic syndrome participating in the PREDIMED-PLUS study, were assessed with a battery of cognitive tests and a medical interview. ANOVA showed a significantly worse performance on EF in type 2 diabetes vs. non-diabetic individuals. Two complementary models were displayed: (1) in the whole sample, the presence of type 2 diabetes, depressive symptoms and BMI had a direct negative effect on EF, while apnoea had an indirect negative effect; (2) in the diabetes subsample, higher illness duration was associated with worse performance in EF. Participants with type 2 diabetes and HbA1c<53 mmol/mol displayed better cognitive performance when compared to those with HbA1c≥53 mmol/mol. Our results provide a controlled comprehensive model that integrates relevant neuropsychological and physical variables in type 2 diabetes. The model suggests that, to improve treatment adherence and quality of life once diabetes has been diagnosed, cognitive decline prevention strategies need to be implemented while monitoring depressive symptoms, BMI and glycaemia control.

ALZHEIMER’S BIOMARKERS INTERACT DYNAMICALLY TO PREDICT COGNITIVE TRAJECTORIES DIFFERENTIALLY FOR COGNITIVELY EXCEPTIONAL, NORMAL, AND IMPAIRED GROUPS

Alzheimer's disease (AD) risk-related biomarkers may be quantitatively modeled for independent or interactive effects on preclinical trajectories of cognitive change. Biomarkers may alter cognitive trajectories (a) independently as risk-reducing or risk-increasing and (b) interactively as risk-intensifying or protection-enhancing. Both modifiable (e.g., vascular health) and non-modifiable (e.g., genetic) biomarkers may exert effects differentially according to important selection classifications (e.g., sex, cognitive status). We examine a series of dynamic AD biomarker interactions (i.e., insulin degrading enzyme [IDE], pulse pressure [PP]) that predict non-demented cognitive performance and longitudinal change differentially for three cognitive status groups. The participants from the Victoria Longitudinal Study (n=623; 53–95 years, M=70.6) were objectively classified in three cognitive status groups: Cognitively Exceptional (CE, n=79), Cognitively Normal (CN, n=394), and Cognitively Impaired (CI, n=150). All participants contributed executive function (EF) performance (6 tests, one latent variable) on up to three waves across 9 years. Latent growth modeling (Mplus) was used for statistical evaluation. First, for the full sample, overall 40-year EF decrements were moderated by PP. Specifically, higher PP (worse vascular health) was associated with worse EF performance and steeper decline; establishing a benchmark dynamic biomarker fan effect. Second, further moderation by IDE showed a dynamic fan effect similar to the benchmark, although homozygote carriers of the risk-increasing allele (AA) had lower performance and steeper decline. Third, markedly differential biomarker interaction effects were observed for each cognitive status group. For the CE group, the dynamic fan effect was evident but at elevated levels and sustained slopes for all IDE x PP combinations. For the CN group, the pattern mirrored that of the overall benchmark with the AA genotype exhibiting steeper decline at all levels of PP. For the CI group, the dynamic fan effect exhibited lower performance, as well as consolidated and steeper decline. The beneficial effects of better vascular health are evident in genetically low risk and cognitively intact adults. However, once cognitive impairment is established vascular health plays an apparent but not significant role in aging decline. Dementia biomarkers from different modalities interact in distinct patterns across non-demented exceptional, normal, and impaired aging groups.

Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions.

Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60–86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.