## 4 Discussion
### Alzheimer's Disease and Cardiovascular Risk Factors
#### 4.2.4 Diabetes Mellitus and Alzheimer's Disease  
In the early 1990s, the Rotterdam study [73] marked a crucial starting point by establishing the initial link between AD and DM. This research, which included 6330 participants aged 55-59 years, revealed significant data, such as that of the 265 participants diagnosed with dementia, 59 also had DM (22.3%). Multiple regression analysis performed in the research conclusively confirmed a positive association between DM and the incidence of dementia (OR: 1.3). Although the relationship was more evident for vascular dementia, a significant association with AD was also identified [73]. In addition, a subsequent study [74], which included a total of 6370 participants, showed remarkable results. Duringfollow-up, 126 participants developed dementia, of whom 89 had AD. This study revealed that DM almost doubled the risk of dementia and AD, suggesting that DM may play a role in the pathogenesis of AD in a considerable proportion of all patients with dementia [74]. In line with the previously reported studies [73; 74], the results of the present investigation reflected similar findings. Of the 240 participants with available data and diagnosed with AD, 47 also had DM, representing a percentage of 19.58%. In comparison, in the group of healthy individuals, the percentage of DM was 7.26% (18/248). This contrast significantly reveals a higher prevalence of DM in the case group compared to the CG. [PERSON] et al. [47] conducted a more recent study focusing on the impact of DM on the severity of A\(\beta\) plaques measured in vivo in the brains of Rotterdam study participants [73]. The research group of [PERSON] et al. [47] assessed DM in 635 participants without dementia, a few years before performing the PET test. Their findings revealed that DM, 7 years before neuroimaging assessment, was associated with an increased risk of positive amyloid burden. Accordingly, they concluded that DM appears to contribute to the pathophysiology of AD in a general population without dementia. Similarly, [PERSON] et al. [75] showed in their study that subjects with DM have an increased risk of developing dementia. In this investigation, it was observed that participants in the case group had a higher mean glucose level (107.67 mg/dL \(\pm\) 36.52) compared to the mean glucose level of the CG (95.70 mg/dL \(\pm\) 22.08). Based on these findings, [PERSON] et al. [47] also noted in their results that higher glucose levels, measured in blood 7 years prior to PET, were associated with increased accumulation of brain A\(\beta\)-peptide. Specifically, the strongest effects were seen in the posterior cingulate and pracecureus. Another study [76] assessed cognitive impairment in individuals diagnosed with AD and type 2 DM. They divided 104 patients with AD and DM into two groups according to the anti-diabetic drug therapy administered: group A, whose participants were treated with oral anti-diabetic drugs, and group B, whose participants were treated with insulin combined with other oral anti-diabetic drugs. Cognitive functions were assessed via the Mini Mental Scale Examination (MMSE) and showed that there was a significant worsening in 56.7% of participants in group A compared to 23.2% of participants in group B, compared to baseline MMSE scores. These results suggest that insulin therapy may be effective in slowing cognitive decline in diabetic patients with AD [76]. DM is a risk factor for the development of cognitive impairment and, when there is already some impairment, it is associated with a higher risk of worsening to the point of dementia or of progressing to AD [73; 74]. The main mechanisms underlying DM related dementia are cerebral resistance to insulin (causing an alteration in the transmission of this hormone) and amyloidosisoresis (accumulation of A\(\beta\)-peptide deposits in the brain), without excluding the appearance of other processes related to neuroinflammation or oxidative stress [77].