To assess cognitive impairment and affective symptoms and their association with damage to normal-appearing white matter (NAWM) in patients with clinically isolated syndrome (CIS), we compared neuropsychological test scores between patients with CIS and healthy controls, and examined correlations between these and proton magnetic resonance spectroscopy (1H-MRS) outcomes in patients with CIS. Forty patients with CIS and 40 healthy participants were tested with the set of neuropsychological tests, the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Single-voxel 1H-MRS was performed on frontal and parietal NAWM of patients with CIS to assess ratios of N-acetyl-aspartate (NAA) to creatine (Cr), myo-inositol (mI), and choline (Cho), as well as mI/Cr and Cho/Cr ratios. Patients with CIS had lower cognitive performance, higher scores for the BDI and anxiety subscale of HADS than healthy controls. There were significant correlations between the following neuropsychological tests and metabolic ratios in the frontal NAWM: Stroop Color-Word Test and Cho/Cr, Symbol Digit Modalities Test and mI/Cr as well as NAA/mI, Go/no-go reaction time and NAA/Cho as well as NAA/mI, Californian Verbal Learning Test and NAA/Cr. BDI scores were related to frontal NAA/mI and parietal NAA/Cr and Cho/Cr ratios, whereas HADS-depression scores were associated with frontal NAA/Cr and NAA/mI, and parietal NAA/Cr and Cho/Cr ratios. HADS-anxiety correlated with parietal NAA/Cr ratio. This study suggests that neurochemical changes in the NAWM assessed with single-voxel 1H-MRS are associated with cognitive performance and affective symptoms in patients with CIS.

A b s t r a c t Background and aim:As cognitive function is the most vulnerable human feature, its impairment may precede the occurrence of symptoms of cardiovascular system disorders, e.g. atrial fibrillation (AF). In this way, cognitive impairment may not only be a complication of AF, but also a marker of its progression. This study aims to test this hypothesis. Methods:Of 35 patients with AF, 23 (66%) had paroxysmal and 12 (34%) had permanent arrhythmia at the start of the study. At both the start of the study and after 5.86 ± 3.7-7.05 years of follow-up, the following neuropsychological tests were performed using the Beck Depression Inventory, Parts A and B of the Trail Making Test, eight trials from the Rey Auditory Verbal Learning Test (RAVLT), and the Stroop test. Results:Patients who maintained paroxysmal AF for the whole study observation period (n = 10) had a significantly greater score in the sixth (A6) and seventh (A7) RAVLT trials (pertaining to parameters of long-term latent memory) at the start of the study. An association between lower RAVLT A6 and A7 trial scores and the risk of paroxysmal arrhythmia progression to permanent AF was confirmed using the Cox proportional hazards regression model and Kaplan-Meier survival analysis. Conclusions:A better long-term latent memory RAVLT score was associated with a favourable prognosis of sinus rhythm maintenance. Cognitive impairment should be investigated in patients with AF for the purpose of evaluating the patient's prognosis, subclinical injury to the cardiovascular system, and the ability to comply with treatment.

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