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

Summary

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.

Eligibility

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.

Conditions2

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