**4. Discussion**

Recent research, consistent with the results of the present study, indicates that dementia and depression are diseases with a high prevalence and with a remarkable overlap in their epidemiological data [36,37].

However, the temporary sequence of this association is controversial. On the one hand, several authors point out that the presence of late depressive symptoms in older people could be the first manifestation of dementia, so depression, in this case, would be a prodromal factor of dementia [38,39]. On the other hand, some authors state that people with depression have an increased risk of being diagnosed with dementia and/or AD in old ages [40,41], results that are consistent with the present study, where those subjects with a diagnosis of depression had between 13.6 and 15.6 times higher prevalence of dementia than subjects without depression.

Nevertheless, this association between the two diseases, based on the existing literature, will be determined by the severity of the depressive symptoms, the recurrence of episodes, the general state of health of the person, and the presence of depression in adulthood [42–45].

With regard to the latter point, multiple studies indicate that the link between the two diseases would be limited by the time of onset of depression [46,47]. Therefore, age must be understood as a factor of great importance in this relationship, even more when thanks to the development of imaging techniques, it has been possible to compare the causal relationship between these two clinical entities from the pathophysiological point of view, because in people diagnosed with depression at an old age, the presence of β-amyloid plaques and accumulation of tau protein in the brain years before the presentation of dementia have been verified [48,49].

Thus, the onset of these symptoms in old ages can be understood as a prodromal factor, and in turn, the appearance of early depression can be understood as a risk factor for developing dementia and/or AD in both early and old ages [50,51].

In addition, the consideration of depressive symptoms as a prodromal factor would be higher in people diagnosed with dementia with Lewy bodies or VD than in those affected by AD [52,53].

Regarding the pathophysiological link between the two diseases, it appears to be centered on microglia activation as the basis of the process of cerebral neuroinflammation described in both diseases [54]. In this sense, the studies developed by Gathel et al., (2019) take on special relevance, because their objectives were to try to establish a relationship between depressive symptoms, cognition, and cortical amyloid in community-dwelling older adults [29].

Despite the evident relationship between these diseases, health professionals often treat these two diseases independently, focusing the treatment of dementia, particularly in the case of AD, on memory decline and forgetting to include the care of the depressive behavioral symptoms that these patients present as a key element [55]. This inadequate approach to depression in people with dementia increases functional and cognitive impairment, especially if the person also suffers from anxiety as it seems to accentuate the cognitive decline [56], thus intensifying the loss of independence of the person, and ultimately it is associated with an increase in the institutionalization of these patients [57].

Moreover, beyond depression, and as our results show, older age is a risk factor itself for developing dementia and/or AD [58,59]. If the other variables are equal, for every 1-year increase in the person's age, the risk of developing dementia increases by 16%.

Another of the diseases described in the scientific literature due to its potential relationship with the development of dementia, and as has been proven in the results of the present study, is T2DM, which must be understood as a risk factor for dementia [60]. Specifically, the findings of the present study estimate that those with T2DM experienced 2.6 times higher prevalence of dementia than subjects without T2DM. However, this decrease in cognitive functions, particularly memory and reasoning, and therefore the development of dementia seems to depend, according to the existing literature, on two factors in people with TMD2: The duration of the disease and the glycemic control [61].

In addition, T2DM has also been defined as a risk factor specifically for patients with AD with depression, because increased serum levels of glycosylated hemoglobin favor a worsening of depressive symptoms in patients with AD. This is why adequate control of T2DM, through hygienic-dietary measures and appropriate pharmacological treatment, can reduce the severity of depression in patients with this neurodegenerative disease [62].

With regard to the influence of dyslipidemia, and in accordance with our results, it should be noted that low levels of HDL increase the risk of AD [63], as well as a greater progression of the disease [64], whereas high serum HDL levels are associated with improved memory function [65]. In this sense, according to Ward et al. (2010), there is a positive relationship between HDL levels and gray matter volume in the temporal area, and consequently with de cognitive function [66], with this relationship limited by the fact that HDL contains apolipoprotein E (APOE) [67]. In addition, recent studies indicate that increased serum LDL levels are associated with higher deposits of β-amyloid protein in the brain, resulting in increased risk of developing AD [64,68].

However, in addition to the described metabolic relationship between APOE, HDL, and AD, brain neuroinflammation is a fundamental connection point between dyslipidemia and dementia [69]. Thus, the pharmacological approach to dyslipidemia using drugs, such as statins, could not only reduce serum lipid levels, a widely recognized function of this treatment, but would help to mitigate the inflammatory process, thus benefiting all patients with AD, although the progression of this positive effect over time is still unknown [70,71].

In this regard, some studies suggest that treatment of dyslipidemia with statins decreases the risk of dementia and AD [72,73], which would support the results of the present study. Similarly, the use of statins is associated with a decrease in the incidence of all types of dementia, except VD [74]. However, it is not recommended to systematically use statin therapy in all people with dyslipidemia because of its controversial interference with cognitive function [75,76].

Health professionals will be responsible for discerning which subjects may benefit from the dual function of this pharmacological treatment because they present other risk factors contributing to the development of dementia or because they already have cognitive impairment [77,78].
