Insulin-like growth factor 1 (IGF-1) is a potent neuroprotective factor for neurons involved in oligodendrocyte precursor cell proliferation and differentiation as well as in myelin synthesis (Ghassan et al. 2017). As both of cognitive impairment and fatigue can affect up to 70% of MS patients, we conducted this study searching for a possible association between serum IGF-1 levels on the one hand and cognition impairment as well as fatigue on the other hand.
The present study showed that MS patients have a statistically significant higher MFIS score (physical, cognitive, and psychosocial) and a statistically significant low MoCA score than the controlled group. This finding met with those of Pellicano and colleagues (2010) and Freitas and colleagues (2018) respectively.
For data regarding MS patients with cognitive impairment (MoCA score < 26), they had significantly older age, progressive disease course, higher expanded disability status scale (EDSS), longer disease duration, and higher relapse rate than MS patients with normal cognitive function (MoCA score ≥ 26). Our results are supported by that of Aksoy and colleagues (2013) who found that cognitive impairment was significantly higher in advanced age. Also, Ashrafi and colleagues (2016) found that those with cognitive impairment had significantly higher disease duration and higher EDSS.
In regard to the fatigue in MS patients, this study demonstrated that fatigue was statistically significant with higher age, progressive disease course, higher EDSS, longer disease duration, and higher relapse rate when compared with those MS patients without fatigue. In line with the present study, Pellicano and colleagues (2010) found that in MS patients, there was a significant relationship between EDSS and fatigue severity.
According to our results, serum IGF-1 levels in MS patients have no significant difference than those in control group (P = 0.19). Our results corroborate the findings of Gironi et al. (2013) and Lanzillo et al. (2011); they showed no significant difference between MS patients and the control group. Also, Wilczak et al. (1998) found no difference in serum or CSF of IGF-1 between MS patients and controls. However, Ghassan and colleagues (2017) reported that there was a significant increase in serum IGF-1 levels in MS patients when compared to controls but this difference in results could attribute to the change in mean of age and disease duration. The increase in specific components of the peripheral IGF system may be primarily associated with the early stages of MS (Hosback et al. 2007).
In our patient group, serum IGF-1 levels were significantly low in patients with primary progressive MS and those with high EDSS ≥ 6 and with disease duration > 5 years also; IGF-1 showed a significant negative correlation with EDSS, disease duration, and number of attacks suggesting the presence of correlation of serum IGF-1 levels and accumulation of disability in MS. This result is in agreement with a previous study by Akcali et al. (2017).
IGF-1 is involved in the regulation of the immune system, oligodenerocyte proliferation, and survival (El-Tamawy et al. 2016). Fedorishin et al. (2017) evaluated the effect of IGF-1 on demyelination and reported that IGF-1 treatment reduce the clinical deficits, size, and number of lesion.
In this study, serum IGF-1 has no significant difference in patients who received specific treatment for MS and those without specific treatment. This is in parallel to Lanzillo et al. (2017) who reported that serum IGF-1 levels were not significantly modified after 1 and 2 years of treatment by interferon β (INF-β). On the other side, Hosback et al. (2007) observed an increase of serum IGF-1 levels in MS patients on IFN-β therapy compared to untreated MS patients, but high percentages of our patients were not receiving any specific immune modulation treatment which should be considered.
According to this study, IGF-1 has a negative correlation with the age of patients (p < 0.001) similar to those of Akcali et al. (2017) and Lanzillo et al. (2017).
Regarding cognitive function, we found that IGF-1 was significantly lower in MS patients with cognitive impairment than MS patients with normal cognitive function. Also, IGF-1 has a significant positive correlation with MoCA score performance and low level of IGF-1 also was found as a risk factor for cognitive impairment in MS patients. These results are parallel to those of Angelini and colleagues (2009) who found that serum IGF-1 level decline is parallel to age-dependent cognitive impairment and dementia. They also reported that serum IGF-1 level lower than 79.4 μg/L seems to be a biomarker for cognitive function.
Serum IGF-I showed significant positive correlation with cognitive deterioration in Alzheimer’s disease (AD) (Kimoto et al. 2016; Doi et al. 2015). Moreover, increasing serum IGF-1 levels were reported to improve cognition in those at high risk for AD (Baker et al. 2012). In addition, associations between serum IGF-1 levels and cognitive function in patients with growth hormone deficiency (Webb et al. 2012; Licht et al. 2014), infantile spasms (Riikonen et al. 2010), Parkinson’s disease (Pellecchia et al. 2013), and delirium (Adamis and Meagher 2011) were reported.
In a longitudinal study on 1318 elderly people, Dick et al. (2003) have founded that IGF-1 value was directly related to the speed of information processing, memory, and mini-mental state examination (MMSE) score. Also IGF-1 has a significant positive correlation with executive function (Al-Delaimy et al. 2009) and global cognitive function (Erickson and Barnes 2003).
The brain areas pivotal for cognition are the temporal lobe (hippocampus and para hippocampus areas) and prefrontal cortex which are normally rich in IGF-1 receptors (Licht et al. 2014). With aging, there is a significant reduction in both serum level of IGF-1 and its receptors in these areas with possible secondary decline in cognitive function (Lai et al. 2000). Calabrese et al. (2010) demonstrated more thinning in the fronto-temporal prefrontal cortices in mild and severe cognitive impairment MS patients.
According to fatigue, the present study showed a significant negative correlation between serum IGF-1 levels and MFIS results; also, low serum IGF-1 levels were found to be a risk factor for fatigue. In the same line with our results, Allain et al. (1997) reported lower serum levels of IGF-1 in chronic fatigue syndrome compared to those in healthy controls. Also, Bjersing et al. (2013) found evidence of a positive role for IGF-1 on fatigue in patients with fibromyalgia. A higher level of IGF-1 has associated with better physical fitness among both young (Nindl et al. 2011) and older individuals (Taekema et al. 2011).
IGF-1 is a hormone stimulated by the growth hormone, particularly during deeper “slow-wave” sleep (Ursavas et al. 2007). Total sleep deprivation (25 h of continuous wakefulness) in healthy young men is transiently associated with a significant decrease in circulating free IGF-I concentrations that are restored after one night of recovery (Chennaoui et al. 2014). Sleep disorders and obstructive sleep apnea (OSA) may affect the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis with an inverse relationship between IGF-1 plasma concentration and the severity of OSA (Ursavas et al. 2007).
Fatigued MS patients are more likely to have disrupted sleep. Several sleep disorders are reported to be common in the MS population such as sleep-related breathing disorder, insomnia, rapid eye movement sleep behavior disorder, narcolepsy, restless leg syndrome, and circadian sleep rhythm disorders. Moreover, sufficient treatment of an underlying sleep disorder may improve fatigue (Braley and Chervin 2010).