Pharmacologic manipulation of complement receptor 3 prevents dendritic spine loss and cognitive impairment after acute cranial radiation

2020 ◽  
Author(s):  
Joshua J. Hinkle ◽  
John A. Olschowka ◽  
Jacqueline P. Williams ◽  
M. Kerry O’Banion
Keyword(s):  
Quality Of Life ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Dendritic Spine ◽  
Cranial Irradiation ◽  
Complement Receptor ◽  
Spine Density ◽  
Male Mice ◽  
Complement Receptor 3

AbstractCranial irradiation induces healthy tissue damage that can lead to neurocognitive complications and negatively impact patient quality of life. One type of damage associated with cognitive impairment is loss of neuronal spine density. Based on developmental and disease studies implicating microglia and complement in dendritic spine loss, we hypothesized that irradiation-mediated spine loss is microglial complement receptor 3 (CR3)-dependent, and associated with late-delayed cognitive deficits. Utilizing a model of cranial irradiation (acute, 10 Gy gamma) in C57BL/6 mice we found that male mice demonstrate irradiation-mediated spine loss and cognitive deficits whereas female mice and CR3 knockout mice do not. Moreover, pharmacological blockade of CR3 with leukadherin-1 (LA1) prevented these changes in irradiated male mice. Interestingly, CR3 KO mice showed reduced behavioral task performance suggesting that CR3 is important for normal learning and memory. Improving our understanding of irradiation-mediated mechanisms and sexual dimorphic responses is essential for the identification of novel therapeutics to reduce irradiation-induced cognitive decline and improve patient quality of life.

scholarly journals Cranial irradiation mediated spine loss is sex-specific and complement receptor-3 dependent in male mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joshua J. Hinkle ◽  
John A. Olschowka ◽  
Tanzy M. Love ◽  
Jacqueline P. Williams ◽  
M. Kerry O’Banion
Keyword(s):  
Quality Of Life ◽  
Dendritic Spine ◽  
Cranial Irradiation ◽  
Common Mechanism ◽  
Complement Receptor ◽  
Spine Density ◽  
Male Mice ◽  
Activation Markers ◽  
Complement Receptor 3

AbstractCranial irradiation is the main therapeutic treatment for primary and metastatic malignancies in the brain. However, cranial radiation therapy produces long-term impairment in memory, information processing, and attention that contribute to a decline in quality of life. The hippocampal neural network is fundamental for proper storage and retrieval of episodic and spatial memories, suggesting that hippocampal signaling dysfunction could be responsible for the progressive memory deficits observed following irradiation. Previous rodent studies demonstrated that irradiation induces significant loss in dendritic spine number, alters spine morphology, and is associated with behavioral task deficits. Additionally, the literature suggests a common mechanism in which synaptic elimination via microglial-mediated phagocytosis is complement dependent and associated with cognitive impairment in aging as well as disease. We demonstrate sexual dimorphisms in irradiation-mediated alterations of microglia activation markers and dendritic spine density. Further, we find that the significant dendritic spine loss observed in male mice following irradiation is microglia complement receptor 3 (CR3)-dependent. By identifying sex-dependent cellular and molecular factors underlying irradiation-mediated spine loss, therapies can be developed to counteract irradiation-induced cognitive decline and improve patient quality of life.

The influence of cognitive impairment on health-related quality of life in neurological disease

2010 ◽  
Vol 22 (1) ◽  
pp. 2-13 ◽  
Author(s):  
Alex J. Mitchell ◽  
Steven Kemp ◽  
Julián Benito-León ◽  
Markus Reuber
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Neurological Disorders ◽  
Neurological Disease ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related

Mitchell AJ, Kemp S, Benito-León J, Reuber M. The influence of cognitive impairment on health-related quality of life in neurological disease.Background:Cognitive impairment is the most consistent neurological complication of acquired and degenerative brain disorders. Historically, most focus was on dementia but now has been broadened to include the important construct of mild cognitive impairment.Methods:Systematic search and review of articles linked quality of life (QoL) and cognitive complications of neurological disorders. We excluded QoL in dementia.Results:Our search identified 249 publications. Most research examined patients with brain tumours, stroke, epilepsy, head injury, Huntington's disease, motor neuron disease, multiple sclerosis and Parkinson's disease. Results suggested that the majority of patients with epilepsy, motor neuron disease, multiple sclerosis, Parkinson's disease, stroke and head injury have subtle cognitive deficits early in their disease course. These cognitive complaints are often overlooked by clinicians. In many cases, the cognitive impairment is progressive but it can also be relapsing-remitting and in some cases reversible. Despite the importance of severe cognitive impairment in the form of dementia, there is now increasing recognition of a broad spectrum of impairment, including those with subclinical or mild cognitive impairment. Even mild cognitive difficulties can have functional and psychiatric consequences–especially when they are persistent and untreated. Specific cognitive deficits such an inattention, dysexecutive function and processing speed may affect a number of quality of life (QoL) domains. For example, cognitive impairment influences return to work, interpersonal relationships and leisure activities. In addition, fear of future cognitive decline may also impact upon QoL.Conclusions:We recommend further development of simple tools to screen for cognitive impairments in each neurological condition. We also recommend that a thorough cognitive assessment should be a part of routine clinical practice in those caring for individuals with neurological disorders.

Cognitive Impairment and Quality of Life among Stroke Survivors in Nigeria

2007 ◽  
Vol 100 (3) ◽  
pp. 876-882 ◽  
Author(s):  
Femi O. Fatoye ◽  
Morenikeji A. Komolafe ◽  
Benjamin A. Eegunranti ◽  
Abiodun O. Adewuya ◽  
Samuel K. Mosaku ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Poor Performance ◽  
Stroke Survivors ◽  
Life Questionnaire ◽  
Low Education ◽  
State Examination ◽  
Normal Controls

The study investigated cognitive impairment and quality of life (QOL) among 109 consecutive stroke survivors and 109 normal controls. Each group comprised 64 (58.7%) men and 45 (41.3%) women. The modified Mini Mental State Examination (mMMSE) and the WHO Quality of Life Questionnaire (WHOQOL-Bréf) indicated that 19 (17.4%) stroke survivors had cognitive deficits (mMMSE score < 16) compared with 5 (4.6%) control participants (χ12 = 4.27, p<.05). Control participants performed significantly better on orientation, language comprehension, laterality, and the WHOQOL-Bréf. Being GHQ-30 positive predicted poor performance on the mMMSE among the stroke survivors and reduced QOL on three of the four domains of the WHOQOL-Bréf. In addition, previous psychiatric illness, paresis, low education, and shorter time elapsed after a stroke predicted reduced QOL on one or more domains of the WHOQOL-Bréf but age and sex of the stroke survivors were not associated with quality of life, and not with cognitive function.

scholarly journals COGNITIVE IMPAIRMENT AND ITS IMPACT ON QUALITY OF LIFE IN RURAL INDIAN FEMALE AFTER STROKE: A CROSS SECTIONAL STUDY

2021 ◽  
Vol 10 (4) ◽  
pp. 3414-3416
Author(s):  
Nikita S. Deshmukh
Keyword(s):  
Quality Of Life ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Cross Sectional Study ◽  
Life Questionnaire ◽  
Sectional Study ◽  
Cross Sectional ◽  
Indian Women ◽  
Quality Of Life Questionnaire

Stroke is main cause of death and disability which mainly affect higher function like cognitive impairment which affects the quality of life. The MoCA used to assessment of cognitive impairment and stroke specific quality of life for assessment of quality of life. The aim was to assess the effect of Cognitive Impairment on quality of life in Rural Indian women after stroke. The cognitive impairment was measured with the use of the MoCA and Quality of Life was measured by SS-Quality of Life questionnaire. Female stroke patient with age in between 41-70 year who was diagnosed by the physician is included in the study. Result of this study indicated that the cognitive functions ans quality of life significantly affected in rural females following stroke. (0.571; p=0.0001).the finding is the cognitive deficits occurred after stroke and it hamper the quality of life in majority of patient.

scholarly journals What’s going on following acute covid-19? Clinical characteristics of patients in an out-patient rehabilitation program

2021 ◽  
pp. 1-12
Author(s):  
Sergiu Albu ◽  
Nicolas Rivas Zozaya ◽  
Narda Murillo ◽  
Alberto Garcia-Molina ◽  
Cristian Andres Figueroa Chacón ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cognitive Impairment ◽  
Acute Infection ◽  
Rehabilitation Program ◽  
Neuropsychological Impairment ◽  
Outpatient Rehabilitation ◽  
Screening Process ◽  
Icu Patients ◽  
Persistent Symptoms

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients present long-lasting physical and neuropsychological impairment, which may require rehabilitation. OBJECTIVES: The current cross-sectional study characterizes post COVID-19 sequelae and persistent symptoms in patients in an outpatient rehabilitation program. METHODS: Thirty patients [16 post-ICU and 14 non-ICU; median age = 54(43.8–62) years; 19 men] presenting sequelae and/or persistent symptoms (>3 months after acute COVID-19) were selected of 41 patients referred for neurorehabilitation. Patients underwent physical, neuropsychological and respiratory evaluation and assessment of impact of fatigue and quality of life. RESULTS: The main reasons for referral to rehabilitation were: fatigue (86.6%), dyspnea (66.7%), subjective cognitive impairment (46.7%) and neurological sequelae (33.3%). Post-ICU patient presented sequelae of critical illness myopathy and polyneuropathy, stroke and encephalopathy and lower forced vital capacity compared to non-ICU patients. Cognitive impairment was found in 63.3% of patients, with a similar profile in both sub-groups. Increased physical fatigue, anxiety and depression and low quality of life were prevalent irrespective of acute COVID-19 severity. CONCLUSIONS: The variability of post COVID-19 physical and neuropsychological impairment requires a complex screening process both in ICU and non-ICU patients. The high impact of persistent symptoms on daily life activities and quality of life, regardless of acute infection severity, indicate need for rehabilitation.

scholarly journals Implementation and effectiveness of a multi-domain program for older adults at risk of cognitive impairment at neighborhood senior centres

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pei Ern Mary Ng ◽  
Sean Olivia Nicholas ◽  
Shiou Liang Wee ◽  
Teng Yan Yau ◽  
Alvin Chan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Older Adults ◽  
At Risk ◽  
Cognitive Impairment ◽  
Mobile Application ◽  
Intervention Group ◽  
Blood Parameters ◽  
Attrition Rate ◽  
Control Group

AbstractTo address the paucity of research investigating the implementation of multi-domain dementia prevention interventions, we implemented and evaluated a 24-week, bi-weekly multi-domain program for older adults at risk of cognitive impairment at neighborhood senior centres (SCs). It comprised dual-task exercises, cognitive training, and mobile application-based nutritional guidance. An RCT design informed by the Reach, Effectiveness, Adoption, Implementation, Maintenance framework was adopted. Outcome measures include cognition, quality of life, blood parameters, and physical performance. Implementation was evaluated through questionnaires administered to participants, implementers, SC managers, attendance lists, and observations. The program reached almost 50% of eligible participants, had an attrition rate of 22%, and was adopted by 8.7% of the SCs approached. It was implemented as intended; only the nutritional component was re-designed due to participants’ unfamiliarity with the mobile application. While there were no between-group differences in cognition, quality of life, and blood parameters, quality of life reduced in the control group and physical function improved in the intervention group after 24 weeks. The program was well-received by participants and SCs. Our findings show that a multi-domain program for at-risk older adults has benefits and can be implemented through neighborhood SCs. Areas of improvement are discussed.Trial registration: ClinicalTrials.gov NCT04440969 retrospectively registered on 22 June 2020.

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