The interface between delirium and dementia in elderly adults

Abstract

Delirium and dementia are two of the most common causes of cognitive impairment in older populations, yet their interrelation remains poorly understood. Previous studies have shown that dementia is the leading risk factor for delirium and that delirium is an independent risk factor for subsequent development of dementia. However, a major area of controversy is whether delirium is simply a marker of vulnerability to dementia, whether the effect of delirium is solely related to its precipitating factors, or whether delirium itself can cause permanent neuronal damage and lead to dementia. Ultimately, all of these hypotheses are likely to be true. Emerging evidence from epidemiological, clinicopathological, neuroimaging, biomarker, and experimental studies lends support to a strong relation between delirium and dementia, and to both shared and distinct pathological mechanisms. New preventive and therapeutic approaches that target delirium might offer a sought-after opportunity for early intervention, preservation of cognitive reserve, and prevention of irreversible cognitive decline in ageing.

Figure 1

A hypothetical model for the pathophysiologic interrelationship between delirium and dementia. Delirium is a known risk factor for new onset dementia, and this may arise via direct mechanisms such as hypoxia, metabolic abnormalities, stroke, or medications. In turn, delirium is associated with neuronal dysfunction, alterations in neurotransmitters, and neuronal death and this could lead directly to dementia. There is also growing evidence that certain anesthetics associated with postoperative delirium may alter Aβ, which in turn may indicate a role for new onset dementia. Delirium is also likely to be a marker of vulnerability in patients with pre-existing dementia, and might accelerate existing dementia. This may occur indirectly, for example, via inflammation triggered by systemic infection or exaggerated response to a stressor. Ref. Maclullich AM, Anand A, Davis DH, Jackson T, Barugh AJ, Hall RJ, Ferguson KJ, Meagher DJ, Cunningham C. New horizons in the pathogenesis, assessment and management of delirium. Age Ageing. 2013 Nov;42(6):667-74. Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol 2009; 5: 210-220. PMCID: PMC3065676