Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Impact of Pain on Behavioural Disturbances in Patients With Moderate and Severe Dementia. A Cluster Randomized Trial
Brief Summary: In nursing homes (NHs) 80% of the patients have dementia, between 60%-80% exhibit behavioural disturbances (BPSD), and more than 60% have pain. Both pain and BPSD is more common in those with severe dementia. Since older persons with dementia have less communicative skills, suffer from more pain and exhibit more agitation, pain may be a contributing factor in these patients. More than 40% of patients with BPSD are treated with neuroleptics despite described side-effects. There is an urgent need to investigate the impact of individual pain management on BPSD in patients with dementia.

It was hypothesized that

* pain increase BPSD in patients with dementia
* individual pain treatment decrease BPSD in patients with dementia


Options:
A: Inclusion Criteria:

* Aged 65 and older
* Residing in the NHs for at least 4 weeks
* Dementia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (American Psychiatric Association 1994), FAST score \> 4 (Hughes 1982).
* Clinically relevant BPSD, operationally defined as CMAI score ≥ 39 or higher or/and at least one week history of agitation or aggression (Koss 1997).
* Written, informed consent provided by the participant (if they have capacity) or assent (if they do not have capacity) and a written proxy informed consent from a legally authorized representative empowered to make health-related decisions for the potential study participant.

Exclusion Criteria:

* Clinician responsible for care, or study clinician considers that the patient suffers from any physical condition, which would make participation in the trial distressing or likely to increase suffering
* Advanced severe medical disease/disorder with expected survival less than 6 months or that could interfere with participation
* Psychosis or other severe mental disorder prior to dementia diagnosis;
* Severe aggression (≥8) on item 3 of the NPI subscale, with aggression as the predominant symptom
* Schizophrenia, schizoaffective disorder and bipolar disorder
* Uncontrolled epilepsy
* Severe liver impairment
* Renal failure, as measured by or equivalent to an estimated creatinine clearance of \< 50mL/min/1.73m,
* Severe injury or anaemia (Hb \< 8.5 mmol/l), comatose state, current enrolment in another experimental protocol.
* Known allergy or adverse reaction to Paracetamol, Morphine ret, Buprenorphine plaster or pregabalin
B: Inclusion Criteria:

1. Residential/Inpatients at recruitment to the study with a history of at least 2 weeks behavioural disturbance.
2. Alzheimer's Disease only as per McKhann Criteria + Hachinski Score\<=4.
3. Moderately severe to severe Alzheimer's Disease (baseline MMSE \</=19).
4. Clinically significant agitation that requires treatment.
5. Severity of agitation defined by Cohen Mansfield agitation inventory (CMAI) \> /=45.
6. Age \>/= 55.

Exclusion Criteria:

1. Memantine usage in the 4 weeks prior to the start of the study.
2. On Cholinesterase inhibitor for less than 3 months and not on a stable dose.
3. Anti-psychotic, anti-epileptic, antidepressant, benzodiazepine, lithium or hypnotic dosage alteration in the 2 weeks prior to the start of the study.
4. Antiparkinsonian medication.
5. Hypersensitivity to memantine or any of the excipients in the formulation.
6. Severe renal impairment.
7. Epilepsy, history of convulsions or seizure, or receiving any anti-epileptic treatment.
8. Concomitant usage of N-methyl-D-aspartate (NMDA) antagonists such as amantadine, ketamine or dextromethorphan.
9. Recent myocardial infarction, uncompensated congestive heart failure and uncontrolled hypertension.
10. Severe, unstable or poorly controlled medical illness.
11. Any disability that may interfere with the patient completing the study procedure.
12. Active malignancy.
13. Delirium, pain or any medical illness as a clear cause of agitation.
14. Any important drug interactions: Prohibited during study and in the 14 days preceding enrollment/inclusion are: Analgesic dextromethorphan, Dopaminergics- amantadine, Warfarin due to theoretical INR prolongation.
C: Inclusion criteria

* Probable Alzheimer's disease (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria), with Mini-Mental score of 5-28 inclusive
* A medication for agitation is appropriate, in the opinion of the study physician
* Clinically significant agitation for which either

  1. the frequency of agitation as assessed by the Neuropsychiatric Inventory (NPI) is 'Very frequently', or
  2. the frequency of agitation as assessed by the NPI is 'Frequently' AND the severity of the agitation as assessed by the NPI is 'Moderate', or 'Marked'
* Provision of informed consent for participation in the study by patient or surrogate (if necessary) and caregiver
* Availability of primary caregiver, who spends several hours a week with the patient and supervises his/her care, to accompany the patient to study visits and to participate in the study
* No change to Alzheimer's disease (AD) medications within the month preceding randomization, including starting, stopping, or dosage modifications

Exclusion criteria

* Meets criteria for Major Depressive Episode by Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV (TR)) criteria
* Presence of a brain disease that might otherwise explain the presence of dementia, such as extensive brain vascular disease, Parkinson's disease, dementia with Lewy bodies, traumatic brain injury, or multiple sclerosis
* Psychosis (delusions or hallucinations) requiring antipsychotic treatment in the opinion of the study physician
* Prolonged measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval)
* Treatment with citalopram is contraindicated in the opinion of the study physician
* Failure of past treatment with citalopram for agitation after adequate trial at a minimally accepted dose (greater than or equal to 20 mg/day)
* Treatment with a medication that would prohibit the safe concurrent use of citalopram, such as Monoamine oxidases (MAO) inhibitors
* Need for psychiatric hospitalization or suicidal
* Current participation in a clinical trial or in any study that may add a significant burden or affect neuropsychological or other study outcomes
* Current treatment with antipsychotics, anticonvulsants (other than dilantin), other antidepressants (other than trazodone, less than or equal to 50 mg per day at bedtime), benzodiazepines (other than lorazepam), or psychostimulants
* Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the patient to enroll in the trial
D: Inclusion Criteria:

* Diagnosis of Dementia of the Alzheimer's Type
* Ambulatory, Outpatients who have an informant living/visiting at least 8 hours/week over 3-4 days.
* Presence of delusions, hallucinations, agitation impacting functioning and requiring medication treatment
* Agitation or psychotic symptoms began after signs or symptoms of dementia

Exclusion (prospective participants must not:)

* Be benefiting from psychotropic medication, antidepressants or anticonvulsants
* Be diagnosed with schizophrenia, schizoaffective disorder, delusional disorder or mood disorder with psychotic features.
* Have severe or unstable medical illness requiring active treatment
* Have hypersensitivity or intolerance of any of the study medications

Answer: A