Dementia and Delirium Lecture PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Dementia and Delirium Prof. Alan Moore Consultant Geriatrician LEARNING OUTCOMES 1. Define Dementia 2. List the causes/types of dementia 3. Describe how each cause leads to the development of Dementia 4. Outline the...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Dementia and Delirium Prof. Alan Moore Consultant Geriatrician LEARNING OUTCOMES 1. Define Dementia 2. List the causes/types of dementia 3. Describe how each cause leads to the development of Dementia 4. Outline the common symptoms and signs of Dementia 5. Develop a differential diagnosis for Dementia 6. Define Delirium 7. List the causes/risk factors to develop Delirium 8. Outline the common symptoms and signs in Delirium 9. Outline the overarching principles of investigation and management of Dementia and Delirium LEARNING OUTCOME 1 Define Dementia DEMENTIA Dementia is a progressive neurogenerative condition leading to a decline in cognition involving loss of memory AND at least one other cognitive domain:- Language Executive function Perceptual (Motor function) Social cognition Dementia is associated with a decline from a previous level of function – severe enough to interfere with daily function and independence PREVALENCE Age related 4% over 65 years 20% over 80 years 50% over 90 years Very common & often unrecognized in earlier stages LEARNING OUTCOME 2 List the causes/types of dementia OTHER TYPES OF DEMENTIA Mixed Dementia Others: Dementia associated with Parkinson's disease Huntington's disease Alcohol related dementia Progressive supranuclear palsy Multiple systems atrophy Creutzfeldt-Jakob disease HIV – related cognitive impairment  PROGNOSIS Progressive condition with significant morbidity and mortality Alzheimer dementia – 10 years Vascular dementia – 5 years Lewy body dementia – 2-8 years LEARNING OUTCOME 3 Describe how each cause leads to the development of Dementia ALZHEIMER'S DISEASE – MOST COMMON Loss of cholinergic neurons and cholinergic transmission Amyloid plaques and neurofibrillary tangles Macroscopic brain atrophy, especially in the hippocampus with ventricular enlargement APOE4 gene has been implicated but only accounts for 7% of the risk Progression is generally linear, with decline over months to years ALZHEIMER’S DISEASE (AD) SIGNIFICANCE Most common form of dementia Increasing prevalence (stabilized and more recently reducing incidence) Cost of dementia care globally exceeds cost of all cancers, ischemic heart disease and stroke combined Traditionally diagnosis made on the basis of an informant history, normal neuro-imaging and exclusion of dementia mimics and bedside test of cognition Formalized in 1984 with NINDS-ADRDA working group for diagnosis of “probable” AD Downsides to traditional model: even with experienced clinicians' sensitivity of AD diagnosis is 70-87% and specificity 44-71% compared to postmortem validation. ALZHEIMER’S DISEASE (AD) SIGNIFICANCE VASCULAR DEMENTIA Caused by reduced blood flow to the brain secondary to effect of several small strokes Typically, deteriorate in step-wise fashion. Small infarcts leading to new functional decline with period of plateau in- between vascular insults to the brain. Risk factors include diabetes, hypertension, high cholesterol, obesity, smoking and atrial fibrillation Symptoms depend on area of brain affected and can overlap with over forms of dementia FRONTO-TEMPORAL DEMENTIA Progressive degeneration from the temporal and frontal lobes of the brain These areas play a significant role in decision making, behavioral control, emotion and language Frontotemporal dementia is inherited in 1/3 of cases Two principal variants:- primary progressive aphasia; early progressive language disturbance with relative preservation of other cognitive domains Behavioral variant; altered personality and social behavior. Disinhibition and inappropriate behavior might be noted LEWY BODY DEMENTIA Third most common form of dementia Triad of visual hallucinations, fluctuating cognition and Parkinsonism Abnormal collection of proteins within neurons (lewy body) in deep cortical layers and basal ganglia, causing neurons to function less optimally and die LEARNING OUTCOME 4 Outline the common symptoms and signs of Dementia SYMPTOMS Forgetfulness, losing objects, forgetting appointments, unable to follow movies/TV, unable to read books (Amnesia) Word finding difficulties (Aphasia/Dysphasia) Difficulty remembering familiar faces/items (Agnosia) Inability to complete motor tasks, despite previous proficiency (Apraxia) Disorientation in time and place Change in sleep patterns Withdrawal and apathy Behavioral changes/personality changes/agitation and emotional lability Loss of independence SIGNS – GENERAL INSPECTION SIGNS – CLINICAL EXAM  PROGNOSTIC MARKERS Weight loss Functional loss/personal care dependence UTI/LRTI if dependent or NH resident Swallow impairment LEARNING OUTCOME 5 Develop a differential diagnosis for Dementia DIFFERENTIAL DIAGNOSIS Mood disorders – Depression, Anxiety Metabolic – Hypothyroidism Trauma – Subdural hemorrhage Tumor – Glioblastoma, Metastasis Infectious – HIV, Venereal disease, Creutzfeldt Jacob disease Poisons – heavy metals, recreational drugs incl alcohol Nutrition – Thiamine deficiency, B12 deficiency, folate def Medications – sedatives, corticosteroids, anti-Parkinson's medication, anti-psychotic, anti-depressant, anti-convulsant Other – Normal pressure hydrocephalus, mild cognitive impairment, limbic encephalitis LEARNING OUTCOME 6 Define Delirium DELIRIUM An acute, fluctuating change in mental status associated with disorientation in time and place, impaired short-term memory, and altered level of consciousness Types of delirium: Hyperactive: heightened arousal, restlessness, agitation or hallucinations Hypoactive: lethargy, lack of interest, reduced motor activity Mixed: a combination of hyper- and hypo-active LEARNING OUTCOME 7 List the causes/risk factors to develop Delirium CAUSES – DELIRIUM D – Drugs, Dehydration, Detox (withdrawal), Discomfort E – Electrolytes, Environment, Elimination abnormality L – Lungs (hypoxia), Lack of sleep, Long ED/hospital stay I – Infection, Iatrogenic events, Infarction (cardiac/cerebral) R – Renal failure, Restricted mobility I – Injury (and post-op), Impaired hearing/vision, Intoxication U – UTI, Unfamiliar environment M – Metabolic abnormalities (glucose/thyroid) DRUGS WHICH MAY CAUSE OR WORSEN Analgesics especially opioids Alcohol Anxiolytics Anti-cholinergics Anti-epileptics Psychotropics Antihistamines Steroids RISK FACTORS Increased age Physical frailty Existing dementia, stroke, Parkinson's disease Disturbed sleep Infection Trauma eg fractures Visual or hearing impairment Immobility Previous history of delirium Drugs – Polypharmacy, new medication or withdrawal or toxicity LEARNING OUTCOME 8 OUTLINE THE COMMON SYMPTOMS AND SIGNS IN DELIRIUM SYMPTOMS Acute onset Disorientation in time and place Disordered thinking Sharply fluctuating course Agitated and restless, increased wandering Decreased activity, decreased awareness of surroundings Decreased speed of activity and paucity of speech Behavioral disturbances/personality changes/agitation and emotional lability Symptoms suggestive of underlying aetiology SIGNS General Inspection – Patient may be:- - Disoriented in time and place - Sloppily dressed/apathetic - Altered consciousness/loss of awareness - Repetitive physical behaviors/behavioral disturbance - Poor eye contact/affect incongruent with situation - Inattention Speech Exam - Slurred speech - Slow speech/paucity of speech LEARNING OUTCOME 9 OUTLINE THE OVERARCHING PRINCIPLES OF INVESTIGATION AND MANAGEMENT OF DEMENTIA AND DELIRIUM  DIAGNOSIS OF DEMENTIA History (Collateral/informant history) Examination Neuro-imaging Bedside Cognitive Assessments Exclude Dementia mimic  KEY HISTORICAL QUESTIONS DURING FIRST ASSESSMENT Instrumental Activities become impaired (appointments, finances, travel, mobile phone etc) Repetitive/rapid forgetting Circumlocution/word finding difficulties Safety issues (becoming lost, falls, kitchen accidents) Withdrawal from social activity Apathy Weight loss/reduced dietary intake Driving difficulty Personality changes including delusions  MEASURE COGNITION MMSE MOCA RUDAS Addenbrookes’ Cognitive Examination (ACE III)  INVESTIGATIONS Neuroimaging –CT and MRI Brain assess for frontal atrophy (FTD), global atrophy (AD) MRI less sensitive but can be valuable especially if serial) B12/folate, TFTS, routine bloods SPECT/FDG/PET CT may help if diagnosis unclear Lumbar puncture – not routine, can be useful in younger patients NEW DIAGNOSTIC TOOLS PET 18 FDG & PET amyloid scanning (from 2017 in US) PET Tau: research tool Tau serum biomarkers: they are being used in clinical trials but still lack FDA approval. Not currently recommended outside specialized clinical settings or for those patients not showing dementia symptoms Likely ultimately to be used in combination especially with PET scanning (18 FDG & amyloid) P18 FDG PET SCAN 18 FDG & AMYLOID PET SCAN  MANAGEMENT - DEMENTIA Prevention – Can help delay or prevent 35% of cases Active treatment of blood pressure in middle ages and older people can reduce risk of vascular dementia Preventing damage to the brain through exercise, smoking cessation, reducing obesity in midlife and managing diabetes Strengthening the brain through education and maintaining a cognitively enriching environment in adulthood (be socially engaged, manage hearing loss, manage depression FINGER Study Lancet 2015: diet, social, exercise, medication interventions reduce cognitive decline over two-year period NON-PHARMACOLOGICAL MANAGEMENT Multidisciplinary team approach Carer and family support/education Driving assessment Discuss enduring power of attorney and advanced care directives early prior to significant cognitive decline Consider additional home supports Carer stress important to monitor  MULTI-DISCIPLINARY MANAGEMENT OT Medical social work Pharmacist Physiotherapist Dietician Nursing Neuro-psychology (Mental Capacity)  PHARMACOLOGICAL MANAGEMENT Remove or minimize agents that will impair cognition (eg anti- cholinergic Rx) Cholinesterase inhibitors: Donepezil, rivastigmine, galantamine NMDA receptor antagonist: Memantine Manage hypertension Avoid alcohol  1 2 3 4 5 6 7 8 80-year-old male, has been under the care of the geriatric medicine department. He arrived at the outpatient clinic for a follow-up appointment, accompanied by his concerned wife. Over the past few months, she has noticed decline in his memory , which has been distressing for both. 3 PLANNING Following assessment by the consultant It was evident that he has mild- MANAGEMENT moderate dementia. To address this decline, the geriatrician decided to start him on Treatment. Which of the following medications is Most Appropriate? A. Donepezil B. Ketamine C. Dextromethorphan D. Memantine E. Amantadine A Correct Answer: Donepezil is Cholinesterase inhibitors it is the first line treatment for Mild to moderate Dementia.  At present cholinesterase and NMDA inhibitors not indicated for use for vascular dementia, maybe used in mixed dementia. Management is minimizing risk factors. No treatment available for Lewy body dementia No specific treatment available for FTD, medications can be prescribed to reduce agitation, irritability or depression (as with all forms of dementia) NEW DISEASE MODIFYING TREATMENTS Aducanemab (Aduhelm) Lecanemab (Leqembi), lower ADR, quicker amyloid clearance Donanemab (not yet licensed) Biological agents Humanised IgG monoclonal antibodies Target soluble &insoluble oligomers Donanemb targets a pyroglutamate for of A Beta amyloid in plaques DMARDS FOR ALZHEIMER’S DISEASE Infusion therapies Significant benefits but with risks of ARIAs: Amyloid related Imaging abnormalities Cerebral Oedema Cerebral Haemorrhage FDA now specifies anticoagulation is a contra-indication Relative CI s APOE-4 positive, pre existing microhaemorrhages MY CURRENT ADVICE TO PATIENTS… CONCLUSIONS Dramatic advances in the last five years have provided more information to clinicians on the impact of providing a dementia diagnosis At present most evidence exists for combined PET amyloid/FDG in combination CSF analysis may be more helpful for younger patients (to allow FTD to be excluded) Likely serum biomarker will become available in the next 2-5 years, most likely brain derived p-tau217 New Drugs are coming  INVESTIGATIONS - DELIRIUM Cognitive assessments – 4AT is a test across domains of alertness, awareness, attention and change in behavior. Bloods blood gases and cultures, toxicology – infection leading cause of delirium, electrolyte abnormalities, hypoxia CXR and urine dip – check for source of infection CT brain - ICH, stroke or other structural cause ECG – MI as precipitant LP - for source of infection, not routinely done unless heavy suspicion of CNS infection  MANAGEMENT Avoidance – avoid triggers, monitor risk factors Treat underlying cause – early intervention A. Patient centered NON Pharmacological management Nurse in moderately lit room, ideally with same staff Educate family, care givers and ask them to sit with patient Re-orientate the patient – Calander/clock/hearing aids/glasses Normalize sleep – consider moving to a side room Encourage early mobilization and self-care Avoid physical restraints/urinary catheters/IVCs Monitor for dehydration, constipation, pain B. Pharmacological: Avoid sedation if possible. This should be reserved for agitated and aggressive patients who are at risk to themselves or others, due to the increased mortality associated with sedation Start low, go slow Options:- Antipsychotics – Risperidone or Olanzapine (avoid in Parkinson's) Short acting benzodiazepines e.g. Lorazepam COMPLICATIONS Increased risk of falls and fractures Immobility Prolonged hospital stay Pressure sores (particularly hypoactive delirium) Aspiration pneumonia and hospital acquired infection Over sedation Dehydration and malnutrition Incontinence Long term cognitive or functional impairment – may result in a 'new baseline', as patient may not return to physical or cognitive function following episode of delirium PROGNOSIS Hypoactive has worse prognosis – normally later diagnosis and therefore treatment Delirium may last for weeks, even months, after underlying cause has been treated Delirium has significant impact on health of older person Increased length of hospital stay More likely to have long term cognitive problems Higher risk of institutionalization Significant morbidity and mortality Six-month mortality is 22%  DEMENTIA VS DELIRIUM Features​​ Delirium Dementia Onset​​ Acute (hours to Insidious (months to days)​​ years)​​ Course​​ Fluctuating​​ Progressive​​ Duration Hours to weeks​​ Months to years​​ Consciousness​​ Altered​​ Usually clear​​ Attention​​ Impaired​​ Normal except in severe de mentia Psychomotor Increased Often normal​​ changes​​ or decreased​​ Reversibility​​ Usually​​ Irreversible​​