Hemoglobin A1c Serum Level Predicts 5-year Mortality in Patients with Cognitive Impairment

BACKGROUND: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) may occur as preclinical stages of Alzheimer's disease (AD), ultimately leading to dementia. Glycated hemoglobin A1c (HbA1c) is a diagnostic marker for diabetes mellitus and indicates mortality risk. OBJECTIVES: This university-based, exploratory retrospective study examined the impact of HbA1c serum level on 5-year mortality among individuals with cognitive impairment. METHODS: Included were 1076 subjects aged at least 50 years who visited the Memory Outpatient Clinic of the Medical University of Vienna due to memory problems. Participants were diagnosed with SCD, MCI, or AD subsequent to neurological examination, standard laboratory blood tests, and neuropsychological testing. Survival was compared between diagnostic subgroups and with respect to HbA1c categories using log-rank tests based on Kaplan–Meier functions. The Neuropsychological Test Battery Vienna (NTBV) was dimensionally reduced, and a principal component analysis (PCA) was performed to further analyze results. Corresponding factor scores, HbA1c values, and baseline characteristics were included in Cox proportional hazards models to assess 5-year mortality risk. RESULTS: During the observation period, 323 patients (30%) died at a mean age comparable between diagnostic subgroups (SCD 84.2 ± 10.1, MCI 81.2 ± 8.3, AD 82.2 ± 7.4 years). Individuals with normal serum HbA1c levels had significant advantages in survival within the MCI (12.9 ± .3 vs. 10.0 ± .8 years) and the AD subgroups (8.2 ± .4 vs. 5.5 ± .6 years), and metric HbA1c predicted 5-year mortality (HR 1.24). CONCLUSION: This study demonstrates an association between abnormal HbA1c serum levels and increased mortality.