Diverse cognitive impairment after spinal cord injury is associated with orthostatic hypotension symptom burden

Nightingale, Tom E.; Zheng, Mei; Sachdeva, Rahul; Phillips, Aaron A.; Krassioukov, Andrei V.

doi:10.1016/j.physbeh.2019.112742

Cited by 38 publications

(30 citation statements)

References 68 publications

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“…As stated above, there are various factors associated with MCI after SCI. Autonomic nervous system disturbances and associated cardiovascular and cerebrovascular complications following SCI have been studied as risks for the development of cognitive impairment and poor SCI-related outcomes [38,41,53]. All individuals with SCI above the sixth thoracic segment (T6) suffer decentralised cardiovascular control, which has been found to predict cerebral hypoperfusion and consequently impaired cognitive performance [53].…”

Section: Introductionmentioning

confidence: 99%

“…There are, however, many factors that contribute to the development of MCI after SCI [ 11 ]. These may include functional changes to the cardiovascular [ 38 – 40 ] and autonomic nervous system [ 41 ], psychological changes such as mood disturbances [ 42 ], medications [ 43 – 45 ], ageing [ 14 , 46 – 48 ], sleep disorder [ 49 , 50 ], fatigue [ 8 ], and social changes, such as the potential for decreased social participation [ 51 , 52 ]. Some of these risks (e.g., depression, polypharmacy) are transient, while others (e.g., brain injury, cardiovascular dysfunction) contribute to degenerative or long-term courses of cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

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A prospective cohort study investigating contributors to mild cognitive impairment in adults with spinal cord injury: study protocol

et al. 2020

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Background Studies report rates of mild cognitive impairment (MCI) in spinal cord injury (SCI) range between 10 and 60%. This broad estimate of MCI in SCI is most likely a result of: (i) inconsistent operationalization of MCI; (ii) heterogeneity among individuals with SCI; (iii) failure to account for MCI subtypes, thereby adding to the heterogeneity of samples; and, (iv) poor control for traumatic brain injury (TBI) that obscures differentiation of MCI attributable to TBI versus other factors. There is a paucity of longitudinal studies following the course of MCI in SCI, and none that account for multiple predictors of MCI, including interactions among predictors. Methods An inception cohort longitudinal study will assess approximately 100 individuals aged 17–80 years with acute SCI, with measures taken at three timepoints (baseline, 3 months post-baseline, and 12 months post-injury). Data relevant to medical care received within the first 24–48 h of presentation to the emergency department will be analysed, as will measures of cognition, injury characteristics, medical history, personal factors, psychological status, psychosocial functioning, and quality of life. Latent class mixture modelling will determine trajectories for the primary outcome of interest, cognitive functioning and its subtypes, and secondary outcomes of interest such as depression. Multiple regression analyses will identify predictors of MCI and its subtypes. Discussion The prospective design will reveal change in cognitive functioning across time and unveil different outcome trajectories; thus addressing the lack of knowledge on trajectories of MCI and MCI subtypes in SCI. Through subtyping MCI, we hope to yield groups of cognitively impaired individuals with SCI that are potentially more homogenous and thereby stable and predictable. This is the first study to capture emergency department and acute care diagnostic evidence of mild TBI, which has been poorly controlled in previous studies. Our study will also be the first to distinguish the contribution of TBI from other factors to the development of MCI in individuals with SCI. Trial registration The study was prospectively registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12619001702101) on 3rd December 2019.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A prospective cohort study investigating contributors to mild cognitive impairment in adults with spinal cord injury: study protocol

et al. 2020

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“…The expression of brain-derived neurotrophic factor (BDNF) is downregulated for at least 1 week after SCI, which adversely affects the plasticity of the rat hippocampus (Fumagalli et al, 2009). SCIs are reported to result in cognitive impairment (Craig et al, 2017;Sachdeva et al, 2018;Nightingale et al, 2020) and contribute to the development of neurodegenerative diseases, such as AD (Yeh et al, 2018) and PD (Yeh et al, 2016) (blue arrow numbered 5 to red arrow numbered 1, Figure 1). Olfactory dysfunction can predict neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Ultrarapid Inflammation of the Olfactory Bulb After Spinal Cord Injury: Protective Effects of the Granulocyte Colony-Stimulating Factor on Early Neurodegeneration in the Brain

Lin

Chiu

Lin

2021

Front. Aging Neurosci.

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The correlation among olfactory dysfunction, spinal cord injury (SCI), subjective cognitive decline, and neurodegenerative dementia has been established. Impaired olfaction is considered a marker for neurodegeneration. Hence, there is a need to examine if SCI leads to olfactory dysfunction. In this study, the brain tissue of mice with spinal cord hemisection injury was subjected to microarray analysis. The mRNA expression levels of olfactory receptors in the brain began to decline at 8 h post-SCI. SCI promoted neuroinflammation, downregulated the expression of olfactory receptors, decreased the number of neural stem cells (NSCs), and inhibited the production of neurotrophic factors in the olfactory bulbs at 8 h post-SCI. In particular, the SCI group had upregulated mRNA and protein expression levels of glial fibrillary acidic protein (GFAP; a marker of astrocyte reactivation) and pro-inflammatory mediators [IL-1β, IL-6, and Nestin (marker of NSCs)] in the olfactory bulb compared to levels in the sham control group. The mRNA expression levels of olfactory receptors (Olfr1494, Olfr1324, Olfr1241, and Olfr979) and neurotrophic factors [brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor (NGF)] were downregulated in the olfactory bulb of the SCI group mice at 8 h post-SCI. The administration of granulocyte colony-stimulating factor (G-CSF) mitigated these SCI-induced pathological changes in the olfactory bulb at 8 h post-SCI. These results indicate that the olfactory bulb is vulnerable to environmental damage even if the lesion is located at sites distant from the brain, such as the spinal cord. Additionally, SCI initiated pathological processes, including inflammatory response, and impaired neurogenesis, at an early stage. The findings of this study will provide a basis for future studies on pathological mechanisms of early neurodegenerative diseases involving the olfactory bulb and enable early clinical drug intervention.

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“…These impairments lead to altered blood pressure responses to upright positioning, delaying therapeutic interventions, and limiting independence and social engagement, thus drastically decreasing health-related quality of life (Illman et al, 2000;Blackmer, 1997;Carlozzi et al, 2013). Hypotension, even when asymptomatic, adversely impacts the cerebral circulation (Eigenbrodt et al, 2000;Jegede et al, 2010;Nightingale et al, 2020;Wecht & Bauman, 2013;Wu et al, 2012). Identifying those with orthostatic hypotension and unstable blood pressure responses to a postural change is important to improve overall health-related quality of life and decrease morbidity and mortality of individuals with SCI (Carlozzi et al, 2013;Myers et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Heart rate and blood pressure response improve the prediction of orthostatic cardiovascular dysregulation in persons with chronic spinal cord injury

et al. 2020

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Unstable blood pressure after spinal cord injury (SCI) is not routinely examined but rather predicted by level and completeness of injury (i.e., American Spinal Injury Association Impairment Scale AIS classification). Our aim was to investigate hemodynamic response to a sit‐up test in a large cohort of individuals with chronic SCI to better understand cardiovascular function in this population. Continuous blood pressure and ECG were recorded from individuals with SCI (n = 159) and non‐injured individuals (n = 48). We found orthostatic hypotension occurred within each level and AIS classification (n = 36). Moreover, 45 individuals with chronic SCI experienced a drop in blood pressure that did not meet the criteria for orthostatic hypotension, but was accompanied by dramatic increases in heart rate, reflecting orthostatic intolerance. A cluster analysis of hemodynamic response to a seated position identified eight distinct patterns of interaction between blood pressure and heart rate during orthostatic stress indicating varied autonomic responses. Algorithmic cluster analysis of heart rate and blood pressure is more sensitive to diagnosing orthostatic cardiovascular dysregulation. This indicates blood pressure instability cannot be predicted by level and completeness of SCI, and the consensus statement definition of orthostatic hypotension is insufficient to characterize the variability of blood pressure and heart rate responses during orthostatic stress. Both blood pressure and heart rate responses are needed to characterize autonomic function after SCI.

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Diverse cognitive impairment after spinal cord injury is associated with orthostatic hypotension symptom burden

Cited by 38 publications

References 68 publications

A prospective cohort study investigating contributors to mild cognitive impairment in adults with spinal cord injury: study protocol

A prospective cohort study investigating contributors to mild cognitive impairment in adults with spinal cord injury: study protocol

Ultrarapid Inflammation of the Olfactory Bulb After Spinal Cord Injury: Protective Effects of the Granulocyte Colony-Stimulating Factor on Early Neurodegeneration in the Brain

Heart rate and blood pressure response improve the prediction of orthostatic cardiovascular dysregulation in persons with chronic spinal cord injury

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