Browsing by Subject "Cognitive impairment"

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    39. Viruses and Schizophrenia: Implications for Pathophysiology and Treatment
    (Oxford University Press, 2018-04) Breier, Alan; Psychiatry, School of Medicine
    Overall Abstract: The viral hypothesis of schizophrenia posits that viral infections disrupts cortical circuits that give rise to schizophrenia psychopathology. Prenatal viral exposure during key neurodevelopmental periods, either through direct effects on fetal brain or exposure to excessive maternal cytokines and other chemokines, have been implicated. In addition, abnormal activation of dormant neuro-viruses have been linked to the pathophysiology of schizophrenia. Activation of dormant viruses has potentially important treatment implication for therapies, such as valacyclovir, that suppress viral activity. Among the viruses that have been mostly frequently associated with schizophrenia include herpes simplex virus type 1 (HSV1) and Epstein-Barr virus (EBV). The purpose of this symposium is to focus on the role of viruses in the pathophysiology of schizophrenia and results of antiviral treatment trials in this illness.
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    Acute kidney injury in Ugandan children with severe malaria is associated with long-term behavioral problems
    (Public Library of Science, 2019-12-17) Hickson, Meredith R.; Conroy, Andrea L.; Bangirana, Paul; Opoka, Robert O.; Idro, Richard; Ssenkusu, John M.; John, Chandy C.; Pediatrics, School of Medicine
    Background Acute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown. Methods We conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity. Results AKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children <6 years of age. Conclusions AKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.
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    Adverse Outcome Following Mild Traumatic Brain Injury Is Associated with Microstructure Alterations at the Gray and White Matter Boundary
    (MDPI, 2023-08-21) Pankatz, Lara; Rojczyk, Philine; Seitz-Holland, Johanna; Bouix, Sylvain; Jung, Leonard B.; Wiegand, Tim L. T.; Bonke, Elena M.; Sollmann, Nico; Kaufmann, Elisabeth; Carrington, Holly; Puri, Twishi; Rathi, Yogesh; Coleman, Michael J.; Pasternak, Ofer; George, Mark S.; McAllister, Thomas W.; Zafonte, Ross; Stein, Murray B.; Marx, Christine E.; Shenton, Martha E.; Koerte, Inga K.; Psychiatry, School of Medicine
    The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort (n = 147) and the comparison cohort (n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA (p < 0.011), and deep WM FA (p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms (p < 0.039), functional (p < 0.016), and cognitive impairment (p < 0.049). Deep WM FA was associated with functional impairment (p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome (p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI.
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    Aging and Post-Intensive Care Syndrome–Family (PICS-F): A Critical Need for Geriatric Psychiatry
    (Elsevier, 2019) Serrano, Patricia; Kheir, You Na P.; Wang, Sophia; Khan, Sikandar; Scheunemann, Leslie; Khan, Babar; Psychiatry, School of Medicine
    Post-intensive care syndrome–family (PICS-F) describes the psychological symptoms that affect the family members of patients hospitalized in the intensive care unit (ICU) or recently discharged from the ICU. Geriatric psychiatrists should be concerned about PICS-F for several reasons. First, ICU hospitalization in older adults is associated with higher rates of cognitive and physical impairment, compared to older adults hospitalized in non-ICU settings or dwelling in the community. This confers a special burden on the caregivers of these older ICU survivors compared to other geriatric populations. Second, as caregivers themselves age, caring for this unique burden can be more challenging compared to other geriatric populations. Third, evidence for models of care centered on patients with multimorbidity and their caregivers is limited. A deeper understanding of how to care for PICS and PICS-F may inform clinical practice for other geriatric populations with multimorbidity and their caregivers. Geriatric psychiatrists may play a key role in delivering coordinated care for PICS-F by facilitating timely diagnosis and interdisciplinary collaboration, advocating for the healthcare needs of family members suffering from PICS-F, and leading efforts within healthcare systems to increase awareness and treatment of PICS-F. This clinical review will appraise the current literature about the impact of critical illness on the family members of ICU survivors and identify crucial gaps in our knowledge about PICS-F among aging patients and caregivers.
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    Association between Cognitive Function and Physical Function, Frailty, and Quality of Life in Older Breast Cancer Survivors
    (MDPI, 2024-07-31) Von Ah, Diane; Rio, Carielle Joy; Carter, Allie; Perkins, Susan M.; Stevens, Erin; Rosko, Ashley; Davenport, Ashley; Kalady, Mathew; Noonan, Anne M.; Crouch, Adele; Storey, Susan; Overcash, Janine; Han, Claire J.; Yang, Yesol; Li, Haiying; Saligan, Leorey N.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Background: Older cancer survivors in general are at greater risk for cancer-related cognitive impairment (CRCI), yet few studies have explored its association with health outcomes. This study examined the association between subjective and objective measures of cognitive function and physical function, frailty, and quality of life (QoL) among older breast cancer survivors. Materials and methods: Older breast cancer survivors who reported cognitive concerns completed surveys on patient-reported cognitive function, physical function, frailty, and QoL as well as objective tests of visuospatial working memory and sustained attention. Data were analyzed using descriptive statistics and separate linear regression models. Results: A total of 219 female breast cancer survivors completed the study. Perceived cognitive abilities were associated with better physical function, frailty, and QoL (p ≤ 0.001) while cognitive concerns were negatively related with these metrics (p ≤ 0.001). Poorer visuospatial working memory and sustained attention were linked to increased frailty (p ≤ 0.001-0.01), whereas poorer sustained attention was associated with poorer physical function (p < 0.01). Conclusions: Older breast cancer survivors with perceived cognitive impairment and poorer cognitive performance reported poorer physical functioning, increased frailty, and poorer QoL. These findings underscore the importance of assessing cognitive concerns and their associated outcomes in older breast cancer survivors.
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    Association of cognitive impairment and breast cancer survivorship on quality of life in younger breast cancer survivors
    (Springer, 2021) Von Ah, Diane; Crouch, Adele D.; Monahan, Patrick O.; Stump, Timothy E; Unverzagt, Frederick W.; Storey, Susan; Cohee, Andrea A.; Cella, David; Champion, Victoria L.
    Purpose Younger breast cancer survivors (BCS) often report cognitive impairment and poor quality of life (QoL), which could be interrelated. The purpose of this study was to examine the association of cognitive impairment and breast cancer status (BCS versus healthy control (HC)), with QoL, which included psychological (depressive symptoms, well-being, perceived stress, and personal growth) and physical well-being (physical functioning and fatigue). Methods Four hundred ninety-eight BCS (≤45 years at diagnosis) who were 3 to 8 years post-chemotherapy treatment and 394 HC completed subjective questionnaires and a one-time neuropsychological assessment, including tests of attention, memory, processing speed, and verbal fluency. For each test, cognitive impairment was defined as scoring 1.5 and 2.0 standard deviations below the mean of the HC group. Separate linear regression models for each outcome were ran controlling for known covariates. Results BCS reported significantly more memory problems than HC (p < 0.0001), with up to 23% having significant impairment. Cognitive performance did not differ significantly between BCS and HCs. BCS vs. HCs had greater depression and fatigue, yet more personal growth. Objective and subjective cognitive impairment were significantly related to greater depressive symptoms and perceived stress and lower well-being and physical functioning; whereas, objective impairment was related to less personal growth and subjective impairment was related to greater fatigue. Conclusions Younger BCS report significant cognitive impairment years after treatment which may relate to greater decrements in QoL.
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    Associations Between Social Network Characteristics and Brain Structure Among Older Adults
    (Wiley, 2024) Manchella, Mohit K.; Logan, Paige E.; Perry, Brea L.; Peng, Siyun; Risacher, Shannon L.; Saykin, Andrew J.; Apostolova, Liana G.; Neurology, School of Medicine
    Introduction: Social connectedness is associated with slower cognitive decline among older adults. Recent research suggests that distinct aspects of social networks may have differential effects on cognitive resilience, but few studies analyze brain structure. Methods: This study includes 117 cognitively impaired and 59 unimpaired older adults. The effects of social network characteristics (bridging/bonding) on brain regions of interests were analyzed using linear regressions and voxel-wise multiple linear regressions of gray matter density. Results: Increased social bridging was associated with greater bilateral amygdala volume and insular thickness, and left frontal lobe thickness, putamen, and thalamic volumes. Increased social bonding was associated with greater bilateral medial orbitofrontal and caudal anterior cingulate thickness, as well as right frontal lobe thickness, putamen, and amygdala volumes. Discussion: The associations between social connectedness and brain structure vary depending on the types of social enrichment accessible through social networks, suggesting that psychosocial interventions could mitigate neurodegeneration. Highlights: Distinct forms of social capital are uniquely linked to gray matter density (GMD). Bridging is associated with preserved GMD in limbic system structures. Bonding is associated with preserved GMD in frontal lobe regions. Bridging is associated with increased brain reserve in sensory processing regions. Bonding is associated with increased brain reserve in regions of stress modulation.
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    Blood biomarkers of neuronal injury in paediatric cerebral malaria and severe malarial anaemia
    (Oxford University Press, 2023-11-27) Datta, Dibyadyuti; Gopinadhan, Adnan; Soto, Alejandro; Bangirana, Paul; Opoka, Robert O.; Conroy, Andrea L.; Saykin, Andrew J.; Kawata, Keisuke; John, Chandy C.; Pediatrics, School of Medicine
    Persistent neurodisability is a known complication in paediatric survivors of cerebral malaria and severe malarial anaemia. Tau, ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein have proven utility as biomarkers that predict adverse neurologic outcomes in adult and paediatric disorders. In paediatric severe malaria, elevated tau is associated with mortality and neurocognitive complications. We aimed to investigate whether a multi-analyte panel including ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein can serve as biomarkers of brain injury associated with mortality and neurodisability in cerebral malaria and severe malarial anaemia. In a prospective cohort study of Ugandan children, 18 months to 12 years of age with cerebral malaria (n = 182), severe malarial anaemia (n = 158), and asymptomatic community children (n = 118), we measured admission blood levels of ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein. We investigated differences in biomarker levels, associations with mortality, blood–brain barrier integrity, neurodeficits and cognitive Z-scores in survivors up to 24-month follow-up. Admission ubiquitin C-terminal hydrolase-L1 levels were elevated >95th percentile of community children in 71 and 51%, and neurofilament-light chain levels were elevated >95th percentile of community children in 40 and 37% of children with cerebral malaria and severe malarial anaemia, respectively. Glial fibrillary acidic protein was not elevated in disease groups compared with controls. In cerebral malaria, elevated neurofilament-light chain was observed in 16 children who died in hospital compared with 166 survivors (P = 0.01); elevations in ubiquitin C-terminal hydrolase-L1 levels were associated with degree of blood–brain barrier disruption (P = 0.01); and the % predictive value for neurodeficits over follow-up (discharge, 6-, 12-, and 24 months) increased for ubiquitin C-terminal hydrolase-L1 (60, 67, 72, and 83), but not neurofilament-light chain (65, 68, 60, and 67). In cerebral malaria, elevated ubiquitin C-terminal hydrolase-L1 was associated with worse memory scores in children <5 years at malaria episode who crossed to over 5 years old during follow-up cognitive testing [β −1.13 (95% confidence interval −2.05, −0.21), P = 0.02], and elevated neurofilament-light chain was associated with worse attention in children ≥5 years at malaria episode and cognitive testing [β −1.08 (95% confidence interval −2.05, −1.05), P = 0.03]. In severe malarial anaemia, elevated ubiquitin C-terminal hydrolase-L1 was associated with worse attention in children <5 years at malaria episode and cognitive testing [β −0.42 (95% confidence interval −0.76, −0.07), P = 0.02]. Ubiquitin C-terminal hydrolase-L1 and neurofilament-light chain levels are elevated in paediatric cerebral malaria and severe malarial anaemia. In cerebral malaria, elevated neurofilament-light chain is associated with mortality whereas elevated ubiquitin C-terminal hydrolase-L1 is associated with blood–brain barrier dysfunction and neurodeficits over follow-up. In cerebral malaria, both markers are associated with worse cognition, while in severe malarial anaemia, only ubiquitin C-terminal hydrolase-L1 is associated with worse cognition.
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    Brain health: the importance of recognizing cognitive impairment: an IAGG consensus conference
    (Elsevier, 2015-09-01) Morley, John E.; Morris, John C.; Berg-Weger, Marla; Borson, Soo; Carpenter, Brian D.; del Campo, Natalia; Dubois, Bruno; Fargo, Keith; Fitten, L. Jaime; Flaherty, Joseph H.; Ganguli, Mary; Grossberg, George T.; Malmstrom, Theodore K.; Petersen, Ronald D.; Rodriguez, Carroll; Saykin, Andrew J.; Scheltens, Philip; Tangalos, Eric G.; Verghese, Joe; Wilcock, Gordon; Winblad, Bengt; Woo, Jean; Vellas, Bruno; Department of Radiology and Imaging Sciences, IU School of Medicine
    Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care. Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters. An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health. Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world. This conclusion is in keeping with the position of the United States' Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient's right. The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline.
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    Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium
    (Alzheimer’s Association, 2022-09-22) de Erausquin, Gabriel A.; Snyder, Heather; Brugha, Traolach S.; Seshadri, Sudha; Carrillo, Maria; Sagar, Rajesh; Huang, Yueqin; Newton, Charles; Tartaglia, Carmela; Teunissen, Charlotte; Håkanson, Krister; Akinyemi, Rufus; Prasad, Kameshwar; D'Avossa, Giovanni; Gonzalez-Aleman, Gabriela; Hosseini, Akram; Vavougios, George D.; Sachdev, Perminder; Bankart, John; Ole Mors, Niels Peter; Lipton, Richard; Katz, Mindy; Fox, Peter T.; Katshu, Mohammad Zia; Iyengar, M. Sriram; Weinstein, Galit; Sohrabi, Hamid R.; Jenkins, Rachel; Stein, Dan J.; Hugon, Jacques; Mavreas, Venetsanos; Blangero, John; Cruchaga, Carlos; Krishna, Murali; Wadoo, Ovais; Becerra, Rodrigo; Zwir, Igor; Longstreth, William T.; Kroenenberg, Golo; Edison, Paul; Mukaetova-Ladinska, Elizabeta; Staufenberg, Ekkehart; Figueredo-Aguiar, Mariana; Yécora, Agustín; Vaca, Fabiana; Zamponi, Hernan P.; Lo Re, Vincenzina; Majid, Abdul; Sundarakumar, Jonas; Gonzalez, Hector M.; Geerlings, Mirjam I.; Skoog, Ingmar; Salmoiraghi, Alberto; Boneschi, Filippo Martinelli; Patel, Vibuthi N.; Santos, Juan M.; Arroyo, Guillermo Rivera; Moreno, Antonio Caballero; Felix, Pascal; Gallo, Carla; Arai, Hidenori; Yamada, Masahito; Iwatsubo, Takeshi; Sharma, Malveeka; Chakraborty, Nandini; Ferreccio, Catterina; Akena, Dickens; Brayne, Carol; Maestre, Gladys; Williams Blangero, Sarah; Brusco, Luis I.; Siddarth, Prabha; Hughes, Timothy M.; Ramírez Zuñiga, Alfredo; Kambeitz, Joseph; Laza, Agustin Ruiz; Allen, Norrina; Panos, Stella; Merrill, David; Ibáñez, Agustín; Tsuang, Debby; Valishvili, Nino; Shrestha, Srishti; Wang, Sophia; Padma, Vasantha; Anstey, Kaarin J.; Ravindrdanath, Vijayalakshmi; Blennow, Kaj; Mullins, Paul; Łojek, Emilia; Pria, Anand; Mosley, Thomas H.; Gowland, Penny; Girard, Timothy D.; Bowtell, Richard; Vahidy, Farhaan S.; Psychiatry, School of Medicine
    Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection. Key points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility. The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease. We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic. The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.