Time-in-range and hypoglycemia in cognitive health of older adults with Type 2 diabetes: An emerging evidence synthesis

Type 2 diabetes mellitus (T2DM) is a recognized risk factor for cognitive decline and dementia, but the mechanisms linking glycemic dysregulation to brain health remain incompletely understood. Glycated hemoglobin captures long-term average glycaemia but fails to reflect acute fluctuations or hypoglycemia, both of which may contribute to cognitive impairment. Continuous glucose monitoring (CGM) provides new metrics such as Time-in-Range (TIR), yet their relationship with cognitive outcomes is only beginning to be explored. We conducted a systematic review of studies published between January 2020 and August 2025 that investigated associations between TIR, hypoglycemia, and cognitive outcomes in older adults with T2DM. Searches across PubMed, Embase, Web of Science, Scopus, PsycINFO, and Cochrane yielded seven eligible studies, including two observational cohorts, three randomized controlled trials, one narrative review, and one study applying digital biomarkers. Populations spanned Japan, China, Ireland, the United States, and multinational cohorts, with sample sizes ranging from 120 to nearly 5,000 participants. Preliminary findings suggested that higher TIR was associated with better cognitive screening performance and preserved brain connectivity, whereas recurrent hypoglycemia and lower TIR were linked with poorer outcomes. However, considerable heterogeneity in study designs, exposure definitions, cognitive assessments, and follow-up durations, together with the small number of studies, limited the certainty of evidence. In conclusion, CGM-derived metrics such as TIR and hypoglycemia show potential relevance to cognitive health in older adults with T2DM, but current evidence is sparse and hypothesis generating. Larger, standardized, and longitudinal studies are required before clinical recommendations can be made.