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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Alzheimer&#39;s disease &#40;AD&#41; is a chronic&#44; neurodegenerative disorder and the main cause of dementia in the elderly worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This pathology poses one of the greatest challenges to public health today and its prevalence is expected to continue to increase in the coming years&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In Spain&#44; a prevalence of between 2&#46;8&#37; and 3&#46;9&#37; has been reported in the age range of 75&#8211;79 years and between 7&#46;2&#37; and 34&#46;1&#37; in individuals over 85 years old&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">At the anatomopathological level&#44; the presence of extracellular &#946;-amyloid plaques and intraneuronal neurofibrillary tangles is characteristic of this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Over the decades&#44; various hypotheses have been proposed to explain the etiopathogenesis of the disease&#59; however&#44; the debate on the underlying pathophysiology of AD continues to be unknown&#44; considering it multifactorial and lacking a curative treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This uncertainty could be explained by a lack of knowledge about the underlying pathophysiology and suggest the involvement of additional pathways not yet known&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Some studies have demonstrated the role of neuroinflammation in the process of neurodegeneration&#44; with some even considering it may play a central role in both the onset and progression of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The role of the immune function in AD has been a central focus of research in recent decades&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Some studies even suggest that systemic inflammation could negatively influence the underlying pathophysiological process&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> There are even studies referring to systemic inflammation possibly being related to the development of chronic neuroinflammation&#59; however&#44; further studies are needed to confirm this association&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This assumption leads us to consider an interesting research question&#58; could chronic inflammation due to autoimmune diseases lead to an increased predisposition of developing dementia&#44; specifically AD&#63;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Systemic autoimmune diseases represent a constant challenge for healthcare systems worldwide&#46; Despite being a heterogeneous group of pathologies&#44; inflammation plays a key role in their pathophysiology&#46; These pathologies result from dysregulation of the immune system and are characterized by sustained systemic inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The relationship between AD and autoimmune diseases is an actively researched and complex area&#46; Several studies have explored this connection with partly contradictory results&#44; often limited by sample size&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">It has been suggested that inflammatory and autoimmune mechanisms may play a significant role in the development of dementia&#44; including AD&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> A recent study using UK database records showed that the overall incidence of AD was higher among patients with inflammatory diseases such as inflammatory bowel disease&#44; rheumatoid arthritis&#44; and multiple sclerosis&#44; compared to the control group&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">However&#44; few studies have investigated the association between AD and autoimmune diseases&#44; and those that exist have been conducted with small sample sizes and have reported contradictory results&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> New studies on this topic could help understand the role of the immune system in neurodegenerative processes and help delineate the presumed pathogenic link between autoimmune diseases and AD&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Based on this knowledge&#44; we propose a multicenter retrospective cohort study with the aim of analyzing the prevalence AD in patients diagnosed with various autoimmune diseases and the potential association between these pathologies&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0050" class="elsevierStylePara elsevierViewall">In recent years&#44; thanks to artificial intelligence&#44; we have had the opportunity to conduct extensive prevalence studies using tools such as Savana Manager&#174; due to the ability to exploit all patient clinical records data more easily and efficiently&#46; Utilizing this technology&#44; a retrospective&#44; non-interventional&#44; multicenter study was carried out using data obtained from electronic medical records of patients from Castilla-La Mancha &#40;Spain&#41;&#46; In this way&#44; data from the electronic health records &#40;EHRs&#41; of the specialized care network of SESCAM &#40;hospitalization&#44; emergency services&#44; and outpatient consultations&#41; across Castilla-La Mancha between January 1&#44; 2011&#44; and January 24&#44; 2021&#44; were analyzed using the Savana Manager&#174; platform&#46; A system of artificial intelligence was used&#44; which was capable of rephrasing the information in a natural language from the clinical notes&#46; This system maximized a great amount of information found within the electronic medical records &#40;EHRs&#41;&#44; based on the dynamic exploitation in real time of all the information&#46; The program also allowed for immediate descriptive analysis of all patients included in the platform and offered relevant results along with the variables offered by the user&#46; This system significantly expands the sample size&#44; which is essential for attempting to identify relationships such as the one being studied&#46; Additionally&#44; the extraction of this clinical information follows an external validation methodology that ensures the quality of the process&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">At the time of system consultation&#44; a total of 3&#44;309&#44;298 patients from the healthcare area of Castilla-La Mancha were collected from January 1&#44; 2011 to January 24&#44; 2021&#46; Within this group of patients&#44; those over 60 years of age with a diagnosis of AD and various &#40;a total of 12&#41; autoimmune diseases &#40;myasthenia gravis&#44; scleroderma&#44; systemic lupus erythematosus&#44; psoriasis&#44; rheumatoid arthritis&#44; Sjogren&#39;s syndrome&#44; Beh&#231;et&#39;s disease&#44; polymyalgia rheumatica&#44; sarcoidosis&#44; dermatomyositis&#44; vitiligo&#44; and pernicious anemia&#41; were selected&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As for the list of selected autoimmune diseases&#44; we included diseases with a well-defined autoimmune etiopathogenesis that are common&#44; chronic&#44; and long-standing&#46; Additionally&#44; autoimmune diseases that appeared to show a greater association with dementia based on a literature review were included to confirm previous results in this direction through our study&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">As this study was conducted using artificial intelligence&#44; the system is limited to identifying the diagnoses of pathologies made by specialists in the clinical records&#46; The Savana Manager&#174; platform was filtered to analyze the different variables using the term &#8216;Alzheimer&#8217;s disease&#44;&#8217; which includes &#8216;Alzheimer&#8217;s disease&#44;&#8217; &#8216;Alzheimer&#44;&#8217; and &#8216;Alzheimer-type dementia&#44;&#8217; and the terms &#8216;myasthenia gravis&#44;&#8217; &#8216;scleroderma&#44;&#8217; &#8216;systemic lupus erythematosus&#44;&#8217; &#8216;Beh&#231;et&#8217;s disease&#44;&#8217; &#8216;rheumatoid arthritis&#44;&#8217; &#8216;polymyalgia rheumatica&#44;&#8217; &#8216;Sj&#246;gren&#8217;s syndrome&#44;&#8217; &#8216;sarcoidosis&#44;&#8217; &#8216;dermatomyositis&#44;&#8217; &#8216;vitiligo&#44;&#8217; &#8216;psoriasis&#44;&#8217; and &#8216;pernicious anemia&#44;&#8217; respectively&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Ethical considerations</span><p id="par0070" class="elsevierStylePara elsevierViewall">The study was conducted in accordance with legal and regulatory requirements and followed correct clinical practice guidelines from the International Conference on Harmonization&#44; the Declaration of Helsinki in its latest edition&#44; and local regulations&#46; All actions regarding data protection were taken in accordance with the code of good practices of European data protection authorities regarding Big Data projects and the General European Data Protection Regulation &#40;GDPR&#41;&#46; Additionally&#44; this study was approved by the ethics and research committee of our center&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using SPSS v24 software&#46; Qualitative variables are expressed as absolute value and percentage&#44; and quantitative variables as mean&#8201;&#177;&#8201;confidence interval&#46; We used &#967;&#178; or Fisher&#39;s test in order to analyze qualitative variables&#46; In all cases&#44; statistical significance was established with p&#8201;&#60;&#8201;0&#46;05&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">One aspect to consider is that the algorithm uses the available &#39;n&#39; in each operation&#44; excluding cases where variables cannot be determined&#46; While this may be a source of bias&#44; the number of such cases &#40;e&#46;g&#46;&#44; missing diagnosis&#41; is small relative to the total number of patients&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Due to the type of data provided by SAVANA&#44; no statistical corrections for multiple comparisons have been made&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data management</span><p id="par0090" class="elsevierStylePara elsevierViewall">The present study was conducted using the Savana Manager&#174; platform&#46; This platform analyzes data from electronic health records &#40;EHRs&#41;&#46; These data are initially processed and anonymized electronically&#46; Subsequently&#44; using an artificial intelligence system based on mathematical models&#44; the clinical variables of interest are identified and extracted from the free text contained within the records&#46; This generates a structured database based on the information collected from the clinical records&#46; Additionally&#44; the extraction of this clinical information follows an external validation methodology that ensures the quality of the process&#46; Therefore&#44; if a specific diagnosis appears in the clinical information&#44; the system considers that the patient meets this condition&#46; Previous studies have used a similar methodology&#44; applying this data management approach to study other pathologies&#44; such as recent studies on COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0095" class="elsevierStylePara elsevierViewall">A total of 28&#44;920 patients over 60 years of age with a diagnosis of AD were identified during the study period out of a total of 1&#44;028&#44;356 patient records over 60 years of age in the Castilla La-Mancha area&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Distribution of autoimmune diseases</span><p id="par0100" class="elsevierStylePara elsevierViewall">The presence of Alzheimer&#39;s disease &#40;AD&#41; has been analyzed within each of the selected autoimmune diseases&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The distribution of the 12 selected autoimmune diseases &#40;see details in Section &#8220;Materials and methods&#8221;&#41; in both groups was analyzed&#46; The details of these results are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; In the AD population&#44; a total of 1425 patients had autoimmune diseases&#44; with polymyalgia rheumatica being the most frequent pathology &#40;n&#8201;&#61;&#8201;371&#41;&#46; The least prevalent pathology in this group was Beh&#231;et&#39;s disease &#40;n&#8201;&#61;&#8201;1&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">In the group without AD&#44; a total of 33&#44;893 individuals also had these pathologies&#46; In this group&#44; however&#44; psoriasis was the most frequent pathology &#40;n&#8201;&#61;&#8201;9329&#41;&#44; while Beh&#231;et&#8217;s disease was the least prevalent &#40;n&#8201;&#61;&#8201;71&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Prevalence of autoimmune diseases in patients with AD compared to the general population</span><p id="par0115" class="elsevierStylePara elsevierViewall">The prevalence of Alzheimer&#39;s disease &#40;AD&#41; in patients with the selected autoimmune diseases is also analyzed and compared to the general population&#44; with data presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">A statistically significant association was found between myasthenia gravis &#40;OR 1&#46;49&#59; p&#8201;&#61;&#8201;0&#46;007&#41;&#44; systemic lupus erythematosus &#40;SLE&#41; &#40;OR 2&#46;42&#59; p&#8201;&#60;&#8201;0&#46;0001&#41;&#44; rheumatoid arthritis &#40;OR 1&#46;38&#59; p&#8201;&#60;&#8201;0&#46;0001&#41;&#44; polymyalgia rheumatica &#40;OR 2&#46;01&#59; p&#8201;&#60;&#8201;0&#46;0001&#41;&#44; and pernicious anemia &#40;OR 2&#46;06&#59; p&#8201;&#60;&#8201;0&#46;001&#41; and AD&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Other analyzed pathologies that did not show a statistically significant association included scleroderma&#44; Beh&#231;et&#8217;s disease&#44; Sjogren&#8217;s syndrome&#44; sarcoidosis&#44; dermatomyositis&#44; vitiligo&#44; and psoriasis&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0130" class="elsevierStylePara elsevierViewall">Our results indicate that patients over 60 years old with certain autoimmune diseases &#40;systemic lupus erythematosus &#40;SLE&#41;&#44; rheumatoid arthritis&#44; polymyalgia rheumatica&#44; pernicious anemia&#44; and myasthenia gravis&#41; have a higher prevalence of AD compared to the general population&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Therefore&#44; there could be an association between these autoimmune diseases and AD&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Relationship between different autoimmune diseases and AD</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Relationship between rheumatoid arthritis and AD</span><p id="par0140" class="elsevierStylePara elsevierViewall">Regarding the relationship between rheumatoid arthritis &#40;RA&#41; and AD&#44; there is discordance in previous data regarding their association&#46; Epidemiological studies evaluating the co-occurrence of these two conditions have shown conflicting results&#44; with some indicating no significant positive association between RA and AD&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> There are also studies in which the prevalence of AD in rheumatoid arthritis patients was lower than in the control group&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">However&#44; several previous studies have demonstrated an increased risk of dementia in patients with rheumatoid arthritis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> McDowell et al&#46; confirmed the high prevalence of cognitive impairment in rheumatoid arthritis&#44; partly driven and accelerated by chronic systemic inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> The differences in the results found by some authors could be related to the degree of inflammatory activity of the disease&#46; In this direction&#44; a recent meta-analysis provides evidence that elevated CRP could be directly associated with the risk of AD&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Relationship between myasthenia gravis and AD</span><p id="par0150" class="elsevierStylePara elsevierViewall">For myasthenia gravis &#40;MG&#41;&#44; the available data in the literature is very limited and conflicting&#44; with some studies showing no relationship between MG and AD&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> while others associate it with a higher risk of cognitive impairment without distinguishing its etiology&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The association found in our study regarding MG may be of particular interest&#44; as it is not only an autoimmune disease&#44; but also shares involvement of cholinergic neurotransmission &#40;in MG at the peripheral nervous system neuromuscular junction and in AD at the central nervous system&#41; and the cornerstone of treatment &#40;increasing acetylcholine levels with acetylcholinesterase inhibitors&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Relationship between systemic lupus erythematosus and AD</span><p id="par0160" class="elsevierStylePara elsevierViewall">The relationship between systemic lupus erythematosus &#40;SLE&#41; and cognitive impairment &#40;due to AD or other causes&#41; has been investigated in several studies&#44; with results suggesting an association without reaching criteria for causality and variations in the strength and specificity of the association&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a> There have been suggestions of increased cognitive impairment in patients with antiphospholipid antibodies&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> although the vascular burden and cognitive impairment due to this cause in these patients may not be negligible&#46; Conversely&#44; other groups report not finding this association in their studies&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Relationship between polymyalgia rheumatica and AD</span><p id="par0165" class="elsevierStylePara elsevierViewall">Regarding polymyalgia rheumatica&#44; few previous studies have examined the association with cognitive impairment or AD&#44; and the existing studies show conflicting results&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Relationship between pernicious anemia and AD</span><p id="par0170" class="elsevierStylePara elsevierViewall">Pernicious anemia is associated with vitamin B12 deficiency&#44; which has been implicated in multiple psychiatric symptoms such as depression&#44; confusion&#44; and even dementia&#46; Some recent studies suggest that vitamin B12 levels may contribute to cognitive function&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Some studies have described a possible association between pernicious anemia and AD specifically&#44; among other dementias&#44; supporting the results obtained in our sample&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;25</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Relationship between other autoimmune diseases and AD</span><p id="par0175" class="elsevierStylePara elsevierViewall">No association was found with the remaining autoimmune diseases studied&#46; In some cases&#44; the lack of association may be due to low prevalence and small sample size&#46; Previous studies in patients with Beh&#231;et&#39;s disease&#44; scleroderma&#44; and dermatomyositis have not found a relationship with AD&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> More debate may arise regarding Sjogren&#39;s syndrome&#44; sarcoidosis&#44; psoriasis&#44; and vitiligo&#44; as studies have reported contradictory results&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17&#44;25&#44;27</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The differences we have found in the literature regarding the association between some of the diseases analyzed and AD could be related to the low prevalence of autoimmune diseases&#44; which leads to small sample sizes in most previous studies&#46; Therefore&#44; more studies with larger sample sizes would be of interest to analyze this association&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Possible mechanisms</span><p id="par0185" class="elsevierStylePara elsevierViewall">Our study shows the association&#44; but we cannot assume causality or the underlying mechanisms&#46; It is possible that autoimmune diseases predispose to AD due to the inflammatory burden itself or because both share common environmental and&#47;or genetic mechanisms&#46; Another possible mechanism may be that specific treatment used in one of these pathologies alters the risk of the other&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">On the other hand&#44; another potential pathophysiological mechanism could be related to the effect of chronic inflammation from autoimmune diseases at a systemic level&#44; as several studies have suggested a significant role of inflammation in the pathogenesis of dementia&#46; Animal studies have demonstrated elevated levels of inflammatory cytokines in brains with neurodegeneration&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Some studies even suggest that chronic neuroinflammation may be related to systemic inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Another cause may be that exposure to autoimmune diseases leads to changes in AD risk factors&#46; It is known that inflammation in these diseases drives the formation and progression of atherosclerotic plaques&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and studies have shown that carotid atherosclerosis increases the risk of AD&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Clinical implications</span><p id="par0200" class="elsevierStylePara elsevierViewall">Furthermore&#44; it is essential to highlight that knowledge of this association between AD and these autoimmune diseases may underscore the need for close cognitive monitoring of patients with these autoimmune diseases to detect early signs of cognitive impairment&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Strengths and limitations</span><p id="par0205" class="elsevierStylePara elsevierViewall">A notable strength of our study is the large sample size&#44; allowing for the examination of the risk of a wide range of autoimmune diseases in a large cohort of both AD patients and a control group without this pathology in a geographically defined population&#46; Previous studies have investigated this association in smaller populations or in relation to specific autoimmune diseases&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Limitations of our study include inevitable underdiagnosis and undercoding due to the characteristics of our sample&#44; as diagnoses of the studied conditions are limited to those recorded in the summary of the medical history of these patients&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In the data extraction process for this study&#44; each variable analyzed considered all patients in whom the term was recognized in their EHRs throughout their clinical course&#44; regardless of the duration of the condition&#44; the severity of the disorder&#44; the association with other clinical syndromes&#44; the treatment received&#44; or the time of treatment initiation&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Taking all this into account&#44; the lack of analysis of these variables could constitute a possible bias&#44; as certain variables such as sex and some cardiovascular risk factors were not included in our study&#46; These variables could act as confounding factors&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Another limitation inherent to the use of artificial intelligence tools in large databases is the inability to conduct a detailed individual analysis of the subjects under study&#44; preventing the analysis of factors such as disease activity and other variables that could influence the presence of underlying inflammatory processes&#44; among other factors&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Additionally&#44; due to the nature of the data&#44; some misdiagnoses and incorrect coding may occur occasionally&#46; However&#44; it is essential to consider that this lack of diagnostic specificity would affect both cases and controls&#44; so it is not expected to distort the results obtained in our study&#46;</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conclusions</span><p id="par0235" class="elsevierStylePara elsevierViewall">Overall&#44; our results show that patients over 60 years of age with certain autoimmune diseases &#40;SLE&#44; rheumatoid arthritis&#44; polymyalgia rheumatica&#44; pernicious anemia&#44; and myasthenia gravis&#41; are associated with AD&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">The results of this study suggest that systemic inflammation may be related to neurodegeneration and AD&#46; These findings open a new horizon regarding systemic inflammation and autoimmune diseases&#44; their relative contribution to the development and clinical progression of AD&#44; and how this may vary among different autoimmune diseases&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The study of autoimmune diseases and the role of systemic inflammation in the development of AD remains in an early&#44; though promising stage of research&#46; Overall&#44; the scarcity of studies&#44; the low prevalence of some autoimmune diseases&#44; and the conflicting results regarding the relationship between these pathologies and AD make it difficult to draw solid conclusions at present time&#46; The directionality&#44; magnitude&#44; and progression of this association remain unclear&#44; as does the relative role of the underlying processes&#46; Future studies are essential to elucidate the role of autoimmune diseases in the development of AD and the value of modulating inflammation in its treatment&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Funding</span><p id="par0250" class="elsevierStylePara elsevierViewall">The authors received no support from any organization for the submitted work&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conflict of interest</span><p id="par0255" class="elsevierStylePara elsevierViewall">The authors wish to declare that Dr&#46; MI Morales worked for SAVANA MANAGER&#174; until March 2022&#46; The remaining authors have no conflicts of interest to disclose&#46;</p></span></span>"
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              "titulo" => "Ethical considerations"
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              "titulo" => "Statistical analysis"
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          "titulo" => "Results"
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            0 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Distribution of autoimmune diseases"
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            1 => array:2 [
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              "titulo" => "Prevalence of autoimmune diseases in patients with AD compared to the general population"
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          "titulo" => "Discussion"
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            0 => array:3 [
              "identificador" => "sec0050"
              "titulo" => "Relationship between different autoimmune diseases and AD"
              "secciones" => array:6 [
                0 => array:2 [
                  "identificador" => "sec0055"
                  "titulo" => "Relationship between rheumatoid arthritis and AD"
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                1 => array:2 [
                  "identificador" => "sec0060"
                  "titulo" => "Relationship between myasthenia gravis and AD"
                ]
                2 => array:2 [
                  "identificador" => "sec0065"
                  "titulo" => "Relationship between systemic lupus erythematosus and AD"
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                  "identificador" => "sec0070"
                  "titulo" => "Relationship between polymyalgia rheumatica and AD"
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                  "titulo" => "Relationship between pernicious anemia and AD"
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                  "identificador" => "sec0080"
                  "titulo" => "Relationship between other autoimmune diseases and AD"
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              "titulo" => "Possible mechanisms"
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              "titulo" => "Clinical implications"
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              "titulo" => "Strengths and limitations"
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          "titulo" => "References"
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    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2024-04-26"
    "fechaAceptado" => "2024-07-22"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:4 [
            0 => "Autoimmune diseases"
            1 => "Alzheimer&#39;s disease"
            2 => "Systemic inflammation"
            3 => "Neurodegeneration"
          ]
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      ]
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Enfermedades autoinmunes"
            1 => "Enfermedad de Alzheimer"
            2 => "Inflamaci&#243;n sist&#233;mica"
            3 => "Neurodegeneraci&#243;n"
          ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The objective is to analyze the prevalence of Alzheimer&#39;s disease in patients with and without a diagnosis of different autoimmune diseases and the possible association between both pathologies&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A multicenter&#44; retrospective&#44; cohort study was conducted to study the prevalence of Alzheimer&#8217;s disease among patients diagnosed with various autoimmune diseases compared to the general population&#46; Data from electronic medical records from the Castilla-La Mancha healthcare system were analyzed using Natural Language Processing through the Savana Manager&#174; artificial intelligence clinical platform&#46; A total of 1&#44;028&#44;356 patients were analyzed&#44; including 28&#44;920 individuals with Alzheimer&#39;s disease and 999&#44;436 control patients&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Out of the 12 autoimmune diseases analyzed&#44; 5 showed a significant association with Alzheimer&#39;s disease with p&#8201;&#60;&#8201;0&#46;05&#46; Myasthenia gravis had an increased prevalence of AD with OR 1&#46;49 &#40;95&#37; CI 1&#46;11&#8211;2&#41;&#44; systemic lupus erythematosus with OR 2&#46;42 &#40;95&#37; CI 2&#46;02&#8211;2&#46;88&#41;&#44; rheumatoid arthritis with OR 1&#46;38 &#40;95&#37; CI 1&#46;24&#8211;1&#46;54&#41;&#44; polymyalgia rheumatica with OR 2&#46;01 &#40;95&#37; CI 1&#46;08&#8211;2&#46;23&#41;&#44; and pernicious anemia with OR 2&#46;06 &#40;95&#37; CI 1&#46;59&#8211;2&#46;66&#41;&#46; The remaining autoimmune diseases analyzed did not show a higher prevalence of Alzheimer&#39;s disease compared to the general population&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">There may be an association between certain systemic autoimmune diseases and Alzheimer&#39;s disease&#46; Further studies are needed to confirm our findings&#44; establish causality&#44; and explore the underlying mechanisms of this association&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Analizar la prevalencia de la enfermedad de Alzheimer en pacientes con y sin diagn&#243;stico de diferentes enfermedades autoinmunes y la posible asociaci&#243;n entre ambas patolog&#237;as&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se plantea de un estudio retrospectivo de cohortes multic&#233;ntrico estudiando la prevalencia de la enfermedad de Alzheimer &#40;EA&#41; dentro de los pacientes diagnosticados de diversas enfermedades autoinmunes en comparaci&#243;n la poblaci&#243;n general&#46; Para ello se han examinado datos de las historias cl&#237;nicas electr&#243;nicas del sistema de salud de Castilla-La Mancha utilizando el procesamiento de Lenguaje Natural a trav&#233;s de la plataforma cl&#237;nica de inteligencia artificial Savana Manager&#174;&#46; Se analiza un total de 1&#46;028&#46;356 pacientes&#44; 28&#46;920 individuos con EA y 999&#46;436 pacientes control&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">De las 12 enfermedades autoinmunes analizadas 5 mostraron asociaci&#243;n significativa con presentar enfermedad de Alzheimer con una p&#8201;&#60;&#8201;0&#44;05&#46; Presentaron mayor prevalencia de EA la miastenia gravis OR 1&#44;49 &#40;IC95&#37; 1&#44;11&#8211;2&#41;&#44; el lupus eritematoso sist&#233;mico OR 2&#44;42 &#40;IC95&#37; 2&#44;02&#8211;2&#44;88&#41;&#44; la artritis reumatoide OR 1&#44;38 &#40;IC95&#37; 1&#44;24&#8211;1&#44;54&#41;&#44; la polimialgia reum&#225;tica OR2&#44;01 &#40;IC95&#37; 1&#44;08&#8211;2&#44;23&#41; y la anemia perniciosa OR 2&#44;06 &#40;IC95&#37; 1&#44;59&#8211;2&#44;66&#41;&#46; El resto de enfermedades autoinmunes analizadas no presentaron una mayor prevalencia de EA que la poblaci&#243;n general&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Pod&#237;a existir una asociaci&#243;n entre determinadas enfermedades autoinmunes sist&#233;micas y la enfermedad de Alzheimer en pacientes con determinadas enfermedades autoinmunes sist&#233;micas&#44; si bien se necesitan nuevos estudios para confirmar nuestros hallazgos&#44; establecer la posibilidad de causalidad y explorar los posibles mecanismos que subyacen a esta asociaci&#243;n&#46;</p></span>"
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            "identificador" => "abst0035"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Distribution of different autoimmune diseases within the sample&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">Autoimmune Diseases&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Population with EA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">OR &#40;IC 95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">n&#8201;&#61;&#8201;28&#44;920&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Myasthenia gravis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1066 &#40;0&#44;107&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Scleroderma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">19 &#40;0&#44;066&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">496 &#40;0&#44;050&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;32 &#40;0&#44;84&#8211;2&#44;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#61;0&#44;228&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Systemic lupus erythematosus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">131 &#40;0&#44;453&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1885 &#40;0&#44;189&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Beh&#231;et&#39;s disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;0&#44;003&#41;&nbsp;\t\t\t\t\t\t\n
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Uncorrected Proof. Available online 26 September 2024
Association between autoimmune diseases and Alzheimer’s disease: Analysis using big data tools
Asociación entre enfermedades autoinmnues y enfermedad de Alzheimer: análisis a partir herramientas de big data
A.M. Diezma-Martína,1, M.I. Morales-Casadoa,
,1
, L. Jiménez-Díazb, J.D. Navarro-Lópezb, B. Mondéjar-Marína, J. Parra-Serranoa, A. Vadillo-Bermejoa, C. Marsal-Alonsoa, P. Beneyto-Martínc
a Servicio de Neurología, Hospital Universitario de Toledo, Toledo, Spain
b Laboratorio de Neurofisiología y Comportamiento, Facultad de Medicina de Ciudad Real, Ciudad Real, Spain
c Unidad de Investigación, Hospitalario Universitario de Toledo, Toledo, Spain
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Table 1. Cumulative prevalence over the study years of autoimmune diseases.
Abstract
Objective

The objective is to analyze the prevalence of Alzheimer's disease in patients with and without a diagnosis of different autoimmune diseases and the possible association between both pathologies.

Patients and methods

A multicenter, retrospective, cohort study was conducted to study the prevalence of Alzheimer’s disease among patients diagnosed with various autoimmune diseases compared to the general population. Data from electronic medical records from the Castilla-La Mancha healthcare system were analyzed using Natural Language Processing through the Savana Manager® artificial intelligence clinical platform. A total of 1,028,356 patients were analyzed, including 28,920 individuals with Alzheimer's disease and 999,436 control patients.

Results

Out of the 12 autoimmune diseases analyzed, 5 showed a significant association with Alzheimer's disease with p < 0.05. Myasthenia gravis had an increased prevalence of AD with OR 1.49 (95% CI 1.11–2), systemic lupus erythematosus with OR 2.42 (95% CI 2.02–2.88), rheumatoid arthritis with OR 1.38 (95% CI 1.24–1.54), polymyalgia rheumatica with OR 2.01 (95% CI 1.08–2.23), and pernicious anemia with OR 2.06 (95% CI 1.59–2.66). The remaining autoimmune diseases analyzed did not show a higher prevalence of Alzheimer's disease compared to the general population.

Conclusions

There may be an association between certain systemic autoimmune diseases and Alzheimer's disease. Further studies are needed to confirm our findings, establish causality, and explore the underlying mechanisms of this association.

Keywords:
Autoimmune diseases
Alzheimer's disease
Systemic inflammation
Neurodegeneration
Resumen
Objetivo

Analizar la prevalencia de la enfermedad de Alzheimer en pacientes con y sin diagnóstico de diferentes enfermedades autoinmunes y la posible asociación entre ambas patologías.

Pacientes y métodos

Se plantea de un estudio retrospectivo de cohortes multicéntrico estudiando la prevalencia de la enfermedad de Alzheimer (EA) dentro de los pacientes diagnosticados de diversas enfermedades autoinmunes en comparación la población general. Para ello se han examinado datos de las historias clínicas electrónicas del sistema de salud de Castilla-La Mancha utilizando el procesamiento de Lenguaje Natural a través de la plataforma clínica de inteligencia artificial Savana Manager®. Se analiza un total de 1.028.356 pacientes, 28.920 individuos con EA y 999.436 pacientes control.

Resultados

De las 12 enfermedades autoinmunes analizadas 5 mostraron asociación significativa con presentar enfermedad de Alzheimer con una p < 0,05. Presentaron mayor prevalencia de EA la miastenia gravis OR 1,49 (IC95% 1,11–2), el lupus eritematoso sistémico OR 2,42 (IC95% 2,02–2,88), la artritis reumatoide OR 1,38 (IC95% 1,24–1,54), la polimialgia reumática OR2,01 (IC95% 1,08–2,23) y la anemia perniciosa OR 2,06 (IC95% 1,59–2,66). El resto de enfermedades autoinmunes analizadas no presentaron una mayor prevalencia de EA que la población general.

Conclusiones

Podía existir una asociación entre determinadas enfermedades autoinmunes sistémicas y la enfermedad de Alzheimer en pacientes con determinadas enfermedades autoinmunes sistémicas, si bien se necesitan nuevos estudios para confirmar nuestros hallazgos, establecer la posibilidad de causalidad y explorar los posibles mecanismos que subyacen a esta asociación.

Palabras clave:
Enfermedades autoinmunes
Enfermedad de Alzheimer
Inflamación sistémica
Neurodegeneración

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