Could diabetic peripheral neuropathy predict dementia and cerebrovascular disease?
Aims: This study investigated whether diabetic peripheral neuropathy (DPN) is associated with an increased risk of dementia and cerebrovascular disease in adults with type 1 (T1D) and type 2 diabetes (T2D). Previous evidence links DPN to cognitive impairment, dementia, stroke, and cardiovascular disease, although methodological limitations remain. Here, the aim was to determine whether DPN could serve as an independent marker of future neurological and vascular brain complications beyond traditional cardiovascular risk factors in a large population with T1D and T2D.
Methods: This longitudinal, population-based cohort study used data from Steno Diabetes Center Copenhagen and nationwide Danish health registry. Adults with T1D or T2D who had available vibration perception threshold (VPT) measurements were included. DPN was defined using two established criteria: a fixed bilateral VPT cutoff of >25 V, indicating loss of protective sensation, and an age-, sex-, and height-adjusted threshold. Incident all-cause dementia and cerebrovascular disease were identified using ICD-10 and Danish procedure codes. Relevant demographic, clinical, metabolic, lifestyle, medication, and comorbidity data were also considered in the analyses.
Results: The cohort comprised 5,641 individuals with T1D and 9,395 with T2D, with mean ages of 40.5 and 59.9 years, respectively. DPN prevalence was considerably higher with the adjusted VPT threshold than with the fixed >25 V cutoff (55.2% vs. 17.4% in T1D and 55.1% vs. 37.9% in T2D). Individuals with DPN were more often male, had a longer diabetes duration, and higher rate of cardiovascular or other microvascular complications. During a median follow-up of 7 years, 196 participants developed dementia (1.3%) and 899 experienced cerebrovascular disease (6.0%). In T1D, DPN defined by VPT >25 V was associated with a higher incidence of cerebrovascular disease (IRR 1.45, 95% CI 1.11–1.91), but not dementia (IRR 1.61, 95% CI 0.75–3.48). In T2D, DPN was associated with both dementia (IRR 4.36, 95% CI 2.07–9.16) and cerebrovascular disease (IRR 1.45, 95% CI 1.18–1.80). Similar results were obtained using the adjusted threshold. After further adjustment for retinopathy and nephropathy, the association with cerebrovascular disease in T1D was attenuated and no longer statistically significant, whereas findings in T2D remained unchanged.
Conclusions: DPN was associated with a higher risk of dementia and cerebrovascular disease, particularly in T2D. In T1D, DPN was associated with cerebrovascular disease, especially at younger ages, although this relationship was attenuated after accounting for other microvascular complications. Overall, DPN may represent a useful marker of neurological and cerebrovascular risk.
Comments: These findings are consistent with previous literature (well discussed by the authors) linking peripheral neuropathy to cognitive and cerebrovascular outcomes, while providing longitudinal evidence that DPN based on repeated neuropathy assessments over time is associated with subsequent disease incidence. The study strengthens the hypothesis that DPN may reflect broader neurological and microvascular vulnerability with clear examination of the possible mechanisms linking sensory impairment with dementia risk. These results also highlight the potential clinical value of neuropathy assessment as part of broader neurological and cerebrovascular risk stratification in diabetes. However, its longitudinal but observational design, potential residual confounding, and possible misclassification of registry-based diagnoses prevent causal conclusions. Further research should validate these associations in other populations and clarify the mechanisms connecting peripheral nerve damage with brain and vascular injury.
Ilenia D’Ippolito
Reference. Wiggers A, Kosjerina V, Nilsson M, Brock B, Andersen S, Reynolds EL, Callaghan BC, Feldman EL, Rungby J, Hansen CS. Diabetic Peripheral Neuropathy May Be an Independent Risk Marker for Dementia and Cerebrovascular Disease. Diabetes Obes Metab. 2026 Aug;28(8):6618-6629. doi: 10.1111/dom.70842. Epub 2026 May 10. PMID: 42108425; PMCID: PMC13341399.
