Subclinical Cognitive Impairment Research Articles

Levetiracetam Prevents Neurophysiological Changes and Preserves Cognitive Function in the Human Immunodeficiency Virus (HIV)-1 Transactivator of Transcription Transgenic Mouse Model of HIV-Associated Neurocognitive Disorder.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects nearly half of the 39 million people living with HIV. HAND symptoms range from subclinical cognitive impairment to dementia; the mechanisms that underlie HAND remain unclear and there is no treatment. The HIV protein transactivator of transcription (TAT) is thought to contribute to HAND because it persists in the central nervous system and elicits neurotoxicity in animal models. Network hyperexcitability is associated with accelerated cognitive decline in neurodegenerative disorders. Here we show that the antiepileptic drug levetiracetam (LEV) attenuated aberrant excitatory synaptic transmission, protected synaptic plasticity, reduced seizure susceptibility, and preserved cognition in inducible TAT (iTAT) transgenic male mice. iTAT mice had an increased frequency of spontaneous excitatory postsynaptic currents in hippocampal slice recordings and impaired long-term potentiation, a form of synaptic plasticity that underlies learning and memory. Two-week administration of LEV by osmotic minipump prevented both impairments. Kainic acid administered to iTAT mice induced a higher maximum behavioral seizure score, longer seizure duration, and shorter latency to first seizure, consistent with a lower seizure threshold. LEV treatment prevented these in vivo signs of hyperexcitability. Lastly, in the Barnes maze, iTAT mice required more time to reach the goal, committed more errors, and received lower cognitive scores relative to iTAT mice treated with LEV. Thus, TAT expression drives functional deficits, suggesting a causative role in HAND. As LEV not only prevented aberrant synaptic activity in iTAT mice but also prevented cognitive dysfunction, it may provide a promising pharmacological approach to the treatment of HAND. SIGNIFICANCE STATEMENT: Approximately half of people living with human immunodeficiency virus (HIV) also suffer from HIV-associated neurocognitive disorder (HAND), for which there is no treatment. The HIV protein transactivator of transcription (TAT) causes toxicity that is thought to contribute to HAND. Here, the antiepileptic drug levetiracetam (LEV) prevented synaptic and cognitive impairments in a TAT-expressing mouse. LEV is widely used to treat seizures and is well-tolerated in humans, including those with HIV. This study supports further investigation of LEV-mediated neuroprotection in HAND.

Impact of frailty, early vascular decline and subclinical cognitive impairment in midlife adults: study protocol of the Toledo Study for Healthy Ageing in middle age.

Life expectancy has increased worldwide alongside a rise in disability prevalence during old age. The impact and interrelationship among the precursors of disability in midlife remain to be better understood. Furthermore, investigating whether lifestyle factors may potentially influence health outcomes and the prognosis of vascular disease could be especially relevant among the middle-aged population, which is a priority subpopulation when prevention is the goal. This is an observational, cross-sectional and population-based study. Participants, between 50 and 55 years old, are randomly selected from the municipality of Toledo (Spain). There are six non-consecutive days for the assessments, providing enough rest between evaluations. Participants perform the interview of the Toledo Study for Healthy Aging. Blood pressure monitoring and a resting electrocardiogram are also recorded. Then, resting peripheral and cerebral vascular measurements along with muscle size and architecture are assessed. Blood and urine samples, and body composition data are collected after an overnight fasting. On a different visit, physical performance and muscle function tests are performed. Additionally, brain magnetic resonance imaging is conducted. And finally, an accelerometer is given to the participants for a week. Frailty is evaluated by Frailty Trait Scale and Fried Frailty Phenotype. This project will shed light on the associations between frailty, early cognitive impairment, and vascular aging during midlife, and on the role that lifestyles play in their development. Lastly, this project will provide meaningful implications for public health strategies aimed at promoting healthy aging in later life.

HDAC1/2/3-mediated downregulation of neurogranin is involved in cognitive impairment in offspring exposed to maternal subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase the risk of neurodevelopmental disorders after birth. However, the mechanism of the effect of maternal subclinical hypothyroidism on fetal brain development and behavioral phenotypes is still unclear and requires further study. In this study, we constructed a mouse model of maternal subclinical hypothyroidism by exposing dams to drinking water containing 50 ppm propylthiouracil (PTU) during pregnancy and found that its offspring were accompanied by severe cognitive deficits by behavioral testing. Mechanistically, gestational SCH resulted in the upregulation of protein expression and activity of HDAC1/2/3 in the hippocampus of the offspring. ChIP analysis revealed that H3K9ac on the neurogranin (Ng) promoter was reduced in the hippocampus of the offspring of SCH, with a significant reduction in Ng protein, leading to reduced expression levels of synaptic plasticity markers PSD95 (a membrane-associated protein in the postsynaptic density) and SYN (synaptophysin, a specific marker for presynaptic terminals), and impaired synaptic plasticity. In addition, administration of MS-275 (an HDAC1/2/3-specific inhibitor) to SCH offspring alleviated impaired synaptic plasticity and cognitive dysfunction in offspring. Thus, our study suggests that maternal subclinical hypothyroidism may mediate offspring cognitive dysfunction through the HDAC1/2/3-H3K9ac-Ng pathway. Our study contributes to the understanding of the signaling mechanisms underlying maternal subclinical hypothyroidism-mediated cognitive impairment in the offspring.

Subclinical Cognitive Impairment in Chronic Pancreatitis Is Associated With Reduced Mobility and Quality of Life.

This study explores how chronic pancreatitis (CP) relates to subclinical cognitive impairment (SCI) and its prevalence, characteristics, risk factors, and effects on patients' quality of life (QoL) and physical performance. Patients with fulfilled CP criteria in imaging were prospectively enrolled. Overt encephalopathy, neurodegenerative disorders, decompensated cirrhosis, and sepsis were exclusion criteria. All patients underwent psychometric testing and assessment of health-related QoL, such as mobility and strength. SCI was diagnosed when at least 1 test of the psychometric test battery was pathological. Seventy-one patients were enrolled. The etiology was toxic (alcohol/smoking) in most (49%) of the cases. SCI was prevalent in 41% of the patients while 25% had only 1 and 16% had 2 or more pathological tests. Patients with SCI exhibited diminished overall QoL scores ( P = 0.048), primarily affecting physical functionality ( P < 0.001). This was reaffirmed in mobility tests, where patients with SCI were slower in the timed up-and-go test ( P = 0.008) and showed increased prevalence of abnormal chair rising tests ( P = 0.004). Among all variables analyzed, only alcohol abuse was an independent risk factor of SCI (odds ratio 3.46; P = 0.02) in a multivariable regression model together with the variables age, sex, education, and compensated cirrhosis. Despite SCI affecting global QoL, sleep disturbance seemed to be the strongest variable independently associated with impaired QoL (odds ratio 9.9; P = 0.001). The largest study to the subject to date shows that SCI is common in patients with CP and is linked to significant morbidity. These findings suggest the need for addressing modifiable risk factors in patients with CP to improve outcomes.

P300 in peripheral neuropathy: cognitive functions assessment and gender effect

BackgroundPatients with peripheral neuropathy (PN) have subtle central pathology that might contribute to cognitive impairment. P300 is a cognitive potential that is connected to both sensory and cognitive processes. Subjects with neurocognitive disorders have considerably longer P300 latency. This study aims to investigate P300's potential as a marker of early-stage cognitive deterioration in PN patients and also, the effect of gender on P300 in patients with PN.ResultsA study group of 60 subjects with PN of various etiologies and no other neurological conditions was included, in addition to, a control group of 40 volunteers with normal hearing sensitivity and no central or peripheral auditory neurological abnormalities. P300 response showed significant delayed latencies in study group when compared to control group. Male group had significant delayed P300 latencies in comparison to female group. As regard P300 amplitude, male group showed no statistically significant differences in comparison to female group.ConclusionsAlthough patients with PN apparently have normal cognitive function, the results in this study revealed the possibility of subtle cognitive impairment. Cognitive functions are affected in both axonal PN and demyelinating PN, however there were no differences found between the two subgroups. Auditory evoked potentials, particularly P300 can be used easily for early detection of subclinical cognitive impairment before appearance of any neurological manifestations. P300 latencies are more important than amplitudes and may be used alone or in addition to amplitudes in cognitive function assessment.

Elderly people with human T-cell leukemia virus type 1-associated myelopathy present an early impairment in cognitive skills

Cerebral changes occur in individuals with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) and seem to predominate in subcortical areas. Little is known about the cognitive decline in the elderly living with HTLV-1. To evaluate the cognitive aging of individuals infected with HTLV-1 aged ≥ 50 years. This is a cross-sectional study of former blood donors infected with HTLV-1 who have been followed in the cohort of the Interdisciplinary Research Group on HTLV-1 since 1997. The groups of study consisted of 79 HTLV-1 infected individuals aged ≥ 50 years, with 41 of them presenting symptomatic HAM and 38 being asymptomatic carriers, and 59 seronegative individuals (controls) aged ≥ 60 years. All were submitted to the P300 electrophysiological test and neuropsychological tests. Individuals with HAM presented delayed P300 latency in relation to the other groups, and this latency delay increased progressively with aging. The performance of this group in the neuropsychological tests was also the worst. The HTLV-1- asymptomatic group performance was similar to that of the control group. Individuals with HAM presented cognitive decline that progressed with aging and, although HTLV-1-asymptomatic carriers appear to present cognitive aging similar to that of healthy elderly people, concern about a subclinical cognitive impairment is warranted in this population.

Cognitive Function Deterioration After Cardiopulmonary Bypass: Can Intraoperative Optimal Cerebral Regional Tissue Oxygen Saturation Predict Postoperative Cognitive Function?

Cognitive impairment is a common neurologic complication after cardiac surgery with cardiopulmonary bypass (CPB). This study evaluated postoperative cognitive function to determine predictors of cognitive dysfunction, including intraoperative cerebral regional tissue oxygen saturation (rSO2). A prospective observational cohort study. At a single academic tertiary-care center. A total of 60 adults undergoing cardiac surgery with CPB from January to August 2021. None. All patients underwent Mini-Mental State Examination (MMSE) and quantified electroencephalography (qEEG) 1 day before cardiac surgery, 7 days postoperatively (POD7), and POD60. Intraoperative cerebral rSO2 was monitored continuously. For MMSE, no significant decrease in MMSE score was found on POD7 versus preoperatively (p=0.09), but POD60 scores showed significant improvement compared with both preoperative (p=0.02) and POD7 scores (p < 0.001). On qEEG, relative theta power on POD7 was increased versus preoperatively (p < 0.001), but it was decreased on POD60 (POD7 versus POD60, p < 0.001), and was close to preoperative data (p > 0.99). Baseline rSO2 was an independent factor for postoperative MMSE. Both baseline and mean rSO2 showed a significant influence in postoperative relative theta activity, whereas mean rSO2 was the only predictor for the theta-gamma ratio (p=0.04). The MMSE in patients undergoing CPB declined at POD7 and recovered by POD60. Lower baseline rSO2 indicated a higher potential for MMSE decline at POD60. Inferior intraoperative mean rSO2 was related to higher postoperative relative theta activity and theta-gamma ratio, implying subclinical or further cognitive impairment.

MASCoD-Multidimensional Assessment of Subjective Cognitive Decline.

Subjective cognitive decline (SCD) is a subclinical cognitive impairment that is complained by the individual without being objectively supported at clinical, diagnostic, and neuropsychological levels. It can negatively impact on patient's frailty and quality of life, as well as on the caregiver's burden. Moreover, it can be prodromal to Mild Cognitive Impairment or dementia. Although the clinical manifestations of SCD can differ along with several cognitive domains, to date there are only screening tools to investigate subjective memory complaints. Thus, the first aim of this paper is to propose a preliminary English and Italian version of a new screening tool called MASCoD (Multidimensional Assessment of Subjective Cognitive Decline); the second aim is to propose its preliminary adoption on a pilot sample. This schedule is a brief test derived from the review of the literature and the clinical experience provided by an experts panelist. From pilot tests, it seems promising as it can help the professional to make differential diagnosis and to predict the risk of developing severe cognitive impairment over time, developing a personalized care path. This screening tool is brief, easily embeddable in usual clinical assessment, and administrable by different professionals. Furthermore, following validation, it will allow to collect manifold cognitive manifestations of SCD, addressing the shortage of previous validated instruments globally assessing cognition affected by this condition.

Subclinical cognitive impairment in chronic kidney disease is associated with frailty and reduced quality of life.

Cognitive impairment (CI) in chronic kidney disease (CKD) is highly prevalent and is associated with multiple limitations to patients as well as a higher mortality, more days of hospitalisation and a lower quality of life. Frailty in CKD is associated with adverse health outcomes and is also highly prevalent. The aim of our study was to determine the prevalence and characteristics of CI and relate the findings to frailty, mobility, muscle strength and health-related quality of life (HRQOL). Non-dialysis patients with CKD stages 3-5 were prospectively evaluated for inclusion. Excluded were patients with other cognitive disorders, signs of overt uraemic encephalopathy, severe infection and hyponatraemia. All patients underwent psychometric testing (five different tests): assessments of mobility, strength and frailty and an evaluation of HRQOL. Based on the number of pathological psychometric test results, we established two different definitions of CI: subclinical uraemic encephalopathy 1 (SUE1: one pathological test) and subclinical uraemic encephalopathy 2 (SUE2: two or more pathological test results). Sixty-two patients were included [median age 66years (interquartile range 57-75), male 55%]. Most patients had CKD stage 3 (48%; stage 4: 32%; stage 5: 19%). CI was highly prevalent (SUE1: 60%; SUE2: 42%) and associated with a higher risk of falls (pathological tandem gait test; SUE1: 50% versus 16%, P=.023; SUE2: 69% versus 15%, P=.001), lower muscle strength (SUE2-pathological: 39% versus 7%, P=.008), frailty (SUE1: 59% versus 28%, P=.038; SUE2: 67% versus 33%, P=.028) and HRQOL. CI is highly prevalent in non-dialysis CKD patients. Even mild CI is associated with decreased mobility, muscle strength and HRQOL and increased frailty.

EEG-ERP Correlates of Cognitive Dysfunction in Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) has been shown to affect the psychological and cognitive status of a woman. However, amidst various conflicting reports in this regard, very few studies attempted to assess these aspects objectively using electroencephalography (EEG) and event-related potential (ERP). To assess changes in neurocognitive and psychological parameters of PCOS women without any other comorbidities. PCOS women aged 18 years to 35 years, diagnosed from obstetrics and gynecology OPD who are otherwise free of any other comorbidities, were assessed for psychological status (anxiety and depression using the State-Trait Anxiety Inventory and Beck Depression Inventory, respectively). Thereafter, a cognitive assessment was done subjectively by the Montreal Cognitive Assessment (MoCA) questionnaire and objectively by using EEG [absolute and relative power of alpha, beta, and theta waves along with theta/beta ratios (TBR) and theta/alpha ratio (TAR)] and P300 amplitude and latency of ERP during a visual oddball paradigm task in control (n = 30) and PCOS (n = 37) subjects. PCOS women showed significantly higher anxiety and depression scores along with low MoCA scores. Significantly reduced absolute alpha, increased frontal beta, and markedly increased theta (relative) power with increased TAR in the PCOS group were seen. Also, a significant reduction in P300 amplitude with prolonged latency during the visual oddball paradigm task was evident in them. Reduced alpha and higher theta activity with increased TAR are indicative of poor neural processing ability. Reduced P300 amplitude with more latency also suggests a cognitive decline, which is corroborated by reduced MoCA scores. Our study objectively indicates the presence of subclinical cognitive impairment in PCOS patients even without any comorbidities.

Subclinical Hypothyroidism and Cognitive Impairment.

Although thyroid dysfunction has been considered as a cause of reversible cognitive impairment, association between subclinical hypothyroidism and cognitive impairment is controversial. We compared cognitive profiles of patients in an euthyroid or subclinical hypothyroid (sHypo) state, as well as their disease progression from mild cognitive impairment (MCI) to dementia within 3 years. We included 2,181 patients in a euthyroid and 284 in a sHypo state over 60 years of age who underwent an extensive cognitive assessment at Seoul National University Bundang Hospital but were not prescribed levothyroxine, methimazole, carbimazole, or propylthiouracil. After propensity score matching for age, sex, and education level, 1,118 patients in a euthyroid and 283 patients in a sHypo state were included. Attention, language, memory, visuocontructive, and executive functions were compared between the groups using Student's t-test or the Mann-Whitney U test. To investigate the association between disease progression and subclinical hypothyroidism, a Cox regression analyses was performed in 379 patients with MCI. Patients with thyroid-stimulating hormone levels over 10 mlU/L was classified as the "sHypo10", and hazard ratios for sHypo or sHypo10 were assessed. There was no difference in attention, language, memory, visuoconstructive, and executive functions between the patient groups. Progression from MCI to dementia was not associated with sHypo or sHypo10. There was no difference in cognitive profile between euthyroid and sHypo patients, and no association between subclinical hypothyroidism and disease progression. This might suggest a clue of strategies regarding hormone therapy in subclinical hypothyroidism with cognitive impairment.

Abstract 13586: Association Between Subclinical Atherosclerosis and Midlife Cognitive Function: The Bogalusa Heart Study

Introduction: Alzheimer’s disease and related dementias (ADRD) are increasing in prevalence. While overt atherosclerosis is recognizable from childhood and has been linked to cognitive impairment and dementia in late life, information is scant on the association between subclinical atherosclerosis and cognitive impairment in midlife. We examined this observation in a cohort of middle-aged noninstitutionalized participants living in a semirural community. Hypothesis: Increased cIMT is associated with worse cognitive performance in midlife. Methods: The analysis included 1,217 participants (age 48 ± 5.28 years; 66% white, 58% women) of the Bogalusa Heart Study. Multivariable-adjusted regression models were used to determine the association between composite cIMT, dichotomized at the 50thpercentile, and a standardized global cognitive z-score (GCS), as well as individual cognitive domains z-scores. Results: The composite cIMT (&gt;0.87mm) was inversely associated with GCS (B= -0.39, SE= 0.18, p = 0.03), independent of cardiovascular risk factors (CVRF’s) and education. (Table1) The cIMT-composite was independently associated with poorer episodic memory (B= -0.23, SE=0.10, p = 0.015). The effect remained significant in Black and White participants after adjustment for CVRF’s (Blacks:B= -0.45, SE: 0.17, p = 0.008; Whites: B= -0.29, SE= 0.13, p = 0.028), but not for education. Conclusions: Subclinical atherosclerosis, as assessed via cIMT, is associated with worse cognitive function in midlife, independent of major CVRFs. The association is buffered by education, and this effect may be stronger among black participants than white. These findings reinforce the importance of establishing preventive measures in midlife and suggest subclinical atherosclerosis as a potential target to prevent cognitive decline.

Prevalence and patterns of subclinical motor and cognitive impairments in non-disabled individuals with early multiple sclerosis: A multicenter cross-sectional study

BackgroundMotor and cognitive disorders appear early in the course of multiple sclerosis (MS) and develop gradually over time. ObjectiveTo study the frequency and pattern of subtle functional disorders in people with MS (PwMS) with no overt signs of disability in an early phase of the disease and their association with walking impairments in daily activities. MethodsIn this cross-sectional study, we recruited PwMS with an Expanded Disability Status Scale (EDSS) score≤2.5 and disease duration≤5years. Participants were assessed with functional scales rating walking endurance (6-Min Walk Test), perceived walking ability (Twelve-item Multiple Sclerosis Walking Scale), balance (Fullerton Advanced Balance scale_short), manual dexterity (Nine Hole Peg Test), fatigue (Fatigue Severity Scale), and cognitive impairments (Brief International Cognitive Assessment). ResultsAbout 90% of the 82 PwMS (mean [SD] EDSS score 1.5 [0.7] and disease duration 2.2 [1.7] years) showed endurance values below the expected score; almost 30% showed impairment, and for 57%, perceived walking ability score was abnormal. Balance was impaired in 48% of participants, as was manual dexterity (29%) and fatigue (24%), but only a few showed cognitive impairments. Only 11% of PwMS had no abnormal score on the scales used in the assessment. As compared with EDSS score 0 to 1.5, with EDSS score 2 to 2.5, performance was worse for endurance (difference±61.0m, P=0.016), perceived walking ability (−11 points, P=0.002), balance (+1.9 points, P=0.005), manual dexterity (−2.8 s, P=0.004), and fatigue (−1.3 points, P=0.013). Factors that predicted perceived walking ability were balance (B=−1.37, P<0.001) and fatigue (B=5.11, P<0.001) rather than endurance (B=−0.01, P=048). ConclusionEven PwMS with no clinical disability and classified as having “no problem walking” present walking and other functional deficits when assessed with specific functional tests. The addition of specific tools could better identify subtle motor and cognitive deficits. Finally, the assessment of balance disorders and fatigue is important to understand individuals’ perceived walking impairments in daily activities.

Comparing different approaches for operationalizing subjective cognitive decline: impact on syndromic and biomarker profiles

Subjective cognitive decline (SCD) has been proposed as a risk factor for future cognitive decline and dementia. Given the heterogeneity of SCD and the lack of consensus about how to classify this condition, different operationalization approaches still need to be compared. In this study, we used the same sample of individuals to compare different SCD operationalization approaches. We included 399 cognitively healthy individuals from a community-based cohort. SCD was assessed through nine questions about memory and non-memory subjective complaints. We applied four approaches to operationalize SCD: two hypothesis-driven approaches and two data-driven approaches. We characterized the resulting groups from each operationalization approach using multivariate methods on comprehensive demographic, clinical, cognitive, and neuroimaging data. We identified two main phenotypes: an amnestic phenotype characterized by an Alzheimer’s Disease (AD) signature pattern of brain atrophy; and an anomic phenotype, which was mainly related to cerebrovascular pathology. Furthermore, language complaints other than naming helped to identify a subgroup with subclinical cognitive impairment and difficulties in activities of daily living. This subgroup also showed an AD signature pattern of atrophy. The identification of SCD phenotypes, characterized by different syndromic and biomarker profiles, varies depending on the operationalization approach used. In this study we discuss how these findings may be used in clinical practice and research.

Examining the causal mediating role of cardiovascular disease on the relationship between subclinical cardiovascular disease and cognitive impairment: The Cardiovascular Health Cognition Study

AbstractBackgroundSubclinical cardiovascular disease (sCVD) is associated with an increased risk of incident Mild Cognitive Impairment (MCI) or Alzheimer’s disease (AD). However, relatively little is known about the mechanisms by which sCVD leads to MCI or AD. One hypothesis is that cardiovascular disease (CVD) mediates the relationship between sCVD and MCI or AD.MethodUsing data from the Cardiovascular Health Cognition Study (N=3,602) and the R package medflex, we fit natural effects causal mediation models to test the hypothesis that CVD is a causal mediator of the effect of sCVD on the risk of MCI or AD within 10 years. All models were adjusted for age, sex, race, education, diabetes status, smoking status, and body mass index, and we excluded those with baseline CVD. We also stratified our analyses by apolipoprotein (APOE)‐4 carrier status and conducted several sensitivity analyses to assess the robustness of our results to violations of our assumptions.ResultAmong those in our analytic sample (N=2,377), sCVD significantly increased the odds of MCI or AD by 35% (OR: 1.35, 95% CI: (1.14, 1.56)) in total. Both the natural direct effect (OR = 1.31, 95% CI: (1.10,1.52)) and the natural indirect effect (OR=1.02, 95% CI: (1.01, 1.05)) were significant as well. CVD mediated approximately 9.5% of the total effect. Among APOE‐4 allele noncarriers, we also found a significant total effect (OR = 1.50, 95% CI: (1.25, 1.76)), natural direct effect (OR=1.44, 95% CI: (1.17, 1.70)), and natural indirect effect (OR=1.04, 95% CI: (1.01, 1.08)) of sCVD on MCI or AD risk through CVD, with approximately 11% of the total effect being mediated. Among APOE‐4 carriers, however, we failed to see any significant effects. Multiple sensitivity analyses showed our results were robust.ConclusionWe found that CVD causally mediates the relationship between sCVD and the risk of MCI or AD within 10 years for APOE‐4 noncarriers, provided that our analytic and causal assumptions hold. Interestingly, the proportion mediated by CVD was only 9‐11% in our analyses, indicating that there are other, possibly substantial, etiological pathways by which sCVD increases the risk of MCI or AD; future research is needed.

Plasma YKL40 as a biomarker for brain aging and injury in three community cohorts

AbstractBackgroundYKL40 is expressed in reactive astrocytes and microglia and is upregulated in numerous neurological conditions associated with heightened neuroinflammation. We explored the utility of circulating YKL40 as a biomarker of accelerated brain aging and subclinical brain injury.MethodYKL40 was measured using the Mesoscale Discovery (MSD) multi‐array assay system from stored plasma in three community‐based cohorts: the Atherosclerosis Risk in the Communities Study (ARIC), the Coronary Artery Risk Development in Young Adults (CARDIA), and the Framingham Heart Study (FHS). MRI‐derived outcomes of total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) were expressed as a percentage of total intracranial volume. We derived a general cognitive factor from multiple neuropsychological tests capturing multiple domains using cohort‐specific principal component analysis with a forced single factor solution. We examined the association between log‐transformed and standardized YKL40 levels and MRI and cognitive phenotypes separately in each cohort using linear regression. Cohort specific results were then pooled in random‐effects meta‐analysis. Analyses were cross‐sectional and adjusted for age, age squared, sex, education (for cognition), and the time interval between the blood draw for YKL40 and outcome assessment. A second model included additional adjustments for vascular risk factors and presence of the APOE ε4 allele.ResultAcross cohorts, there were 2782 dementia‐free participants (mean age, 64 years; 45% male; Mean(SD) YKL40 levels = 50689(7114)pg/mL; YKL40 Coefficient of Variation = 7.5%). In random‐effects meta‐analysis, higher YKL40 levels were associated with smaller total brain volume (β±SE, ‐0.24±0.05 per percentage change in brain volume, p&lt;0.0001) and poorer cognitive function (β±SE, ‐0.04±0.02 per unit change in cognitive composite, p=0.03). The association between YKL40 levels and total brain volume remained significant following full multivariable adjustments (β±SE, ‐0.23±0.05 p&lt;0.0001) whereas the association between YKL40 and cognition was attenuated (β±SE, ‐0.04±0.02, p=0.06). YKL40 levels were not associated with hippocampal volume or WMHV (P&gt;0.05).ConclusionHigher plasma YKL40 levels were associated with MRI and cognitive markers of accelerated brain aging, suggesting involvement of astrocytic or microglial mediated neuroinflammation in subclinical brain atrophy and cognitive impairment.

Frequent neurocognitive deficits after recovery from mild COVID-19.

Neuropsychiatric complications associated with coronavirus disease 2019 caused by the Coronavirus SARS-CoV-2 (COVID-19) are increasingly appreciated. While most studies have focussed on severely affected individuals during acute infection, it remains unclear whether mild COVID-19 results in neurocognitive deficits in young patients. Here, we established a screening approach to detect cognitive deficiencies in post-COVID-19 patients. In this cross-sectional study, we recruited 18 mostly young patients 20–105 days (median, 85 days) after recovery from mild to moderate disease who visited our outpatient clinic for post-COVID-19 care. Notably, 14 (78%) patients reported sustained mild cognitive deficits and performed worse in the Modified Telephone Interview for Cognitive Status screening test for mild cognitive impairment compared to 10 age-matched healthy controls. While short-term memory, attention and concentration were particularly affected by COVID-19, screening results did not correlate with hospitalization, treatment, viremia or acute inflammation. Additionally, Modified Telephone Interview for Cognitive Status scores did not correlate with depressed mood or fatigue. In two severely affected patients, we excluded structural or other inflammatory causes by magnetic resonance imaging, serum and cerebrospinal fluid analyses. Together, our results demonstrate that sustained sub-clinical cognitive impairments might be a common complication after recovery from COVID-19 in young adults, regardless of clinical course that were unmasked by our diagnostic approach.

Effects of Brain Games on Global Cognition among Older Filipinos

Objective. This study ascertained the effects of brain games on global cognition among older Filipinos. Methods. A quasi-experimental design was used. The participants were 60 elderly Filipinos, aged 60 to 93 years, residing in Baguio City, and were not engaging in any physical or nutritional interventions to improve cognitive function. None have subclinical cognitive impairments as screened using the Mini-Cognitive Examination. The Addenbrooke's Cognitive Examination-III (ACE-III) tool which correlated significantly with standard neuropsychological tests, and provided a high internal reliability score of 0.88, was used. Data were analyzed using descriptive and inferential statistics.Results. Pretest mean scores of both active control and experimental groups increased in the posttest. Additionally, both coloring and brain games had extremely significant effects on global cognition (p=0.0001). Lastly, the unrelated t-test revealed extremely significant difference between the effects of brain games and coloring on global cognition (p=0.0001).Conclusions. Based on the results, brain games showed evidence of effectiveness in improving global cognition, and that compared to coloring, it is more effective in improving global cognition among older Filipinos. Variables like motivation and expectancy effects influence the improvement in global cognition among older Filipinos. Lastly, cognitive training using brain games show promise as a non-pharmacologic intervention to address cognitive decline.

ASSOCIATION BETWEEN CARDIAC VARIABLES AND COGNITIVE FUNCTION IN MIDDLE-AGED ADULTS: ANALYSIS FROM THE DALLAS HEART STUDY-2

Previous studies have demonstrated a relationship between subclinical cardiac dysfunction and cognitive impairment in older adults. However, association between hemodynamic variables and cognitive function has not been determined in an ethnically diverse middle-aged population. Furthermore, previous

Evaluation of cognitive function in systemic sclerosis patients: a pilot study

To investigate cognitive dysfunction in adult patients with systemic sclerosis (SSc) who had no known clinical neurological manifestations and to relate it with other disease severity parameters. In the present study, 20 SSc consecutive female patients, who met the 2013 American College of Rheumatology SSc criteria, were compared with 20 healthy age-, gender-, and educational status-matched volunteer hospital workers. Mean age and duration of illness were 41.8 ± 12.52 and 6.9 ± 5.4years respectively. Mini-Mental State Examination (MMSE), Wechsler Adult Intelligence scale (WAIS-III), and P300 component of event-related potentials (ERPs) were used to evaluate cognitive function in SS subjectively and objectively respectively. Sixty-five percent (13 out of 20) of SSc patients had MMSE score < 25, and cognitive impairment. Despite the lack of clinically apparent neurological manifestations, SSc patients had significantly low MMSE score, high Deterioration Index (DI), and prolonged P300 latency compared with that of the control group (P = 0.0001; 0.010 and 0.008 respectively). A significant positive association was found between (DI) and the Medsger severity vascular score (r = 0.518; P = 0.012).There were few differences between limited and diffuse SSc. To our knowledge, few studies highlighted that subclinical cognitive impairment can occur in the course of SSc disease. Early diagnosis of cognitive impairment should be investigated either subjectively (using psychometrics tests as MMSE or WAIS-III) or objectively using P300 evoked related potentials. Medsger severity vascular score seems to be closely related to cognitive impairment.Key points• Cognitive impairment can be associated with Medsger Vascular severity score and the duration of illness.• Further larger studies will be needed to estimate the effect of disease activity on cognitive function, to further delineate the differences between limited and diffuse SSc in this area, and to understand the underlying pathophysiological mechanisms causing cognitive impairment in patients with SSc.• To investigate impaired cognitive function in patients with SSc, even in the absence of clinically apparent neurological and vascular disease.