Delirium clinical and research challenges

Transcription

1 Delirium clinical and research challenges Daniel Davis Senior Clinical Researcher Consultant in Geriatric Medicine University College London London Memory Assessment Network 4 th May 2016

2 Overview Core concepts and challenges Epidemiological observations Delirium pathophysiology Clinical approach to delirium

3 Starting point

4 Core concepts and challenges

5 A neuropsychiatric syndrome DSM-IV: A. Disturbance of consciousness B. Change in cognition C. Acute D. Physiological precipitant Cognitive decompensation under stress conditions

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7 Why delirium matters Common Serious Marker for dementia Costly 15% hospital 20% mortality 60% underlying 13k / admission Distressing

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9 Concepts and issues Marker of acute brain injury Peripheral/systemic illness, or drugs Level and content of consciousness Features not fully characterised Measurement still problematic Mechanisms largely unknown Accelerated dementia?

10 Epidemiological observations

11 A central question Delirium? cognitive decline 1. Unmask an unrecognised dementia? 2. Lead to chronic cognitive impairment?

12 A central question The most common problem in acute geriatric medicine a public health challenge costing 26 billion?

13 Delirium: long-term outcomes Systematic review of hospital cohorts Outcomes Death HR 2.0 Dementia OR 13 But selection bias? But undiagnosed dementia?

14 Years in study

15 MMSE No delirium Delirium Years in study

16 MMSE Years in study No delirium Delirium Amyloid Vascular Tau Lewy bodies

17 ?

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19 Epidemiological observations Hospitalisation heralds cognitive decline Delirium is a likely driver Pathology may be distinct from dementia Methodological limitations temporality selection bias confounding

20 Delirium pathophysiology

21 direct brain insults DELIRIUM

22 stressor steroids inflammation aberrant stress responses direct brain insults DELIRIUM

23 stressor steroids inflammation aberrant stress responses direct brain insults DELIRIUM

24 LHPA feedback regulation limbic cortex (eg. anterior cingulate) negative feedback loops hypothalamus + pituitary + adrenal + Cortisol

25 Atrophy is associated with LHPA dysregulation MacLullich et al., 2006

26 CSF cortisol

27 CSF inflammatory cytokines

28 stressor steroids inflammation aberrant stress responses direct brain insults DELIRIUM

29 Inflammation and microglia

30 Microglial priming morphology function

31 Microglial priming morphology function

32 Microglial priming morphology function

33 Cognitive sequlae

34 Cognitive sequlae

35 Cognitive sequlae

36 Functional sequelae

37 Pathophysiology: summary Aberrant stress responses may be driver HPA axis mediated Neuroinflammatory

38 Clinical approach

39 Action plan Diagnose Precipitating and predisposing Optimise environment Treat specific symptoms

40 Confusion Assessment Method

41 Confusion Assessment Method

42 Initial approach [1] Assess arousal [2] Test cognition [3] Acute onset and/or fluctuating course?

43 Observational Scale of Level of Arousal (OSLA): example items Eye Opening Eye Contact Posture Open on arrival? Open to voice? Holds eye contact? Eyes wandering? Slumped in chair? Lying in bed?

44 4 A s Test (4AT)

45 Causes Precipitants Infections Drugs (on/off) Specific organ failures Pain Bladder Bowels Predisposing Dementia Frailty Mobility

46 Optimise environment

47 Treat specific symptoms Antipsychotics Not benzodiazepines Melatonin? Anticholinesterases? Memantine? Anti-inflammatories?

48 Future speculations As much to do with arousal as cognition Frailty is more important than acute precipitant Physical function will improve cognitive function Follow-up of delirium patients will be routine Delirium subtypes will link to dementia outcomes Delirium interventions prevent/reduce dementia Single drugs for specific pathological pathways CT brain requests will decrease