A multimodal approach to the prevention of AD and related dementias in patients with MDD
| Principle | Applications |
|---|---|
| Drug development | Use existing antidepressants with neuroprotective and anti-inflammatory properties in animal or in vitro models as “leads” to develop agents that reduce neuroinflammation and have a favorable risk-benefit ratio |
| Antidepressant therapy | Provide adequate antidepressant therapy for moderate and severe MDD Avoid antidepressants with the potential to worsen cognition (e.g., drugs with anticholinergic properties) Ensure adequate long-term adherence to treatment Monitor cognitive function periodically In selected cases, consider novel antidepressant agents (e.g., ketamine, psilocybin) |
| Reduction of peripheral inflammation | Encourage appropriate lifestyle modifications (e.g., exercise, dietary components with anti-inflammatory or anti-oxidant properties) Select antidepressants with documented anti-inflammatory effects Consider adjunctive anti-inflammatory agents after appropriate controlled trials |
| Reduction of infection | Screen for and treat infections in the elderly, even if common or minor (e.g., oral or respiratory infections) Monitor white cell counts and consider changing or discontinuing antidepressant therapy if counts are low |
| Correction of gut dysbiosis | If a patient does not respond to an antidepressant, consider using a drug from a different class or a novel antidepressant Adopt lifestyle modifications, particularly with regards to diet Consider adjunctive probiotics or “psychobiotics” after appropriate controlled trials |
| Correction of stress axis dysregulation | Combine antidepressant therapy with psychological interventions to modulate the stress response, enhance coping, and build resilience Advocate for social welfare interventions to reduce social isolation and economic hardship in the elderly |
