OBJECTIVE: To investigate the risk of incident dementia according to fasting glucose levels and presence of comorbidities. RESEARCH DESIGN AND METHODS: Using a health insurance claims database and the results of biennial health examinations in South Korea, we selected 8,400,950 subjects aged ≥40 years who underwent health examinations in 2009–2010. We followed them until 2016. Subjects’ baseline characteristics were categorized by presence of diabetes (yes/no) and glycemic status as normoglycemia, impaired fasting glucose (IFG), new-onset diabetes, or known diabetes (duration <5 years or ≥5 years). We estimated adjusted hazard ratios (aHRs) for dementia occurrence in each category. RESULTS: During the observation period of 48,323,729 person-years, all-cause dementia developed in 353,392 subjects (4.2%). Compared with normoglycemia, aHRs (95% CI) were 1.01 (1.01–1.02) in IFG, 1.45 (1.44–1.47) in new-onset diabetes, 1.32 (1.30–1.33) in known diabetes <5 years, and 1.62 (1.60–1.64) in known diabetes ≥5 years. We found that associations between ischemic heart disease and chronic kidney disease with incident dementia were affected by the presence of diabetes. Ischemic stroke showed a greater association with incident dementia than diabetes. CONCLUSIONS: Mild degrees of hyperglycemia and presence of comorbidities were associated with incident dementia. Intervention during the prodromal stage of a chronic disease (e.g., prediabetes) could be considered for dementia prevention.

Previous studies have indicated that obsessive-compulsive disorder (OCD) is associated with alexithymic traits. The purpose of the current study was to evaluate the difference of alexithymia in OCD patients and healthy controls. This study was also designed to elucidate a specific link between certain OCD symptom dimensions and alexithymia. Forty-five patients with OCD and 45 healthy controls completed measures of the OCD symptom severity, alexithymia, anxiety, and depression. Patients with OCD had significantly higher scores of alexithymia than did the healthy controls. Multiple regression analysis revealed that age at onset and the level of anxiety were significantly associated with alexithymia. "Sexual/religious obsessions" was the only symptom dimension that showed a positive association with alexithymia in OCD patients. These findings suggest that OCD patients with a high level of anxiety and an early age of onset may have greater alexithymic tendency. We also found the first evidence for a specific link between sexual/religious obsessions and alexithymia in patients with OCD.

Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain. To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA). Target trial emulation study. Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022. Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide. The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders. Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16). Residual confounding is possible; there was no adjustment for hemoglobin A_1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly. Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required. Ministry of Food and Drug Safety of South Korea.

Objectives: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a recently introduced method for the assessment of the glymphatic system without the need for contrast injection. The purpose of our study was to assess the glymphatic system in cognitively normal older adults with or without subjective cognitive decline (SCD) using DTI-ALPS, and correlating with amyloid PET.Design and participants: To evaluate the glymphatic system in cognitively normal older adults using DTI-ALPS, we built a prospective cohort including a total of 123 objectively cognitively normal older adults with or without SCD. The ALPS index was calculated from DTI MRI and was assessed by correlating it with standardized uptake value ratios (SUVRs) from amyloid PET and clinically relevant variables. The study subjects were also divided into amyloid “positive” and “negative” groups based on the result of amyloid PET, and the ALPS indices between those two groups were compared.Results: The ALPS index was not significantly different between the normal and SCD groups (P = 0.897). The mean ALPS index from the amyloid positive and amyloid negative group was 1.31 and 1.35, respectively, which showed no significant difference (P = 0.308). Among the SUVRs from variable cortices, that of the paracentral cortex was negatively correlated with the ALPS index (r = −0.218, P = 0.016). Multivariate linear regression revealed that older age (coefficient, −0.007) and higher SUVR from the paracentral cortex (coefficient, −0.101) were two independent variables with a significant association with a lower ALPS index (P = 0.015 and 0.045, respectively).Conclusion: DTI-ALPS may not be useful for evaluation of the glymphatic system in subjects with SCD. Older age was significantly associated with lower ALPS index. Greater amyloid deposition in the paracentral cortex was significantly associated with lower glymphatic activity in cognitively normal older adults. These results should be validated in future studies on the relationships between ALPS index and other fundamental compartments in glymphatic system, such as perivenous space and the meningeal lymphatic vessels.