Cognitive Battery Research Articles

Differences in brain structure and cognitive performance between patients with long-COVID and those with normal recovery

BackgroundThe pathophysiology of protracted symptoms after COVID-19 is unclear. This study aimed to determine if long-COVID is associated with differences in baseline characteristics, markers of white matter diffusivity in the brain, and lower scores on objective cognitive testing. MethodsIndividuals who experienced COVID-19 symptoms for more than 60 days post-infection (long-COVID) (n = 56) were compared to individuals who recovered from COVID-19 within 60 days of infection (normal recovery) (n = 35). Information regarding physical and mental health, and COVID-19 illness was collected. The National Institute of Health Toolbox Cognition Battery was administered. Participants underwent magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). Tract-based spatial statistics were used to perform a whole-brain voxel-wise analysis on standard DTI metrics (fractional anisotropy, axial diffusivity, mean diffusivity, radial diffusivity), controlling for age and sex. NIH Toolbox Age-Adjusted Fluid Cognition Scores were used to compare long-COVID and normal recovery groups, covarying for Age-Adjusted Crystallized Cognition Scores and years of education. False discovery rate correction was applied for multiple comparisons. ResultsThere were no significant differences in age, sex, or history of neurovascular risk factors between the groups. The long-COVID group had significantly (p < 0.05) lower mean diffusivity than the normal recovery group across multiple white matter regions, including the internal capsule, anterior and superior corona radiata, corpus callosum, superior fronto-occiptal fasciculus, and posterior thalamic radiation. However, the effect sizes of these differences were small (all β<|0.3|) and no significant differences were found for the other DTI metrics. Fluid cognition composite scores did not differ significantly between the long-COVID and normal recovery groups (p > 0.05). ConclusionsDifferences in diffusivity between long-COVID and normal recovery groups were found on only one DTI metric. This could represent subtle areas of pathology such as gliosis or edema, but the small effect sizes and non-specific nature of the diffusion indices make pathological inference difficult. Although long-COVID patients reported many neuropsychiatric symptoms, significant differences in objective cognitive performance were not found.

Comparative study about the therapeutic effect of cTBS and rTMS in the treatment of auditory verbal hallucinations in schizophrenia.

This study aims to compare the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) and continuous theta-burst stimulation (cTBS) treatment in schizophrenia patients with auditory verbal hallucinations (AVHs). We enrolled 64 schizophrenia patients with AVHs who were treated with either rTMS (n = 32) or cTBS (n = 32), and we compared the clinical outcomes by evaluating parameters from motor evoked potentials, Positive and Negative Syndrome Scale (PANSS), Auditory Hallucination Rating Scale (AHRS), and MATRICS Consensus Cognitive Battery (MCCB), as well as the changes of serum neurotrophic factors before and after the treatment. After the treatment, both treatments resulted in reduced PANSS scores, with the cTBS group showing more substantial symptom improvement across positive, negative, and general symptoms, highlighting the enhanced efficacy of cTBS. Cognitive functions assessed by MCCB also improved in both groups, with cTBS showing a generally higher therapeutic effect. Serum levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) increased following treatment in both groups, with a more notable increase after cTBS, while GABA and glutamate levels remained unchanged. Cardiovascular indices were unaffected by either treatment, suggesting no significant impact on cardiovascular health. Our study found that both rTMS and cTBS treatment can exhibit therapeutic effects in the management of AVHs in patients with schizophrenia. However, cTBS treatment generally shows a higher therapeutic effect than rTMS treatment.

Intact HIV Reservoir in Monocytes Is Associated With Cognitive Function in Virally Suppressed Women With HIV

Abstract Background Monocytes are susceptible to human immunodeficiency virus (HIV) infection, form HIV reservoirs, and contribute to central nervous system complications (eg, cognitive impairment) in virally suppressed women with HIV (vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH. Methods Sixty-two vsWWH (mean age = 56.1 years, SD = 7.1; 93% Black, non-Hispanic; all HIV RNA &amp;lt;250 copies/mL) completed a cognitive test battery, blood draw, and whole-blood immunophenotyping. Monocytes and CD4 T cells were isolated from a subset of 53 participants and the HIV reservoir was assessed using cell-specific intact proviral DNA assays (IPDA). Demographically adjusted z-scores were calculated for each outcome using data from participants without HIV in the Women's Interagency HIV Study. Cognitive outcomes of interest included domain-specific and global z-scores. Results Thirty-Eight percent of vsWWH had detectable intact HIV genomes in monocytes (median = 21.5 copies/million). Higher levels of intact HIV genomes per million monocytes were associated with poorer verbal memory (delayed recall, r = 0.55, P = .01; recognition, r = 0.46, P = .04), fine motor skills (r = 0.50, P = .03), and global function (r = 0.47, P = .04). Higher levels of intact HIV genomes in monocytes were associated with percent intermediate monocytes (r = 0.60, P = .008), and the ratio of intact per intermediate monocyte was associated with worse memory (r = −0.59, P = .008). There were no associations between CD4 reservoir and cognition. Conclusions The number of intact HIV genomes per million monocytes was related to poorer cognition and the percentage of intermediate monocytes. These findings suggest that the presence of HIV genomes in general do not relate to cognitive complications, but intact, and therefore potentially replication-competent HIV, may contribute to cognitive complications in vsWWH.

Cognitive screening for children: Piloting a new battery of interactive games in 4- to 8-year-old children

Cognitive screening at the preschool age can be helpful in the early detection of possible difficulties before the start of school attendance as problems during schooling can have profound consequences. While interactive tools are still limited for the Czech population, tools used for cognitive screening at a younger age often consist of traditional pen-and-paper methods. Such examinations can be very demanding and time-consuming. This pilot study therefore focuses on the usability testing of a newly developed battery of interactive games used for the screening of selected cognitive functions in children aged four to eight in a less demanding and more attractive way. The battery consists of three interactive games testing (1) attention (selective attention), (2) executive functions (inhibitory control), (3) memory (episodic-like memory). The study sample included 24 participants of preschool or younger school age, ranging from 4 to 8 years old, girls = 12 (50%). The analyses also concentrated on the comparison of the newly designed screening tool with selected traditional test methods. The results suggest that the newly developed battery is feasible, and for children, it is entertaining and attractive. The designed cognitive battery is a promising tool for the screening of cognitive functions in younger school-age children.

Life-space mobility and cognition in community-dwelling late-life women: A cross-sectional analysis.

Life-space mobility captures the daily, enacted mobility of older adults. We determined cross-sectional associations between life-space mobility and cognitive impairment (CI) among community-dwelling women in the 9th and 10th decades of life. A total of 1375 (mean age 88 years; 88% White) community-dwelling women enrolled in a prospective cohort of older women. Life-space score was calculated with range 0 (daily restriction to one's bedroom) to 120 (daily trips leaving town without assistance) and categorized (0-20, 21-40, 41-60, 61-80, 81-120). The primary outcome was adjudicated CI defined as mild cognitive impairment or dementia; scores on a 6-test cognitive battery were secondary outcomes. Compared to women with life-space scores of 81-120 and after adjustment for demographics and depressive symptoms, the odds of CI was 1.4-fold (OR 1.36, 95% CI 0.91-2.03) higher for women with life-space scores of 61-80, twofold (OR 1.98, 95% CI 1.33-2.94) higher for women with life-space scores of 41-60, 2.6-fold (OR 2.62, 95% CI 1.71-4.01) higher for women with life-space scores of 21-40, and 2.7-fold (OR 2.71, 95% CI 1.27-5.79) higher for women with life-space scores of 0-20. The association of life-space scores with adjudicated CI was primarily due to higher odds of dementia; the odds of dementia versus normal cognition was eightfold (OR 8.63, 95% CI 3.20-23.26) higher among women with life-space scores of 0-20 compared to women with life-space scores of 81-120. Lower life-space scores were associated in a graded manner with lower mean scores on tests of delayed recall (California Verbal Learning Test-II delayed recall) and language and executive function (phonemic fluency, category fluency, and Trails B). Life-space score was not associated with scores on tests of attention and working memory (forward and backward digit span). Lower life-space mobility is associated in a graded manner with CI among community-dwelling White women in the 9th and 10th decades of life.

Abnormal resting-state functional connectivity of the right anterior cingulate cortex in chronic ketamine users and its correlation with cognitive impairments

BackgroundChronic ketamine use leads to cognitive impairments, however, the neural mechanisms underpinning these impairments are still unclear. AimsMany studies showed Anterior cingulate cortex (ACC)is strongly involved in cognition and drug addiction, as supported by our previous studies. The objective of this study was to assess the variations in resting-state functional connectivity (FC) changes in the right anterior cingulate cortex (ACC) of chronic ketamine users (CKUs) and their relationship with cognitive performance. MethodsThe study enrolled 28 chronic ketamine users (CKUs) and 30 healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from both groups. Cognitive functions were evaluated using the MATRICS Consensus Cognitive Battery (MCCB). ResultsCKUs demonstrated significantly poorer cognitive performance than HCs in various cognitive domains, including Visual Learning, Speed of Processing, Working Memory, and the composite score of MCCB. Group-level comparisons revealed that CKUs exhibited enhanced functional connectivity between the right ACC and the right postcentral gyrus (PCG) compared to HCs. There was a positive relationship between the connectivity of right ACC-PCG and reasoning and problem-solving score, but there was no significant association with the characteristics of ketamine use. ConclusionCKUs showed enhanced connectivity between the right ACC and the right PCG. This enhanced functional connectivity may indicate functional compensation for cognitive deficits in CKUs, especially for reasoning and problem-solving impairments in CKUs.

A - 125 Exploring the Relationship between the NIH Toolbox-Cognitive Battery &amp; the Alzheimer’s Disease Cooperative Study-Preclinical Cognitive Composite

Abstract Objective The computerized NIH Toolbox–Cognitive Battery (NIHTB-CB) is efficient but has not been widely used clinically. The Alzheimer’s Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite (ADS-PACC) has good sensitivity and correlates with amyloid pathology. This study examined the relationship between the NIHTB-CB and ADS-PACC in an aging adult population. Method Baseline data from the Risk Reduction for Alzheimer’s Disease (rrAD) study were analyzed. Cognitively intact individuals (n = 511, M MMSE = 29) with hypertension and subjective cognitive complaints and/or a first degree relative with dementia were included (M age = 68.73, 63% female; 84% White, M education = 16.24). Multiple regression examined the relationship between the NIHTB-CB subtests and ADS-PACC composite score. Results NIHTB-CB subtests demonstrated small to moderate positive correlations with the ADS-PACC total score (r = 0.19–0.43, p &amp;lt; 0.001). ADS-PACC performance explained 23.5% of the variance for NIHTB-CB Flanker Inhibitory Control/Attention [F, (4, 510) = 40.19, p &amp;lt; 0.001], 18.1% for Pattern Comparison Processing Speed, 13.9% for List Sorting Working Memory [F, (4, 508) = 21.53, p &amp;lt; 0.001], and 13.2% for Dimensional Change Card Sort [F, (4, 510) = 20.43, p &amp;lt; 0.001]. Conclusions The NIHTB-CB and ADS-PACC showed modest correlations, but PACC scores explained a sizeable amount of variance of NIHTB-CB performance. Previous research supports convergent validity of the NIHTB-CB with other commonly used neuropsychological measures; however, results of this study indicate these batteries may assess different aspects of cognitive functioning. Future research may explore the relationship between the two batteries and their components in the assessment of longitudinal changes in neurocognitive function in individuals with cognitive decline/dementia.

Long-Term Dementia Risk in Parkinson Disease.

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. Participants from the Parkinson's 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 <21 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I cognition score ≥3 as secondary end points for PPMI. In addition, estimated dementia probability by PD disease duration was tabulated for each study and end point. For the PPMI cohort, 417 participants with PD (mean age 61.6 years, 65% male) were followed, with an estimated probability of dementia at year 10 disease duration of 9% (site investigator diagnosis), 15% (MoCA), or 12% (MDS-UPDRS Part I cognition). For the Penn cohort, 389 participants with PD (mean age 69.3 years, 67% male) were followed, with 184 participants (47% of cohort) eventually diagnosed with dementia. The interval-censored curve for the Penn cohort had a median time to dementia of 15 years (95% CI 13-15); the estimated probability of dementia was 27% at 10 years of disease duration, 50% at 15 years, and 74% at 20 years. Results from two large, prospective studies suggest that dementia in PD occurs less frequently, or later in the disease course, than previous research studies have reported.

Comparing psychometric characteristics of a computerized cognitive test (BrainCheck Assess) against the Montreal cognitive assessment.

Previous validation studies demonstrated that BrainCheck Assess (BC-Assess), a computerized cognitive test battery, can reliably and sensitively distinguish individuals with different levels of cognitive impairment (i.e., normal cognition (NC), mild cognitive impairment (MCI), and dementia). Compared with other traditional paper-based cognitive screening instruments commonly used in clinical practice, the Montreal Cognitive Assessment (MoCA) is generally accepted to be among the most comprehensive and robust screening tools, with high sensitivity/specificity in distinguishing MCI from NC and dementia. In this study, we examined: (1) the linear relationship between BC-Assess and MoCA and their equivalent cut-off scores, and (2) the extent to which they agree on their impressions of an individual's cognitive status. A subset of participants (N = 55; age range 54-94, mean/SD = 80/9.5) from two previous studies who took both the MoCA and BC-Assess were included in this analysis. Linear regression was used to calculate equivalent cut-off scores for BC-Assess based on those originally recommended for the MoCA to differentiate MCI from NC (cut-off = 26), and dementia from MCI (cut-off = 19). Impression agreement between the two instruments were measured through overall agreement (OA), positive percent agreement (PPA), and negative percent agreement (NPA). A high Pearson correlation coefficient of 0.77 (CI = 0.63-0.86) was observed between the two scores. According to this relationship, MoCA cutoffs of 26 and 19 correspond to BC-Assess scores of 89.6 and 68.5, respectively. These scores are highly consistent with the currently recommended BC-Assess cutoffs (i.e., 85 and 70). The two instruments also show a high degree of agreement in their impressions based on their recommended cut-offs: (i) OA = 70.9%, PPA = 70.4%, NPA = 71.4% for differentiating dementia from MCI/NC; (ii) OA = 83.6%, PPA = 84.1%, NPA = 81.8% for differentiating dementia/MCI from NC. This study provides further validation of BC-Assess in a sample of older adults by showing its high correlation and agreement in impression with the widely used MoCA.

Neuroinflammatory Biomarkers and Their Associations With Cognitive, Affective, and Functional Outcomes 3 to 12 Months After a Traumatic Brain Injury: A Pilot Study.

Neuroinflammation is an important feature of traumatic brain injury (TBI) that remains poorly understood in the 3- to 12-month period post-TBI. The purpose of our pilot study was to examine the relationships between biomarkers of neuroinflammation and functional outcomes in TBI patients 3 to 12months postinjury. TBI patients (n =36) 3 to 12months post-TBI were recruited from a South Florida TBI clinic from May 2022 to June 2023. The Disability Rating Scale, Satisfaction with Life Scale, NIH Toolbox Sorting Working Memory, Neuro-Quality of Life Cognitive Function, Anxiety, Depression, and Sleep assessments were performed. Multiple plasma biomarkers were assayed. Analysis of variance was used to compare between-group results. Linear regression was performed to analyze relationships between biomarkers and outcomes. Brain-derived neurotrophic factor concentrations were higher as postinjury time interval increased and were associated with cognitive battery outcomes. S-100β and glial fibrillary acidic protein were associated with anxiety score and hospital length of stay; S-100β was also associated with depression. Interleukin 6 was associated with cognitive function score and time since injury. We found S-100β, glial fibrillary acidic protein, Interleukin 6, and brain-derived neurotrophic factor to play a larger role in the TBI recovery period than other biomarkers examined. Clinicians should continue to monitor for symptoms post-TBI, as the neuroinflammatory process continues to persist even into the later rehabilitation stage.

Exploring the relationship between lipid metabolism and cognition in individuals living with stable-phase Schizophrenia: a small cross-sectional study using Olink proteomics analysis

BackgroundCognitive impairment is a core symptom of schizophrenia. Metabolic abnormalities impact cognition, and although the influence of blood lipids on cognition has been documented, it remains unclear. We conducted a small cross-sectional study to investigate the relationship between blood lipids and cognition in patients with stable-phase schizophrenia. Using Olink proteomics, we explored the potential mechanisms through which blood lipids might affect cognition from an inflammatory perspective.MethodsA total of 107 patients with stable-phase schizophrenia and cognitive impairment were strictly included. Comprehensive data collection included basic patient information, blood glucose, blood lipids, and body mass index. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the MATRICS Consensus Cognitive Battery (MCCB). After controlling for confounding factors, we identified differential metabolic indicators between patients with mild and severe cognitive impairment and conducted correlation and regression analyses. Furthermore, we matched two small sample groups of patients with lipid metabolism abnormalities and used Olink proteomics to analyze inflammation-related differential proteins, aiming to further explore the association between lipid metabolism abnormalities and cognition.ResultsThe proportion of patients with severe cognitive impairment (SCI) was 34.58%. Compared to patients with mild cognitive impairment (MCI), those with SCI performed worse in the Attention/Alertness (t = 2.668, p = 0.009) and Working Memory (t = 2.496, p = 0.014) cognitive dimensions. Blood lipid metabolism indicators were correlated with cognitive function, specifically showing that higher levels of TG (r = -0.447, p < 0.001), TC (r = -0.307, p = 0.002), and LDL-C (r = -0.607, p < 0.001) were associated with poorer overall cognitive function. Further regression analysis indicated that TG (OR = 5.578, P = 0.003) and LDL-C (OR = 5.425, P = 0.001) may be risk factors for exacerbating cognitive impairment in individuals with stable-phase schizophrenia. Proteomics analysis revealed that, compared to individuals with stable-phase schizophrenia and normal lipid metabolism, those with hyperlipidemia had elevated levels of 10 inflammatory proteins and decreased levels of 2 inflammatory proteins in plasma, with these changes correlating with cognitive function. The differential proteins were primarily involved in pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.ConclusionBlood lipids are associated with cognitive function in individuals with stable-phase schizophrenia, with higher levels of TG, TC, and LDL-C correlating with poorer overall cognitive performance. TG and LDL-C may be risk factors for exacerbating cognitive impairment in these patients. From an inflammatory perspective, lipid metabolism abnormalities might influence cognition by activating or downregulating related proteins, or through pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.

Adverse Childhood Experiences and Cognitive Change in Late-Life Depression

ObjectivesTo determine the relationship of adverse childhood experiences (ACEs) with change in cognitive performance over a 1-year period among older adults in treatment for depression. MethodsOlder depressed adults completed the ACEs questionnaire and the Consortium to Establish a Registry of Alzheimer's disease (CERAD) cognitive battery at baseline and were re-assessed with the CERAD 1 year later. ResultsChildhood physical abuse, sexual abuse, and verbal/emotional abuse, respectively, were reported by 25%, 17.5%, and 42% of participants. Total ACEs score was not associated with baseline cognitive performance or 1-year change. However, sexual abuse, physical abuse, and a measure of cumulative verbal/emotional, physical, and sexual abuse were inversely associated with 1-year change in total CERAD score. ConclusionsChildhood abuse may have long-term adverse effects, including placing depressed older adults at risk for progressive cognitive decline. ACEs should be considered in research and clinical management of depression in older adults.

Neurocognitive function and medical care utilization in Veterans treated for substance use disorder

BackgroundVeterans with substance use disorder (SUD) are at high risk for cognitive problems due to neurotoxic effects of chronic drug and alcohol use coupled in many cases with histories of traumatic brain injury (TBI). These problems may in turn result in proneness to SUD relapse and reduced adherence to medical self-care regimens and therefore reliance on health care systems. However, the direct relationship between cognitive function and utilization of Veterans Health Administration (VHA) SUD and other VHA health care services has not been evaluated. We sought initial evidence as to whether neurocognitive performance relates to repeated health care engagement in Veterans as indexed by estimated VHA care costs.MethodsNeurocognitive performance in 76 Veterans being treated for SUD was assessed using CNS-Vital Signs, a commercial computerized cognitive testing battery, and related to histories of outpatient and inpatient/residential care costs as estimated by the VHA Health Economics Resource Center.ResultsAfter controlling for age, an aggregate metric of overall neurocognitive performance (Neurocognition Index) correlated negatively with total VHA health care costs, particularly with SUD-related outpatient care costs but also with non-mental health-related care costs. Barratt Impulsiveness Scale scores also correlated positively with total VHA care costs.ConclusionsIn Veterans receiving SUD care, higher impulsivity and lower cognitive performance were associated with greater health care utilization within the VHA system. This suggests that veterans with SUD who show lower neurocognitive performance are at greater risk for continued health problems that require healthcare engagement. Cognitive rehabilitation programs developed for brain injury and other neurological conditions could be tried in Veterans with SUD to improve their health outcomes.

Measuring Cognitive Function In-Person and Remotely in Round 4 of the National Social Life, Health, and Aging Project (NSHAP).

This paper describes the changes made to the collection of cognitive measures when the National Social Life, Health, and Aging Project (NSHAP) introduced remote modes of data collection. In Round 4 (2021-23), the longitudinal study transitioned from being conducted in-person to collecting data via multiple modes including in-person and remote modes: web, phone, and paper-and-pencil. The team began with the measures used in Rounds 2 and 3 of NSHAP-the survey-adapted Montreal Cognitive Assessment (MoCA-SA)-and evaluated which measures could be administered remotely, introducing new measures for each cognitive subdomain, as needed, to compensate for items that could not be administered remotely. Cognitive items used in Rounds 2 and 3 that could not be administered remotely were dropped from the respective modes, and items selected from the Rush Alzheimer's Disease Center's (RADC) global cognition battery were added as substitutes. For comparison, the RADC substitute items were added to the in-person mode making it longer in R4. The changes in cognitive measures resulted in different numbers of cognitive items across the four modes of survey administration in Round 4. Analysts should be aware of these changes when creating a single global cognition score for the entire NSHAP sample in Round 4, and aware that there may be mode effects that could impact cognition scores.

Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits

Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

Cognitive Intraindividual variability in injection drug use among Hispanic residents of Puerto Rico

Despite a high prevalence of injection drug use (IDU) in Puerto Rico, little is known about how it affects neuropsychological functioning in this population. Investigations of intra-individual variability (IIV) have alluded to its utility as a potential indicator of neural decline. The purpose of this study was to characterize IIV among Hispanic residents of Puerto Rico who engage in IDU. Injectors and non-injectors completed the Neuropsí Atención y Memoria battery. Measures of IIV were calculated for the overall test battery (OTB), the three battery indices, and three domains of attention, memory, and executive functioning. The injector group showed significantly greater IIV than the non-injector group on all measures (OTB, indices, and individual domains). Additionally, injectors showed significantly higher IIV in the domain of executive functioning compared to other cognitive domains and battery indices. In contrast, non-injectors did not show any significant within-group differences on any IIV measures. The higher performance variability observed in the IDU group suggests a negative influence of IDU on cognition, with executive functioning being more susceptible to these effects. These findings support the need for continued investigations into the clinical application of IIV for diagnostic and prognostic purposes in the Hispanic IDU population.

The Common Marmoset as a Translational Model for Longitudinal Studies of Cognitive Aging and Individual Vulnerability to Decline.

In humans, cognitive aging is highly variable, with some individuals experiencing decline while others remain stable, and different cognitive domains exhibiting uneven vulnerability to aging. The neural mechanisms driving this intra- and inter-individual variability are not fully understood, making longitudinal studies in translational models essential for elucidating the timelines and processes involved. The common marmoset (Callithrix jacchus), a short-lived nonhuman primate, offers an unprecedented opportunity to conduct longitudinal investigations of aging and age-related disease over a condensed time frame, in a highly translatable animal model. The potential of the marmoset as a model for cognitive aging is indisputable, but a comprehensive cognitive battery tailored for longitudinal aging studies has not yet been developed, applied, or validated. This represents a critical missing piece for evaluating the marmoset as a model and understanding the extent to which marmoset cognitive aging mirrors the patterns found in humans, including whether marmosets have individual variability in their vulnerability to age-related cognitive decline. To address this, we developed a comprehensive touchscreen-based neuropsychological test battery for marmosets (MarmoCog), targeting five cognitive domains: working memory, stimulus-reward association learning, cognitive flexibility, motor speed, and motivation. We tested a large cohort of marmosets, ranging from young adults to geriatrics, over several years. We found significant variability in cognitive aging, with the greatest decline occurring in domains dependent on the prefrontal cortex and hippocampus. Additionally, we observed significant inter-individual variability in vulnerability to age-related cognitive decline: some marmosets declined across multiple domains, others in just one, and some showed no decline at all. This pattern mirrors human cognitive aging, solidifies the marmoset as an advantageous model for age-related cognitive decline, and provides a strong foundation for identifying the neural mechanisms involved.

Hypertensive Disorders of Pregnancy and Brain Health in Midlife: The CARDIA Study.

To understand the role of hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension (GH), in brain health earlier in life, we investigated the association of HDP with midlife cognition and brain health. We studied a prospective cohort of women, baseline age 18 to 30 years, who were assessed at study years 25 and 30 with a cognitive battery and a subset with brain magnetic resonance imaging. A history of HDP was defined based on self-report. We conducted linear regression to assess the association of a history of preeclampsia, GH, or no HDP with cognition and brain magnetic resonance imaging white matter hyperintensities. Among 1441 women (mean age, 55.2±3.6 years), 202 reported preeclampsia and 112 reported GH. GH was associated with worse cognitive performance: global cognition (mean score, 23.2 versus 24.0; P=0.018), processing speed (67.5 versus 71.3; P=0.01), verbal fluency (29.5 versus 31.1; P=0.033), and a trend for executive function (24.3 versus 22.6; P=0.09), after multivariable adjustment. GH was associated with a greater 5-year decline in processing speed (mean change, -4.9 versus -2.7; P=0.049) and executive function (-1.7 versus 0.3; P=0.047); preeclampsia was associated with a greater 5-year decline on delayed verbal memory (-0.3 versus 0.1; P=0.041). GH and preeclampsia were associated with greater white matter hyperintensities in the parietal and frontal lobes, respectively. GH and preeclampsia are associated with cognition and white matter hyperintensities during midlife, with differences in cognitive domains and brain lobes. Women with HDP may need to be closely monitored for adverse brain outcomes starting in midlife.

Feasibility and reliability of online vs in-person cognitive testing in healthy older people.

Early evidence in using online cognitive assessments show that they could offer a feasible and resource-efficient alternative to in-person clinical assessments in evaluating cognitive performance, yet there is currently little understanding about how these assessments relate to traditional, in-person cognitive tests. In this preliminary study, we assess the feasibility and reliability of NeurOn, a novel online cognitive assessment tool. NeurOn measures various cognitive domains including processing speed, executive functioning, spatial working memory, episodic memory, attentional control, visuospatial functioning, and spatial orientation. Thirty-two participants (mean age: 70.19) completed two testing sessions, unsupervised online and in-person, one-week apart. Participants were randomised in the order of testing appointments. For both sessions, participants completed questionnaires prior to a cognitive assessment. Test-retest reliability and concurrent validity of the online cognitive battery was assessed using intraclass correlation coefficients (ICCs) and correlational analysis, respectively. This was conducted by comparing performance in repeated tasks across testing sessions as well as with traditional, in-person cognitive tests. Global cognition in the NeurOn battery moderately validated against MoCA performance, and the battery demonstrated moderate test-retest reliability. Concurrent validity was found only between the online and paper versions of the Trail Making Test -A, as well as global cognitive performance between online and in-person testing sessions. The NeurOn cognitive battery provides a promising tool for measuring cognitive performance online both longitudinally and across short retesting intervals within healthy older adults. When considering cost-effectiveness, flexible administration, and improved accessibility for wider populations, online cognitive assessments show promise for future screening of neurodegenerative diseases.

Cognitive Function during and after Pregnancy and One-Year Postpartum in Type 1 Diabetes: A Longitudinal Study.

This study aims to compare the cognitive function of women with T1DM during and after pregnancy, as well as one year post-delivery. Additionally, it aims to investigate the impacts of leptin and body mass index on cognitive function. A prospective longitudinal cohort study was conducted involving 64 pregnant women with T1DM. Cognitive function was assessed using a cognitive assessment battery during the first trimester, immediately after delivery, and one year postpartum for the final assessment. This program evaluates a wide range of cognitive abilities and provides a comprehensive cognitive well-being score (high-moderate-low), identifying strengths and weaknesses in reasoning, memory, attention, coordination, and perception. The average age of the participants was 30.9 years, with a mean diabetes duration of 14.9 years. Pregnant women with a BMI of 30 kg/m2 or higher faced an increased risk of reduced cognitive function, memory, and reasoning. Additionally, mothers with lower overall cognitive function and memory levels had significantly higher concentrations of leptin in their blood. Cognitive functions-particularly reasoning and attention-are adversely affected in women with T1DM during pregnancy and shortly after delivery. Elevated BMI and leptin levels can be linked to worse cognitive outcomes in this population.