The aim of this clinical trial is to investigate the effects of L-serine supplementation on cognitive decline and psychosocial functioning in older adults with late-life depression (LLD). The study will evaluate changes in depressive symptoms, neural and cognitive functioning, and will assess neurophysiological, metagenomic, and biochemical alterations associated with L-serine supplementation compared with placebo.
The main research questions are:
* Does L-serine supplementation affect cognitive function, depressive symptoms, and neural functioning in individuals with late-life depression? * What biological mechanisms may underlie the effects of L-serine on cognitive decline? Participants will be randomly assigned to one of two study arms: an intervention group (total n = 42) receiving L-serine at a dose of 6 g/day for 48 weeks, and a placebo group (total n = 42) receiving 6 g/day of maltodextrin for the same duration.
All participants will be assessed at three time points: T0 (baseline, prior to trial initiation), T18 (after 18 weeks), and T48 (after 48 weeks, at the end of the trial).
At each assessment, participants will:
* complete clinical questionnaires and a neuropsychological assessment; * provide blood, fecal, and urine samples; * undergo electroencephalographic (EEG) recordings.
Age 65-85 years;
Presence of depressive symptoms, defined as a score ≥ 5 on the Geriatric Depression Scale-15 items (GDS-15) or ≥ 5 on the Patient Health Questionnaire-9 (PHQ-9).
Diagnosis of dementia;
Use of antibiotics or anti-inflammatory medications within the previous 8 weeks;
Active gastrointestinal disease;
Severe chronic medical conditions (e.g., advanced-stage cancer, severe cardiac or renal disorders, or other debilitating diseases);