Predictors of Affective and Cognitive Alterations in Minor Stroke Patients: clinical, omics, neuropsychological and radiological signatures

Background. Despite the mild severity of initial symptoms, minor stroke (MS) is a common clinical condition that can be associated with significant affective and cognitive alterations. Methods. The PSICOICTUS project aimed to investigate the predictors of these alterations in a cohort of 118 consecutive MS patient. This observational, longitudinal, and prospective study included comprehensive evaluation at baseline (within the first five days of symptom onset) and follow-ups at 15 days, 6 months, and 12 months. A screening battery consisting of the Montreal Cognitive Assessment (MoCA), Montgomery-Åsberg Depression Rating Scale (MADRS), and Apathy Evaluation Scale-Clinician version (AES-c) was used to identify patients with affective and/or cognitive alterations. Results. Cognitive alterations were further assessed using a comprehensive neuropsychological battery. Screening tests revelated that 17.0% of patients had affective alterations, 9.3% had cognitive alterations, and 14.4% presented with both affective and cognitive alterations. Among patients with cognitive alterations, executive functions, attention and processing speed were found to be the most affected domains. The study also concluded a biomarker discovery analysis involving MRI-based neuroimaging and untargeted metabolomics/lipidomics analysis. Several predictors of affective and cognitive alterations were identified. A history of previous depressions, lower levels of Isoleucyl-Isoleucine, and PC (38:4) were associated with affective alterations. On the other hand, age above 70, the presence of a middle cerebral artery ischemic lesion, higher creatinine levels, lower triglyceride levels, and higher concentrations of 2-hydroxyhexadecanoylcarnitine were predictive of cognitive alterations. Female sex, previous history of depressive syndrome, and a higher number of chronic strokes were identified as predictors for both affective and cognitive alterations. Conclusions. These findings highlight the importance of considering affective and cognitive alterations in the management of patients with MS. The identification of specific predictors would improve the development of a differential management approach tailored to the needs of MS patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement CP was supported by a grant from Contracte Predoctoral en formació de la Universitat de Lleida (FP: PI17 -01725); INVICTUS plus Research Network (Carlos III Health Institute) (FP, CP, and GA: RD16-0019-0017). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The local ethics committee approved the study (Hospital Universitari Arnau de Vilanova, code: 1838), and written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Requests for access to the data reported in this paper will be considered by the Lead contact on reasonable basis.