## 4 Discussion
### Socio-Demographic Data of Participants  
It is observed from the results that the mean age of the participants was 76.95 years, with participants diagnosed with pAD being significantly older in age than control individuals. The observation that participants in the case group are significantly older than those in the CG reinforces the well-established notion that age remains the most important risk factor for the development of AD [24]. In Spain, the life expectancy in 2022 was 80.4 years for men and 85.7 years for women, highlighting the relevance of aging as a key factor in AD development [25]. Such results are in line with the extensive evidence suggesting that ageing is a major factor driving the development of the AD [24; 26; 27], which would support therapeutic interventions on the biological mechanisms of aging as precursors of nicotinamide adenine dinucleotide (NAD\({}^{+}\)), inducers of mitophagy and inhibitors of cellular senescence and stimulation of muscle satellite cells [28; 29]. The results of this study revealed a significant prevalence of female gender in both groups, with a statistical association (\(p\) = 0.0343), although there were more women in the CG (83.75%) compared to the case group (76.15%). Recent findings [30; 31; 32] have pointed out \begin{table}
\begin{tabular}{c c c c c c c} \hline \multirow{2}{*}{**Medical Diseases and Conditions**} & \multicolumn{3}{c}{**pAD Group**} & \multicolumn{3}{c}{**Control Group**} & \multirow{2}{*}{\(p\)**-Value**} \\ \cline{3-3} \cline{5-6}  & & _Frequency_ & \% & & _Frequency_ & \% & \\ \hline \multirow{3}{*}{High blood pressure} & _Yes_ & 94 & 39.17 & 61 & 24.60 & \multirow{3}{*}{0.0005 ***} \\ \cline{2-6}  & _No_ & 146 & 60.83 & 187 & 75.40 & \\ \cline{2-6}  & _Not available_ & 20 & – & 3 & – & \\ \hline \multirow{3}{*}{Hypercholesterolemia} & _Yes_ & 73 & 30.42 & 91 & 36.69 & \multirow{3}{*}{0.1422} \\ \cline{2-6}  & _No_ & 167 & 69.58 & 157 & 63.31 & \\ \cline{2-6}  & _Not available_ & 20 & – & 3 & – & \\ \hline \multirow{3}{*}{Cardiac pathology} & _Yes_ & 49 & 20.42 & 22 & 8.87 & \multirow{3}{*}{0.0003 ***} \\ \cline{2-6}  & _No_ & 191 & 79.58 & 226 & 91.13 & \\ \cline{2-6}  & _Not available_ & 20 & – & 3 & – & \\ \hline \multirow{3}{*}{Diabetes mellitus} & _Yes_ & 47 & 19.58 & 18 & 7.26 & \multirow{3}{*}{\(<\)0.0001 ***} \\ \cline{2-6}  & _No_ & 193 & 80.42 & 230 & 92.74 & \\ \cline{2-6}  & _Not available_ & 20 & – & 3 & – & \\ \hline \end{tabular}
\end{table} 
Table 2: Clinical information of the study participants per group. that women exhibit a more pronounced development, progression and clinical presentation of AD compared to men. Advanced age is one of the most important risk factors for AD. In this regard, women have a higher prevalence and risk of suffering from AD throughout life than men, mainly due to their longer life expectancy. Hormones and sex chromosomes interact differentially with several AD triggering mechanisms during the aging process such as neuroinflammation, metabolism and autophagy, the microbiome and genetic polymorphisms, among others [31; 32]. In this way, the critical factor that contributes to more women suffering from AD than men is due to sex differences in cognition and brain function caused by steroid sex hormones. Estrogen, progesterone and androgen increase substantially the resistance of neurons to AD by preventing amyloidosis, tauopathy and the regulation of gliosis. Based on the high incidence of AD after menopause, exposure to estrogens during a shorter life span may be associated with an increased risk of AD, because it makes the female brain more physiologically vulnerable to the pathophysiology of AD [33], especially of metabolic and inflammatory pathways, increasing vulnerability to AD [6]. Specifically, estrogen appears to play a protective role by reducing A\(\beta\) accumulation through the regulation of amyloid precursor protein (APP) processing, while its loss may contribute to increased A\(\beta\) burden. In contrast, the gradual decline of testosterone in men may mitigate these effects [34].