Delirium is a serious condition characterized by a rapid decline in cognitive functioning; it affects up to 50% of hospitalized adults aged 65 years and older.1 The symptoms of delirium vary in severity2 and may include confusion, disorientation, incoherent speech or lack of speech, restlessness/irritability or aggression, depression, fear, or severe personality changes. Although clinicians frequently perceive patients with delirium as being agitated and irritable, most present with the “quiet” hypoactive form and not the hyperactive type.2

Despite being preventable in 30% to 40% of cases,3 delirium accounts for as much as $152 billion in healthcare costs annually in the United States4 and remains poorly understood.1

With existing management strategies for delirium limited in effectiveness, emerging research points to the importance of studying the association between cognitive and brain reserve, and delirium.5 Scientists are hopeful that improvements in prevention strategies for delirium, and neuropsychiatric disease in general, may be achieved by gaining a better understanding of the role of reserve.5

In an interview with Psychiatry Advisor, Richard N. Jones, ScD, director of the Quantitative Science Program and professor in the Department of Psychiatry & Human Behavior and Department of Neurology at the Warren Alpert Medical School of Brown University, in Providence, Rhode Island, and Donna Marie Fick, PhD, RN, FGSA, FAAN, director of the Center of Geriatric Nursing Excellence and Elouise Ross Eberly Endowed Professor, at Penn State College of Nursing in University Park, Pennsylvania, discussed the latest insights and research on delirium.

Psychiatry Advisor: How does an aging brain contribute to the development of delirium?

Richard N. Jones, ScD: We, as a field, and I myself, know very little regarding the pathophysiology of delirium. Theoretical models are hopelessly complex or too simplistic. Statistical prediction rules based on delirium risk factors fail to replicate. This may be a question that cannot be answered simply. But why does an aging brain contribute to the development of delirium? Well, if we view delirium very broadly as some cognitive/behavioral manifestation of a breakdown of normal brain functioning, any impairment or dysregulation of body systems that can influence normal brain functioning can be associated with risk for delirium in the right environment. One hypothesis is that delirium can be an abnormal inflammatory response.6,7

Psychiatry Advisor: Can you please explain the concepts of cognitive and brain reserve?

Dr Jones: Cognitive reserve and brain reserve are concepts used to account for the imperfect relationship between observable brain damage and cognitive or behavioral manifestations of brain damage. The notion of cognitive reserve is an old one, but in its current role as an explanation for the unexplained variance in cognitive performance given brain pathology, the attribution can be given to Blessed, Tomlinson, and Roth, who wrote a pioneering article in 1968 describing the association of cognitive performance and brain pathology in dementia patients.8 In more recent years, Dr Yaakov Stern at Columbia University has popularized the term and led the field in studying cognitive reserve and brain reserve.9 Brain reserve refers to those aspects of the brain structure and function that provide a buffer against impairment in the presence of accumulating pathology. Examples of such structure include brain size, number of neurons, and density of synapses. Cognitive reserve refers to those cognitive and neural mechanisms that provide resilience to pathology, and mechanisms have been proposed, including efficiency of neural processing.10 

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Psychiatry Advisor: Are these traits dynamic and which factors influence their development?

Dr Jones: Many researchers do think that these concepts are dynamic or change over the course of a lifetime.

To understand what factors researchers believe influence the development of reserve, we need look no further than the factors researchers use to measure the presence or magnitude of reserve. These are so-called reserve proxies or reserve markers: head size, intracranial volume, intelligence, educational attainment, and exposure to cognitively stimulating environments, such as through occupations and hobbies.

The preceding 2 paragraphs identify an important problem: if reserve is dynamic, but many if not most of the proxy measures of reserve are static, we have a clear problem of measurement. The field needs measures of reserve that are based on the presumed outcomes or effects of reserve, not the putative causes of reserve.

These things said, there are 3 important challenges to the field: the first is the absence of clear definitions of brain and cognitive reserve; the second is an articulation of the extent to which these concepts overlap with other aspects of cognitive health (eg, intelligence); and the third is the level of understanding of the extent to which the mechanisms of brain disease are distinct from other somatic diseases where markers of socioeconomic status are known and powerful predictors of variability in outcomes.

Psychiatry Advisor: How much research supports an association between cognitive and brain reserve and vulnerability to delirium? What is the relationship between the two?