Management of behavioural and psychological symptoms of dementia: Belgium, Greece, Italy, United Kingdom

European Geriatric Medicine 4 (2013) 50–58

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The same patient in various European countries

Management of behavioural and psychological symptoms of dementia: Belgium, Greece, Italy, United Kingdom M. Azermai a, J. Kane b, R. Liperoti c, M. Tsolaki d, F. Landi c, A.P. Passmore b, M. Petrovic a,e, A.J. Cruz-Jentoft f,* a

Heymans Institute of Pharmacology, Division of Clinical Pharmacology, Ghent University, Gent, Belgium Ageing Group, Centre for Public Health, Queen’s University Belfast, Institute of Clinical Sciences, Royal Victoria Hospital, Belfast, United Kingdom Centro di Medicina dell’Invecchiamento, Dipartimento di Scienze Gerontologiche, Geriatriche e Fisiatriche, Universita` Cattolica del Sacro Cuore, Rome, Italy d Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece e Service of Geriatrics, Ghent University Hospital, Gent, Belgium f Servicio de Geriatrı´a, Hospital Universitario Ramo´n y Cajal, Madrid, Spain b c

A R T I C L E I N F O

Article history: Received 21 June 2012 Accepted 23 June 2012 Available online 18 January 2013 Keywords: Dementia BPSD Europe

Mrs D. is a 75-year-old woman who lives alone. One year ago she started having memory problems, which were noticed by her only daughter, together with reduced ability to perform some instrumental activities of daily living. After an extensive diagnostic work-up, a diagnosis of mild Alzheimer’s disease was reached, and treatment with donepezil was started. She had no other relevant diseases and was taking no other medication. Mrs D. insisted in living alone and accepted no help. She denied having memory problems (‘‘no more than anybody else’’) but seemed to accept taking the medication. In the following months, her daughter, who lived in the same town and visited her two or three times a week, noticed a fast impairment in the care of her house, which was dirtier, with expired food in the refrigeration. She reported to the family doctor that her mother was feeling sad, depressed and occasionally anxious. She had problems falling asleep, and wandered in the nights. At least twice she was found in the street in sleeping clothes by a neighbour. She complained of being followed by some people who entered her house when she was unaware and stole her personal belongings. She had occasional

* Corresponding author. E-mail address: [email protected] (A.J. Cruz-Jentoft). 1878-7649/$ – see front matter ß 2013 Published by Elsevier Masson SAS. http://dx.doi.org/10.1016/j.eurger.2012.06.008

bursts of anger. The family doctor recommended starting an antidepressant, but the patient refused to take anything (‘‘it may be venom, they want to kill me’’). Expert geriatricians from different countries explain how this patient with behavioural and psychological symptoms of dementia (BPSD) is cared for locally, and what would be considered standard care in each country. Are BPSD routinely assessed in demented patients, or only on demand? Who performs this assessment? What instruments are used? Is there a common language to refer to each symptom, or are general words (‘‘agitated’’, ‘‘psychotic’’) used to describe such patients? Who manages patients with BPSD? Are family doctors competent in this area? What specialists are complex or unresponsive patients referred to? Is there any specific care in nursing homes for these patients? What are usual treatments for the most frequent BPSD? Are different syndromes managed differently? Are local/national guidelines available and widely used to manage this complex syndrome? Have recent data on the safety of different drugs being debated or changed usual practice? What is the role of nonpharmacologic measures (availability, standardization)? How is response to treatment assessed? Is variability of care within the country high or low? 1. Introduction Dementia is a progressive disease affecting multiple higher cortical functions and resulting in psychological and physical dependency. Dementia and cognitive impairment remain important contributors to institutionalisation, but the associated behavioural and psychological symptoms (BPSD) have been recognised as an important component of the dementia syndrome, being clinically as significant as cognitive disorders [1]. The term Behavioural and Psychological Symptoms of Dementia (BPSD) describes a wide spectrum of non-cognitive symptoms of dementia including agitation, oppositional behaviour, verbal

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and physical aggression, socially inappropriate behaviour, delusions, hallucinations, apathy, anxiety, sleep disturbances and wandering [2]. They may cause considerable suffering, and affect the quality of life of the patient and the carer, perhaps more than the cognitive difficulties themselves [3]. Several studies have shown that most of BPSD do not appear in isolation, but tend to occur together in clusters or syndromes. These clusters vary by time, severity, and diagnosis. Generally, four Neuropsychiatric Inventory (NPI) - based clusters have been identified across various dementia types and include: psychomotor cluster (agitation, aggression, euphoria, disinhibition, irritability, aberrant motor activity), psychosis cluster (hallucinations and delusions), mood liability cluster (depression and anxiety) and instinctual cluster (appetite disturbance, sleep disturbance and apathy) [4]. It is estimated that up to 80% of older individuals with dementia develop BPSD at some point during the course of their illness [5,6]. These behavioural problems cannot solely be explained by the cognitive impairment, but rather by the interaction between the pathology, a person’s capabilities and the physical and social environment in which the disruptive behaviour occurs. BPSD heavily contribute to the burden of dementia being the most disruptive symptoms of this disease. Families and health care professionals struggle to manage such symptoms that represent a primary reason for patients’ institutionalization. BPSD have been also associated with accelerated cognitive and functional decline, hospitalization, emergency room visits and with an overall increase in dementia care costs [7]. We are assisting to an epidemic spreading of dementia with over 40 million cases expected by 2020 worldwide [8]. In this respect, BPSD have been recognized as a major public health issue for our societies. 2. An overview from Belgium 2.1. Scope of the problem Dementia is one of the chronic mental health conditions that will continue to pose tremendous challenges in the future, as the population grows older. For Belgium, it is no different. The last available data of the Qualidem study (1999–2006) estimated that 9% of the persons older than 65 years suffered from dementia [9] accounting for 170,000 individuals when calculated on Belgium’s population [10]. Since the introduction of chlorpromazine in the 1950s, antipsychotics have been increasingly used to manage BPSD [11], especially since atypical antipsychotics have been promoted as having less adverse effects. Despite the global and embedded use of antipsychotics for BPSD, the evidence and rationale for the use of this drug class is proven to be modest. Antipsychotics may be more effective than other psychotropic drugs for some specific symptoms within the BPSD spectrum such as aggression, and paranoid ideas, still they appear neither to improve functioning, care needs nor quality of life [12]. Moreover, several warnings [13,14] have been issued regarding the adverse effects (e.g. mortality and cerebrovascular events) in older persons, suggesting that the risks may outweigh the benefits. Therefore, non-pharmacological interventions are becoming increasingly important as first-line treatment options for BPSD. 2.2. The Belgian residential care setting In 2005, 17.2% of the Belgian population was represented by persons of 65 years or older (1.6% was 85+), of which 8% (42% of the 85+) resided in a nursing home. The Belgian long-term residential care infrastructure for older persons consists of nursing homes, offering home replacement care with and without nursing care

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(help with activities of daily living, paramedical and/or physiotherapeutic care), allowing older individuals whose condition deteriorates to stay in the same residential facility [15]. 2.2.1. The role of a general practitioner In Belgium, the general practitioner (GP) has an important role in the management of dementia patients in a home environment as well as in a nursing home setting. When dementia patients transition from their home environment to the nursing home, they are still supervised by the same general practitioner, resulting in an average of 32 visiting GPs per nursing home [16]. When a patient is presented with cognitive problems, first cognitive screening is generally performed by the GP with a Mini Mental State Examination (MMSE) or a Clock drawing test. Behavioural problems are usually assessed by interviewing the accompanying care giver, but a standardised screening of BPSD using a validated assessment tool such as the Neuropsychiatric Inventory (NPI) is rather the exception in primary care. Also the referral of patients by GPs to geriatrics day hospitals, specialised memory clinics, geriatricians, neurologists or old age psychiatrists has still not become a rule. The use of anti-dementia agents is not fully embedded in primary care for the management of mild to moderate dementia. Among Belgian nursing home residents only 8% use anti-dementia agents [17]. Additionally, in order to obtain reimbursement for cholinesterase inhibitors in mild to moderate Alzheimer’s disease, a confirmation of the diagnosis, in the absence of other diseases, is needed by a geriatrician, neurologist or a psychiatrist. This limits the prescribing practice of anti-dementia agents for the GP. 2.2.2. The role of nurses Dementia and the associated behavioural problems are an important contributing factor for distress and caregiver burden, often resulting in institutionalisation. Behavioural and psychological symptoms associated with dementia are part of nurses’ observations. These observations are usually registered per day and per responsible nurse, but are not reported in a standardised manner with a differentiation for type of symptom, frequency of occurrence or severity. In that sense, there is need for a standardised assessment tool to clearly differentiate between several types of disturbing behaviours associated with dementia. For example, it is important to differentiate agitation from resistance to care because these are two separate behavioural syndromes that may occur together, but more importantly, require different management strategies [18]. Especially when pharmacological treatment is initiated, a standardised assessment tool would be beneficial to monitor adverse effects and to follow-up behavioural problems or improvements. Given the fact that there is an average of 32 treating GPs in Belgian nursing homes, nurses have to consult different GPs for each resident which leads to varying management strategies of BPSD depending on the treating GP. Very often, the need for an intervention to reduce behavioural problems results in pharmacological treatment with antipsychotics. 2.2.3. The role of a geriatrician Traditionally, the geriatrician works in a hospital setting where dementia patients often present complex clinical conditions in addition to suboptimal social conditions. These patients are therefore being cared for by a multidisciplinary team, led by a geriatrician. The role of a geriatrician lies primarily in the assessment of the patient’s rest capacities and tailoring the care plan. In dementia patients with increased dependency and a lack of social support, hospitalisation is often an important trigger for institutionalisation. In some hospitals, patients with more severe cognitive impairment and behavioural disorders but without

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previous thorough diagnostic work-up are transferred to psychogeriatric units as a transition period, pending institutionalisation. Behavioural disorders in older persons emerge frequently during hospitalisation. The suboptimal clinical condition of patients and changes in environment for which patients with dementia are particularly sensitive may be contributing factors leading to exacerbation of behavioural symptoms. Antipsychotics are mainly initiated in the residential care setting, but a significant number of dementia patients start with antipsychotics during hospitalisation. The prescription of the antipsychotic initiated during hospitalisation is often insufficiently reviewed by the GPs after discharge, indicating a lack of reassessment [16]. Therefore, antipsychotics used during a hospitalisation might be justified only in severe distress. However, the geriatrician should re-assess the prescription of the antipsychotic drug before discharging patients to their home environment or a nursing home since it is likely that the prescription will be continued by the GP, potentially resulting in long-term use of antipsychotic treatment.

discontinuation should be perceived as a way to differentiate between individuals where antipsychotics have no added value and individuals where the benefits of continuing treatment may outweigh the risks. Given the complex management of BPSD, modest efficacy of antipsychotics and the risks associated with antipsychotic treatment, non-pharmacological interventions are becoming increasingly important and should be stimulated in clinical practice. These facts highlight the need for studies on the efficacy of non-pharmacological alternatives in older persons with varying dementia stages. Both physicians and nurses should be educated on non-pharmacological interventions across dementia levels and should adopt dementia stage-specific treatment plans. Given the increasing proportion of the very old people with dementia in our population and projections for the future, the management of BPSD will become increasingly important. Therefore, more pivotal trials in older persons with dementia should be undertaken to actively search for credible nonpharmacological and pharmacological alternatives. 3. Assessment and management in Italy

2.3. The patient case The patient case clearly indicates the complexity of managing a patient with dementia and a variety of behavioural and psychological symptoms including depression, anxiety and anger bursts. In addition, the case nicely illustrates the fact that care giver burden is often associated with the non-cognitive problems rather than the cognitive impairment. The progressing disease, the increased dependency and the lack of sufficient social support increase the likelihood of institutionalisation. 2.4. Future perspectives In contrast to other European countries where specialised physicians are working in nursing homes, in Belgium, general practitioners are still supervising their patients with dementia who moved from their home environment and reside in a nursing home. The high use of psychotropic drugs (79%) [17], and especially the long-term use of antipsychotics (33%) [16] mainly for BPSD indicate a lack of re-assessment and discontinuation efforts. Training of general practitioners in the management of BPSD and appropriate prescribing of psychotropic drugs in general, and antipsychotics in particular, need to be implemented. Given the vulnerability of older persons with dementia and the off-label indication of BPSD, clinicians should have strong arguments to justify antipsychotic treatment and change their psychotropic prescribing practices given the high prevalence of antipsychotic use in Belgian nursing homes. Nurses play an important role in caring for institutionalised older persons, and their role in the non-pharmacological and pharmacological management of BPSD should be better exploited. There is need for a standardised assessment tool to clearly differentiate between several types of BPSD and more knowledge on the limited evidence of pharmacological treatment options (especially antipsychotics). Nurses are often involved in initiating of antipsychotic treatment, but they should equally be involved in reassessing and discontinuing of antipsychotic treatment. A complimentary collaboration between GP and nurses – especially in nursing homes – is needed to make a proper risk-benefit analysis of antipsychotic treatment, making sure that antipsychotics are taken by the individuals who really need them. This expanding role of nurses necessitates an improvement in the pharmacological knowledge and risks of antipsychotic use and, by extrapolation, of psychotropic drugs in frail older persons with dementia. There should be more attention to discontinuation efforts and less fear with regard to recurrence of disruptive behaviour. Antipsychotic

The proposed vignette describes a case of a 75-year-old woman with dementia receiving specific treatment (donepezil) and also showing a wide array of BPSD including, apathy, depression, anxiety, sleep disturbances, wandering, socially inappropriate behaviour, aggression, agitation, delusions. This case is common in clinical practice and its management represents a challenge for health care professionals and families. According to international clinical guidelines, non-pharmacological interventions must be the first–choice treatment strategy for BPSD [19]. A pharmacological approach to these symptoms should be considered only after non-pharmacological interventions have failed. Non-pharmacological treatments, targeting the patient, the family or the environment, include a variety of interventions (e.g. music therapy, art therapy, touch therapy, physical exercise, light therapy, environmental manipulation, multi-sensorial stimulation, behaviour management). Among the possible options for pharmacological treatment, antipsychotic medications represent the most frequently prescribed drugs for the treatment of BPSD. Several different psychotropic medications including antidepressants, benzodiazepines, mood stabilizers, cholinesterase inhibitors, N-methyl-D-aspartate receptor modulators are also used for controlling BPSD. 3.1. Dementia care units In Italy, special dementia care units called ‘Unita` Valutative Alzheimer’ (UVA) are in charge of the diagnosis and management of dementia. Such units have been established in all parts of the Country although availability of diagnostic resources largely differs according to geographic areas and local policies. Physicians working in the UVA include dementia specialists, mostly neurologists and geriatricians (psychiatrists are much less represented). They work in conjunction with a wide range of health care professionals such as neuropsychologists, occupational therapists, speech therapists, cognitive rehabilitation therapists, nurses. Family physicians, family members, friends, or other specialists refer patients to the UVA. The UVA identify and diagnose dementia among community dwelling individuals and manage all the clinical aspects of the disease. Home care services are available only from several UVA according to local policies and resources. Institutionalized patients receive care from specialists working within the facility or from their own family physician. The presence of specialized dementia care units in nursing home is not frequent although huge geographic variation exists in this respect.

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The term BPSD has been generally adopted in clinical practice in Italy to indicate non-cognitive symptoms of dementia. However, it is not infrequent to use terms as neuropsychiatric symptoms or behavioural disturbances to refer to these symptoms. The assessment of BPSD is routinely conducted in the UVA and it includes a detailed collection of information from the caregiver regarding the type, frequency and severity of symptoms. A complete physical and neurological examination together with a blood sample collection for haematological and biochemical analyses are also performed to identify physical or neurological trigger factors or reversible causes of BPSD. A measurement and grading of BPSD is often conducted with a variety of rating scales among which the Neuropsychiatry Inventory is the most commonly used [20]. 3.2. Management With respect to treatment, non-pharmacological interventions are initially discussed and proposed to the patient and the caregiver. In particular, caregiver counselling on how to prevent and manage BPSD represents a huge part of the initial approach to such symptoms. Generally, physicians do the counselling while psychologists contribute to a lesser extent. Environment manipulation is also discussed with the caregiver. Finally, structured nonpharmacological interventions are proposed if such treatments are available within the unit or the nursing home. In Italy, the use of structured non-pharmacological interventions is not frequent in clinical practice. This may derive from the perception of limited evidence of efficacy together with the current low feasibility of such interventions (e.g. lack of specifically trained health care professionals, lack of economic resources for these programs, requirement of specific caregiver training). Antipsychotics are the most frequently used medications for the pharmacological treatment of BPSD in Italy with the atypical agents representing nearly two thirds of antipsychotic prescriptions to patients with dementia [21]. The only agents approved for the treatment of psychosis in dementia include haloperidol, zuclopentixole, and risperidone for up to 6 weeks period. 3.3. Safety issues Over the past decade, safety data from randomized clinical trials and observational studies have led international regulatory agencies worldwide to issue official warnings on a possible increased risk of ischemic cerebrovascular events and death associated with the use of both atypical and conventional antipsychotics in patients with dementia [22–24]. In Italy, similar warnings came from the Ministry of Health and the national drug regulatory agency (Agenzia Italiana del Farmaco – AIFA) since 2004 [25,26]. In 2005 and 2006, the AIFA provided official rules that currently apply to the use of antipsychotic medications in patients with dementia in Italy [26]. According to AIFA regulations, specialists working in the UVA can prescribe antipsychotics to patients with dementia. Following the current national regulations for the offlabel use of drugs, patients or their legal representatives are required to sign an informed consent including exhaustive information on antipsychotic medications and the risk of adverse reactions. Patients who have been prescribed antipsychotics by UVA specialists have free dispensation of drugs. Antipsychotic prescriptions may last for up to 2 months. At the end of this period, a complete clinical assessment of patients together with an EKG examination are required in order to re-evaluate treatment indication and safety, and then renew antipsychotic prescription. Since 2006, a national program of active pharmacosurveillance is in place to monitor antipsychotic prescriptions in patients with

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dementia. All prescribing UVA in the Country are required to join the program and collect clinical and drug data and potential adverse reaction information at the time of the first antipsychotic prescription and every two months thereafter for the entire duration of the treatment. The family physician is not allowed to prescribe antipsychotics to patients with dementia but is called to monitor possible side effects and adverse reactions to treatment. Specialists operating in nursing homes may prescribe antipsychotics to institutionalized patients according to the same regulations that apply to UVA prescriptions. AIFA has also provided the prescribing specialist with clinical recommendations on the use of antipsychotics in patients with dementia [25]. According to such recommendations antipsychotics should be used only for the treatment of severe symptoms and after non-pharmacological interventions have failed. The lowest effective dose should be used and an efficacy and safety evaluation should be performed regularly and at least every two months. Attempts to discontinue antipsychotic treatment should be conducted regularly. The concomitant administration of multiple antipsychotics or the combination of an antipsychotic and a benzodiazepine should be avoided. Extreme caution should be used in prescribing antipsychotics to patients with a high-risk cardiovascular profile. Although antipsychotics are usually prescribed for treating BPSD, clinicians are also confident in using other psychotropic medications, especially antidepressants and benzodiazepines, to target specific symptoms such as anxiety, depression, apathy, aggression, agitation, sleep disturbances. However, the choice of a specific agent depends on clinician’s individual knowledge of evidence, personal belief, experience and confidence with the treatment while no recommendations exist in this respect. 3.4. Summary In conclusion, structural non-pharmacological treatments of BPSD are poorly implemented in clinical practice in Italy while the use of medications, with respect to antipsychotic treatment, is highly regulated and prescriptions are monitored nationally. Several criticisms to the current regulations have been raised especially regarding the appropriateness of administering an informed consent to a patient with dementia or having someone else deciding about his/her health. Also, there is a general perception that the contribution of the family physician to the care of patients is marginal in the current system and needs to grow. It is much requested by clinicians in the field that, in the near future, economic resources would be directed to the promotion and implementation of non-pharmacological interventions in clinical practice all over the Country. 4. United Kingdom ‘‘My argument today is that we’ve got to treat this like the national crisis it is. We need an all-out fight-back against this disease; one that cuts across society. We did it with cancer in the 70s; With HIV in the 80s and 90s. We fought the stigma, stepped up to the challenge and made massive in-roads into fighting these killers. Now we’ve got to do the same with dementia.’’ [27]. In his speech at the London Alzheimer’s society in March 2012, United Kingdom (UK) Prime Minister David Cameron announced a number of measures that his cabinet intended to implement in order to support a cause that, although long supported by charities [28], government reports [29,30] and vocal media campaigns, he felt had gone under-recognised and underfunded by successive parliaments [27]. An estimated 800,000 of people in the UK suffer from dementia, with 670,000 family and friends acting as primary carers [28]. The financial cost of the condition is estimated at

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£23 billion (s28 billion) per year and expected to rise to £27 billion (s28 billion) by 2018 [28]. Whilst the majority of healthcare provision throughout Britain is run by the state funded National Health Service (NHS), delivery has long been subject to considerable variation in standard and availability. The devolution of the nations that comprise the UK; England, Scotland, Wales, and Northern Ireland (NI), and the subsequent decentralisation of responsibility for health and social care provision, have arguably exacerbated this variation. The National Institute for Health and Clinical Excellence (NICE) was formed in 1999 with the aim of reducing such variation in the availability and quality of NHS treatments and care – the so-called ‘postcode lottery’ [31]. 4.1. Presentation & Referral Family doctors (general practitioners [GPs]) are the first point of contact for most patients suffering from any degree of memory loss, and play a considerable role in their referral, investigation, management and follow-up. It is likely that Mrs D. would have undergone a consultation with her GP prior to initial diagnosis before subsequent referral to specialist services for assessment and diagnosis, as recommended by NICE for all patients with a possible dementia diagnosis [31]. Investigations such as baseline blood tests, urine sampling, electrocardiographs and radiological examinations are often arranged within primary care prior to referral. Preliminary cognitive assessment, using instruments such as the General Practitioner Assessment of Cognition (GPCOG) or Clifton Assessment Procedure Examination (CAPE), may also be performed [31]. The importance of early detection and intervention in dementia has been underlined by a number of local and national healthcare strategies [27,29,30]. As the first point of contact for patients presenting with memory loss, GPs have been targeted by user groups [28] and regional reviews [32] as potential obstacles towards referral to specialist agencies, and may be partly responsible for the widespread variation in rates of diagnosis in different regions throughout the UK; whilst 70% of people with dementia in Belfast are believed to have been identified, only 26.5% of those living in Dorset can expect identification and diagnosis [28]. Nationwide, 43% of patients are believed to have been formally identified [28]. Furthermore, 68% of respondents to a 2012 Alzheimer’s Society survey reported a period of greater than 12 months between onset of symptoms and diagnosis [28]. Whilst public attitudes and knowledge, as well as patients’ reluctance to present to their GP, are undoubtedly a factor in this statistic, early diagnosis of dementia has been identified as both cost effective and an important indicator of quality of care [33]. The National Audit Office in England has identified an improvement in the knowledge of, and attitudes towards, early diagnosis when compared with samples in 2009 [32]. The Commissioning for Quality and Innovation (CQUIN) payment framework, launched in April 2012, proposes financial incentives to healthcare organisations for identifying hospital inpatients ‘‘at risk’’ of dementia. All patients over the age of 75 who are admitted for periods of over 72 hours, should be assessed under these proposals, and referral to specialist services made where appropriate [34]. In January 2011, Andrew Lansley, Conservative Health Secretary to the UK Coalition Government, outlined plans to give GPs greater capacity to commission local services, including those run by private companies. The ‘‘NHS Bill’’ became law in March 2012 despite widespread opposition from professional bodies [35]. Although the impact of this legislation remains to be seen, the aforementioned variation in diagnosis and the considerable costs involved in managing patients with dementia, indicate that in

coming years, primary care teams are likely to play an even greater role in the care of patients such as Mrs D. 4.2. Memory Assessment Services Once referred to her local Memory Assessment Service (MAS), Mrs D. would have undergone comprehensive assessment at her local clinic. Although there is scope for neurologists, geriatricians, clinical psychologists, neuropsychiatrists, liaison psychiatrists or general adult psychiatrists to perform this role [31]. The vast majority of these services is coordinated by Psychiatry of Old Age (POA) services and are comprised of multidisciplinary team members that include specialist dementia nurses [36]. Patients under 65 years of age presenting with cognitive impairment may be more likely to be reviewed by a neurologist or general adult psychiatrist but should be referred to specialist dementia services thereafter if required [30,31]. Although the Royal College of Psychiatrists suggests that initial contact should be made within 2 to 3 weeks of referral and the assessment process within four to 6 weeks [36] the current Department of Health target for a first outpatient appointment following GP referral is 18 weeks; in NI, this target is 9 weeks. The assessments themselves may be performed by medical staff or specialist nurse under the supervision of consultant psychiatrist. A history would have been obtained from both Mrs D. and, if present, an informant, usually independently, including history of presenting complaint, past medical history and current social circumstances. In particular, the assessor will focus on the patient’s functional ability and relevant risks before performing a mental state examination that includes formal cognitive testing. In the majority of cases this assessment will last approximately 1 hour. Despite recent controversy surrounding the Folstein Mini Mental State Examination (MMSE), it remains in frequent use at MAS, although the six-item Cognitive Impairment test and the Montreal Cognitive Assessment (MoCA) test may be used as alternatives. Where MMSE is used, frontal lobe testing using may be assessed using methods such as the Clock Drawing Test. NINCDS/ADRDA (National Institute of Neurological and Communicative disease and Stroke/Alzheimer’s disease and Related Disorders Association) criteria for diagnosis of Alzheimer’s disease is the preferred diagnostic system, although ICD 10 or DSM IV criteria are suggested by NICE as alternatives [31]. Mrs D. should have been asked whether or not she wished to know her diagnosis and with whom she wished this information to be shared with [28,31]. At an early stage following diagnosis, patients and their carers should be made aware of both voluntary services likely to be useful in providing support and advice and advocacy services where required. It is also recommended that discussions surrounding Lasting Power of Attorney, a Preferred Place of Care Plan and advance directives are conducted at early as possible, while the patient has capacity to make such decisions [28,31]. Where radiological investigations have not already been performed, structural imaging is arranged in order to exclude the presence of other cerebral pathologies and to help establish subtype diagnosis [31]. Although magnetic resonance imaging remains the modality preferred by NICE, variation in local resources and waiting lists may necessitate the use of computed tomography in its place; a 2007 National Audit Office survey indicated that approximately one quarter of CMHTs request MRI and two thirds CT, with waiting times of about 10 and 7 weeks respectively [32]. NICE does not advocate the routine use of electroencephalography or lumbar puncture in assessment but single photon emission computed tomography (SPECT) is recommended where subtype diagnosis is in doubt [31].

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4.3. Accommodation and social care Once a diagnosis or dementia has been established, many patients are assigned a ‘‘Care Manager’’, usually a community psychiatric nurse (CPN) or approved social worker (ASW) who coordinates the combined health and social care of the person thereafter, liaising with medical teams, GPs, families, care facilities and the patient themselves [31]. The joint organisation of health and social services at a local level in the UK supports the delivery of such management. A documented care plan is developed, endorsed and implemented by the care manager in conjunction with the aforementioned services and is reviewed formally at regular intervals. Care Managers may also arrange carers’ needs assessment, to which all carers of patients with dementia are entitled, or may direct patients and carers towards voluntary services and financial entitlements [31]. A central tenet of dementia services in the UK is managing the patient in his/her own environment for as long as possible [29,31,32], through the provision of domiciliary care and risk management, a stance supported by patient groups [28]. In Mrs D.’s case, this might constitute regular care calls throughout the day, medication supervision, meal provision, and assistance with domestic chores. Where significant risk-taking behaviour occurs, such as wandering or aggressive behaviour, alternative accommodation arrangements may be required. This may range from sheltered housing to specialist nursing home facilities. One third of patients with dementia in the UK reside in a care home [28]. The cost of providing these services is means tested and varies greatly amongst regions. Partly subsidised periods of respite care are also available for patients living with carers, although the standard and nature of these services are also variable nationally [28]. Housing and respite care are both areas identified by the Alzheimer’s Society as currently lacking in their availability and standard [27,28]. 4.4. Review Although Mrs D. does not suffer from any chronic medical disorders, her GP will provide an important role in the coordinating her continuing care of after diagnosis, with regional guidelines recommending that patients undergo routine review every 12– 15 months [29,30]. This is further incentivised by the Quality of outcomes Framework (QoF), which allocates financial awards to practices that have reviewed 60% of registered patients with dementia [28]. Ninety-eight percent of practices achieved this goal in 2011, with an estimated 79.2% and 78.9% of patients in England and Wales undergoing review in this time, although patient groups have campaigned for QoF awards to further incentivise review by awarding higher percentages of patients reviewed. Eighty 6% of GPs polled undertook a medication review of their patients with dementia at least once a year [28]. Practice with respect to specialist review varies greatly throughout the UK. Where routine review is arranged, discussion and examination of behavioural and psychological symptoms of dementia is likely to occur. Where the patient has ceased contact with specialist services, further referral, requested by his/her GP, care manager or nursing home is likely to occur. Where significant risk-taking behavioural symptoms occur, or where establishment of therapy is not possible within the community, inpatient admission to a specialist unit may be required. 4.5. Charities & Voluntary Agencies Voluntary organisations are recognised by local and national authorities to play an important part in supporting patients, carers and organisations. In particular, the Alzheimer’s Society,

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comprising over 25,000 members, operates a prominent role in government lobbying, public education, research and patient and carer support. The organisation estimates that one million people per year access their various fact sheets and other resources, many of which are available in GP surgeries or MAS clinics [28]. 4.6. Pharmacological management The initiation of donepezil shortly following Mrs D.’s diagnosis is consistent with recently updated NICE guidelines recommending the prescription of cholinesterase (AChE) inhibitors donepezil, galantamine and rivastigmine in the management of mild and moderate Alzheimer’s disease [31,37]. Previously published guidelines, issued in 2006, encouraged their use in moderate disease only. Memantine, also previously subject to differing advice from local authorities, is now recommended in these national guidelines in both patients intolerant to AChE inhibitors and in those suffering from severe Alzheimer’s disease [31,37]. The NICE guidance is explicit in its recommendation that such agents should only be initiated by specialists in the care of patients with dementia (‘‘psychiatrists, including those specialising in leaning disability, neurologists and physicians specialising in the care of older people’’), although titration to optimum dose is often performed by GPs or specialist nurses. Regular review of patients prescribed these agents is recommended but no suggested frequency of review is made [31]. Whilst there has been evidence of widespread variability in the prescription of AChE inhibitors and memantine in England and Wales, with a 30-fold difference between the local authorities with the lowest and highest prescription (2005/6) [38], these findings predate recent NICE guidelines. Although no data is not yet available on variability of prescription since March 2011, one would expect use to have become more uniform in recent years. Nevertheless, Cooper et al. (2012) identified the presence of significant variability in levels of prescription of AChE inhibitors amongst different socioeconomic classes; patients with dementia who owned their home were four times more likely to be prescribed such agents than those who did not own their home. The study also determined a higher rate of prescription amongst younger patients [39]. DOMINO–AD, a pragmatic, double blind randomised placebo control trial, conducted at 15 centres across the UK, suggested that patients prescribed donepezil for moderate dementia continued to experience cognitive and functional benefits of the agent following progression to severe dementia [40]. Combination therapy of memantine and donepezil is neither supported by NICE guidelines, nor data from DOMINO–AD, although in the latter a non-significant improvement in behavioural symptoms was observed when memantine was employed alone and in combination with donepezil. This is consistent with other studies that have suggested memantine’s efficacy in treating agitation [40]. The addition of the agent to donepezil is not uncommon in many areas of the UK and it may be considered in a case such as that of Mrs D. No particular agent or class of antidepressant is recommended in the management of depression in patients with dementia, or indeed, older patients, but it is advocated that, like AChE inhibitor prescription, treatment should be started by staff with specialist training [31]. The respected South London & Maudsley NHS Foundation Trust guidelines emphasise the importance of choosing agents that do not interact with existing medications or comorbidities [37], whilst NICE recommends only the avoidance of antidepressants with significant anticholinergic effects [31]. It is the author’s experience that serotonin specific reuptake inhibitor (SSRI) agents remain the most prevalent antidepressant class due to their relative safety and tolerability in older patients; however, the recent emergence of concerns over an association with falls and

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dose-dependent QTc prolongation may see this practice change in coming years. The lack of efficacy of antidepressant agents, as reported in the HTA-SADD trial, further questions the role of such medications in the management of depression in Alzheimer’s Disease [41]. Patients experiencing sleep disturbance, like in Mrs D.’s case, may be prescribed mirtazapine in lieu of an SSRI or a ‘‘Z drug’’ hypnotic added.

be around s4756 million. The annual total cost per dementia patient, including direct and informal cost, has been estimated to be in the range from s20,966 to s27,058. 5.1. The seven stage model A seven stage model has been proposed for planning dementia services for Alzheimer’s disease in Greece [48].

4.7. Non-pharmacological management One of the most significant trends in the treatment of patients with dementia in recent years has been the gravitation of practitioners away from pharmacological investigations for challenging behaviour associated with dementia, with such agents only advocated if there is deemed to be a significant risk of harm to the patient or other people [31]. Non-pharmacological management of such challenging behaviours has been shown to be more cost effective, less hazardous [42] and is supported by both patient groups and independent review [28–31]; it is therefore recommended before any antipsychotic management is only considered where these strategies have been tried and have failed. Risperidone, as the only agent licensed by the Medicines & Healthcare products Regulatory Agency (MHRA) for behavioural disturbances in dementia, is the most frequently prescribed antipsychotic agent, although olanzapine and quetiapine are also prescribed commonly, despite limited evidence to support their use. Whilst NICE recommends that patients with mild to moderate dementia should be given the opportunity to participate in a structured group cognitive stimulation programme, these are not widespread outside of the care home or hospital setting. Other interventions, such as aromatherapy, multisensory stimulation, therapeutic use of music, animal assisted therapy and massage, are suggested by NICE but abutted with the recommendation that research into their respective cost effectiveness is required and the organisation encourages the role of the voluntary sector in delivering these treatments [31]. Provision of non-pharmacological treatments is one of the many challenges that dementia care in UK is likely to face in the coming years, particularly as the aforementioned NHS Bill provides the potential to institute the most sweeping changes to healthcare and social welfare since the NHS was created in 1948. An aging population and continued global austerity will ensure that dementia services must be efficient, effective and, perhaps above all, adaptable in order to meet Mr Cameron’s goals and expectations. 5. Greece-Hellas There are many studies about BPSD in Europe. In some of them patients with dementia from Greece are included [1,4,43]. Alzheimer’s disease International (ADI) has conducted a new systematic review of the global prevalence of dementia, identifying 147 studies in 21 Global Burden of Disease world regions. This review estimates there are around 35.6 million people with dementia worldwide in 2010, the numbers nearly doubling every 20 years, to 65.7 million in 2030 and 115.4 million in 2050 [44]. In Greece, the estimated prevalence of dementia will increase from 196,000 in 2010 to 365,000 in 2050. We found a prevalence of dementia of 9% in a study in Greece for a population above 70 years old [45]. The costs of dementia account for around 1% of the world’s gross domestic product. The cost of caring for AD and other dementias in Greece depends on the source [46,47]. Direct medical costs are around s1000 million, social care costs may double this amount and informal care can triple it. Total costs of care may thus

5.1.1. First stage: pre-diagnosis The focus of the pre-diagnosis period is to increase awareness of the disease, including BPSD, and educating people about where to go for help when someone is worried that he/she may suffer from dementia. Lectures have been planned all over Greece on the topic ‘‘Clever ideas for Successful Ageing’’, and Radio and TV weekly broadcasts on the topic are taking place. Every 3 months, a 2-day Seminar with different topics related to dementia is organized. Recent topics include legal and social issues, dental problems, neuropsychology and the role of exercise in dementia. Weekly 4 hours distance educational program for health care professionals are organized, together with educational programs for caregivers who live in small towns and villages with little access to day care centres. For professional education and awareness, Seven PanHellenic Inter-Scientific Alzheimer Conferences have been carried out until now, including a partnership with the 13th European Alzheimer Conference in Thessaloniki in March 2010. This is a project of the Panellenic Federation of Alzheimer’s Disease and Related Disorders in cooperation with other Societies such as the Hellenic Neurological Society. These efforts are trying to foster educational programs on dementia in Europe, which seem to be limited [49]. 5.1.2. Second stage: diagnosis Responsibility for diagnosis in Greece lies on Memory Clinics in Universities and General Hospitals, and on Day care centres. People with dementia and their carers can also be educated about dementia, countering the lack of understanding and awareness about the nature of the problems faced. They can also be trained to better manage the most common behavioural symptoms, trying to reduce the frequency and intensity of caregiver burden. 5.1.3. Third stage: information Information and support to the patient with dementia and his/ her family caregivers aims to empower them to confront the disease, to plan for the future and to make an optimal use of their current circumstances; strengthening the preserved abilities and not on growing disabilities. There is a fantastic network in Greece where University Memory Clinics, in collaboration with Alzheimer Associations, Church and Municipalities try to give information and support to families of patients with dementia. If the daughter of a patient like Mrs D. had an improved knowledge about dementia, she might well try to live with her from the first stages of the disease and she would perhaps try to cover her mother’s needs before the onset of her altered behaviour. She could also learn that she had to ask for help not only from a doctor, but also from other available services for people with dementia. 5.1.4. Fourth stage: post-diagnostic support This stage aims to assess (and regularly re-assess) the needs of people with dementia and to organize care accounting for patient’s and caregiver’s needs. In Greece, this responsibility lays on day care centres, where people with dementia, their caregivers and their families receive support programs. Alzheimer Hellas operates fourday care centres in Thessaloniki and has over 2900 members. Consistent with its mission to be an aid to those affected by the

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disease and their families, the Greek Association offers to the patients and caregivers a number of services for AD patients, including neuropsychological assessment, educational programs, cognitive therapy (attention and language exercises through reality orientation, cognitive tasks, cognitive exercises designed for illiterate patients, cognitive music therapy), psychotherapeutic programs (stress management techniques, assistive music therapy, art therapy, occupational therapy, reminiscence, relaxation techniques, mental imagery therapy, counselling for patients with early dementia), or physical therapy. Services to caregivers include family therapy, individual counselling, educational programs, relaxation techniques and support groups.

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Ministry of Health and Social Solidarity. This proposal is based in other European dementia plans, in an effort to cover the major issues that need to be addressed in Greece. The proposed plan covers three theme areas: care-prevention, awareness-training and research. It is expected that soon a dementia plan will become true for Greece and will assist professionals in their efforts to provide a better quality of life to patients with dementia [50–52]. We believe that families demand to have their needs of all patients with dementia covered before the patient with BPSD need medications.

Disclosure of interest 5.1.5. Fifth stage: co-ordination and care management When care is needed at increasingly short intervals, BPSD symptoms become more prevalent and the person with dementia is less able to care for themselves, the needs for support increase. This is done through different community based services, in the patient’s own home or at community facilities. The programs described above are also provided at this stage. 5.1.6. Sixth stage: continuing care At this state, the need of care is continuous or unpredictable, and BPSD symptoms become more demanding; this stage also includes patients with dementia who require acute hospital care for whatever reason. At this stage in our Day Care Centres have adapted programs that combine music, physical exercise, art therapy, Montessori techniques, sand therapy, and space retrieval methods. 5.1.7. Seventh stage: end of life/palliative care When a person with dementia reaches a profound stage and is approaching the end of his or her life, home care services take the lead. The home care team includes a physician, a dentist, a psychologist and a social worker. The objective of this team is to implement home care of patients with end stage dementia, although it also cares earlier stages when patients do not have access to day care centres for many reasons. Main concern of these teams is permanent education of the caregivers as well as the clarification of queries about the disease and the learning of simple abilities that can effectively improve the daily care of the patient and the quality of life of the caregiver. 5.2. BPSD Clinicians – neurologists, psychiatrists, and geriatricians – usually focus diagnostic assessments on impairments in memory and other cognitive functions, and loss of independence in daily activities. For caregivers, and, arguably, for people with dementia, behavioural and psychological symptoms of dementia, typically occurring later in the course of the disease, are most relevant and have a higher impact on quality of life. BPSD are an important cause of caregiver’s burden, and a common reason for institutionalization as the family’s coping reserves become exhausted. Patients with dementia need to be treated at all times with patience and respect for their dignity and personhood. Caregivers also need support and understanding–thus their needs should also be measured and tackled. Both parties need to be supported to continue with their usual lives and in their own communities for as long as practicable. Above all, the person with dementia and his/ her family caregivers need to be supported over the longer term. Long-term support to family caregivers includes the preservation of their own health in order to continue their care giving tasks. Currently, Greece does not have an approved governmental national dementia plan. In order to foster a national plan, the Greek Federation has prepared a draft plan submitted to the Greek

The authors declare that they have no conflicts of interest concerning this article.

References [1] Aalten P, Verhey FR, Boziki M, Bullock R, Byrne EJ, Camus V, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement Geriatr Cogn Disord 2007;24(6):457–63. [2] Finkel SI. Behavioral and psychological symptoms of dementia. Assisting the caregiver and managing the patient. Geriatrics 2002;57(11):44–6. [3] Burns A. The burden of Alzheimer’s disease. Int J Neuropsychopharmacol 2000;3(7):31–8. [4] Petrovic M, Hurt C, Collins D, Burns A, Camus V, Liperoti R, et al. Clustering of behavioural and psychological symptoms in dementia (BPSD): a European Alzheimer’s disease consortium (EADC) study. Acta Clin Belg 2007;62(6): 426–32. [5] Finkel SI, Costa e Silva Cohen G, Miller S, Sartorius N. Behavioral and psychological signs and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment. Int Psychogeriatr 1996;8(Suppl. 3):497–500. [6] Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 2000;157(5):708–14. [7] Scarmeas N, Brandt J, Blacker D, Albert M, Hadjigeorgiou G, Dubois B, et al. Disruptive behavior as a predictor in Alzheimer disease. Arch Neurol 2007;64(12):1755–61. [8] Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366(9503): 2112–7. [9] KU Leuven en Universite´ de Lie`ge. Resultaten dementie-onderzoek 1999– 2006. [10] Kroes M G-SSAFEMPD. Dementia: which non-pharmacological interventions? Good Clinical Practice (GCP). Brussels: Belgian Health Care Knowledge Centre (KCE); 2011. KCE Reports 160C. D/2011/10.273/37. [11] Glick ID, Murray SR, Vasudevan P, Marder SR, Hu RJ. Treatment with atypical antipsychotics: new indications and new populations. J Psychiatr Res 2001;35(3):187–91. [12] Sultzer DL, Davis SM, Tariot PN, Dagerman KS, Lebowitz BD, Lyketsos CG, et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer’s disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry 2008;165(7):844–54. [13] European Medicine Agency. Public statement on the safety of Olanzapine. http://apps who int/medicinedocs/en/d/Js4975e/1 4 html [2004, cited 2012 Feb. 1]; available from: URL: http://apps.who.int/medicinedocs/en/d/Js4975e/ 1.4.html. [14] US Food and Drug Administration Public Health Advisory. Public Health Advisory: Deaths with antipsychotics in elderly patients with behavioral disturbances. http://www.fda gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor PatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/Public HealthAdvisories/ucm053171.htm [2005, cited 2012 Feb. 1]. [15] Vander Stichele, Van de Voorde C, Elseviers MM, Verrue C, Soenen K, Smet M, et al. Medication use in Belgian rest and nursing homes. KCE reports vol. 47 A, 2006. [16] Azermai M, Elseviers M, Petrovic M, van Bortel L, Stichele RV. Assessment of antipsychotic prescribing in Belgian nursing homes. Int Psychogeriatr 2011;23(8):1240–8. [17] Azermai M, Elseviers M, Petrovic M, van Bortel L, Stichele RV. Geriatric drug utilisation of psychotropics in Belgian nursing homes. Hum Psychopharmacol 2011;26(1):12–20. [18] Volicer L, Bass EA, Luther SL. Agitation and resistiveness to care are two separate behavioral syndromes of dementia. J Am Med Dir Assoc 2007;8(8): 527–32. [19] American Geriatrics Society and American Association for Geriatric Psychiatry. Consensus statement on improving the quality of mental health care in US nursing homes: management of depression and behavioral symptoms associated with dementia. J Am Geriatr Soc 2003;51:1287–98.

58

M. Azermai et al. / European Geriatric Medicine 4 (2013) 50–58

[20] Jeon YH, Sansoni J, Low LF, Chenoweth L, Zapart S, Sansoni E, et al. Recommended measures for the assessment of behavioral disturbances associated with dementia. Am J Geriatr Psychiatry 2011;19(5):403–15. [21] L’uso dei farmaci in Italia. Rapporto OSMED 2010. Available at http://www. agenziafarmaco.gov.it/it/content/luso-dei-farmaci-italia-rapporto-osmed2010 (accessed on April 5, 2012). [22] Liperoti R, Onder G, Landi F, Lapane KL, Mor V, Bernabei R, et al. All-cause mortality associated with atypical and conventional antipsychotics among nursing home residents with dementia: a retrospective cohort study. J Clin Psychiatry 2009;70(10):1340–7. [23] FDA. Public Health Advisory. Deaths with antipsychotics in elderly patients with behavioral disturbances. April 11, 2005. Available at: http://www.fda.gov/cder/drug/advisory/antipsychotics.htm (accessed April 11, 2005). [24] EMEA 2010 Priorities for Drug Safety Research. Safety aspects of antipsychotics in demented patients. London, August 4, 2009. Doc. Ref: EMEA/493730/ 2009. Available at http://www.ema.europa.eu/docs/en_GB/document_ library/Other/2010/03/WC500076323.pdf (accessed August 9, 2009). [25] Agenzia Italiana del Farmaco (AIFA). Il trattamento farmacologico dei disturbi psicotici nei pazienti affetti da demenza. Comunicato del 21/07/2005. Available at http://www.agenziafarmaco.gov.it/it/content/il-trattamentofarmacologico-dei-disturbi-psicotici-pazienti-affetti-da-demenza-0 (accessed July 21, 2005). [26] Agenzia Italiana del Farmaco (AIFA). Il trattamento farmacologico dei disturbi psicotici nei pazienti affetti da demenza. Aggiornamento. Comunicato del 28/12/ 2006. Available at http://www.agenziafarmaco.gov.it/it/content/trattamentofarmacologico-dei-disturbi-psicotici-nei-pazienti-affetti-da-demenzaaggiornamen (accessed December 28, 2006). [27] Cameron, David, 2012. Public address speech. Alzheimer’s Society, London. 26th March 2012. [28] Alzheimer’s Society. Dementia 2012: a national challenge. Alzheimer’s Society; 2012. [29] The Bamford Review of Mental Health and Learning Disability (Northern Ireland). Living Fuller Lives. Belfast: DHSSPS, 2007. [30] Department of Health. Living well with dementia: a national dementia strategy. Department of Health; 2009. [31] National Institute for Health and Clinical Excellence. Dementia–Supporting people with dementia and their carers in health and social care. National Institute for Health and Clinical Excellence; 2012. [32] National Audit Office. Improving dementia services in England - an interim report. The Stationary Office; 2010. [33] Todd S, Passmore AP. Alzheimer’s disease: the importance of early detection. Eur Neurological Rev 2008;3:18–22. [34] Department of Health. Using the Commissioning for Quality and Innovation payment framework–Guidance on new national goals for 2012–2013. Department of Health; 2009. [35] McLellan A, Middleton J, Godlee F. Lansley’s NHS reforms (Editorial). BMJ 2012;344:e709.

[36] Royal College of Psychiatrists’ College Centre for Quality Improvement. Memory Services National Accreditation Programme (MSNAP): standards for memory services – assessment and diagnosis. London: Royal College of Psychiatrists; 2009. [37] Taylor D, Paton C, Kapur S. Maudsley Prescribing Guidelines, 10th ed, Informa Healthcare; 2009. [38] Knapp M, Prince M, Albanese E, et al. Dementia UK: a report into the prevalence and cost of dementia prepared by the Personal Social Services Research Unit (PSSRU) at the London School of Economics and the Institute of Psychiatry at King’s College London, for the Alzheimer’s Society. London: Alzheimer’s Society; 2007. [39] Cooper C, Adelman N, Livingston G. Anti-dementia drugs: another example of health inequality? Neuropsychiatry News 2012;5:8–10. [40] Howard R, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med 2012;366:893–903. [41] Banerjee S, et al. Sertraline or mirtazapine for depression in dementia (HTASADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet 2011;378:403–11. [42] Banerjee S. The use of antipsychotic medication for people with dementia: time for action. Department of Health; 2009. [43] Aalten P, Verhey FR, Boziki M, Brugnolo A, Bullock R, Byrne EJ, et al. Consistency of neuropsychiatric syndromes across dementias: results from the European Alzheimer Disease Consortium. Part II. Dement Geriatr Cogn Disord 2008;25(1):1–8. [44] ADI World Alzheimer Report 2009. [45] Tsolaki M, Fountoulakis C, Pavlopoulos I, Chantzi E, Kazis A. Prevalence of Alzheimer’s disease and other dementing disorders in Pilea, Greece. Am J Alzheimers Dis 1999;14:138–48. [46] ADI 2010: World Alzheimer Report 2010, The Global Economic Impact of Dementia. [47] EuroCoDe: http://www.alzheimer-europe.org. [48] Tsolaki M, Papaliagkas V, Kounti F, Tsantali E, Papapostolou P, Kotras N, et al. Memory and dementia clinic in Thessaloniki: twenty years of experience. Mid East Age Ageing 2007;4:7–11. [49] Tsolaki M, Papaliagkas V, Anogianakis G, Bernabei R, Emre M, Frolich L, et al. Consensus statement on dementia education and training in Europe. J Nutr Health Aging 2010;14(2):131–5. [50] Tsolaki M, Sakka P, Karamavrou S, Degleris N. Attitudes and perceptions regarding Alzheimer’s disease in Greece. Am J Alzheimers Dis Other Demen 2009;24:21–6. [51] Kounti F, Bakoglidou E, Agogiatou C, Emerson Lombardo NB, Serper LL, Tsolaki M. RHEA, a nonpharmacological cognitive training intervention in patients with mild cognitive impairment. Topics Geriatr Rehab 2011;27(4): 289–300. [52] Tsolaki M, Kounti F, Agogiatou C, Poptsi E, Bakoglidou E, Zafeiropoulou M, et al. Effectiveness of nonpharmacological approaches in patients with mild cognitive impairment. Neurodegener Dis 2011;8(3):138–45.