Alzheimer's disease (AD) exhibits significant clinical variability in symptom onset, progression rates, neuropsychiatric symptoms and treatment responses. This variability reflects a range of underlying biological, genetic and environmental factors. This review summarizes recent advances in leveraging real-world electronic health records (EHRs) and clinical brain MRI to enhance precision medicine in dementia care. Traditional MRI research has identified consistent subtypes of atrophy associated with AD. However, these models often struggle to apply to routine clinical imaging, which can vary widely in contrast, resolution and acquisition protocols. Recent technological developments now allow for reliable measurement of gray matter, white matter, brainstem and cerebellar structures from routine clinical scans, effectively overcoming long-standing limitations of conventional neuroimaging methods. Additionally, efforts in EHR analysis, including the use of natural language processing on unstructured clinical notes, have enabled large-scale extraction of cognitive scores, neuropsychiatric symptoms and treatment responses. By integrating structured EHR data with detailed imaging markers, researchers have enabled predictive modeling of cognitive decline and treatment responses, though generalizability across settings remains a challenge. Federated learning frameworks offer a privacy-preserving approach to collaboratively develop models across multiple institutions. Together, these strategies outline a practical, data-driven approach to individualized diagnosis, prognosis and treatment planning for dementia.

Ischemic stroke (IS) is a leading cause of neurological disability, yet the molecular basis of neuronal injury and repair remains unclear. Three Gene Expression Omnibus datasets (GSE22255, GSE58294, and GSE37587) were integrated for differential expression analysis. Candidate genes were identified by combining protein-protein interaction network analysis with weighted gene co-expression network analysis and validated in GSE16561. The effects of transmembrane channel-like 6 (TMC6) were investigated in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated HT22 cells and a rat middle cerebral artery occlusion (MCAO) model. Rap1/Rac1-related signaling was examined using geranylgeranyltransferase I inhibitor-298 (GGTI-298) and Rac1 knockdown. TMC6 was downregulated in IS. TMC6 overexpression reduced cortical and striatal infarction and mitigated neurological deficits in the MCAO rat. TMC6 overexpression alleviated neuronal apoptosis and improved cell viability in OGD/R-treated HT22 cells. Inflammatory response was suppressed, and mitochondrial membrane potential was preserved after TMC6 overexpression. TMC6 reprogrammed mitochondrial dynamics and quality control by increasing mitofusin 1 (MFN1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), suppressing dynamin-related protein 1 (DRP1), and restoring the expression of the mitophagy-associated proteins PTEN-induced putative kinase 1 (PINK1) and Parkin RBR E3 ubiquitin-protein ligase (Parkin). TMC6 knockdown exacerbated OGD/R-induced injury.. Pharmacological inhibition of Rap1 using GGTI-298 or genetic silencing of Rac1 markedly abrogated TMC6-mediated neuroprotection. TMC6 alleviates experimental ischemic neuronal injury and preserves mitochondrial homeostasis. Rap1/Rac1-related signaling may be involved in these protective effects. These findings identify TMC6 as a potential therapeutic target for IS.

Serum 25-hydroxyvitamin D [25(OH)D] exhibits a seasonal pattern in temperate populations, typically peaking in late summer and declining in winter. It is still not clear whether this pattern also exists in tropical monsoon climates. To characterize the annual pattern of 25(OH)D in a tropical megacity and identify environmental synchronizers of its seasonal variation, a laboratory-based retrospective cross-sectional study was performed on 1,202 adult outpatients from Dhaka, Bangladesh. Serum 25(OH)D was measured with chemiluminescence immunoassay method. Thirty‑day moving averages of weather variables UV Index, temperature, relative humidity, cloud cover, and AQI were linked to each specimen date. Multivariable linear and logistic regression was performed. A phase shifted seasonal l rhythm was observed: 25(OH)D peaked in December (22.96 ng/mL) and declined in July (12.94 ng/mL). Deficiency prevalence doubled during monsoon months (May-August, OR 2.03-2.27 vs. January). Humidity was negatively associated with 25(OH)D (β = -0.764, p = 0.005), while cloud cover showed a positive association (β = 0.267, p = 0.015). UV index did not independently predict 25(OH)D after adjustment for calendar month. Age was protective against deficiency (OR = 0.975 per year, p < 0.001). In tropical monsoon Dhaka, the seasonal rhythm of 25(OH)D is phase-shifted relative to temperate populations, with summer nadir and winter peak. This pattern may be better explained by behavioral responses to heat and humidity than by UV availability alone. Chronobiological models of seasonal Vitamin D rhythms require climate-specific parameters.