## 3 Results
### Omega-3 Supplementation in AD  
One of the most important characteristics of AD is the persistent state of neuroinflammation, driven by the activation of microglia and astrocytes [40]. The continued release of pro-inflammatory cytokines, such as tumour necrosis factor-\(\alpha\) (TNF-\(\alpha\)), interleukin (IL)-1\(\beta\), and IL-6, is correlated with memory impairment and a decline in cognitive performance [41; 42]. The potential role of \(\omega\)-3 FAs, particularly docosahexaenoicenoic acid (DHA), which is abundant in the membrane phospholipids of brain gray matter [43], and eicosapentaenoic acid (EPA) has been investigated by several research groups because of its potential anti-inflammatory effects. Table 3 reports the main characteristics of the reviewed RCTs that evaluated the \(\omega\)-3 FAs\({}^{\prime}\) effects in AD patients. [PERSON] et al. [44] conducted two studies to test the effects of \(\omega\)-3 polyunsaturated FAs on weight and appetite in mild-to-moderate AD [44], as well as their impact on levels of transthyretin (TTR), an A\(\beta\)-binding protein that reduces brain A\(\beta\) accumulation [45]. In both studies, one group received \(\omega\)-3 supplementation for 12 months, while the other group was initially treated with the placebo for the first 6 months and then switched to the same \(\omega\)-3 supplementation regimen as the first group for the remaining 6 months. A progressive weigh gain was recorded in the supplemented group, whereas no weight gain was observed in the group receiving the placebo until they switched to active treatment [44; 45]. This weight gain was particularly evident in participants with a body mass index at baseline of less than 23 (\(p<0.01\)). Additionally, caregiver assessments indicated an increase in appetite in the \(\omega\)-3/\(\omega\)-3 group after 12 months (\(p<0.01\)). No treatment effect related to APOE4 allele status was found. Overall, the results suggest that \(\omega\)-3 FA supplementation is related to increases in weight and appetite in patients with mild AD [44]. [PERSON] et al., [45] in 2013, reported that after 6 months, the patients administered with the placebo showed decreased plasma TTR levels (\(p<0.001\) within a group and \(p<0.015\) between groups), whereas the \(\omega\)-3 FA supplementation group did not experience this effect. During the subsequent 6 months, when both groups were supplemented with \(\omega\)-3 FAs, TTR levels increased in both groups (\(p<0.01\) for the \(\omega\)-3/\(\omega\)-3 group and \(p<0.001\) for the placebo/\(\omega\)-3 group) [45]. After 12 months, TTR increased significantly only in the group that received \(\omega\)-3 FA supplementation through the entire study period (\(p=0.04\)). Notably, in this group of patients, increased plasma concentrations of TTR were associated with improved cognitive function [45]. [PERSON] et al. conducted four studies between 2008 and 2014 to test the effects of \(\omega\)-3 FAs on AD-related pro-inflammatory biomarkers [46; 47; 48] and their impact on psychiatric and behavioural symptoms [49]. In 2008 [48], 174 patients with mild AD were given a dose a \(\omega\)-3 FAs or placebo for 6 months, followed by 6 months of \(\omega\)-3 FAs for both groups. The supplementation consisted of 1.7 g of DHA and 0.6 g of EPA. At baseline, there were no significant differences in the use of antidepressants and neuroleptics in the two groups. The \"Neuropsychiatric Inventory (NPI)\", used to measure neuropsychiatric symptoms, and the \"Montgomery Asberg Depression Scale (MADRS)\" for depressive symptoms showed low total scores at baseline for both groups. At 6 and 12 months, no significant differences between the groups were observed in total NPI scores. However, in the first 6 months, hallucinations (\(p=0.04\)) and irritation (\(p=0.008\)) improved in the \(\omega\)-3 FA group and placebo group, respectively. These effects disappeared when both groups received \(\omega\)-3 FA supplementation [48].