Clinical and neuropsychological variables associated with subjective cognitive decline and its progression

Abstract Background and Objectives: This study aimed to compare clinical and neuropsychological variables between patients with subjective cognitive decline (SCD) and healthy controls in a memory clinic, while identifying variables associated with progression to mild cognitive impairment (MCI) or dementia. Methods: We retrospectively analysed data from 945 patients with SCD and 68 healthy controls (HCs) who visited the Clínica Universidad de Navarra memory clinic between 2001 and 2017. Among them, 450 participants were followed up longitudinally in at least one visit until January 2020. All patients underwent medical interviews, laboratory tests, neuropsychological assessments (during the first interview and follow-ups) and brain magnetic resonance imaging. Of the 945 participants, 131 progressed to MCI or dementia due to Alzheimer’s disease. The neuropsychological assessment encompassed the following domains: cognitive functions (i.e. global cognition, episodic visual and verbal memory, executive functions, phonetic fluency, cognitive flexibility, interference and language), neuropsychiatric symptoms and functional status. All variables were adjusted for age, sex and education. Results: Participants with subjective cognitive decline were younger and had higher education than HCs. Additionally, they presented more vascular risk factors. Age at diagnosis, years of education and the presence of hypercholesterolemia were among the demographic variables that were positively associated with the development of MCI or dementia. In the neuropsychological assessment, individuals with SCD showed worse results in global cognition, verbal memory and semantic and phonetic fluency and exhibited more depressive symptoms. Moreover, exhibiting worse performance on tests evaluating episodic verbal memory was found to be correlated with an elevated likelihood of transitioning to MCI and dementia. Discussion: The development of SCD and its progression to MCI or dementia is a multifaceted process involving clinical and neuropsychological factors. Younger age and increased vascular risk factors are characteristics of individuals with SCD. Neuropsychologically, they tend to display weaker performance in global cognition, fluency tasks, verbal memory and executive functions. Several variables were identified as potential indicators of disease progression. These include age at diagnosis, hypercholesterolemia and poorer results in tests measuring semantic fluency, verbal and visual memory and executive functions.