Effects of Specific Amino Acid Supplementation and Lifestyle Factors on Brain Ageing

Translational Investigation of Specific Amino Acid Supplementation and Lifestyle Factors in Brain Ageing

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.

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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);
• Renal dysfunction;
• Current alcohol or substance abuse;
• Major surgical procedures within the previous 6 months.