In clinical studies, the prevalence of cognitive impairments in MS is estimated to be between 54% and 65% [1]. These impairments tend to increase with worsening physical disability, disease duration, and a progressive course [6]. The cognitive domains most frequently affected in MS are speed of information processing, sustained attention, memory, and visuospatial perception [3]. Cognitive impairment significantly affects patients’ quality of life, social integration, and ability to work [18]. Levels of anxiety and depression can have a negative impact on patients’ cognitive performance, leading to poorer outcomes [8]. However, research has demonstrated that higher levels of cognitive reserve are linked to less cognitive impairment in pwMS [11].
The objective of this study was to investigate the relationship between depressive symptoms, CR, sustained attention, and semantic fluency in individuals with impairment. Our hypothesis was that CR predicts the relationship between depressive symptomatology and cognitive function. The main aim was to examine the role of CR as a moderator of the relationship between BDI, PASAT, and WLG.
The findings suggest a consistent association between increased depressive symptomatology and lower performance in sustained attention, and semantic fluency.
Depression affects over 20% of MS patients [19], leading to reduced quality of life, increased hospitalisation and mortality rates, and worse disability progression [20, 21]. Research has demonstrated a correlation between symptoms of depression in patients and a decline in attention and executive function, particularly in tasks that involve distractions [22, 23]. A subsequent study revealed that symptoms of depression are more closely linked to cognitive efficiency, specifically speed, rather than memory [24]. Several studies have shown that pwMS with depression perform worse on the PASAT than non-depressed MS patients and normal control participants [25, 26]. A meta-analysis of 10 studies on MS patients with depression also found a correlation between major depression and lower PASAT scores [27]. It has been widely demonstrated that high levels of depression are associated with worse performance on verbal semantic fluency tests [28].
However, the importance of CR as a predictor of cognitive functioning in persons with disabilities was reiterated [11]. Studies have indicated how CR predicts performance in tests of processing speed and memory [29]. However, it has also been shown the central role played by CR on all aspects of cognition such as executive functions, visuospatial processing and the various cognitive indices measured by the verbal fluency test [30].
To understand whether higher levels of cognitive reserve (CR) could influence the relationship between cognitive performance and depressive symptoms, we conducted a mediation analysis in our study. The analysis considered CR as a potential moderator in the model, based on the direct correlations observed. The results of the mediation analyses indicate that depressive symptoms did not have a direct negative impact on performance in working memory, sustained attention, and verbal fluency. Instead, cognitive reserve (CR) played a protective role in this relationship, resulting in better performance.
Previous research has investigated the relationship between cognitive reserve (CR) and depression. It has been suggested that CR may have a protective effect against the negative impact of increased neurological disability on an individual’s level of depression [31].
Additionally, the correlation between the CRIq score and cognitive performance suggests that patients with higher CRIq scores exhibit better information processing speed, as well as verbal and visuospatial memory performance, compared to those with lower CRIq scores [10]. Cognitive function is differentially protected by CR [32]. High CR predicts the preservation of functional brain connectivity despite grey matter atrophy and attenuates the detrimental effect of white matter alteration on information processing speed in MS patients [33]. In another MS study, high CR was found to selectively protect against the effect of peripheral grey matter atrophy on verbal memory [34].
Previous studies have examined the protective role of CR on cognitive function in patients without multiple sclerosis, but none have specifically focused on the moderating role of CR in the relationship between cognition and depression. Wight and colleagues [35] investigated the impact of education, post-school training, and occupation on cognitive function in a sample of older men living in the community. The study found that a higher level of education moderated the effect of depressive symptoms on cognition, but only when the symptoms were more severe. Bhalla et al. [36] found no moderating effect of education level on neuropsychological performance in a sample of depressed patients. In a study designed to examine the mediation of cognitive reserve in the relationship between cognitive performance and late-life depression, subjects with higher levels of education and/or higher reading scores showed greater declines in cognitive performance with increasing depressive symptoms than those with lower levels of education or reading scores in the reference sample [37]. In agreement with the literature, we also found better performance on cognitive tasks in our study in the presence of higher levels of cognitive reserve, which acts as a protective factor when higher levels of depressive symptoms are registered. While the effect size of -0.044 might be considered weak according to Cohen’s standards, it is important to note that even small effects can have substantial clinical implications for MS patients. The attenuation of cognitive reserve benefits by depressive symptoms highlights the need for integrated therapeutic approaches that address both cognitive and emotional health in MS care.
A few limitations must be considered when interpreting our results. The cross-sectional design, utilizing self-reported measures of CR and neuropsychiatric symptoms, was performed at a single center with a relatively small patient sample and a limited neuropsychological battery. It would be interesting to observe changes in cognitive profiles in larger cohorts over long-term follow-up with a more comprehensive neuropsychological evaluation (including the SDMT and other relevant tests), which could serve as a future goal for this preliminary cross-sectional study. Our findings are specific to the RR-MS population and may not be generalizable to patients with secondary progressive MS (SP-MS). The relatively low percentage of patients on DMTs highlights the variability in treatment practices and patient circumstances. Further research could explore the impact of cognitive reserve and depressive symptoms in other MS subtypes, including SPMS.
Additionally, recognizing the potential limitation of including only newly diagnosed PwMS, who may exhibit higher levels of depression or increased depressive symptoms, future research should compare this group with patients diagnosed for at least two years. This comparison will help clarify the impact of disease duration on depression and cognitive functions.
Finally, another limitation of this study is the absence of specific inclusion criteria for anxiety, fatigue, and sleep quality, despite their known effects on depression in people with disabilities. The sole reliance on the BDI is an additional limitation, as depression can be a secondary symptom in individuals with multiple sclerosis, complicating the relationship between depression and cognitive performance. Future studies should incorporate assessments of anxiety, fatigue, and sleep quality to provide a more comprehensive understanding of the behavioral factors influencing cognitive functions in individuals with multiple sclerosis.