The inter-relationship between delirium and dementia: the importance of delirium prevention

Abstract

Delirium and dementia are two frequent causes of cognitive impairment among older adults and have a distinct, complex and interconnected relationship. Delirium is an acute confusional state characterized by inattention, cognitive dysfunction and an altered level of consciousness, whereas dementia is an insidious, chronic and progressive loss of a previously acquired cognitive ability. People with dementia have a higher risk of developing delirium than the general population, and the occurrence of delirium is an independent risk factor for subsequent development of dementia. Furthermore, delirium in individuals with dementia can accelerate the trajectory of the underlying cognitive decline. Delirium prevention strategies can reduce the incidence of delirium and associated adverse outcomes, including falls and functional decline. Therefore, delirium might represent a modifiable risk factor for dementia, and interventions that prevent or minimize delirium might also reduce or prevent long-term cognitive impairment. Additionally, understanding the pathophysiology of delirium and the connection between delirium and dementia might ultimately lead to additional treatments for both conditions. In this Review, we explore mechanisms that might be common to both delirium and dementia by reviewing evidence on shared biomarkers, and we discuss the importance of delirium recognition and prevention in people with dementia.

Abstract

In this Review, Fong and Inouye explore mechanisms that might be common to both delirium and dementia. They present delirium as a possible modifiable risk factor for dementia and discuss the importance of delirium prevention strategies in reducing this risk.

Key points

• Delirium and dementia are frequent causes of cognitive impairment among older adults and have a distinct, complex and interconnected relationship.

• Delirium prevention strategies have been shown to reduce not only the incidence of delirium but also the incidence of adverse outcomes associated with delirium such as falls and functional decline.

• Adverse outcomes associated with delirium, such as the onset of dementia symptoms in individuals with preclinical dementia, and/or the acceleration of cognitive decline in individuals with dementia might also be delayed by the implementation of delirium prevention strategies.

• Evidence regarding the association of systemic inflammatory and neuroinflammatory biomarkers with delirium is variable, possibly as a result of co-occurring dementia pathology or disruption of the blood–brain barrier.

• Alzheimer disease pathology, even prior to the onset of symptoms, might have an effect on delirium risk, with potential mechanisms including neuroinflammation and gene–protein interactions with the APOE ε4 allele.

• Novel strategies, including proteomics, multi-omics, neuroimaging, transcranial magnetic stimulation and EEG, are beginning to reveal how changes in cerebral blood flow, spectral power and connectivity can be associated with delirium; further work is needed to expand these findings to patients with delirium superimposed upon dementia.