OBJECTIVE: To evaluate changes in cognitive performance in the early postoperative (1 month) and late (1 year) postoperative period in patients undergoing aortic valve replacement (SVAo) with surgery (SVA_Q) or transcatheter aortic valve implant (TAVI), by neuropsychological study (NRP), structural Brain Magnetic Resonance (sMRI) and functional MRI (fMRI). The specific objectives are: (1) to compare the early and late clinical-functional consequences with NRP study in both groups; (2) to compare the occurrence of cerebral clinical events during follow-up; (3) to quantify and compare the appearance of silent lesions in the early postoperative period and late of SVAo with sMRI with respect to the baseline MRI in both groups; (4) study with fMRI changes in the activity and functional connectivity and correlate them with the NRP findings in all patients in the early and late phase in comparison with the basal MRI. METHODOLOGY: Prospective longitudinal, unicentric, nonrandomized cohort study of consecutive patients> 70 years, with indication for SVAo and intermediate and high surgical risk. One month before surgery will be performed an sMRI and fMRI and a baseline NRP study. One month after surgery, sMRI, fMRI and NRP study will be performed to assess the appearance of new lesions, as well as changes in cognitive performance with respect to baseline cognitive status. One year later, sMRI, fMRI and NRP study will be performed to assess changes in cognitive status with respect to baseline and early postoperative. Response variables: changes in cognitive performance measured by a Global Cognitive Impairment Index and in cognitive status (normal vs. Mild Cognitive Impairment vs Moderate Impairment), number, size and location of new silent brain lesions, cerebral vascular clinical events, and changes in advanced neuroimaging (image by diffusion tensor (DTI), resting-state fMRI) and its relationship with cognitive changes.

Design: Prospective, single-center, longitudinal cohort study with consecutive inclusion of patients older than 70 years of intermediate or high surgical risk who present Aortic Stenoses (AoS) that requires Aortic Valve Replacement (AVS). Two groups will be compared based on the type of treatment received, surgical valve replacement (SVA_Q) or transcatheter aortic valve implantation (TAVI). The choice of treatment will be made according to medical criteria decided by the "heart team" in which clinical cardiologists, hemodynamics and cardiac surgeons participate who follow the recommendations of the European Society Cardiology (ESC / EACTS) 2017 Guidelines. However, only those patients susceptible to treatment with both techniques, will be included. The decision will be agreed with the patient. A complete neuropsychological study and structural and functional MRI will be carried out, one month prior to treatment and one month and year after the procedure. Throughout the study, clinical follow-up will be carried out with evaluation of the appearance of clinical cerebrovascular events.

Study investigators will record the following variables; Once the patient is assigned to treatment, a visit will be scheduled where the surgeon in the case of SVA_Q or the cardiologist in the case of TAVI will assess whether the patient meets the eligibility criteria for the study. If patient fullfill all inclusion and none of exclusion criteria, study investigators will request the Informed Consent.

Baseline clinical variables:

• Age and sex
• Vascular risk factors
• Dyspnea: Functional class (New York Heart Association)
• Chronic obstructive pulmonary disease
• Preoperative Renal Insufficiency
• EuroScore II scale score
• Barthel scale score
• MMSE. The NRP study and neuroimaging will be scheduled for a maximum of one month before the procedure

Intraoperative characteristics:

• Time of extracorporeal circulation, coronary ischemia and orotracheal intubation
• Bleeding from drains
• Blood products transfusion
• Types of prostheses and approach
• Type and anesthetic drugs

During hospital admission:

Defined morbidity at discharge:

• ICU stay> 48 hours, in ward> 10 days
• Respiratory, kidney (RIFLE criteria), infectious, heart rhythm complications (endocavitary pacemaker implant)
• Neurological complications: stroke, transient ischemic attack, disorientation episodes and seizures
• Degree of dependency
• Readmissions (in critical / semi-critical unit)
• Valvular hemodynamics (echocardiographic data)

Mortality at discharge:

• Immediate: <72 hours post-procedure
• Hospital: during hospitalization and / or first 30 days post-procedure Follow-up clinical variables: All complications and mortality at 6 months and 1 year will be collected, as well as valve hemodynamics and functional class in both groups.

Neuropsychological (NPS) variables:

The NRP study scores will be recorded at three times; basal, early and late phase.

Acquisition, analysis of neuropsychological variables:

Neuropsychological tests:

The NPS evaluation will consist of a battery of tests sensitive to vascular pathology (VCI), with an approximate duration of an hour and a half, by a neuropsychologist blind to the patient's treatment group, and will include:

• Attention: Direct Digits subtest (Wechsler Memory Scale III;, WMS III); Symbol Digit Modality Test (SDMT); Symbol Search subtest (Wechsler Adult Intelligence Scale, Wechsler Adult Intelligence Scale (WAIS-III);
• Memory: Rey's 15-word verbal learning test (RAVLT) and Rey's complex figure (RCF) 's Alternative versions of the RAVLT will be used to avoid the retest effect
• Working memory: Digits inverses (WMS III) and Trail Making Test part-B
• Verbal fluency phonetic (P, A, S) and semantics (Animals)
• Visuospatial functions: copy of Rey's complex Figure
• Inhibition: Stroop test
• Visuospatial Speed: Grooved Pegboard and Trail Making Test part-A
• Language: Boston Denomination Test (BNT)
• General cognitive functioning: MMSE and Montreal Cognitive Assessment (MoCA) tests.

The order in the administration of the tests will be constant to avoid variability between subjects due to fatigue. The tests will be administered and scored according to standardized criteria.

To compute the Global Cognitive Impairment Index (IDCG) or Impairment Index (II), first the direct scores obtained in the different neuropsychological tests will be transformed into z scores according to the scales of the normal population and taking into account age and level of schooling. The different tests will be grouped into cognitive domains that have been identified as relevant to detect the cognitive vascular impairment (CVI) to obtain subscripts of speed, attention, memory, language, visuospatial capacity and executive functions. The IDCG will include an average of the different domains evaluated.

In addition, changes in the cognitive status of the patients will also be assessed between the baseline examination, the early and late postoperative period. Specifically, the subjects will be grouped into 3 categories based on performance in the NRP tests: normal, mild cognitive impairment (MCI) and moderate cognitive impairment.

The MCI is defined when the results of the cognitive tests in one or more cognitive domains are 1.5 standard deviations below the mean. The degree of cognitive impairment will be considered moderate when the results of the cognitive tests of one, two or three domains are 2 deviations below the mean or when there is a specific neuropsychological function with 3 standard deviations below the mean.

Image variables

Image acquisition, analysis and variables:

Patients will be assessed by structural and functional MRI at three different times during the study: (1) one month before; (2) one month later, and (3) one year after treatment. These evaluations will be carried out at the Center for Comparative Medicine and Bioimaging of Catalonia (CMCiB) with an MRI (Cannon-3020 Vantage Galen 3 Teslas, with 32-channel cranial bovine) dedicated to biomedical research.

Structural MRI acquisitions will include the acquisition of a high resolution T1-weighted image (MPRAGE), as well as T2-weighted images and fluid attenuated inversion recovery image (FLAIR) with the objective of assessing the presence of lesions of the white matter and lacunar infarcts as well as the appearance of silent lesions. Diffusion-weighted images (DWI) will also be included, which will allow us to assess the integrity of the white matter in the main tracts of the brain. The functional MRI (fMRI) images will include the acquisition of images in a resting-state state and the acquisition of images during the execution of an information processing speed task and an interference inhibition and control task.

In the functional MRI task, two cognitive tasks will be used focused on (a) control and interference (STROOP effect), (b) information processing (Symbol Digit Modality Test, SDMT) that represent the neuroradiological counterpart of neuropsychological tests. These images will allow us to visualize the functional brain areas both in a resting state (changes in the basal functioning of the brain) and during the execution of two tasks that assess cognitive functions (processing speed, working memory, and executive functions) that appear impaired. in vascular-type cognitive impairment. For the correction of the geometric distortions of the magnetic field in the images of MRI both in rest and in task, between 2 and 3 acquisitions of field maps will be carried out. The pre-processing of the images will be carried out with the Finite State Language (FSL) v6 program (FMRIB's Software Library, httpp://www.fmrib.ox.ac.uk/fsl/) and with the Statistical Parametric Mapping program, httpp: / /www.fil.ion.ucl.ac.uk/spm/ (SPM12) . Cortical thickness analysis will be carried out using the Freesurfer program. (httpp://www.surfer.nmr.mgh.harvard.edu/). For the analysis of brain activity at rest, the Analysis of Functional Neuroimages (AFNI) program (httpp://afni.nimh.nih.gov/about_afni) and MELODIC (Multivariate Exploratory Linear Optimized Decomposition into Independent Components) tool included in FSL will be used. For the analysis of fMRI images in task, you wil use (FMRI Expert Analysis tool) v5.98 to explore the functional connectivity between specific brain anatomical regions. The analysis of the diffusion images will be carried out using Tract-Based Spatial Statistics (TBSS), a tool also included in the FSL program, which allows the quantitative comparison of the integrity of the main white matter tracts. For the analysis of structural connectivity, the probabilistic tractography analysis Probabilistic Tracking (Probtrackx2) will be used, included in the FSL program.

Inclusion Criteria:

1. presence of severe / symptomatic aortic stenosis with indication for elective Aortic Valve Replacement
2. patients with intermediate or high surgical risk evaluated by EuroScore II 3-10%, susceptible to be treated with both techniques
3. age> 70 years

Exclusion Criteria:

1. contraindication to perform an MRI
2. severe renal failure
3. severe psychiatric illnesses
4. Diagnosed dementia or Mini Mental State Examination (MMSE) <19/35 corrected for age and education
5. surgical reintervention
6. patients with preoperative comorbidities that condition difficulties for a one-year clinical follow-up
7. aortic surgery concomitant to AVS or other than coronary revascularization

The population that will be analyzed in this study are those patients with severe aortic stenosis that are candidates on valve replacement treatment. Those who present an intermediate or high surgical risk, over 70 years and who are candidates for both a surgical replacement and a TAVI and who present a normal cognitive state evaluated by a neurologist will be included.