Biological Aging Following Full-Arch Implant-Supported Fixed Rehabilitation in Edentulous Patients

Complete edentulism is associated with impaired masticatory function, altered nutritional intake, reduced oral health-related quality of life, and potential deterioration in systemic health. Previous studies have suggested associations between tooth loss, accelerated biological aging, physical frailty, cognitive decline, and alterations in brain structure and function. However, prospective longitudinal evidence regarding changes in biological aging and brain function following full-arch implant-supported fixed dental rehabilitation remains limited.

This study is a prospective, longitudinal, observational cohort study designed to investigate the association between full-arch implant-supported fixed dental rehabilitation and changes in biological aging, physical frailty, cognitive function, and brain function among adults with complete edentulism.

The study will be conducted at the Department of Oral Implantology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. A total of 60 adults aged 50 years or older with complete edentulism will be enrolled.

Participants will be classified into two cohorts according to their voluntary treatment decisions and routine clinical arrangements:

Implant Rehabilitation Cohort (n=30): Patients with complete edentulism who elect to undergo full-arch implant-supported fixed dental rehabilitation without an additional voluntary treatment delay.

Delayed-Treatment Comparison Cohort (n=30): Patients with complete edentulism who voluntarily elect to postpone full-arch implant-supported fixed dental rehabilitation for approximately three months.

Treatment decisions and the timing of implant rehabilitation will be determined independently of the research protocol. The investigators will not assign participants to treatment groups or determine treatment timing for research purposes. All implant procedures and prosthetic rehabilitation will be performed according to routine clinical indications and standard clinical practice.

The primary objective is to evaluate longitudinal changes in biological age acceleration, defined as the difference between saliva DNA methylation-derived biological age and chronological age, and to compare these changes between the two cohorts.

Secondary objectives include evaluating longitudinal changes in facial biological age, physical frailty, nutritional status, oral health-related quality of life, psychological well-being, cognitive performance, fine motor function, and brain structure and function. The study will also explore associations between changes in oral function and changes in biological aging and neurological outcomes.

At baseline (T0), participants will undergo comprehensive assessments, including demographic characteristics, medical history, lifestyle factors, body mass index, oral health status, and clinical evaluation of complete edentulism.

Saliva samples will be collected for DNA methylation analysis to estimate biological age. Standardized facial photographs and three-dimensional facial scans will be obtained to evaluate facial biological age and morphological changes.

Physical function and frailty will be assessed using handgrip strength, gait speed, and the Fried frailty phenotype.

Patient-reported outcomes will include oral health-related quality of life measured using the Oral Health Impact Profile-14 (OHIP-14), nutritional assessments, anxiety symptoms assessed using the Generalized Anxiety Disorder-7 (GAD-7), and depressive symptoms assessed using the 15-item Geriatric Depression Scale (GDS-15).

Cognitive and fine motor function will be evaluated using the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), and Pegboard Test.

Brain structure and function will be assessed using multimodal neurophysiological and neuroimaging techniques. Resting-state electroencephalography (EEG) will be used to evaluate spontaneous brain activity and functional connectivity. Magnetic resonance imaging (MRI), including structural T1-weighted imaging, T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), diffusion tensor imaging (DTI), and resting-state functional MRI, will be used to investigate brain structure, white matter characteristics, and functional connectivity.

Functional near-infrared spectroscopy (fNIRS) will be performed during standardized chewing tasks under different chewing conditions to evaluate cortical hemodynamic responses, particularly in sensorimotor and prefrontal regions.

Participants in both cohorts will undergo longitudinal follow-up assessments at baseline and at approximately 3, 12, and 24 months after baseline. Assessments will include repeated measurements of biological aging markers, facial biological age, physical function, patient-reported outcomes, cognitive performance, and brain function. Clinical information regarding implant rehabilitation, occlusal function, masticatory efficiency, prosthesis use, and complications will also be recorded as applicable.

Longitudinal changes in the primary and secondary outcomes will be analyzed using linear mixed-effects models incorporating cohort, time, and cohort-by-time interaction terms, with participant-specific random effects. Multivariable analyses will account for potential confounding factors, including baseline age, body mass index, lifestyle characteristics, and underlying medical conditions. Available longitudinal observations will be retained in the analysis, and missing-data patterns will be examined with sensitivity analyses or multiple imputation when appropriate.

This study aims to provide prospective observational evidence regarding the relationships among full-arch implant-supported fixed dental rehabilitation, biological aging, physical function, cognitive performance, and brain function in adults with complete edentulism. The findings may contribute to a broader understanding of the potential systemic and neurological associations of restoring oral function in patients with complete tooth loss.