Background/Objectives: The Diabetes-Specific Dementia Risk Score (DSDRS) integrates clinical and metabolic markers to predict cognitive decline in Type 2 diabetes mellitus (T2DM), yet its association with key modifiable risk factors remains unvalidated in Latin American cohorts. This study aimed to assess the relationship between the DSDRS and clinical, biochemical, anthropometric, and neuropsychological variables in older adults with T2DM. Methods: A cross-sectional study of 291 Mexican adults aged ≥ 60 with T2DM was conducted, including assessments of cognitive function (MoCA), depression (BDI), sleep quality (AIS), and metabolic parameters. Results: Higher DSDRS correlated with lower cognitive scores, poorer sleep quality, reduced muscle mass, and smoking status. Multiple regression explained 32% of DSDRS variance, highlighting these factors as significant contributors. Conclusions: The DSDRS reflects multifactorial influences on dementia risk in older adults with T2DM and may aid early identification of individuals at increased cognitive vulnerability in this population.

Introduction: Type 2 diabetes mellitus (T2DM) is known to increase the risk of Alzheimer’s disease (AD), but the role of the gut microbiota in this relationship is not fully understood. This study investigated the gut microbiota profiles of adults with T2DM, adults with AD, both conditions (AD–T2DM), and healthy controls to identify patterns associated with metabolic and neurodegenerative conditions. Methods: A cross‐sectional study was conducted with 148 participants divided into six groups: CTRL < 60 years, CTRL ≥ 60 years, T2DM < 60 years, T2DM ≥ 60 years, AD, and AD–T2DM. Clinical assessments and 16S rRNA gene sequencing of fecal samples were performed to analyze microbial diversity and composition. Results: Compared with controls, older adults with T2DM, AD, and AD–T2DM presented reduced microbial diversity and distinct microbial compositions. Notably, SCFA‐producing genera ( Veillonella and Dialister ) decreased in T2DM patients ≥ 60 years, whereas Roseburia and Blautia were more abundant in AD patients and those with AD–T2DM . GDP‐mannose biosynthesis was downregulated in AD–T2DM patients. Conclusion: This study highlights changes in the microbiota in T2DM and AD–T2DM patients, suggesting that targeting these microbial alterations could offer new prevention strategies for metabolic‐neurodegenerative comorbidities. Significance Statement: T2DM and AD share metabolic and inflammatory pathways, yet their combined impact on the gut microbiota remains unexplored. By profiling 148 adults, healthy individuals, those with T2DM, AD, and co‐occurring AD–T2DM, using 16S rRNA gene V4 region sequencing, we identified specific dysbiosis in AD–T2DM. Rather than examining T2DM and AD as independent conditions, the present study conceptualizes their coexistence as a metabolic–neurodegenerative interaction state and assesses whether this comorbidity is associated with a distinct gut microbiota composition and predicted functional profile. Therefore, we examine the gut microbiota of adults with AD–T2DM using an age‐stratified design in an underrepresented Mexican population, integrating clinical, metabolic, cognitive, taxonomic, and functional data to explore potential mechanisms underlying metabolic–neurodegenerative crosstalk. These findings identify microbial genera that may mediate the “diabeto‐neuro” crosstalk, offering novel targets for early intervention and precision microbiota‐based therapies to mitigate metabolic‐neurodegenerative comorbidity.

Background: Recently, the importance of the role of the gut microbiota in our organism has been highlighted, intervening mainly in immune activity and in the regulation of various metabolic pathways. Different studies have shown that both the gut microbiota of patients with T2DM and that of patients with AD present moderate dysbiosis, so we sought to characterize the gut microbiota of people with both pathologies. Method: The study population consisted of a total of 148 individuals, divided into four different groups: CTRL ( n = 60), T2DM ( n = 60), AD ( n = 17), AD‐T2DM ( n = 11). Stool samples were collected from the participants and DNA extraction was performed using the Quick‐DNA Fecal/Soil Microbe Miniprep Kit, following the manufacturer's instructions. Subsequently, the quality and concentration of the extracted DNA were evaluated by spectrophotometry using a NanoDrop 2000 (Thermo Scientific) and the integrity of the samples was verified by 1% agarose gel electrophoresis. The V4 region of the 16S rRNA gene was amplified by PCR. Library preparation was carried out using the Illumina MiSeq platform protocol. The raw sequencing reads were processed and phylum abundance analyses of the study groups were performed, as well as alpha and beta diversity to estimate differences within and between group samples. Result: The phylum Verrucomicrobiota showed significant differences in the AD group compared to the rest of the groups. In the case of the AD‐T2DM group, the phylum Bacteroidota was found to be significantly reduced when compared to the rest of the groups. Significant differences were found in the abundance of Firmicutes_A in the T2DM A subgroup compared to CTRL A. Regarding beta diversity, the CTRL A and CTRL B groups had a similar behavior, showing significant differences compared to the T2DM A and T2DM B groups. Conclusion: Gut microbiota dysbiosis in T2DM increases concomitantly with aging to a diversity similar to the gut microbiota of people with AD, contributing to the dysregulation of molecular networks leading to AD pathophysiology.