Etiology Of Cognitive Impairment Research Articles

SLC39A8.p.(Ala391Thr) is associated with poorer cognitive ability: a cross-sectional study of schizophrenia and the general UK population.

The missense SNP NC_000004.12:g.102267552C>T (SLC39A8.p.(Ala391Thr), rs13107325) in SLC39A8, which encodes a zinc transporter, has been linked to schizophrenia and is the likely causal variant for one of the genome-wide association loci associated with the disorder. We tested whether the schizophrenia-risk allele at p.(Ala391Thr) was associated with schizophrenia-related phenotypes, including positive, negative, and disorganised symptoms, cognitive ability, educational attainment, and age of psychosis onset, within three schizophrenia cohorts (combined N=1,232) and, with equivalent phenotypes, in a sample of population controls (UK Biobank, N=355,069). We used regression analyses controlling for age, sex, and population stratification. Within the schizophrenia cohorts, after correction for multiple testing, p.(Ala391Thr) was not significantly associated with any schizophrenia-related phenotypes. In the unaffected participants from the UK Biobank, the schizophrenia-risk allele at p.(Ala391Thr) was associated with significantly poorer cognitive ability and fluid intelligence, a lower probability of obtaining GCSEs or a degree-level qualification, and fewer years in education. There was no association between p.(Ala391Thr) and self-reported psychotic experiences in this cohort. The schizophrenia-risk allele was associated with poorer cognitive ability, but not psychotic experiences, in a volunteer sample drawn from of the general population. To determine whether p.(Ala391Thr) is associated with cognitive phenotypes in people with schizophrenia, and to understand the role of p.(Ala391Thr) in the aetiology of cognitive impairment in schizophrenia, larger independent samples are required.

Factors associated with cancer-related cognitive impairment in patients with lung cancer: A systematic review

PurposeCognitive impairment is common in lung cancer patients and impacts their quality of life. Little is known about the etiology of cognitive impairment in lung cancer patients. However, the associated factors of cognitive impairment among lung cancer patients have not been systematically reviewed. This review aimed to summarize the factors related to cognitive impairment among lung cancer patients. MethodsPubMed, EMBASE, PsycINFO, CINAHL Plus, and Web of Science were searched to retrieve articles published from data inception until January 21, 2024, focusing on factors associated with cognitive impairment among lung cancer patients. Critical appraisal was undertaken by two reviewers independently using the Newcastle–Ottawa Scale. ResultsA total of 17 observational studies were included. The results showed that 20 factors are associated with cognitive impairment, including psychological factors (loneliness, fatigue, anxiety, depression, high symptom burden, and baseline cognitive impairment), lifestyle and functional factors (daily step counts, smoking, and activities of daily living or instrumental activities of daily living impairments), medical treatment factors (cranial irradiation, chemotherapy, lobar resection, postoperative delirium, and on medication), and neuroimmunological factors (have neuronal autoantibodies, altered Default Mode Network connectivity, dysregulation in glutamate and glutamate metabolism, mitochondrial dysfunction, blood-brain barrier leakage, and reduced T-lymphocytes). ConclusionThis is the first study to systematically review 20 factors associated with cognitive impairment among lung cancer patients, encompassing psychology, lifestyle and functional, medical treatment, and neuroimmunological factors. These findings can help clinicians identify at-risk patients and develop evidence-based interventions to prevent cognitive impairment among lung cancer patients.

Spotlight on pro-inflammatory chemokines: regulators of cellular communication in cognitive impairment.

Cognitive impairment is a decline in people's ability to think, learn, and remember, and so forth. Cognitive impairment is a global health challenge that affects the quality of life of thousands of people. The condition covers a wide range from mild cognitive impairment to severe dementia, which includes Alzheimer's disease (AD) and Parkinson's disease (PD), among others. While the etiology of cognitive impairment is diverse, the role of chemokines is increasingly evident, especially in the presence of chronic inflammation and neuroinflammation. Although inflammatory chemokines have been linked to cognitive impairment, cognitive impairment is usually multifactorial. Researchers are exploring the role of chemokines and other inflammatory mediators in cognitive dysfunction and trying to develop therapeutic strategies to mitigate their effects. The pathogenesis of cognitive disorders is very complex, their underlying causative mechanisms have not been clarified, and their treatment is always one of the challenges in the field of medicine. Therefore, exploring its pathogenesis and treatment has important socioeconomic value. Chemokines are a growing family of structurally and functionally related small (8-10 kDa) proteins, and there is growing evidence that pro-inflammatory chemokines are associated with many neurobiological processes that may be relevant to neurological disorders beyond their classical chemotactic function and play a crucial role in the pathogenesis and progression of cognitive disorders. In this paper, we review the roles and regulatory mechanisms of pro-inflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CCL11, CCL20, and CXCL8) in cognitive impairment. We also discuss the intrinsic relationship between the two, hoping to provide some valuable references for the treatment of cognitive impairment.

Cognitive impairment in Chinese traumatic brain injury patients: from challenge to future perspectives.

Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients.

Cognitive decline in post-COVID-19 syndrome does not correspond with persisting neuronal or astrocytic damage

Cognitive impairment is the most frequent symptom reported in post-COVID-19 syndrome (PCS). Aetiology of cognitive impairment in PCS is still to be determined. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are increased in acute COVID-19. Their role as biomarkers in other neurological disorders is under debate. We analysed serum levels of NfL and GFAP as markers for neuronal and astrocytic damage in 53 patients presenting to a PCS Neurology outpatient clinic. Only individuals with self-reported cognitive complaints were included. In these individuals, cognitive complaints were further assessed by comprehensive neuropsychological assessment (NPA). Patients were categorized into subgroups of subjective cognitive decline, single domain impairment, or multi-domain impairment. Serum NfL was in normal range, however an increase of serum GFAP was detected in 4% of patients. Serum NfL and GFAP levels correlated with each other, even when adjusting for patient age (r = 0.347, p = 0.012). NPA showed deficits in 70%; 40% showing impairment in several tested domains. No significant differences were found between serum NfL- and GFAP-levels comparing patients with subjective cognitive decline, single domain impairment, or multi-domain impairment. Persistent neuronal or astrocytic damage did not correlate with cognitive impairment in PCS.

A Comprehensive, Community‐Engaged Recruitment Strategy to Increase Minority Representation in New IDEAS – an Amyloid Imaging Study

AbstractBackgroundAlthough Black and Hispanic/Latino people have higher rates of clinical Alzheimer disease (AD), evidence indicates lower proportions and odds of positive amyloid positron emission tomography (PET). This may indicate differences in etiology of cognitive impairment, which has implications for prevention and treatment (ie, anti‐amyloid treatments). Unfortunately, Black and Hispanic/Latino people are underrepresented in AD research.MethodTo evaluate amyloid PET in a diverse sample, we designed culturally‐informed, community‐engaged recruitment strategies for New IDEAS (Imaging Dementia—Evidence for Amyloid Scanning), an observational, open‐label, longitudinal cohort study of beta‐amyloid PET. New IDEAS intends to recruit 7,000 U.S. Medicare beneficiaries with mild cognitive impairment (MCI) or dementia including 2,000 Black/African American and 2,000 Latino/Hispanic individuals. To ensure diversity, we developed a comprehensive recruitment strategy using a diverse, culturally‐trained staff that includes:• Identifying Dementia Specialists experienced recruiting minorities• Embedding high‐impact community engagement in select regions• Increasing capacity of specialists and PET facilities to engage minorities• Increasing pipeline of referrals to Dementia Specialists• Creating a culturally‐informed awareness campaignResultNew IDEAS has enrolled 4,524 participants including 954 (21.1%) Black/African American, and 842 (18.6%) Hispanic/Latinx. Median age is 76 years; 54% are female. More Black/African American (46.6%) and Hispanic/Latinx (42.6%) participants had a dementia diagnosis compared to the overall cohort (33.9%). More Black/African American (37.4%) and Hispanic/Latinx (37%) participants were enrolled in Medicare Advantage compared to the overall cohort (19.5%).During implementation, we encountered additional barriers to minority participation including: dementia specialists and PET facilities located greater distance from minority neighborhoods, lack of transportation to visits, fewer academic medical sites registered, concerns about co‐pays, and dementia specialists not accepting new patients. New strategies are being implemented to address some of barriers including coverage of co‐pays and assistance with transportation.ConclusionNew IDEAS has enrolled more Black/African American and Hispanic/Latinx participants than any amyloid PET study published to date. Despite some success with minority enrollment, recruitment has been hampered by underlying structural barriers such as lack of access to dementia care in minority communities and higher Medicare Advantage rates. Additional resources and policy changes are needed to allow more equitable access to research and dementia care.

Causal relationship between sleep traits and cognitive impairment: A Mendelian randomization study.

Observational studies had demonstrated a link between sleep disturbances and cognitive decline. Here, we aimed to investigate the causal association between genetically predicted sleep traits and cognitive impairment using Mendelian randomization (MR). Using strict criteria, we selected genetic variants from European ancestry Genome-wide association studies (GWAS) from the Sleep Disorders Knowledge Portal and UK Biobank as instrumental variables for several sleep traits, including insomnia, sleep duration, daytime sleepiness, daytime napping, and chronotype. Summary statistics related to cognitive impairment were derived from five different GWAS, including the Social Science Genetic Association Consortium. The role of self-reported sleep trait phenotypes in the etiology of cognitive impairment was explored using inverse-variance weighted (IVW) tests, MR-Egger tests, and weighted medians, and sensitivity analyses were conducted to ensure robustness. In the main IVW analysis, sleep duration (reaction time: β=-0.05, 95% CI -0.07 to -0.04, p=1.93×10-12 ), daytime sleepiness (average cortical thickness: β=-0.12, 95% CI -0.22 to -0.02, p=0.023), and daytime napping (fluid intelligence: β=-0.47, 95% CI -0.87 to -0.07, p=0.021; hippocampal volume in Alzheimer's disease: β=-0.99, 95% CI -1.64 to -0.35, p=0.002) were significantly negatively correlated with cognitive performance. However, any effects of insomnia and chronotype on cognitive impairment were not determined. Our findings highlighted that focusing on sleep behaviors or distinct sleep patterns-particularly sleep duration, daytime sleepiness, and daytime napping, was a promising approach for preventing cognitive impairment. This study also shed light on risk factors for and potential early markers of cognitive impairment risk factors.

4 Traumatic Brain Injury Does Not Alter the Course of Neurocognitive Functioning Later in Life

Objective:History of traumatic brain injury (TBI) is associated with increased risk of dementia, but few studies have evaluated whether TBI history alters the course of neurocognitive decline, and existing literature on this topic is limited to short follow-up and smaller samples. The primary aim of this study was to evaluate whether a history of TBI (TBI+) influences neurocognitive decline later-in-life among older adults with or without cognitive impairment [i.e., normally aging, Mild Cognitive Impairment (MCI), or dementia].Participants and Methods:Participants included individuals from the National Alzheimer’s Coordinating Center (NACC) who were at least 50 years old and with 3 to 6 visits (M number of visits = 4.43). Participants with any self-reported history of TBI (n = 1,467) were matched 1:1 to individuals with no reported history of TBI (TBI-) from a sample of approximately 45,000 participants using case-control matching based on age (+/- 2 years), sex, education, race, ethnicity, cognitive diagnosis [cognitively normal (CN), MCI, or all-cause dementia], etiology of cognitive impairment, functional decline (Clinical Dementia Rating Scale, CDR), number of Apolipoprotein E4 (APOE ε4) alleles, and number of annual visits (3 to 6). Mixed linear models were used to assess longitudinal neuropsychological test composites (using NACC normative data) of executive functioning/attention/speed (EFAS), language, and memory in TBI+ and TBI- participants. Interactions between TBI and demographics, APOE ε4 status, and cognitive diagnosis were also examined.Results:Following matching procedures, TBI+ (n=1467) and TBI- (n=1467) groups were nearly identical in age (TBI+ M = 71.59, SD = 8.49; TBI- M = 71.63, SD = 8.44), education (TBI+ M = 16.12, SD = 2.59; TBI- M = 16.10, SD = 2.52), sex (both 55% male), race (both 90% White), ethnicity (both 98% non-Hispanic), APOE ε4 alleles (both 0 = 62%, 1 = 33%, 2 = 5%), baseline cognitive diagnoses (both CN = 60%, MCI = 18%, dementia = 12%), and global CDR (TBI+ M = 0.30, SD = 0.38, TBI- M = 0.30, SD = 0.38). At baseline, groups had similar Z-scores of in EFAS (TBI+ Mefas = -0.02, SD = 1.21; TBI- Mefas = -0.04, SD = 1.27), language (TBI+ MLanguage = -0.48, SD = 0.98; TBI- MLanguage = -0.55, SD = 1.05), and memory (TBI+ MMemory = -0.45, SD = 1.28; TBI- MMemory = -0.45, SD =1.28). The course of change in neuropsychological functioning worsened longitudinally, but did not differ between TBI groups (p’s > .110). There were no significant interactions between TBI history and age, sex, education, race/ethnicity, number of APOE ε4 status, or cognitive diagnosis (all p’s > .027).Conclusions:In this matched case-control design, our findings suggest that a history of TBI, regardless of demographic factors, APOE ε4 status, and cognitive diagnosis, does not significantly alter the course of neurocognitive functioning later-in-life in older adults with and without cognitive impairment. Future clinicopathological longitudinal studies with well characterized TBI histories and the associated clinical course are needed to help clarify the mechanism by which TBI may increase dementia risk for some individuals, without affecting course of decline.

A Case of Progressive Left Leg Weakness and Vision Changes: Focal Inflammatory Cerebral Amyloid Angiopathy Masquerading as a Glioma (P12-5.003)

<h3>Objective:</h3> To emphasize the need to consider tumefactive focal inflammatory cerebral amyloid angiopathy (CAA) in the differential diagnosis of CNS lesions. <h3>Background:</h3> Although classically considered an etiology of cognitive impairment in the elderly, CAA represents a spectrum of disease. CAA-related inflammation (CAA-ri), a distinct CAA phenotype, is characterized by vascular inflammation from amyloid deposition. CAA-ri may rarely appear as a tumefactive lesion, mimicking CNS malignancy. We present a case of biopsy-proven focal CAA-ri initially misidentified as a glioma, with the goal of increasing awareness of this entity. <h3>Design/Methods:</h3> Not applicable <h3>Results:</h3> A 68-year-old man with Parkinson’s disease presented with progressive left lower extremity weakness, word finding difficulty and vision changes. Neurological examination revealed Parkinsonian features, left homonymous superior quadrantanopia and left leg weakness. Brain MRI revealed a non-enhancing FLAIR hyperintensity in the subcortical right parieto-occipital lobe, with numerous susceptibility-weighted foci within this area, consistent with microhemorrhages versus vascular inflammation. Flash frozen pathology was initially suggestive of glioma, prompting lesionectomy. Final pathology revealed inflammation of small and medium sized blood vessels, multinucleated giant cells and positive Congo-red staining, consistent with necrotizing vasculitis and amyloid angiopathy. Treatment with steroids was deferred following risk-benefit analysis. <h3>Conclusions:</h3> We report a unique case of tumefactive CAA-ri, a clinicopathologic variant of CAA, manifesting as a mass-like lesion with distinguishing radiographic features. Our literature review identified only three prior reports of this entity. Clinical presentation depends on lesion size, location, and presence of edema and inflammation. While our patient lacked systemic co-pathologies, uterine involvement and carpal tunnel syndrome have been reported. Management relies on vascular risk modification, and steroids or immunosuppressants for active inflammation. Our case underscores the need to recognize CAA-ri in the differential of mass-like lesions. Recognizing the spectrum of CAA-related disease is key in understanding the natural history of the disease, and potential benefit of future anti-amyloid therapies. <b>Disclosure:</b> Dr. Mohammadi has nothing to disclose. Dr. Lilian has nothing to disclose. Mr. Chen has received research support from National Institues of Health. Michelle Offit, MS has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Streicher has nothing to disclose. Dr. Sabharwal has nothing to disclose.

Hippocampal volume and cognitive performance in children with congenital heart disease

BackgroundCongenital heart disease (CHD) is associated with an increased risk of brain abnormalities. Studies indicate a particular vulnerability of the hippocampus to hypoxia and inflammation. Yet, information regarding the hippocampus and its relation to cognitive function in school-age children with CHD remains scarce.MethodsChildren who underwent cardiopulmonary bypass surgery for CHD (N = 17) and healthy controls (N = 14) at 10 years of age underwent neurodevelopmental assessment and cerebral magnetic resonance imaging to measure IQ, working memory performance and hippocampal volume.ResultsIQ was significantly lower in children with CHD compared to controls (98 vs 112, P = 0.02). Children with CHD showed worse working memory performance with significantly lower scores in the letter-number sequencing test (P = 0.02). After adjusting for total brain volume, hippocampal volume was smaller in children with CHD compared to controls (P < 0.01). Smaller hippocampal volume was associated with lower IQ (P = 0.04), and digit span scaled score (P = 0.03), but not with other working memory tests (P > 0.1).ConclusionThis study suggests that the hippocampus may be particularly susceptible in children with CHD thereby contributing to cognitive impairments. Further research is necessary to understand the contribution of the hippocampus to cognitive impairments in children with CHD.ImpactIQ is significantly lower in school-age children with congenital heart disease compared to controls.Working memory performance seems to be worse in children with congenital heart disease.Smaller hippocampal volume is associated with lower IQ and seems to be associated with lower working memory performance.The study adds knowledge on the etiology of cognitive impairments in school-age children with congenital heart disease.

Is Periodontitis Associated with Age-Related Cognitive Impairment? The Systematic Review, Confounders Assessment and Meta-Analysis of Clinical Studies.

It has been suggested that molecular pathological mechanisms responsible for periodontitis can be linked with biochemical alterations in neurodegenerative disorders. Hypothetically, chronic systemic inflammation as a response to periodontitis plays a role in the etiology of cognitive impairment. This study aimed to determine whether periodontitis (PDS) is a risk factor for age-related cognitive impairment (ACI) based on evidence of clinical studies. A comprehensive, structured systematic review of existing data adhering to the Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) guidelines was carried out. Five electronic databases, PubMed, Embase, Scopus, Web of Science, and Cochrane, were searched for key terms published in peer-reviewed journals until January 2021. The Newcastle-Ottawa scale was used to assess the quality of studies and risk of bias. The primary and residual confounders were explored and evaluated. A meta-analysis synthesizing quantitative data was carried out using a random-effects model. Seventeen clinical studies were identified, including 14 cohort, one cross-sectional, and two case-control studies. Study samples ranged from 85 to 262,349 subjects, with follow-up between 2 and 32 years, and age above 45 years, except for two studies. The findings of studies suggesting the PDS-ACI relationship revealed substantial differences in design and methods. A noticeable variation related to the treatment of confounders was observed. Quality assessment unveiled a moderate quality of evidence and risk of bias. The subgroups meta-analysis and pooled sensitivity analysis of results from seven eligible studies demonstrated overall that the presence of PDS is associated with an increased risk of incidence of cognitive impairment (OR = 1.36, 95% CI 1.03-1.79), particularly dementia (OR = 1.39, 95% CI 1.02-1.88) and Alzheimer's disease (OR = 1.03 95% CI 0.98-1.07)). However, a considerable heterogeneity of synthesized data (I2 = 96%) and potential publication bias might affect obtained results. While there is a moderate statistical association between periodontitis and dementia, as well as Alzheimer's disease, the risk of bias in the evidence prevents conclusions being drawn about the role of periodontitis as a risk factor for age-related cognitive impairment.

Exposure to a mixture of heavy metals induces cognitive impairment: Genes and microRNAs involved

Converging evidence demonstrates that microRNAs (miRNAs) play an important role in the etiology of cognitive impairment. Thus, we aim to: (i) identify the molecular mechanisms of heavy metals, particularly miRNAs involved in the development of cognitive impairment; and (ii) generate miRNA sponges to prevent them from binding with their target messenger RNAs. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org), MicroRNA ENrichment TURned NETwork (MIENTURNET, http://userver.bio.uniroma1.it/apps/mienturnet/) and the microRNA sponge generator and tester (miRNAsong, http://www.med.muni.cz/histology/miRNAsong) were used as the core data-mining approaches in the current study. We observed that lead acetate, arsenic, gold, copper, iron, and aluminum, as well as their mixtures, had significant effects on the development of cognitive impairment. Although prevalent genes obtained from investigated heavy metals of cognitive impairment were different, the "PI3K-Akt signaling pathway", "pathways of neurodegeneration-multiple diseases", "apoptosis", "apoptosis-multiple species", "p53 signaling pathway", "NF-kappa B signaling pathway", and "Alzheimer’s disease pathway" were highlighted. The mixed heavy metals altered the genes BAX, CASP3, BCL2, TNF, and IL-1B, indicating the significance of apoptosis and pro-inflammatory cytokines in the pathogenesis of cognitive impairment and the possibility of targeting these genes in future neuroprotective therapy. In addition, we used a network-based approach to identify key genes, miRNAs, pathways, and diseases related to the development of cognitive impairment. We also found 16 significant miRNAs related to cognitive impairment (hsa-miR-1–3p, hsa-let-7a-5p, hsa-miR-9–5p, hsa-miR-16–5p, hsa-miR-17–5p, hsa-miR-20a-5p, hsa-miR-26a-5p, hsa-miR-26b-5p, hsa-miR-34a-5p, hsa-miR-101–3p, hsa-miR-106a-5p, hsa-miR-128–3p, hsa-miR-144–3p, hsa-miR-199a-3p, hsa-miR-204–5p, and hsa-miR-335–5p). Finally, we created and evaluated miRNA sponge sequences for these miRNAs in silico. Further studies, including in vivo and in vitro, are needed to assess the link between these genes, miRNAs, pathways, and cognitive impairment.

Silent Cerebral Infarction on Brain MRI Is Associated with Cognitive Impairment in Ittp Survivors in Hematological Remission

▪BACKGROUND: Individuals with immune mediated thrombotic thrombocytopenic purpura (iTTP) frequently exhibit cognitive impairment and are at higher risk of stroke than matched controls. However, the etiology of cognitive impairment in these individuals has not been established. We conducted this prospective study to examine the patterns of cognitive impairment and to test the hypothesis that cognitive impairment in iTTP survivors is associated with silent cerebral infarction (SCI, ischemic lesions on brain MRI without corresponding overt neurodeficits), which are also a risk factor for future stroke.METHODS: We prospectively enrolled adult (age ≥ 18 years) patients with iTTP and age- and sex-matched controls without prior iTTP or stroke. iTTP was diagnosed based on ADAMTS13 activity <10% during an acute episode. All study assessments were performed after achieving hematological remission (platelet count >150x10 9/L for at least 30 days after stopping plasma exchange and/or caplacizumab). Participants undergo annual study visits including the following study measures: 1) NIH stroke scale to rule out acute stroke, 2) NIH ToolBox Cognition battery, a comprehensive iPad based neurobehavioral tool that has been validated across multiple populations and for which normative control data are available. The NIH ToolBox Cognition Battery tests multiple cognitive domains (Figure 1) including executive function (dimensional change card sort test, flanker inhibitory control and attention test), processing speed (pattern comparison test), episodic memory (picture sequence memory test), working memory (list sort working memory test), language (oral reading recognition, picture vocabulary test). We used T scores adjusted for age, sex, race and educational attainment where the normative mean T score is 50 with standard deviation (SD) of 10. Mild and major cognitive impairment are defined as a T scores that are 1-2 SD below mean and > 2SD below mean for any domain, respectively; 2) Brain MRI: SCI is defined as a infarct-like lesion (punctate T2 and FLAIR hyperintensity) without corresponding neurodeficits. The Chi-squared test and Mann Whitney test were used to compare categorical and continuous variables across groups, respectively.RESULTS: Between September 2020 and June 2021, we enrolled 34 participants including 28 iTTP patients and 6 controls. Demographics and clinical characteristics of patients and controls are summarized in Table 1. NIH Stroke Scale score was 0 in all controls and all but one iTTP patient (score = 1). Among iTTP patients, 28.6% (8/28) had prior stroke (including during acute episodes).(i) iTTP survivors demonstrate cognitive deficits affecting executive function and processing speed: Among iTTP patients, 46.4% had cognitive impairment in at least one domain including 25% (7/28) with major cognitive impairment and 21.4% (6/28) with mild cognitive impairment (> 1 SD below mean T score). Among controls, 0% had major cognitive impairment and 16.6% (1/6) had mild cognitive impairment. Figure 1 shows detailed cognitive testing results for iTTP patients and controls. iTTP patients most commonly had deficits (T score < 40) in executive function (flanker inhibition test, dimensional change card sort test) and processing speed (pattern comparison test) (Table 1).(ii) Silent cerebral infarction is associated with major cognitive impairment: MRI was completed in 24 iTTP patients and all controls. SCI was present in 50% (12/24) of iTTP patients (representative image, figure 2A) and 16.6% (1/6) controls. Another 29.1% (7/24) had evidence of prior stroke. Rate of SCI was 35.7% in patients without cognitive deficits, 50% in those with minor cognitive deficits and 83.3% in those with major cognitive deficits. SCI was present in 83.3% (5/6) with major cognitive impairment versus 38.9% (7/18) without major cognitive impairment (P = 0.05) (Figure 2B).CONCLUSIONS: Cognitive deficits in iTTP survivors primarily affect executive function and processing speed and are associated with SCI suggesting ischemic etiology. Whether SCI occur during acute episodes or during remission (with remission ADAMTS13 as a risk factor) is being studied prospectively with serial MRI and cognitive assessment. iTTP patients may benefit from neurocognitive testing and referral to neuropsychological therapy, where appropriate, and aggressive measures to address risk factors for cerebrovascular disease. [Display omitted] DisclosuresNaik: Rigel: Research Funding. Lanzkron: GBT: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company; Novartis: Research Funding; Novo Nordisk: Consultancy; Imara: Research Funding; CSL Behring: Research Funding; Shire: Research Funding; Bluebird Bio: Consultancy. Chaturvedi: Sanofi Genzyme: Other: Advisory board member; Argenx: Other: Advisory board member; UCB: Other: Advisory board participation; Dova: Other: Advisory board member; Alexion: Other: Advisory board member.

A Modified CAIDE Risk Score as a Screening Tool for Cognitive Impairment in Older Adults.

Although an efficacious dementia-risk score system, Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) was derived using midlife risk factors in a population with low educational attainment that does not reflect today's US population, and requires laboratory biomarkers, which are not always available. Develop and validate a modified CAIDE (mCAIDE) system and test its ability to predict presence, severity, and etiology of cognitive impairment in older adults. Population consisted of 449 participants in dementia research (N = 230; community sample; 67.9±10.0 years old, 29.6%male, 13.7±4.1 years education) or receiving dementia clinical services (N = 219; clinical sample; 74.3±9.8 years old, 50.2%male, 15.5±2.6 years education). The mCAIDE, which includes self-reported and performance-based rather than blood-derived measures, was developed in the community sample and tested in the independent clinical sample. Validity against Framingham, Hachinski, and CAIDE risk scores was assessed. Higher mCAIDE quartiles were associated with lower performance on global and domain-specific cognitive tests. Each one-point increase in mCAIDE increased the odds of mild cognitive impairment (MCI) by up to 65%, those of AD by 69%, and those for non-AD dementia by > 85%, with highest scores in cases with vascular etiologies. Being in the highest mCAIDE risk group improved ability to discriminate dementia from MCI and controls and MCI from controls, with a cut-off of ≥7 points offering the highest sensitivity, specificity, and positive and negative predictive values. mCAIDE is a robust indicator of cognitive impairment in community-dwelling seniors, which can discriminate well between dementia severity including MCI versus controls. The mCAIDE may be a valuable tool for case ascertainment in research studies, helping flag primary care patients for cognitive testing, and identify those in need of lifestyle interventions for symptomatic control.

How can automated linguistic analysis help to discern functional cognitive disorder from healthy controls and mild cognitive impairment?

AimsThe disease burden of cognitive impairment is significant and increasing. The aetiology of cognitive impairment can be structural, such as in mild cognitive impairment (MCI) due to early Alzheimer's disease (AD), or in functional cognitive disorder (FCD), where there is no structural pathology. Many people with FCD receive a delayed diagnosis following invasive or costly investigations. Accurate, timely diagnosis improves outcomes across all patients with cognitive impairment. Research suggests that analysis of linguistic features of speech may provide a non-invasive diagnostic tool. This study aimed to investigate the linguistic differences in conversations between people with early signs of cognitive impairment with and without structural pathology, with a view to developing a screening tool using linguistic analysis of conversations.MethodIn this explorative, cross-sectional study, we recruited 25 people with MCI considered likely due to AD, (diagnosed according to Petersen's criteria and referred to as PwMCI), 25 healthy controls (HCs) and 15 people with FCD (PwFCD). Participants’ responses to a standard questionnaire asked by an interactional virtual agent (Digital Doctor) were quantified using previously identified parameters. This paper presents statistical analyses of the responses and a discussion of the results.ResultPwMCI produced fewer words than PwFCD and HCs. The ratio of pauses to speech was generally lower for PwMCI and PwFCD than for HCs. PwMCI showed a greater pause to speech ratio for recent questions (such as ‘what did you do at the weekend?’) compared with the HCs. Those with FCD showed the greatest pause to speech ratio in remote memory questions (such as ‘what was your first job?’). The average age of acquisition of answers for verbal fluency questions was lower in the MCI group than HCs.ConclusionThe results and qualitative observations support the relative preservation of remote memory compared to recent memory in MCI due to AD and decreased spontaneous elaboration in MCI compared with healthy controls and patients with FCD. Word count, age of acquisition and pause to speech ratio could form part of a diagnostic toolkit in identifying those with structural and functional causes of cognitive impairment. Further investigation is required using a large sample.

Cognitive impairment in schizophrenia: relationships with cortical thickness in fronto-temporal regions, and dissociability from symptom severity

Cognitive impairments are a core and persistent characteristic of schizophrenia with implications for daily functioning. These show only limited response to antipsychotic treatment and their neural basis is not well characterised. Previous studies point to relationships between cortical thickness and cognitive performance in fronto-temporal brain regions in schizophrenia patients (SZH). There is also evidence that these relationships might be independent of symptom severity, suggesting dissociable disease processes. We set out to explore these possibilities in a sample of 70 SZH and 72 age and gender-matched healthy controls (provided by the Center of Biomedical Research Excellence (COBRE)). Cortical thickness within fronto-temporal regions implicated by previous work was considered in relation to performance across various cognitive domains (from the MATRICS Cognitive Battery). Compared to controls, SZH had thinner cortices across most fronto-temporal regions and significantly lower performance on all cognitive domains. Robust relationships with cortical thickness were found: visual learning and attention performance correlated with bilateral superior and middle frontal thickness in SZH only. Correlations between attention performance and right transverse temporal thickness were also specific to SZH. Findings point to the importance of these regions for cognitive performance in SZH, possibly reflecting compensatory processes and/or aberrant connectivity. No links to symptom severity were observed in these regions, suggesting these relationships are dissociable from underlying psychotic symptomology. Findings enhance understanding of the brain structural underpinnings and possible aetiology of cognitive impairment in SZH.

Gene polymorphisms of cognitive function in patients with bipolar disorder: A systematic review and meta-analysis

Objectives: Evidence showed that the etiology of cognitive impairment in bipolar disorder (BD) is related to genetic susceptibility. But results from many studies evaluating the association between candidate genes and cognitive function in BD are inconsistent. To define the effect of risk target single-nucleotide polymorphisms (SNPs) on the association of cognition in BD, we did a systematic review and meta-analysis to study the risk genetic variants. Methods: A search for literature was conducted through online databases updated as of October 2018. Recruited studies were compared for cognitive difference in BD patients with certain gene polymorphisms. Results: Meta-analyses were conducted, for two SNPs of target genes including brain-derived neurotrophic factor (rs6265) and calcium channel, voltage-dependent, L type, alpha 1C subunit (rs1006737), in the recruited seven studies. Quantitative analysis showed no significance in the association between the polymorphisms of rs6265 or rs1006737 with global intelligence quotient or rs6265 with Wisconsin Card Sorting test in BD. Conclusion: Our results implied that the cognitive impairment in patients with BD might not be explained by a SNP in current evidence. We suggest that further studies with larger sample size and deeper phenotype are needed to elucidate the relevance of gene variant model contributed to the susceptibility of cognitive dysfunction in patients with BD.

P5347Pulse wave velocity is associated with cognitive impairment in older adults with heart disease

Abstract Introduction Cognitive impairment is highly frequent in adults older than 50 years as well as classical cardiovascular risk factors which cause vascular and endothelial dysfunction. The vascular etiology of cognitive impairment is well known, but it has been poorly studied the possible association between this cognitive status and the arterial stiffness evaluation in patients with heart disease. Purpose The aim of our study was to evaluate the association between cognitive impairment and vascular function in subjects with heart disease. Methods By an analytic transversal study, we included any sex patients older than 50 years, with known chronic cardiovascular disease (ischemic, valvular or conduction abnormalities). All of them were evaluated by Blessed Orientation-Memory-Concentration (BOMC) Test and Mini Mental State Examination (MMSE) to determine cognitive impairment; all patients underwent vascular function evaluation at same time with Arteriograph device, to determine augmentation index (AI) and aortic pulse wave velocity (PWV). All subjects gave informed consent. Protocol was authorized by ethics and science committee. Quantitative variables are resumed as median (interquartile range) and qualitative variables as absolute and relative frequencies. Mann-Whitney's and χ2 (or Fisher exact) tests were used for association analysis. For potentially confounders variables we use logistic regression; alpha confidence level was 0.05 for all tests. Results One-hundred and seven patients were included; 43 (40.1%) had cognitive impairment (CIm). Age was 76 (71–83) years vs. 64 (59–70) years in the non-cognitive impairment (NCIm), p&lt;0.001; cerebrovascular accident history was more frequent in CIm group [13 (30.2%) vs. 9 (14.0%), p=0.04). Sex, diabetes mellitus, hypertension, current smoke, lipids alteration, body mass index, serum glucose, creatinine, cholesterol, HDL-cholesterol, non-HDL cholesterol, hemoglobin, ischemic, valvular or conduction abnormalities pathology, atrial fibrillation, left atrial enlargement, left ventricle ejection fraction and treatment with statins, antiplatelet or anticoagulants had not significant differences between groups with or without CIm. Pulse wave velocity and In CIm group, the PWV was 9.4 (7.4–11.4) m/s vs. 8.2 (7.2–9.3) m/s, p=0.016; augmentation index showed no significant differences between groups [29 (10–48) vs. 27 (13–47) m/s, p=0.78]. In multivariate analysis, PWV (Odds ratio 1.27, confidence interval 1.15–1.69, p=0.03), and age (Odds ratio 1.19, confidence interval 1.10–1.30, p=0.01), remain as independent predictors of cognitive impairment. Conclusions In older adults with cardiovascular disease, pulse wave velocity and age are associated with cognitive impairment independently of other risk classical risk factors and cardiovascular drugs treatment. Acknowledgement/Funding FOSISS 290480

Systemic inflammatory impact of periodontitis on cognitive impairment.

The role in dementia of systemic inflammation derived from periodontal disease is not fully elucidated. The objective of our study was to examine the impact of inflammation on the relationship between periodontitis and cognitive impairment. We have designed a case (n=171) and control (n=131) study to determine the periodontal health status, grade of cognitive impairment/dementia and systemic inflammation level, the last being measured by analysis of 29 inflammatory biomarkers using multiplex techniques. At the time of sampling, 11 of the 29 inflammatory biomarkers were associated with cognitive impairment in patients with more severe periodontitis. However, the inflammatory response to severe periodontitis was more reduced (lower biomarker concentrations) in cases (with cognitive impairment or dementia) than in (cognitively healthy) controls, an unexpected finding. Based on these results, we cannot confirm that systemic inflammation derived from periodontal disease plays a relevant role in the aetiology of cognitive impairment.

Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia

Amyloid positron emission tomography (PET) detects amyloid plaques in the brain, a core neuropathological feature of Alzheimer disease. To determine if amyloid PET is associated with subsequent changes in the management of patients with mild cognitive impairment (MCI) or dementia of uncertain etiology. The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study was a single-group, multisite longitudinal study that assessed the association between amyloid PET and subsequent changes in clinical management for Medicare beneficiaries with MCI or dementia. Participants were required to meet published appropriate use criteria stating that etiology of cognitive impairment was unknown, Alzheimer disease was a diagnostic consideration, and knowledge of PET results was expected to change diagnosis and management. A total of 946 dementia specialists at 595 US sites enrolled 16 008 patients between February 2016 and September 2017. Patients were followed up through January 2018. Dementia specialists documented their diagnosis and management plan before PET and again 90 (±30) days after PET. Participants underwent amyloid PET at 343 imaging centers. The primary end point was change in management between the pre- and post-PET visits, as assessed by a composite outcome that included Alzheimer disease drug therapy, other drug therapy, and counseling about safety and future planning. The study was powered to detect a 30% or greater change in the MCI and dementia groups. One of 2 secondary end points is reported: the proportion of changes in diagnosis (from Alzheimer disease to non-Alzheimer disease and vice versa) between pre- and post-PET visits. Among 16 008 registered participants, 11 409 (71.3%) completed study procedures and were included in the analysis (median age, 75 years [interquartile range, 71-80]; 50.9% women; 60.5% with MCI). Amyloid PET results were positive in 3817 patients with MCI (55.3%) and 3154 patients with dementia (70.1%). The composite end point changed in 4159 of 6905 patients with MCI (60.2% [95% CI, 59.1%-61.4%]) and 2859 of 4504 patients with dementia (63.5% [95% CI, 62.1%-64.9%]), significantly exceeding the 30% threshold in each group (P < .001, 1-sided). The etiologic diagnosis changed from Alzheimer disease to non-Alzheimer disease in 2860 of 11 409 patients (25.1% [95% CI, 24.3%-25.9%]) and from non-Alzheimer disease to Alzheimer disease in 1201 of 11 409 (10.5% [95% CI, 10.0%-11.1%]). Among Medicare beneficiaries with MCI or dementia of uncertain etiology evaluated by dementia specialists, the use of amyloid PET was associated with changes in clinical management within 90 days. Further research is needed to determine whether amyloid PET is associated with improved clinical outcomes. ClinicalTrials.gov Identifier: NCT02420756.