Authors reply: Delirium and frailty in older adults: Clinical overlap and biological underpinnings

Dear Editor,

We thank Drs. da Silva and Caldas for showing interest in our review paper recently published in the Journal of Internal Medicine and for their thoughtful contributions, which enrich the discussion on this topic [1, 2].

A highlighted key point pertains to the pathophysiology of frailty and delirium. As acknowledged, the biological mechanisms underlying these two conditions remain largely unknown. This limited understanding explains why current prevention and treatment strategies predominantly focus on minimizing observable clinical manifestations (i.e., secondary rather than primary prevention). From a biological perspective, identifying whether certain individuals have an increased susceptibility to develop frailty and delirium remains a key challenge. This underscores the urgent need for a paradigm shift in our approach to these conditions.

In our review, we proposed a unifying framework aimed at offering a novel reading of the complex pathophysiological mechanisms underlying these conditions and, most importantly, providing research perspectives for future etiological studies. While recognizing frailty and delirium as distinct clinical entities, we postulated that they may reflect different manifestations of accelerated biological aging. This viewpoint opens new avenues from a geroscience perspective, particularly in identifying individuals at higher risk of developing delirium when frail or presenting with worsening frailty status after a delirium episode. Additionally, exploring upstream interventions targeting shared biological mechanisms holds significant promise for mitigating both conditions, as well as other burdensome geriatric syndromes. Advancing this line of research could lead to breakthroughs in risk stratification and the development of early, personalized interventions, ultimately improving care outcomes for older adults.

The letter by da Silva and Caldas also raises the critical issue of cognitive decline underdiagnosis, which we fully acknowledge. Cognitive impairment often goes unnoticed, either because healthcare access is strongly influenced by one's socioeconomic status or because healthcare providers often lack the necessary training to identify it. Expanding awareness among healthcare professionals about the interplay among frailty, delirium, and cognitive decline is essential to enhance prevention efforts and foster a more integrated, multidisciplinary approach to the care of, among others, at-risk hospitalized older adults. Equally important is educating communities to recognize cognitive decline as a serious issue that impacts the quality of care for older individuals.

Although our review is not systematic, we believe that its narrative approach offers valuable insights by synthesizing fragmented evidence and generating hypotheses for future studies. Addressing the identified gaps will enable healthcare systems and caregivers to implement interventions that prioritize frailty and delirium as critical components of comprehensive geriatric care. Such efforts could disrupt the vicious circle between these conditions and reduce adverse outcomes across the care continuum.

We are grateful for the opportunity to expand this discussion in meaningful directions and hope our response underscores the importance of ongoing research to better understand and address frailty and delirium in older adults.

The authors declare no conflicts of interest.