Frontiers in aging neuroscience · 2026
Long-term risk of incident dementia following documented COVID-19 among older adults with type 2 diabetes: a propensity score-matched cohort study.
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Chen I-Wen, Chang Li-Chen, Ho Chun-Ning, Hung Kuo-Chuan
Аннотация
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a well-established risk factor for dementia, and COVID-19 has been associated with persistent neurological and cognitive sequelae. However, whether this association extends beyond the early post-infection period among older adults with T2DM-a population with compounded vascular and metabolic vulnerability-remains unclear.
METHODS: Using the TriNetX Global Collaborative Network, we conducted a retrospective cohort study of patients aged ≥65 years with T2DM, comparing those with documented COVID-19 to a matched unexposed cohort (1:1 propensity score matching). A 1-year landmark design was applied, with follow-up extending to 6 years after the index date. The primary outcome was incident overall dementia, which is a composite of vascular dementia, Alzheimer's disease, and unspecified/other dementia. The secondary outcomes included individual dementia subtypes, mild cognitive impairment, all-cause mortality, and cerebral infarction.
RESULTS: After matching, 449,745 patients were included in each group with well-balanced covariates (all standardized mean differences <0.1). Documented COVID-19 was associated with a significantly increased risk of overall dementia [hazard ratio (HR 1.51), 95% confidence interval (CI) 1.47-1.55, p < 0.001]. The secondary outcomes were similarly elevated, such as vascular dementia (HR 1.61), Alzheimer's disease (HR 1.41), mild cognitive impairment (HR 1.66), all-cause mortality (HR 1.56), and cerebral infarction (HR 1.33; all p < 0.001). The hazard ratio for overall dementia increased progressively across sequential landmark periods (1.51 at 1 year, 1.66 at 2 years, and 2.09 at 3 years), and the findings remained robust across sensitivity analyses, addressing survival, healthcare utilization, and exposure misclassification. The findings were consistent in separately constructed and propensity score-matched additional cohorts restricted to adults aged 50-65 years and to patients indexed during the Omicron-predominant period.
CONCLUSION: In this large propensity score-matched cohort study, documented COVID-19 was associated with an increased long-term risk of incident dementia among older adults with T2DM, with the association persisting and strengthening beyond the early post-infection period. These findings support sustained attention to cognitive health in this metabolically susceptible population following COVID-19; however prospective studies incorporating standardized cognitive and biomarker assessments are needed to clarify underlying causes.
METHODS: Using the TriNetX Global Collaborative Network, we conducted a retrospective cohort study of patients aged ≥65 years with T2DM, comparing those with documented COVID-19 to a matched unexposed cohort (1:1 propensity score matching). A 1-year landmark design was applied, with follow-up extending to 6 years after the index date. The primary outcome was incident overall dementia, which is a composite of vascular dementia, Alzheimer's disease, and unspecified/other dementia. The secondary outcomes included individual dementia subtypes, mild cognitive impairment, all-cause mortality, and cerebral infarction.
RESULTS: After matching, 449,745 patients were included in each group with well-balanced covariates (all standardized mean differences <0.1). Documented COVID-19 was associated with a significantly increased risk of overall dementia [hazard ratio (HR 1.51), 95% confidence interval (CI) 1.47-1.55, p < 0.001]. The secondary outcomes were similarly elevated, such as vascular dementia (HR 1.61), Alzheimer's disease (HR 1.41), mild cognitive impairment (HR 1.66), all-cause mortality (HR 1.56), and cerebral infarction (HR 1.33; all p < 0.001). The hazard ratio for overall dementia increased progressively across sequential landmark periods (1.51 at 1 year, 1.66 at 2 years, and 2.09 at 3 years), and the findings remained robust across sensitivity analyses, addressing survival, healthcare utilization, and exposure misclassification. The findings were consistent in separately constructed and propensity score-matched additional cohorts restricted to adults aged 50-65 years and to patients indexed during the Omicron-predominant period.
CONCLUSION: In this large propensity score-matched cohort study, documented COVID-19 was associated with an increased long-term risk of incident dementia among older adults with T2DM, with the association persisting and strengthening beyond the early post-infection period. These findings support sustained attention to cognitive health in this metabolically susceptible population following COVID-19; however prospective studies incorporating standardized cognitive and biomarker assessments are needed to clarify underlying causes.