1. Emotional and Behavioural Complications of Dementia – Recognition, Assessment and Management Prof Philip Morris MB BS, BSc(med), PhD, FRANZCP, FAChAM (RACP) Consultant Psychiatrist/Psychogeriatrician Medical Advisor – DBMAS NT Medical Director Gold Coast – Tweed Memory Clinic 36 Beryl St, Tweed Heads, NSW, Australia Ph 07 55992220 and Suite 2, Level 5, 123 Nerang St, Southport, Qld, Australia Ph 07 55327655 www.drphilipmorris.com

2. Dementia ‘epidemic’ explodes Main types of dementia Alzheimer’s disease (35%) Vascular dementia (20%) Mixed Alzheimer’s/vascular (20%) Dementia with Lewy bodies (10%) Focal lobar atrophies (frontal variant FTD, semantic dementia, progressive non-fluent aphasia, and motor neuron dementia) (5%) Sub cortical dementias (Parkinson’s disease, progressive supranuclear palsy, multiple system atrophy, Huntington’s disease) (5%) Alcohol related (3%) Head injury (2%) Memory loss a cardinal feature of dementia along with either aphasia, apraxia, agnosia or a disturbance of executive functioning (planning, organizing, sequencing, abstracting) causing impaired function

3. Alzheimer’s disease Most common. Inflammatory plaques of amyloid outside neurones, and deposition of tau inside neurones producing tangles. Initially concentrated in hippocampus and acetylcholine producing neurones in the basal forebrain. First causes new learning problems and recent memory recall problems, and attention difficulties. Most later onset cases (over age 65) are ‘sporadic’. Early onset Alzheimer’s disease more often inherited (mutations on chromosomes 14, 1, and 21 including Down’s syndrome – trisomy 21)

4. Brain atrophy – general and hippocampus – coronal view Peter Tori

5. Clinical Features of Alzheimer’s Disease Cognitive Symptoms Attention problems Memory – recent narrative recall Language - dysphasia Visuo-spatial dysfunction Praxis - apraxia Executive Dysfunction – planning, organizing, abstraction, sequencing

6. Structure of Memory Memory – 3 Rs: registration (encode - needs attention and arousal), retain (store), and recall (retrieve) Implicit/procedural Declarative/explicit (unconscious) (conscious) (learning of skills and (learning of information) automatic behaviours) Motor/conditioning/primingWorking/short term memory ( over seconds ) ( over seconds to minutes ) Phonological loop Visuo-spatial sketch pad Long term memory ( over days ) Semantic memory (knowledge and memory about things) Episodic memory (narrative memories)

7. Clinical Features of Alzheimer’s Disease Cognitive Symptoms Attention problems Memory – recent narrative recall Language - dysphasia Visuo-spatial dysfunction Praxis - apraxia Executive Dysfunction – planning, organizing, abstraction, sequencing

8. Clinical Features of Alzheimer’s Disease Non-cognitive Neuropsychiatric Symptoms – Emotional and Behavioural Complications of Alzheimer’s Disease Affective Disturbance Psychotic Disturbance Sleep Disturbance Apathetic Syndrome Executive Dysfunction Syndrome Other Clinical Features

9. Clinical Features of Alzheimer’s Disease Non-cognitive Neuropsychiatric Symptoms – Emotional and Behavioural Complications of Alzheimer’s Disease Affective Disturbance Depression 40% - mild to moderate dementia, less symptoms of ‘sadness’, more of frustration, anxiety and loss of interest Irritability - anger, poor tolerance Agitation 25% – verbal or motor behaviour not directly related to the needs of the patient Elation - unusual Demoralization – despair, loss of control, not depression, early stage problem

10. Clinical Features of Alzheimer’s Disease Non-cognitive Neuropsychiatric Symptoms – Emotional and Behavioural Complications of Alzheimer’s Disease Psychotic Disturbance Delusions 23% – poorly developed paranoid delusions (theft, infidelity) and misidentification syndromes (family/carers as imposters or strangers) Hallucinations 15% - visual misperceptions or misinterpretation (if early onset – consider Lewy body dementia)

11. Clinical Features of Alzheimer’s Disease Non-cognitive Neuropsychiatric Symptoms – Emotional and Behavioural Complications of Alzheimer’s Disease Sleep Disturbance 60% at some time in course of illness Insomnia, wandering/pacing, excessive daytime sleeping, decreased REM sleep Eating problems 40% - loss of interest in food, leads to poor nutrition Apathetic Syndrome 70% over the course of the illness Anterior cingulate gyrus and adjacent medial frontal lobe involved Loss of motivation first, then gradual withdrawal from all interaction Executive Dysfunction Syndrome Planning, organizing, abstraction, sequencing problems, personality change, disinhibition, verbal and motor perseveration Other Clinical Features Balance and gait problems, poor coordination, falls, subdural bleeds, skin ulcers, chest and urinary infection, delirium

13. Pharmacological Management of Emotional and Behavioural Complications of Alzheimer’s Disease Psychotropic Medications Antipsychotic agents ‘Typical’ antipsychotics (haloperidol, chlorpromazine) ‘Atypical’ or new generation antipsychotics (risperidone, olanzapine, quetiapine, aripriprazole) Cognitive enhancers (‘nootropics’) Acetyl cholinesterase inhibitors (donepezil, galantamine, rivastigmine patches) Glutamate (NMDA) antagonist Antidepressants Tricyclics SSRIs SNRIs Mirtazapine, agomelatine Mood stabilizers Valproate Carbamazepine Lithium Others

14. Pharmacological Management of Emotional and Behavioural Complications of Alzheimer’s Disease Psychotropic Medications General approach Target specific symptoms or behaviours First try non-pharmacologic methods Then choose psychotropic agent – start with low dose Review response Monitor progress for adverse effects Consider drug withdrawal Antipsychotic agents For psychotic symptoms and severe agitation ‘Typical’ antipsychotics (haloperidol [high potency], chlorpromazine [low potency]) ‘Atypical’ or new generation antipsychotics (risperidone, olanzapine, quetiapine, aripriprazole) No significant differences between types in effectiveness at small doses Side effects differ between classes and within classes (sedation, EPS, raised prolactin, postural hypotension, anticholinergic effects, weight gain) Clinical effects modest Safety concerns – cerebrovascular incidents, death

15. Pharmacological Management of Emotional and Behavioural Complications of Alzheimer’s Disease Psychotropic Medications Cognitive enhancers (‘nootropics’) Acetyl cholinesterase inhibitors (donepezil, galantamine, rivastigmine patches) For mood (depressive) symptoms, psychotic symptoms, agitation, apathy Modest benefit on emotional and behavioural problems Also helpful to enhance attention and cognitive symptoms Give in usual doses Glutamate (NMDA) antagonist – memantine Few studies Reduced agitation Improved appetite/eating behaviours Watch for over-sedation Reduce dose in renal impairment

16. Pharmacological Management of Emotional and Behavioural Complications of Alzheimer’s Disease Psychotropic Medications Antidepressants For depression, agitation, aggression, anxiety, psychotic symptoms Tricyclic antidepressants Avoid due to anticholinergic effects SSRIs, SNRIs, mirtazapine and agomelatine A small number of studies have shown effect for treatment of agitation, aggression, and psychotic symptoms in non- depressed patients with dementia Use as usual for depressive illness complicating dementia Mirtazapine is sedative, improves appetite and is anxiolytic Caution with agomelatine in liver impairment

17. Pharmacological Management of Emotional and Behavioural Complications of Alzheimer’s Disease Psychotropic Medications Mood stabilizers No information on lithium Negative trials for valproate Carbamazepine Improved agitation and behavioural disturbance in two studies Other medications Benzodiazepines – can induce calming and sedation for short periods, beware ‘paradoxical’ response Beta blockers Hormones (estrogen, anti androgen agents) Stimulants (dexamphetamine, methylphenidate, modafinil) Parkinson’s disease medications (selegiline)

18. Effects of treatment on target symptoms

19. Pharmacological Management of Emotional and Behavioural Complications of Alzheimer’s Disease Non-pharmacological methods Reduce agitation and problem behaviours Theoretical framework Behavioural model Environmental vulnerability model Unmet needs model Behavioural model Antecedents (triggers) and consequences shape and can modify behaviour ‘Carrot and stick’ – reward and discourage approach Environmental vulnerability model Dementia results in increased vulnerability to the environment and lowers threshold of response to environmental or stressful stimulus Unmet needs model Behaviours arise out of difficulty of person with dementia to control their environment and to communicate needs – problem behaviours emerge as attempts to communicate those needs

20. Pharmacological Management of Emotional and Behavioural Complications of Alzheimer’s Disease Non-pharmacological methods An approach to using non-pharmacological methods for managing emotional and behavioural complications of Alzheimer’s disease involves - Determining the problem behavious to be addressed Sets out measurable goals Analyzes the problem behaviours from the behavioural perspective, the environmental vulnerability perspective, and the unmet needs perspective Develops a plan that takes into account the unique individual characteristics and circumstances of the patient and the caring environment Implements the plan Monitors the response Revises the plan as needed