Neuropsychiatric Symptoms in Dementia PDF

Neuropsychiatric symptoms of dementia Gill Livingston @Gill_Livingston Plan What are neuropsychiatric symptoms? Measurement Prevalence Psychosis Depression Agitation Sleep Impact Management-medication Future research  Neuropsychiatric symptoms Di...

Neuropsychiatric symptoms of dementia Gill Livingston @Gill_Livingston Plan What are neuropsychiatric symptoms? Measurement Prevalence Psychosis Depression Agitation Sleep Impact Management-medication Future research  Neuropsychiatric symptoms Disturbed perception, thought, mood, or behaviour symptoms of dementia Also called BPSD (behavioural and psychological symptoms of dementia) They may come separately or cluster Cluster analyses most commonly define subgroups of - agitation, psychosis and mood disorder The Neuropsychiatric Inventory (NPI) Semi-structured instrument administered to the caregiver. 12 domains – delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviour, sleep disturbance, and appetite disturbance. Each symptom is rated by frequency (score: 1–4) and severity (score: 1–3) or as absent (score: 0), and the overall severity score is their product Delusions Does …….have beliefs that you know are not true? For example, insisting that people are trying to harm him/her or steal from him/her. Has he/she said the family members are not who they say they are or that the house is not their home? I’m not asking about mere suspiciousness, I am interested if ………is convinced that these things are happening to him/her. Mild Cognitive Impairment Significant neuropsychiatric symptoms in 25% with MCI. 75% persistent at 6 months. Persistent symptoms were more at severe baseline Delusions, agitation, apathy, sadness most persistent Clinically significant NPS ↔↓ quality of life. – Ryu et al 2011 Pre-cognitive impairment New neuropsychiatric symptoms in older people w/o cognitive impairment may be pre-dementia New onset agitation has highest odds ratio of becoming MCI over 5 years NPS pre-dementia associated with tau and amyloid neuropathology. – Ehrenberg et al 2018 Underlying neurobiological mechanisms might underpin symptoms. Neurodegeneration → increased vulnerability to stressors or triggers – Genetics, personal history, comorbidities – environment including carer response Prevalence of neuropsychiatric symptoms in dementia 75 % with AD 1+ clinically significant symptom, 80% persistent significant symptoms at 6-month Apathy, aberrant motor behaviour and agitation commonest (34%, 30%, 20% significant) Persistence predicted by severity at baseline Apathy, agitation (motor) and delusions most persistent NPS deterioration predicted by MMSE deterioration – Ryu et al 2005 Prevalence in nursing homes (special population) > 90% of patients had 1+ clinically significant NPS Irritability (63.5%), agitation (51.0%) disinhibition (50.0%) highest cumulative prevalence NPS may be reason for admission; Delusions, agitation, apathy and irritability were enduring symptoms 88% with no agitation did not develop it over 16 months, 70% of those with symptoms still had it. However those without agitation did not develop it – Bergh S et al 2011, Selbaek et al 2008, Livingston et al 2014, Marston et al 2020  Summary Neuropsychiatric symptoms generally increase from MCI to mild to moderate dementia. Clinically significant symptoms rise from 25% of those with MCI to 90% of those in nursing homes. It may be that this is not representative of people at home 75% persistence over a year in each setting with current management. Agitation and apathy are persistent at all severities. Psychosis in dementia- how common? Prevalence about 18% cross –sectionally. Prevalence increasing from mild to moderate dementia and then flattens out. Psychotic symptoms tend to persist in most people for at least some months. Psychosis in dementia- What are the symptoms? Delusions (commoner) – usually simple, not systematised or bizarre; eg theft, abandonment, infidelity or poisoning. – Misidentification symptoms – the belief that the identity of a person, has been changed or replaced, the “phantom boarder”. Hallucinations – visual are more common than auditory hallucinations (in contrast to say schizophrenia). – Auditory hallucinations are usually sounds, individual words or phrases, and rarely commenting or commanding voices. Assessment Is this really a delusion or is it memory loss? – so that when an 87 year old widow believes she is aged 30 and her husband is still alive, this my be forgetfulness rather than a delusion. Is this delirium? – People with dementia are vulnerable to delirium in which psychotic symptoms can be prominent, so this should also be considered. – Treating the underlying causes of delirium will often relieve the symptoms. Risk factors Misinterpretations of reality by a person with dementia are often contributed to by sensory deprivation: – vision loss, – hearing loss – Being alone Type of dementia – well-formed visual hallucinations particularly prominent in DLB – Less common in FTD No genetic contribution identified despite familial aggregation. Imaging shows greater changes in grey matter volumes, blood flow or glucose metabolism in neocortical regions than in temporal lobe structures in AD and psychosis. Significance of psychosis in dementia Distress: – Substantial proportion of people with dementia not distressed by psychotic symptoms. Others are. Psychotic symptoms associated with – more rapid cognitive decline (precedes onset), – greater family carer distress, – greater rate of care home admission, – worse general health, – and increased mortality. Psychosis in dementia-how to manage Need to explain – Part of illness – Do not treat pharmacologically if not distressing or causing problems – Antipsychotics may cause significant side effects Consider contributors and address them – (lighting, eyesight, hearing aids, isolation) DLB -visual hallucinations frequently respond to ChEIs. Psychosis may respond to some antipsychotics. Only risperidone licensed. Use low dosage (0.5 mg) Need to discuss risk/benefit and monitor  Antipsychotics in dementia Management of psychosis in dementia should start with non-pharmacological interventions But, evidence for their effectiveness for psychosis in dementia is weaker than for agitation. Antipsychotics for psychosis in dementia should be in as low a dose and shortest duration possible. Two trials with participants who had responded to antipsychotic treatment; stopping antipsychotics was associated with symptomatic relapse for some, Cautious medication withdrawal in this group. Not psychosis in dementia Charles Bonnet syndrome (CBS) is defined as complex persistent visual hallucinations in the absence of mental disorder in visually impaired Usually insightful. Commonly but not always pleasant. Well-defined, complex and clear images over which the person has little control.  Medication individual antipsychotic drugs have different mortality risks, – quetiapine with the lowest risk (but ineffective) and haloperidol highest risk of death. Antipsychotics in dementia -1% mortality Increased risk of stroke Cognitive decline EPSE..but perhaps less risk in delusions than in agitation Meta-analysis of Janssen RCTs – (Howard et al 2016) Overall antipsychotic side effects Cognitive worsening Falls Immobility CVA Death The relationship of depression and dementia Depression is a risk for future dementia. Direction of causation? Vulnerable (pre-dementia brain) ↔depression. ↑number of depressive episodes →↑ dementia risk. Depression -↑stress hormones, ↓neuronal growth factors and ↓hippocampal volume. Is this changing? – Three decades of ↑ SSRI use. Animal data suggests that antidepressants, including citalopram, decrease amyloid production. Treated depression not a risk factor (liu Yang et al 2022) Depression in dementia Depression occurs in at least 20% of people with Alzheimer’s disease (AD) and more in VD. Burns et al 1990; Ballard et al 1996 It causes distress and reduces quality of life. – Burns 1991 It exacerbates cognitive and functional impairment – Greenwald et al 1989 Associated with increased mortality and carer distress. Assessment of depression in dementia Risk assessment: self-neglect or intentional self harm. Mental state Examination: differentiate apathy,↓concentration or memory; Management of triggers: isolation, physical illness, concern about money. Comparative efficacy of interventions for reducing symptoms of depression in people with dementia: systematic review and network meta-analysis Randomised trials comparing interventions with usual care or any other intervention 256 studies included, 7 interventions better than UC for symptoms Exercise + social interaction +cognitive stimulation (mean difference −12.37, −19.01 to −5.36), Cognitive stimulation + cholinesterase inhibitor (−11.39, −18.38 to −3.93), Massage + touch therapy (−9.03, −12.28 to −5.88), Cognitive stimulation (−2.93, −4.35 to −1.52), occupational therapy (−2.59, −4.70 to −0.40), reminiscence therapy (−2.30, −3.68 to −0.93) Multidisciplinary care (−1.98, −3.80 to −0.16), – Watt et al 2021 Other treatments for depression in dementia SSRIs –RCTs sertraline, fluoxetine, citalopram, escitalopram and placebo, Also mirtazapine and venlafaxine vs placebo Mirtazapine and sertraline no different to placebo Sertraline had lots more side effects People with AD 3x rate antidepressants as people same age without dementia No good evidence that drugs work Exercise and psyhctherapy by themselves not shown to work More trials currently ongoing Agitation: What is agitation in dementia Agitation is inappropriate verbal, vocal or motor activity. It encompasses “purposeless activity”, shouting out, physical and verbal aggression and wandering. It has a behavioural component and is not solely emotional. The person is usually distressed. Often thought to be a form of communication.  Why is agitation important in dementia research? Agitation may be more important than cognition. Agitation is common, persistent and distressing symptom. 80% of those with clinically significant symptoms still symptomatic 6 months later. Agitation leads to: Decreased quality of life. Excess cost Care breakdown. Care home admission. Agitation affects family relationships adversely. Assessment of agitation Ask the person what is wrong. If unable to say, think about – psychological- frightened or anxious – physical comfort, hungry, thirsty, hot or cold or in pain. – If sudden onset may be new physical problem – Reaction to other’s stress Systematic review: Interventions which worked While it is happening Activities Music therapy to a protocol Sensory interventions Over months Supervised person centred care Supervised communication skills Dementia mapping with supervision Activity Intervention Tailored Activity Program (TAP) - Carers trained to use activities tailored to interests and abilities of people with dementia, disease education and stress reduction techniques systematic review and meta-analysis of 7 studies of the tailored activity programmes TAP interventions found a moderate effect on improving quality of life (standardised ES Cohen’s d 0.79, 0.39–1.18; 7 studies, n=160), decreasing neuropsychiatric symptoms (0.62; 0.40–0.83) – and decreasing carer burden(0.68, 0.29–1.07 Exercise no effect in good quality RCT  RCTs of activity programmes for people with dementia Citation Intervention Target population Study Design Key Outcomes Ballard.495 WHELD (Well-being and health Staff trained by trial team. Cluster randomised Improved quality of life, for people with dementia) controlled trial (RCT) agitation and neuropsychiatric Staff and nursing home trained care staff to promote intention to treat with symptoms and cost savings residents tailored person-centred 69 UK care homes in 9- activities and social interactions. month clinical trial -847 System for changing participants inappropriate medications. 496 Gitlin Tailored Activity Program (TAP) Trained occupational Single-blind, parallel, For person with dementia, - Carers trained to use activities therapists (OT) provided RCT 160 dyads of ↓behavioural symptoms, tailored to interests and abilities activities to veterans at Veterans with dementia maintenance of daily function, of veterans with dementia. home and their family carers and ↓pain. Carer distress from Disease education and stress behaviours reduction techniques Gitlin et al TAP OT provided 8 sessions TAP Single-blind RCT of 250 Carers report TAP made life 497 in the home to individuals US dyads with a easier, ↑ ability to provide care, with agitation with moderate dementia diagnosis and and person with dementia’s life dementia clinically significant somewhat or very much. TAP agitation/aggression group had fewer deaths/ hospitalisation 498 Gitlin TAP programme with subsample OT provided tailored Single-blind, two-arm Behavioural benefits for people of white and black dyads activities and instructions to RCT. 193 White and with dementia at 3 months. More carers at home. Black dyads benefit for Black dyads than White dyads. 499 Lamb Aerobic and strength exercises Physiotherapists and Multicentre, pragmatic, Greater cognitive impairment in tailored to fitness and health exercise assistants investigator masked, exercise group. No effect on status. (DAPA trial) prescribed and supervised RCT N=494 quality of life or neuropsychiatric interventions for people with symptoms. dementia Sanders49 Research staff trained Health care staff selected RCT-91 participants No effects on cognition, 3 participants in combined participants with mild-to- endurance, mobility, balance, and walking and strength exercise moderate dementia in day or leg strength. Gait speed improved Aerobic and strength training residential care. after high-intensity exercise. intervention (“exercise”) Harwood Dementia-specific programme Mild dementia or Mild RCT- 365 participants Did not improve ADLs, physical 494 focussing on strength, balance, Cognitive Impairment activity, quality of life, reduce falls physical activity and performance of ADL. Tailored and progressive. Person centred care Training paid caregivers in communication or person centred care skills or dementia care mapping with supervision works for symptomatic and severe agitation, during the intervention and for six months afterwards. The standardised effect sizes suggest they are similarly efficacious, Light therapy Light therapy is hypothesised to reduce agitation through manipulation of the disrupted circadian rhythms of dementia, typically by 30-60mins of daily bright light exposure Three large RCTs showed light therapy increases agitation The SES was from 0.2 for improvement to 4.0 for worsening symptoms Aromatherapy Blinded assessments found it was ineffective. Results of non-blinded studies were mixed. Aromatherapy not been shown to work for agitation Training family caregivers in behavioural management or CBT for people with dementia living at home Three RCTs Ineffective (harmful) for severe agitation No immediate or long term effect to decrease agitation symptoms Training family caregivers in behavioural management or CBT for people with dementia living at home Three RCTs Ineffective (harmful) for severe agitation No immediate or long term effect to decrease agitation symptoms Antipsychotics Limited efficacy. Increase cognitive decline; parkinsonism; mortality. Evidence that haloperidol, risperidone (licensed and evidence in low doses -0.5mg), aripiprazole and olanzapine work sometimes. Quetiapine does not. Atypicals increase mortality 1.5-1.7 x in first 90 days.  Other medication Benzodiazepines increase cognitive decline. Cholinesterase inhibitors and memantine ineffective. One randomised (non-placebo controlled) study of analgesics improved agitation in people with dementia. Effect size comparable to antipsychotics Citalopram 30mg decreases agitation but not severe agitation but cardiac and cognitive impairment Preliminary evidence with carbamazepine Valproate ineffective Overall limited efficacy and risks Care homes Simply making activity available is ineffective Better staffing level does not equate to less agitation More pleasant environment does not mean less agitation – Need to target interventions to individuals Livingston et al 2017/2019 Care home interventions Intensive professionally delivered multicomponent interventions reduced agitation (control ↓ but less) – RCT - (TIME) vs education and WHELD vs TAU Tailored treatment plan Adding activity individually for people Reviewing medications and physical health Teaching staff about communication Case conferences and individual plans – Selbaek 2017, Ballard 2018  UK cost of agitation in dementia Adjusted annual cost/person with AD with significant agitation =£33 075 Vs £28 983 Excess cost associated with agitation =£4091/person/year. So….agitation accounts for 12% of health and social care costs of AD each year. The expected excess cost associated with agitation in people with AD is therefore £2.0 billion a year. Potential to save money ++ with effective interventions. – Morris et al 2014 When to use drugs Risk Failure of other treatment  Summary - agitation in dementia? Way of communicating that someone feels bad Pain, constipation, thirst, boredom, lack of touch, loneliness, discomfort, worry Brain changes Communication and listening plus sensory activity may make the difference Medication often not really relevant Sometimes may be Need RCT-effectiveness but not cost effectiveness Lots more work at home where most people are Dementia care management RCT in German primary care Nurses discussed and finalized care in a weekly interdisciplinary case conference (senior nurse, neurologist/psychiatrist, psychologist, pharmacist) Six months of dementia care management by trained nurses (mean 6 visits) – decreased overall neuropsychiatric symptoms (mean baseline score =7- went up less in intervention group) – No effect on QoL (primary outcome) or prescription of inappropriate medication Thyrian et al 2017 Sleep and dementia? Sleep disturbances are common in dementia - 39% in AD; higher in DLB Impaired sleep initiation, reduced night- time sleep, night- time wandering, excessive daytime sleep, behavioural changes at night Sleep disturbance in DLB 49% of those living at home with DLB experienced sleep disturbance Difficulty staying alert during the day – apathy, napping. Visual hallucinations and delusions. Restlessness Rapid eye movement (REM) sleep behaviour disorder  The impact of sleep disturbances in dementia Sleep disturbances are distressing for people living with dementia Even when they don’t remember them Lower quality of life Sleep during day means often do not eat or drink well, agitated and falls DIVISION OF PSYCHIATRY Why does it matter for carers? Sleep disturbances predict family carer depressive symptoms, burden Family carers become unable to cope Some get night carers but most can not afford it increased risk of care home admission What causes sleep problems in dementia? Suprachiasmatic nucleus degenerates → sleep–wake cycle impairment → disrupting normal circadian rhythm Inactivity / napping impact on sleep pressure Decreased ability to capture & transmit light due to eye diseases People with dementia have physical illnesses too - pain, medication Environment –temperature, noise, light People with dementia anxious when wake  What works? Bright light therapy to strengthen circadian rhythmicity and CBT - effective in other populations Cochrane review of light therapy in dementia found insufficient evidence for light therapy alone. Pilot studies in dementia show potential benefits of combining light with sleep education and hygiene, exercise, daytime activities and CBT (except DREAMS >80% ). NICE recommends them as best evidence but no full trial  What treatment now Medication often used melatonin, mirtazapine, analgesics ineffective. No RCT of hypnotics Known to increase falls and deaths Possibly increase cognitive impairment Association with death may be confounding by indication Adverse effects of hypnotics Hypnotics twice as likely to cause harm than benefit (Glass et al 2015) Increased risk of fractures, falls and strokes. (Richardson et al 2020) Higher doses more problematic (=zopicolone 7.5mg or higher) Association of BZ If you have to use then, use less Summary of neuropsychiatric symptoms Common Often clustered Distressing Costly First consider medical comorbidities eg pain, infection Specific multicomponent interventions decrease neuropsychiatric symptoms in people with dementia and are the treatments of choice. Psychotropic drugs- often ineffective. Might have severe adverse effects. Use when benefit >harm.