Lídia Mulet-Pons ^1,2 Cristina Solé-Padullés ^1,2 María Cabello-Toscano ^1,2 Kilian Abellaneda Pérez ^1,3,4 Ruben Perellón-Alfonso ^1,2,3 Gabriele Cattaneo ^3,4,5 Javier Solana-Sánchez ^3,4,5 Vanessa Alviarez ^3,4,5 Nuria Bargalló ^1,2,6 Jose M. Tormos ^3,7 Alvaro Pascual-Leone ^8,9 David Bartrés-Faz ^1,2,3* Lídia Vaqué-Alcázar ^1,10,2*

• ¹ Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Balearic Islands, Spain
• ² August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Catalonia, Spain
• ³ University Institute for Neurorehabilitation, Guttmann Institute, Barcelona, Catalonia, Spain
• ⁴ Autonomous University of Barcelona, Barcelona, Catalonia, Spain
• ⁵ Germans Trias i Pujol Health Science Research Institute (IGTP), Barcelona, Catalonia, Spain
• ⁶ Department of Radiology, Clinical Imaging Diagnostic Center, Hospital Clinic of Barcelona, Barcelona, Catalonia, Spain
• ⁷ Catholic University of Valencia San Vicente Mártir, Valencia, Valencian Community, Spain
• ⁸ Hinda and Arthur Marcus Institute for Aging Research, Harvard Medical School, Roslindale, Massachusetts, United States
• ⁹ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
• ¹⁰ Alzheimer-Down Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Balearic Islands, Spain

Individuals with subjective cognitive decline (SCD) express concern about self-perceived cognitive decline despite no objective impairment and are at higher risk of developing Alzheimer's disease. Despite documented links between SCD and repetitive negative thinking (RNT), the specific impact of RNT on brain integrity and cognition in exacerbating the SCD condition remains unclear. We aimed to investigate the influence of RNT on global cognition and brain integrity, and their interrelationships among healthy middle-aged and older adults experiencing SCD. Out of 616 individuals with neuroimaging and neuropsychological data available, 89 (mean age = 56.18 years; 68.54% females) met SCD criteria. Eighty-nine non-SCD individuals matched by age, sex, and education were also selected and represented the control group (mean age = 56.09 years; 68.54% females). Global cognition was measured using the preclinical Alzheimer's cognitive composite (PACC5), which includes dementia screening, episodic memory, processing speed, and category fluency tests. RNT was calculated through three questionnaires assessing intrusive thoughts, persistent worry, and rumination. We generated cortical thickness (CTh) maps and quantified the volume of white matter lesions (WML) in the whole brain, as grey and white matter integrity measures, respectively. SCD individuals exhibited higher RNT scores, and thinner right temporal cortex compared to controls. No differences were observed in PACC5 and WML burden between groups. Only the SCD group demonstrated positive associations in the CTh-PACC5, CTh-RNT, and WML-RNT relationships. In this cross-sectional study, RNT was exclusively associated with brain integrity in SCD. Even though our findings align with the broader importance of investigating treatable psychological factors in SCD, further research may reveal a modulatory effect of RNT on the relationship between cognition and brain integrity in SCD.