Progress in Neuro-psychopharmacology & Biological Psychiatry · Mar 22, 2026

Dementia, depression, and heart failure: Central role of brain-derived neurotrophic factor and possible common neurobiological pathways

By Sustar A, Nadalin S, Pivac N

Heart failure (HF) is a complex systemic syndrome with major neuropsychiatric consequences. Cognitive impairment (e.g., dementia) and depression are common among HF patients, worsening prognosis, increasing hospital admissions, and impairing quality of life. Despite their prevalence, the neurobiological basis of these comorbidities is not yet fully understood. This review uniquely discusses converging neuroendocrine, inflammatory, and neuroplastic mechanisms linking HF, depression, and dementia inside an integrative heart-brain axis highlighting brain-derived neurotrophic factor (BDNF) as an important modulator of synaptic plasticity, neurogenesis, and stress resilience. Understanding the interactions between HF-induced hypothalamic-pituitary-adrenal axis activation, systemic inflammation, and impaired BDNF signaling may contribute to the development of novel multimodal therapeutic strategies targeting neurotrophic pathways and improving cognitive and mental health outcomes in HF.

doi.org/10.1016/j.pnpbp.2026.111677PubMed 41875965Mechanisms