Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic

Abstract

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD.

Keywords: COVID-19 pandemic; epidemiology; late-life depression (LLD); pathogenesis; phenotype; treatment.

FIGURE 1

The effects of the COVID-19 pandemic on late-life depression (LLD). The COVID-19 pandemic increased the prevalence of LLD significantly. The prevalence of clinically significant depressive symptoms during the COVID-19 pandemic, which was more than two times higher than before the COVID-19 pandemic. The main risk factors associated with LLD during the COVID-19 pandemic were female sex, loneliness, poor sleep quality, and poor motor function. During the COVID-19 pandemic, owing to the possibility of virus transmission via bag-mask ventilation in the electroconvulsive therapy (ECT) procedure, many ECT units in hospitals worldwide were closed. During the COVID-19 pandemic, the conventional medical and healthcare service mode was “devastating,” while modern digital health intervention technology developed rapidly.

FIGURE 2

The multiple pathogenesis of late-life depression (LLD) include insufficient monoamine neurotransmission, increased inflammation, abnormal glutamate input, decreased neurotrophic factor production, the dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, age-related Aβ deposition and low diversity of the gut microbiome. The interplay between the different pathogenesis of LLD and the partial localization of some of the mechanisms in the brain was also shown. Pro-inflammatory cytokines can dysregulate the glutamate system, reduces the synthesis of serotonin and affect HPA axis.