S-50-4: increased plasma neurofilament light and cerebral atrophy in patients with type 2 diabetes and left ventricular hypertrophy

Objective: Left ventricular hypertrophy (LVH) is common in people with type 2 diabetes mellitus (T2DM), and both are independently associated with increased dementia risk. Neurofilament light chain protein (NfL) is exclusively expressed in neurons and is an emerging plasma marker of neurodegeneration. We investigated the relationship between LVH, plasma NfL levels and brain atrophy in people with T2DM. Design and method: Participants with T2DM aged ≧ 50 years (n = 137) from the Diabetes and Dementia study (ACTRN126160005464590) in Melbourne, Australia completed detailed assessments including 3T brain MRI, transthoracic echocardiograms, and 24-hour ambulatory blood pressure. FreeSurfer estimated brain volume measures; plasma NfL assayed on Simoa® Quanterix HD-X Analyzer. Differences in the mean cortical thickness and average cortical gray matter volume were examined using multivariate general linear models. Multiple linear regression models examined the relationship between NfL and LVH. Comparisons were made between those with and without LVH. Results: Participant details: age = 65 ± 7 (mean ± SD) years, BMI = 30 ± 6 kg/m 2 , 44% women, HbA1c = 60 ± 14 mmol/mol, median diabetes duration = 15 [25th, 75th quartiles 7, 22] years, 21% APOE ε4 carriers; 25% educated < 12 years; 28% LVH. LVH was significantly associated with older age, female sex, obesity (BMI 33 ± 6 vs. 29 ± 5 kg/m 2 ), hypertension history (95% vs. 67%), less education (37% vs. 20%), greater cortical thinning and lower cortical gray matter volume. Plasma NfL was correlated positively with age, HbA1c, and LV mass and negatively with cortical thickness. Median plasma NfL levels were significantly higher in LVH participants (21 [14, 28] vs. 15 [11, 22] pg/mL). Differences with LVH remained significant after adjustment for age, BMI, sex, education, and total intracranial volume for cortical thickness and average cortical gray matter volume, but not after adjustment for hypertension. LVH was an independent predictor of NfL levels (coefficient 0.19, p = 0.04). Conclusion: Accelerated structural brain aging is seen in people with LVH and T2DM. LVH and hypertension appear conflated as risk factors for brain atrophy. Plasma NfL levels are associated with LVH and cortical thickness. LVH and plasma NfL are potential early biomarkers of neurodegeneration in T2DM.