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ORIGINAL RESEARCH article

Front. Aging Neurosci.

Sec. Alzheimer's Disease and Related Dementias

Clinical and neuropsychological features associated with progression in subjective cognitive decline

Provisionally accepted
Rafael  VillinoRafael Villino1*Mirla  Ríos-RiveraMirla Ríos-Rivera1Genoveva  Montoya-MurilloGenoveva Montoya-Murillo1Jonathan  Patricio BalderaJonathan Patricio Baldera2Salomón  Salaza-LondoñoSalomón Salaza-Londoño3Maria  Cruz Rodríguez-OrozMaria Cruz Rodríguez-Oroz1Miguel  German BordaMiguel German Borda1,2Adolfo  Jimenez-HueteAdolfo Jimenez-Huete1Mario  RiverolMario Riverol1
  • 1University Clinic of Navarra, Pamplona, Spain
  • 2Centre for Age-Related Medicine (SESAM), Stavanger University Hospital,, Stavanger, Norway
  • 3Semillero de Neurociencias y Envejecimiento, Ageing Institute, Medical School, Pontificia Universidad Javeriana,, Bogota, Colombia

The final, formatted version of the article will be published soon.

Background and Objectives: Subjective Cognitive Decline (SCD) is recognized as an early indicator of neurodegeneration, yet factors that predict its progression to mild cognitive impairment (MCI) or dementia remains not fully understood. In this study, we aim to identify clinical and neuropsychological features associated with the progression of SCD. Methods: 450 persons with SCD were included, consisting in 319 non progressors (SCDnp) and 131 progressors (SCDp) to MCI or dementia due to AD. The study was conducted at the Clínica Universidad de Navarra Memory Clinic between 2001 and 2017. We included data on medical interviews and neuropsychological evaluations. Differences between SCDnp and SCDp were assessed and, to evaluate the association between exposure variables and progression in time, proportional-hazards Cox models were applied. In addition to the exposure variables, the models were adjusted for age, sex, and years of education. Results: At baseline, SCDp were older, had a higher prevalence of hypertension and hypercholesterolemia and had worst performance on tests related to processing speed, verbal fluency, visual memory, verbal memory, and executive functioning. Factors associated with progression at follow-up were lower scores in some cognitive tests: MMSE, TMT-B, and the CERAD regarding trial 1 of immediate recall, trial 2 of immediate recall, trial 3 of immediate recall and the delay recall score. Discussion: Lower scores on global cognition, executive functioning and verbal memory tests were predictors of progression to MCI or dementia in patients with SCD. These findings underscore the importance of nuances in neuropsychological evaluation, even with a normal score, for detecting high-risk individuals for early intervention.

Keywords: subjective cognitive decline1, Alzheimer's Disease2, mild cognitive impairment3, neuropsychological assessment4, Disease Progression5

Received: 06 Aug 2025; Accepted: 27 Oct 2025.

Copyright: © 2025 Villino, Ríos-Rivera, Montoya-Murillo, Baldera, Salaza-Londoño, Rodríguez-Oroz, German Borda, Jimenez-Huete and Riverol. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Rafael Villino, rvillino@gmail.com

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