Background: Cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers of neurodegenerative diseases are relatively sensitive and specific in highly curated research cohorts, but proper validation for clinical use is mostly missing. Objective: We studied these biomarkers in a novel memory clinic cohort with a variety of different neurodegenerative diseases. Methods: This study consisted of 191 patients with subjective or objective cognitive impairment who underwent neurological, CSF biomarker (A 42 , p-tau, and tau) and T1-weighted MRI examinations at Kuopio University Hospital. We assessed CSF and imaging biomarkers, including structural MRI focused on volumetric and cortical thickness analyses, across groups stratified based on different clinical diagnoses, including Alzheimer's disease (AD), frontotemporal dementia, dementia with Lewy bodies, Parkinson's disease, vascular dementia, and mild cognitive impairment (MCI), and subjects with no evidence of neurodegenerative disease underlying the cognitive symptoms. Imaging biomarkers were also studied by profiling subjects according to the novel amyloid, tau, and, neurodegeneration (AT(N)) classification. Results: Numerous imaging variables differed by clinical diagnosis, including hippocampal, amygdalar and inferior lateral ventricular volumes and entorhinal, lingual, inferior parietal and isthmus cingulate cortical thicknesses, at a false discovery rate (FDR)-corrected threshold for significance (analysis of covariance; p < 0.005). In volumetric comparisons by AT(N) profile, hippocampal volume significantly differed (p < 0.001) between patients with normal AD biomarkers and patients with amyloid pathology. Conclusion: Our analysis suggests that CSF and MRI biomarkers function well also in clinical practice across multiple clinical diagnostic groups in addition to AD, MCI, and cognitively normal groups.
Background Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. Method A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman’s criteria, hence referred to as symptomatic controls. Results The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05). Conclusions Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.
Purpose Automated analysis of neuroimaging data is commonly based on magnetic resonance imaging (MRI), but sometimes the availability is limited or a patient might have contradictions to MRI. Therefore, automated analyses of computed tomography (CT) images would be beneficial. Methods We developed an automated method to evaluate medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and the severity of white matter lesions (WMLs) from a CT scan and compared the results to those obtained from MRI in a cohort of 214 subjects gathered from Kuopio and Helsinki University Hospital registers from 2005 - 2016. Results The correlation coefficients of computational measures between CT and MRI were 0.9 (MTA), 0.82 (GCA), and 0.86 (Fazekas). CT-based measures were identical to MRI-based measures in 60% (MTA), 62% (GCA) and 60% (Fazekas) of cases when the measures were rounded to the nearest full grade variable. However, the difference in measures was 1 or less in 97–98% of cases. Similar results were obtained for cortical atrophy ratings, especially in the frontal and temporal lobes, when assessing the brain lobes separately. Bland–Altman plots and weighted kappa values demonstrated high agreement regarding measures based on CT and MRI. Conclusions MTA, GCA, and Fazekas grades can also be assessed reliably from a CT scan with our method. Even though the measures obtained with the different imaging modalities were not identical in a relatively extensive cohort, the differences were minor. This expands the possibility of using this automated analysis method when MRI is inaccessible or contraindicated.
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