## 3 Results
### Vitamin Supplementation in AD
[31] tested whether vitamin D supplements could slow cognitive decline in AD patients by also assessing cognitive performance in relation to the amyloid-\(\beta\) (A\(\beta\)) 42 protein, the deposition of which is a major cause of neuronal dysfunction and cell death, progressively leading to dementia. Interestingly, the results showed reduced levels of A\(\beta\)42 in the intervention group (11.31%) compared to the control group (0.27%) (\(p<0.001\)) [31]. In contrast, the study by [PERSON] et al. [32] investigated the effect of a high dose of vitamin D2 after a nasal administration of insulin. This approach is based on the observation that nasally administered insulin improves cognitive function, while vitamin D2 increases the expression of insulin receptors and enhances the action of insulin [33]. The initial treatment consisted of 1000 IU of vitamin D2 daily for 8 weeks. Subsequently, the dosage was increased to 6000 IU, divided into two capsules and administered three times a day together with nasal insulin four times a day. The results demonstrated a significant increase in 25-hydroxyvitamin D [25 (OH)D], a recognized biomarker of vitamin D status. Specifically, the median concentration of 25(OH)D increased from 60 nM to 187 nM (\(p<0.001\)) in the high-dose vitamin D group, while in the placebo group it only varied from 64 nM to 72 nM. Another significant finding was the reduction in disability assessed in 11 out of 13 participants (\(p<0.02\)) using the \"Disability Assessment for Dementia (DAD) score\". Based on these results, the study by [PERSON] et al. suggests that high-dose vitamin D providesno benefit for cognition or disability compared to low-dose vitamin D in individuals with mild-to-moderate AD [32]. Vitamin E is known for its antioxidant and anti-inflammatory effects, which could protect against neurodegenerative disorders. Numerous studies have shown that people with AD or age-related cognitive decline have significantly reduced levels of vitamin E in serum and cerebrospinal fluid (CSF) compared to healthy people [23; 34; 35; 36]. The potential interaction between vitamin E, mementine, and cholinesterase (ChE) inhibitors, such as rivastigmine (RIV) or donepezil (DPZ), for the treatment of AD has been investigated to test whether vitamin E could enhance the therapeutic effects of these drugs, improving cognitive function and slowing down the neurodegenerative process. The basic theory is that vitamin E combined with DPZ (which increases brain acetylcholine levels) or mementine (which modulates N-methyl-D-aspartic acid receptor activity) may have a synergistic effect in protecting neurons from oxidative damage and improving synaptic transmission [23]. [PERSON] et al. [37] investigated the effects of 800 IU/d of \(\alpha\)-tocopherol, 500 mg/d of vitamin C, and 900 mg/d of \(\alpha\)-lipoic acid (E/C/ALA) together with 400 mg of coenzyme Q (CoQ) three times a day with ChE inhibitors. This treatment provided a 19% reduction in F2-isoprostane levels in CSF and an improvement in the \"MMSE\" score in the treated group compared to the control group (\(p\) = 0.02) [37]. [PERSON] et al. [38] performed a study to estimate the efficacy and safety of 2000 IU/day of alpha-tocopherol (a type of vitamin E), and 20 mg/day of mementine alone or combined with alpha-tocopherol. Patients with mild-to-moderate AD treated with alpha-tocopherol showed a greater slowing of cognitive decline than those treated with a placebo (\(p\) = 0.03). However, unexpectedly, the combined administration of alpha-tocopherol and mementine had a smaller effect than the single treatments. The mechanism is unclear, but it is possible that mementine interfered with the action of alpha-tocopherol. Moreover, infestation or infection were reported more frequently in the groups treated with mementine (31 events in 23 subjects) and the vitamin E/mementine (44 events in 31 subjects), compared to the placebo group (13 events in 11 participants) [38]. In contrast, [PERSON] et al.