Long-Term Outcomes of Delirium

An episode of delirium can have devastating short- and long-term consequences. Impairments of executive function, language, praxis, planning activities, attention, and concentration are often the earliest impairments seen post-delirium, both in older [121] and younger adults (49-65 years; [122]). Evidence suggests selfreported memory and executive functioning deficits appear to be somewhat persistent over the first 12 months after delirium [123].

Persistent delirium (duration > 1 week) occurs in up to 24 % of people after an episode of delirium [124]. Persistent delirium is associated with older age, male gender and delirium severity, and is more frequent in those with preexisting comorbid dementia [125]. Furthermore, certain forms of cancer (e.g., breast cancer) and terminal malignant diseases in general [126,127], as well as infections that respond late to delirium management (e.g., > 1 week) are also associated with persistent delirium [125].

In older people, delirium on its own or when superimposed on dementia [128, 129] is a strong predictor of functional dependence, institutionalization, and mortality in older patients. Residual subsyndromal delirium is a predictor of slower recovery and is associated with a higher degree of cognitive and functional impairment during the acute episode [130]. Meagher et al. suggest that subsyndromal delirium has a prevalence of 27 % post episode of delirium [131].

The relationship between dementia and delirium remains an important issue, both in terms of risk factors and long-term outcome. On average, 20-28 % of subjects with an episode of delirium remain cognitively impaired at 6 months’ period [132, 133]. The prevalence of long-term cognitive impairment (consisting of worsening of both global cognition and executive function; [122]) following delirium increases to 40 % after 2 years [134] and 69 % after 5 years [135]. Although there is limited evidence to link certain delirium subtypes to dementia progression, hypoac- tive delirium may be associated with prolonged cognitive impairment with disorientation to time and place and visuospatial impairment, thought to serve as predictors of both hypoactive and mixed delirium subtypes [136]. Hypoactive delirium, especially in conjunction with psychosis, is characterized with more severe cognitive impairment compared to hyperactive delirium [137].

A Finnish longitudinal population-based study of general-aged communitydwelling individuals found the use of benzodiazepines, psychotropics, and antidepressants to be associated with more rapid cognitive decline when used alone or in combination [138]. This finding was consistent with another study that reported an association between commonly prescribed medications and cognitive decline in Alzheimer’s disease [139].

The studies addressing the relationship between delirium and post-delirium cognitive functioning are largely conducted on a smaller number of subjects and with variable duration of follow-up, from 1 week [140] to several years (2-10 years; [134, 135, 141-146]). Variable cognitive outcomes following an episode of delirium can range from no significant detriment to an increased risk of cognitive deterioration [143,147]. In particular, a higher risk of post-delirium cognitive decline is asociated with stroke and hip fracture [146]. Interestingly, studies on post-delirium cognitive decline following hip fracture indicate a potential long-term risk which may increase with time, OR = 5.8 at 6 months [148] and 12.2 at 38 months [144], with a high rate of cognitive impairment post-delirium remaining for years (OR = 8.7 in a community-based study with a follow-up of up to 10 years; [55]). In summary, there is a clear evidence that delirium accelerates cognitive decline.

Variability exists between studies that examined the risk of developing dementia following delirium. In part, this was secondary to variations in assessment protocols and instruments utilized with only a number of studies throughout the last two decades meeting either DSM-III-R, DSM-IV, NINCDS-ADRDA, or NINDS- AIREN criteria for dementia [55,134,135,141,145,146,148]. However, evidence would support the notion that delirium is a risk factor for developing dementia in cognitively intact people [135].

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