Behavioural symptoms of dementia

Neuropsychiatric symptoms (NPSs), also called behavioural and psychological symptoms of dementia (BPSD), are defined as signs and symptoms of disturbed perception, thought content, mood or behaviour occurring in a person with dementia.

They encompass depression, anxiety, apathy, irritability, disinhibition, agitation, rejection of care, aggression, elation, and problems with eating or sleeping. They may occur before, during or after the diagnosis of dementia, and may be among the earliest signs of incipient cognitive decline.

90 to 98% of people with dementia develop at least one NPS over the course of the disease; the prevalence of NPS therefore mirrors the overall prevalence of dementia. NPSs occur across all dementia types and all stages.

In Alzheimer’s disease the commonest NPS is apathy, followed by depression, aggression, anxiety, sleep disturbance, irritability, appetite disturbance, motor problems, delusions, disinhibition, hallucinations and euphoria.

Neurodegeneration-associated factors — the underlying disease process itself, with cholinergic, serotonergic and frontal-subcortical circuit disruption.

Acute medical issues — pain, infection (especially urinary and respiratory), constipation, urinary retention, dehydration, drug changes, poor sleep and sensory impairment. Pain is a common and frequently missed cause of agitation, and occasionally a trial of a scheduled analgesic is the only way to establish it.

Pre-existing personality and psychiatric illness, unmet needs (hunger, boredom, need for toileting, need for company), caregiver factors (communication style, unrealistic expectations, countertherapeutic approach) and environmental factors (clutter, poor lighting, over- or under-stimulation, unfamiliar surroundings).

The standard instruments are the Neuropsychiatric Inventory (NPI), its questionnaire form NPI-Q, and the clinician version NPI-C; the Cohen-Mansfield Agitation Inventory (CMAI) for agitation; and the Cornell Scale for Depression in Dementia (CSDD) for mood, which relies on both patient and informant.

Always exclude delirium first. Delirium superimposed on dementia (DSD) is common and is identified by the Confusion Assessment Method (CAM) — acute onset and fluctuating course, plus inattention, plus either disorganised thinking or altered level of consciousness.

DICE — Describe, Investigate, Create, Evaluate — was developed by a US national expert panel (geriatric medicine, geriatric psychiatry, psychology, nursing, social work, pharmacy and behavioural science) as a step-by-step method for assessing and managing NPS, designed for use by any health professional in a team setting.

Describe — elicit a thorough description from the caregiver, characterising the symptom and the context in which it occurs, including possible antecedents or triggers, and identifying which aspects are most distressing to the patient and caregiver.

Investigate — examine, exclude and identify modifiable underlying causes: patient factors (medical issues, pain, medication change, poor sleep, sensory change), caregiver factors (communication and expectations) and environmental contribution (clutter, lighting, stimulation level).

Create — collaborate with caregiver, patient and team on a treatment plan built on five generalised strategies: caregiver education; enhancing effective communication; creating meaningful activities; simplifying tasks and establishing structured routines; and ensuring safety while simplifying and enhancing the environment.

Evaluate — assess whether strategies were implemented, whether target symptoms improved, whether caregiver distress fell and whether there were unintended effects. If a psychotropic was used, consider a trial of dose reduction or discontinuation.

Family and paid caregiver interventions have the strongest evidence base and a greater effect than antipsychotics. Efficacy is best in mild and moderate stages, when cognitive and communication functions are better preserved. Individual approaches such as music therapy and physical activity work best when embedded within tailored-activity programmes. Environmental adjustments work best in combination rather than singly.

There are no FDA-approved drugs for NPSs in AD in the classical position — the sole exception being pimavanserin for hallucinations and delusions in Parkinson’s disease. In the European Union and Canada, risperidone is indicated for short-term treatment of severe aggression. Most agents are therefore used off-label.

Antipsychotics: modest efficacy for agitation/aggression and psychosis is supported for four atypicals — risperidone, aripiprazole, olanzapine and quetiapine — with risperidone having the best evidence for short-term (6–12 week) efficacy in agitation. Use is limited by increased risk of stroke and death.

Antidepressants: the DIADS trial showed benefit of sertraline in AD with major depression, but DIADS-2 was negative, as was the HTA-SADD comparison of sertraline, mirtazapine and placebo; meta-analysis shows small-to-null effect sizes. Citalopram (target 30 mg) in the CitAD trial reduced agitation, anxiety, irritability and caregiver distress, but caused cognitive decline and QTc prolongation at that dose. Trazodone is widely used for night-time agitation and sleep, stabilising circadian rhythm.

Other classes: benzodiazepines lack trial evidence and should be reserved for crises only, using short- to intermediate-acting agents such as lorazepam or oxazepam. Valproate and carbamazepine have not shown benefit and cause significant adverse effects — sedation, gait disturbance and tremor. Cholinesterase inhibitors and memantine have not shown sufficient evidence for NPSs in AD, although ChEIs do help NPSs in DLB, Parkinson’s disease dementia and cognitive impairment in PD, at the cost of increased parkinsonian symptoms such as tremor.

Expert consensus (International Delphi process) endorses an escalating approach: identify underlying causes first; then caregiver training, environmental adaptation, person-centred care and tailored activities as first-line for overall NPS and agitation; then, if drugs are needed, citalopram and analgesia before antipsychotics. For psychosis specifically, pharmacological options and particularly risperidone are prioritised after assessing underlying causes. DICE and music therapy were agreed as the most promising non-pharmacological approaches.