Delirium, Dementia, and the Aging Brain: Searching for Answers

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Any impairment or dysregulation of body systems that can influence normal brain functioning can be associated with risk for delirium in the right environment.
Any impairment or dysregulation of body systems that can influence normal brain functioning can be associated with risk for delirium in the right environment.

Dr Jones: Very little research has been completed in the area of cognitive and brain reserve and vulnerability to delirium. Observational studies showing relationships between reserve proxies (eg, educational attainment) and risk for delirium have shown a suggestive relationship11 and this finding has been replicated in some12 but not all attempts.13 There does seem to be strong evidence that intelligence13 and level of cognitive performance14 are very important predictors of delirium in hospitalized older adults. And very recently, we have published a study demonstrating that markers of reserve modify the risk for delirium associated with inflammation.15 The effects of this study are small, but that is expected since inflammation is only one possible causal mechanism underlying the occurrence of delirium. More importantly, this work is significant because our study represents the first attempt to test the reserve hypothesis in the context of delirium. Stronger evidence will come from randomized controlled trials, such as the Cognitive Intervention for Delirium in Dementia trial recently completed at Penn State University by Dr Ann M. Kolanowski and Dr Donna M. Fick [ClinicalTrials.gov Identifier: NCT01267682].

Psychiatry Advisor: Are there interventions that might be beneficial for preventing delirium in persons with dementia? 

Donna Marie Fick, PhD, RN, FGSA, FAAN: This is an area where we need more research, as persons with dementia have been included in intervention studies but their numbers have been very limited and they are sometimes excluded or not well characterized in studies. However, they do seem to benefit from similar interventions as persons without dementia: multicomponent programs like the Hospital Elder Life Program (HELP) that promote mobility, hydration, avoiding physical restraints, sleep hygiene, pain management, and avoiding benzodiazepines and other strong anticholinergic medications like diphenhydramine and antipsychotics

Psychiatry Advisor: Which strategies are more effective in delirium: prevention or management?

Dr Fick: Prevention has been found to be more effective than management in delirium. At Penn State, we conducted an NIH [National Institutes of Health]-funded trial [ClinicalTrials.gov Identifier: NCT01505257] with a nurse-led intervention for delirium superimposed on dementia (DSD) and found that, using the EMR [electronic medical record] and education, we were able to get nurses to better recognize delirium in persons with dementia and to give fewer prn (pro re nata or “as needed”) psychoactive medications.

In this study we found that a tailored person-centered approach may be more important for the prevention and management of delirium in persons with dementia so that the underlying behavior and needs can be better understood if patients are not able to communicate well. We developed an All About Me Board to help us know them better and, if possible, get input from the older adult and family members/caregivers so that clinicians do not resort to using medications that cause harm and lead to delirium or falls.

In a second study (principal investigators Dr Kolanowski and Dr Fick), we did a single-component intervention with tailored cognitive stimulation and, in this randomized controlled trial [ClinicalTrials.gov Identifier: NCT01267682], though we were not able to impact the number or delirium-free days, we were able to improve executive functioning.16

Psychiatry Advisor: What are some of the existing knowledge gaps about delirium, and which topics should future research focus on?

Dr Fick: Dr Sharon Inouye and I published a research agenda for DSD in 200217 and many of these areas are still in need of research. We definitely need more studies that are specifically designed to test whether different interventions and measures are needed for delirium in persons with dementia. A few of the gaps in research are comparing single-component vs multicomponent interventions for DSD, involving stakeholders (clinicians, persons with dementia, and their caregivers) in the design of interventions, prevention approaches in special populations like persons with dementia who live alone (as large as 30%) and those with intellectual disabilities, and comorbidities. In my opinion, one of the biggest areas where more research is needed is in home and community-based care. In our work, we found that more than 25% of persons with dementia come in with delirium, so the prevention needs to move into the community. Another area that needs more attention is understanding and disrupting attitudes, stereotypes, and ageism that may delay recognition of delirium and care for persons with dementia.

References

  1. Inouye, SK, Westendorp RG, Saczynski JS, et al. Delirium in elderly people. Lancet. 2013;383(9920):911-922.
  2. Marcantonio ER. Delirium in hospitalized older adults. N Engl J Med. 2017;377(15):1456-1466.
  3. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669-676.
  4. Leslie DL, Marcantonio ER, Zhang Y, et al. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008;168:27-32.
  5. Jones RN, Fong TG, Metzger E, et al. Aging, brain disease, and reserve: implications for delirium. Am J Geriatr Psychiatry. 2010;18(2):117-127.
  6. Dillon ST, Vasunilashorn SM, Ngo L, et al. Higher C-reactive protein levels predict postoperative delirium in older patients undergoing major elective surgery: a longitudinal nested case-control study. Biol Psychiatry. 2017;81(2):145-153.
  7. Maldando JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21(12):1190-1222.
  8. Blessed G, Tomlinson B, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968;114(512):797–811.
  9. Stern Y. What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc. 2002;8(3):448-460.
  10. Stern Y, Zarahn E, Hilton HJ, et al. Exploring the neural basis of cognitive reserve. J Clin Exp Neuropsychol. 2003;25(5):691-701.
  11. Jones RN, Yang FM, Zhang Y, et al. Does educational attainment contribute to risk for delirium? A potential role for cognitive reserve. J Gerontol A Biol Sci Med Sci. 2006;61(12):1307-1311.
  12. Martins S, Paiva JA, Simões MR, et al. Delirium in elderly patients: association with educational attainment. Acta Neuropsychiatr. 2017;29(2):95-101.
  13. Saczynski JS, Inouye SK, Kosar CM, et al. Cognitive and brain reserve and the risk of postoperative delirium in older patients: analysis of data from a prospective observational study. Lancet Psychiatry 2014;1(6):437-443.
  14. Jones RN, Marcantonio ER, Saczynski JS, et al. Preoperative cognitive performance dominates risk for delirium among older adults. J Geriatr Psychiatry Neurol. 2016;29(6)320-327.
  15. Cizginer S, Marcantonio E, Vasunilashorn, et al. The cognitive reserve model in the development of delirium: The successful aging after elective surgery study. J Geriatr Psychiatry Neurol. 2017;30(6):337-345.
  16. Kolanowski A, Fick D, Litaker M, et al. Effect of cognitively stimulating activities on symptom management of delirium superimposed on dementia: a randomized controlled trial. J Am Geriatr Soc. 2016;64(12):2424-2432.
  17. Fick DM, Agostini JV, Inouye SK, et al. Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc. 2002;50(10):1723-1732.
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