Browsing by Subject "Cognitive Dysfunction"
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Item Open Access Challenges in measuring the effects of pharmacological interventions on cognitive and adaptive functioning in individuals with Down syndrome: A systematic review.(American journal of medical genetics. Part A, 2017-11) Keeling, Lori A; Spiridigliozzi, Gail A; Hart, Sarah J; Baker, Jane A; Jones, Harrison N; Kishnani, Priya SWe systematically reviewed the measures used in pharmaceutical trials in children/adults with Down syndrome without dementia. Our purpose was to identify developmentally appropriate outcome measures capable of detecting changes in cognitive and adaptive functioning in this population. Eleven studies were included and used diverse outcome measures across the domains of language, memory, attention, behavior, and executive/adaptive functioning. Our results highlight the challenges in selecting measures capable of capturing improvements in pharmaceutical trials in individuals with DS. We offer suggestions to enhance future research, including: conducting studies with larger samples of participants with a range of developmental abilities; modifying existing/developing novel outcome measures; incorporating advances from related areas and DS observational studies; and considering alternative analytic techniques to characterize treatment effects.Item Open Access Cognitive Function: Is There More to Anticoagulation in Atrial Fibrillation Than Stroke?(J Am Heart Assoc, 2015-08-03) Cao, Lin; Pokorney, Sean D; Hayden, Kathleen; Welsh-Bohmer, Kathleen; Newby, L KristinItem Open Access Cortical iron mediates age-related decline in fluid cognition.(Human brain mapping, 2022-02) Howard, Cortney M; Jain, Shivangi; Cook, Angela D; Packard, Lauren E; Mullin, Hollie A; Chen, Nan-Kuei; Liu, Chunlei; Song, Allen W; Madden, David JBrain iron dyshomeostasis disrupts various critical cellular functions, and age-related iron accumulation may contribute to deficient neurotransmission and cell death. While recent studies have linked excessive brain iron to cognitive function in the context of neurodegenerative disease, little is known regarding the role of brain iron accumulation in cognitive aging in healthy adults. Further, previous studies have focused primarily on deep gray matter regions, where the level of iron deposition is highest. However, recent evidence suggests that cortical iron may also contribute to cognitive deficit and neurodegenerative disease. Here, we used quantitative susceptibility mapping (QSM) to measure brain iron in 67 healthy participants 18-78 years of age. Speed-dependent (fluid) cognition was assessed from a battery of 12 psychometric and computer-based tests. From voxelwise QSM analyses, we found that QSM susceptibility values were negatively associated with fluid cognition in the right inferior temporal gyrus, bilateral putamen, posterior cingulate gyrus, motor, and premotor cortices. Mediation analysis indicated that susceptibility in the right inferior temporal gyrus was a significant mediator of the relation between age and fluid cognition, and similar effects were evident for the left inferior temporal gyrus at a lower statistical threshold. Additionally, age and right inferior temporal gyrus susceptibility interacted to predict fluid cognition, such that brain iron was negatively associated with a cognitive decline for adults over 45 years of age. These findings suggest that iron may have a mediating role in cognitive decline and may be an early biomarker of neurodegenerative disease.Item Open Access Emergency Department Care Transitions for Patients With Cognitive Impairment: A Scoping Review.(Journal of the American Medical Directors Association, 2022-08) Gettel, Cameron J; Falvey, Jason R; Gifford, Angela; Hoang, Ly; Christensen, Leslie A; Hwang, Ula; Shah, Manish N; GEAR 2.0-ADC NetworkObjectives
We aimed to describe emergency department (ED) care transition interventions delivered to older adults with cognitive impairment, identify relevant patient-centered outcomes, and determine priority research areas for future investigation.Design
Systematic scoping review.Setting and participants
ED patients with cognitive impairment and/or their care partners.Methods
Informed by the clinical questions, we conducted systematic electronic searches of medical research databases for relevant publications following published guidelines. The results were presented to a stakeholder group representing ED-based and non-ED-based clinicians, individuals living with cognitive impairment, care partners, and advocacy organizations. After discussion, they voted on potential research areas to prioritize for future investigations.Results
From 3848 publications identified, 78 eligible studies underwent full text review, and 10 articles were abstracted. Common ED-to-community care transition interventions for older adults with cognitive impairment included interdisciplinary geriatric assessments, home visits from medical personnel, and telephone follow-ups. Intervention effects were mixed, with improvements observed in 30-day ED revisit rates but most largely ineffective at promoting connections to outpatient care or improving secondary outcomes such as physical function. Outcomes identified as important to adults with cognitive impairment and their care partners included care coordination between providers and inclusion of care partners in care management within the ED setting. The highest priority research area for future investigation identified by stakeholders was identifying strategies to tailor ED-to-community care transitions for adults living with cognitive impairment complicated by other vulnerabilities such as social isolation or economic disadvantage.Conclusions and implications
This scoping review identified key gaps in ED-to-community care transition interventions delivered to older adults with cognitive impairment. Combined with a stakeholder assessment and prioritization, it identified relevant patient-centered outcomes and clarifies priority areas for future investigation to improve ED care for individuals with impaired cognition, an area of critical need given the current population trends.Item Open Access Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series.(Clinical nuclear medicine, 2021-07) James, Olga G; Linares, Alexandra R; Hellegers, Caroline; Doraiswamy, P Murali; Wong, Terence ZAbstract
Early, accurate diagnosis of Alzheimer disease (AD) is essential but remains challenging. Neuropathological hallmarks of AD are β-amyloid neuritic plaques and tau protein neurofibrillary tangles. 18F-Florbetapir is one of several available PET tracers for imaging cortical fibrillary β-amyloid plaques. 18F-Flortaucipir PET was recently approved for evaluating the distribution and density of aggregated neurofibrillary tangles. We present cases of mild cognitive impairment or suspected AD to depict the nuances of flortaucipir distribution and scan interpretation as well as how combined information from amyloid and tau PET may help with differential diagnosis and prognosis.Item Open Access Identifying treatment effects of an informal caregiver education intervention to increase days in the community and decrease caregiver distress: a machine-learning secondary analysis of subgroup effects in the HI-FIVES randomized clinical trial.(Trials, 2020-02) Shepherd-Banigan, Megan; Smith, Valerie A; Lindquist, Jennifer H; Cary, Michael Paul; Miller, Katherine EM; Chapman, Jennifer G; Van Houtven, Courtney HBackground
Informal caregivers report substantial burden and depressive symptoms which predict higher rates of patient institutionalization. While caregiver education interventions may reduce caregiver distress and decrease the use of long-term institutional care, evidence is mixed. Inconsistent findings across studies may be the result of reporting average treatment effects which do not account for how effects differ by participant characteristics. We apply a machine-learning approach to randomized clinical trial (RCT) data of the Helping Invested Family Members Improve Veteran's Experiences Study (HI-FIVES) intervention to explore how intervention effects vary by caregiver and patient characteristics.Methods
We used model-based recursive partitioning models. Caregivers of community-residing older adult US veterans with functional or cognitive impairment at a single VA Medical Center site were randomized to receive HI-FIVES (n = 118) vs. usual care (n = 123). The outcomes included cumulative days not in the community and caregiver depressive symptoms assessed at 12 months post intervention. Potential moderating characteristics were: veteran age, caregiver age, caregiver ethnicity and race, relationship satisfaction, caregiver burden, perceived financial strain, caregiver depressive symptoms, and patient risk score.Results
The effect of HI-FIVES on days not at home was moderated by caregiver burden (p < 0.001); treatment effects were higher for caregivers with a Zarit Burden Scale score ≤ 28. Caregivers with lower baseline Center for Epidemiologic Studies Depression Scale (CESD-10) scores (≤ 8) had slightly lower CESD-10 scores at follow-up (p < 0.001).Conclusions
Family caregiver education interventions may be less beneficial for highly burdened and distressed caregivers; these caregivers may require a more tailored approach that involves assessing caregiver needs and developing personalized approaches.Trial registration
ClinicalTrials.gov, ID:NCT01777490. Registered on 28 January 2013.Item Open Access Long-term chemogenetic activation of M1 glutamatergic neurons attenuates the behavioral and cognitive deficits caused by intracerebral hemorrhage.(Biochemical and biophysical research communications, 2020-06) Ling, Wen-Yuan; Cui, Ying; Gao, Jun-Ling; Jiang, Xiao-Hua; Wang, Kai-Jie; Tian, Yan-Xia; Sheng, Hua-Xin; Cui, Jian-ZhongAcute spontaneous intracerebral hemorrhage (ICH) is a life-threatening disease. It is often accompanied by severe neurological sequelae largely caused by the loss of integrity of the neural circuits. However, these neurological sequelae have few strong medical interventions. Designer receptors exclusively activated by designer drugs (DREADDs) are important chemogenetic tools capable of precisely modulating the activity of neural circuits. They have been suggested to have therapeutic effects on multiple neurological diseases. Despite this, no empirical research has explored the effects of DREADDs on functional recovery after ICH. We aimed to explore whether the long-term excitation of glutamatergic neurons in primary motor cortex (M1) by DREADD could promote functional recovery after ICH. We used CaMKII-driven Gq/Gi-DREADDs to activate/inhibit M1 glutamatergic neurons for 21 consecutive days, and examined their effects on behavioral and cognitive deficits caused by ICH in a mouse model of ICH targeting striatum. Long-term chemogenetic activation of the M1 glutamatergic neurons increased the spatial memory and sensorimotor ability of mice suffering from ICH. It also attenuated the mitochondrial dysfunctions of striatal neurons by raising the ATP levels and mitochondrial membrane potential while decreasing the 8-OHdG levels. These results strongly suggest that selective stimulation of the M1 glutamatergic neurons contributes to functional recovery after ICH presumably through alleviation of mitochondrial dysfunctions.Item Open Access Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats.(Neurocritical care, 2016-10) Sasaki, Toshihiro; Hoffmann, Ulrike; Kobayashi, Motomu; Sheng, Huaxin; Ennaceur, Abdelkader; Lombard, Frederick W; Warner, David SBackground
Cognitive dysfunction can be a long-term complication following subarachnoid hemorrhage (SAH). Preclinical models have been variously characterized to emulate this disorder. This study was designed to directly compare long-term cognitive deficits in the context of similar levels of insult severity in the cisterna magna double-blood (DB) injection versus prechiasmatic blood (PB) injection SAH models.Methods
Pilot work identified blood injectate volumes necessary to provide similar mortality rates (20-25 %). Rats were then randomly assigned to DB or PB insults. Saline injection and naïve rats were used as controls. Functional and cognitive outcome was assessed over 35 days.Results
DB and PB caused similar transient rotarod deficits. PB rats exhibited decreased anxiety behavior on the elevated plus maze, while anxiety was increased in DB. DB and PB caused differential deficits in the novel object recognition and novel object location tasks. Morris water maze performance was similarly altered in both models (decreased escape latency and increased swimming speed). SAH caused histologic damage in the medial prefrontal cortex, perirhinal cortex, and hippocampal CA1, although severity of injury in the respective regions differed between DB and PB.Conclusion
Both SAH models caused long-term cognitive deficits in the context of similar insult severity. Cognitive deficits differed between the two models, as did distribution of histologic injury. Each model offers unique properties and both models may be useful for study of SAH-induced cognitive deficits.Item Open Access Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms.(Critical care (London, England), 2019-11) Sasannejad, Cina; Ely, E Wesley; Lahiri, ShouriAcute respiratory distress syndrome (ARDS) survivors experience a high prevalence of cognitive impairment with concomitantly impaired functional status and quality of life, often persisting months after hospital discharge. In this review, we explore the pathophysiological mechanisms underlying cognitive impairment following ARDS, the interrelations between mechanisms and risk factors, and interventions that may mitigate the risk of cognitive impairment. Risk factors for cognitive decline following ARDS include pre-existing cognitive impairment, neurological injury, delirium, mechanical ventilation, prolonged exposure to sedating medications, sepsis, systemic inflammation, and environmental factors in the intensive care unit, which can co-occur synergistically in various combinations. Detection and characterization of pre-existing cognitive impairment imparts challenges in clinical management and longitudinal outcome study enrollment. Patients with brain injury who experience ARDS constitute a distinct population with a particular combination of risk factors and pathophysiological mechanisms: considerations raised by brain injury include neurogenic pulmonary edema, differences in sympathetic activation and cholinergic transmission, effects of positive end-expiratory pressure on cerebral microcirculation and intracranial pressure, and sensitivity to vasopressor use and volume status. The blood-brain barrier represents a physiological interface at which multiple mechanisms of cognitive impairment interact, as acute blood-brain barrier weakening from mechanical ventilation and systemic inflammation can compound existing chronic blood-brain barrier dysfunction from Alzheimer's-type pathophysiology, rendering the brain vulnerable to both amyloid-beta accumulation and cytokine-mediated hippocampal damage. Although some contributory elements, such as the presenting brain injury or pre-existing cognitive impairment, may be irreversible, interventions such as minimizing mechanical ventilation tidal volume, minimizing duration of exposure to sedating medications, maintaining hemodynamic stability, optimizing fluid balance, and implementing bundles to enhance patient care help dramatically to reduce duration of delirium and may help prevent acquisition of long-term cognitive impairment.Item Open Access Prefrontal contributions to relational encoding in amnestic mild cognitive impairment.(Neuroimage Clin, 2016) Foster, Chris; Addis, Donna; Ford, Jaclyn; Kaufer, Daniel; Browndyke, Jeffrey; Welsh-Bohmer, Kathleen; Giovanello, KellyRelational memory declines are well documented as an early marker for amnestic mild cognitive impairment (aMCI). Episodic memory formation relies on relational processing supported by two mnemonic mechanisms, generation and binding. Neuroimaging studies using functional magnetic resonance imaging (fMRI) have primarily focused on binding deficits which are thought to be mediated by medial temporal lobe dysfunction. In this study, prefrontal contributions to relational encoding were also investigated using fMRI by parametrically manipulating generation demands during the encoding of word triads. Participants diagnosed with aMCI and healthy control subjects encoded word triads consisting of a category word with either, zero, one, or two semantically related exemplars. As the need to generate increased (i.e., two- to one- to zero-link triads), both groups recruited a core set of regions associated with the encoding of word triads including the parahippocampal gyrus, superior temporal gyrus, and superior parietal lobule. Participants diagnosed with aMCI also parametrically recruited several frontal regions including the inferior frontal gyrus and middle frontal gyrus as the need to generate increased, whereas the control participants did not show this modulation. While there is some functional overlap in regions recruited by generation demands between the groups, the recruitment of frontal regions in the aMCI participants coincides with worse memory performance, likely representing a form of neural inefficiency associated with Alzheimer's disease.Item Open Access RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC).(Trials, 2024-05) Knopman, David S; Laskowitz, Daniel T; Koltai, Deborah C; Charvet, Leigh E; Becker, Jacqueline H; Federman, Alex D; Wisnivesky, Juan; Mahncke, Henry; Van Vleet, Thomas M; Bateman, Lucinda; Kim, Dong-Yun; O'Steen, Ashley; James, Melissa; Silverstein, Adam; Lokhnygina, Yuliya; Rich, Jennifer; Feger, Bryan J; Zimmerman, Kanecia OBackground
Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work.Methods
RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English.Discussion
This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction.Trial registration
ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.Item Open Access Targeting Treatments to Improve Cognitive Function in Mood Disorder: Suggestions From Trials Using Erythropoietin.(The Journal of clinical psychiatry, 2016-12) Miskowiak, Kamilla Woznica; Rush, A John; Gerds, Thomas A; Vinberg, Maj; Kessing, Lars VObjective
There is no established efficacious treatment for cognitive dysfunction in unipolar and bipolar disorder. This may be partially due to lack of consensus regarding the need to screen for cognitive impairment in cognition trials or which screening criteria to use. We have demonstrated in 2 randomized placebo-controlled trials that 8 weeks of erythropoietin (EPO) treatment has beneficial effects on verbal memory across unipolar and bipolar disorder, with 58% of EPO-treated patients displaying a clinically relevant memory improvement as compared to 15% of those treated with placebo.Methods
We reassessed the data from our 2 EPO trials conducted between September 2009 and October 2012 to determine whether objective performance-based memory impairment or subjective self-rated cognitive impairment at baseline was related to the effect of EPO on cognitive function as assessed by Rey Auditory Verbal Learning Test (RAVLT) total recall with multiple logistic regression adjusted for diagnosis, age, gender, symptom severity, and education levels.Results
We included 79 patients with an ICD-10 diagnosis of unipolar or bipolar disorder, of whom 39 received EPO and 40 received placebo (saline). For EPO-treated patients with objective memory dysfunction at baseline (n = 16) (defined as RAVLT total recall ≤ 43), the odds of a clinically relevant memory improvement were increased by a factor of 290.6 (95% CI, 2.7-31,316.4; P = .02) compared to patients with no baseline impairment (n = 23). Subjective cognitive complaints (measured with the Cognitive and Physical Functioning Questionnaire) and longer illness duration were associated with small increases in patients' chances of treatment efficacy on memory (53% and 16% increase, respectively; P ≤ .04). Diagnosis, gender, age, baseline depression severity, and number of mood episodes did not significantly change the chances of EPO treatment success (P ≥ .06). In the placebo-treated group, the odds of memory improvement were not significantly different for patients with or without objectively defined memory dysfunction (P ≥ .59) or subjective complaints at baseline (P ≥ .06).Conclusions
Baseline objectively assessed memory impairments and-to a lesser degree-subjective cognitive complaints increased the chances of treatment efficacy on cognition in unipolar and bipolar disorder.Trial registration
ClinicalTrials.gov identifier: NCT00916552.Item Open Access Trends in functional disability and cognitive impairment among the older adult in China up to 2060: estimates from a dynamic multi-state population model.(BMC geriatrics, 2021-06-22) Ansah, John P; Chiu, Chi-Tsun; Wei-Yan, Aloysius Chia; Min, Tessa Lui Shi; Matchar, David BBackground
Available evidence suggests that cognitive impairment (CI), which leads to deficits in episodic memory, executive functions, visual attention, and language, is associated with difficulties in the capacity to perform activities of daily living. Hence any forecast of the future prevalence of functional disability should account for the likely impact of cognitive impairment on the onset of functional disability. Thus, this research aims to address this gap in literature by projecting the number of older adults in China with functional disability and cognitive impairment while accounting for the impact of cognitive impairment on the onset of functional disability.Methods
We developed and validated a dynamic multi-state population model which simulates the population of China and tracks the transition of Chinese older adults (65 years and older) from 2010 to 2060, to and from six health states-(i) active older adults without cognitive impairment, (ii) active older adults with cognitive impairment, (iii) older adults with 1 to 2 ADL limitations, (iv) older adults with cognitive impairment and 1 to 2 ADL limitations, (v) older adults with 3 or more ADL limitations, and (vi) older adults with cognitive impairment and 3 or more ADL limitations.Results
From 2015 to 2060, the number of older adults 65 years and older in China is projected to increase, of which the number with impairment (herein referred to as individuals with cognitive impairment and/or activity of daily living limitations) is projected to increase more than fourfold from 17·9 million (17·8-18·0) million in 2015 to 96·2 (95·3-97·1) million by 2060. Among the older adults with impairment, those with ADL limitations only is projected to increase from 3·7 million (3·6-3·7 million) in 2015 to 23·9 million (23·4-24·6 million) by 2060, with an estimated annual increase of 12·2% (12·1-12·3); while that for cognitive impairment only is estimated to increase from 11·4 million (11·3-11·5 million) in 2015 to 47·8 million (47·5-48·2 million) by 2060-this representing an annual growth of 7·07% (7·05-7·09).Conclusion
Our findings suggest there will be an increase in demand for intermediate and long-term care services among the older adults with functional disability and cognitive impairment.