Psychiatric symptoms in later life share a complex relation

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1 In Review Psychiatric Complications of Dementia Ravi Bhat, MD 1 ; Kenneth Rockwood, MD 2 Our paper describes the neuropsychiatric signs and symptoms of late-life disorders of cognitive impairment. Late-life cognitive disorders are associated with psychiatric symptoms in various ways from apparent risk factors to pathognomonic features of particular dementias. They contribute greatly to the burden of illness, both in people with dementia, and in those who care for them. Here we consider specific dementia symptoms in relation to dementing illnesses and to the stages of dementia. Recognizing that no one drug is likely to successfully treat all dementia symptoms, we argue for a syndromic approach, which can lead to appropriately targeted therapy. Can J Psychiatry. 2011;56(7): Key Words: neuropsychiatric symptoms, dementia, Alzheimer disease, dementia with Lewy bodies Psychiatric symptoms in later life share a complex relation with dementia. They can be prodromal symptoms, or frequently co-occur with dementia, where they can define dementia subtypes. Psychiatric symptoms vary in type and intensity through the course of dementia, are associated with excess disability and worse quality of life, and morbidity in sufferers can lead to significant burden and psychiatric disorders in caregivers, and can lead treating physicians to therapeutic desperation. After discussing how dementias are conceptualized, we discuss the various psychiatric complications associated with dementias. We will offer only a few comments on the treatment of neuropsychiatric signs and symptoms, noting that there are more drugs used in practice than is supported by evidence for their use. We will also suggest that the notion that one drug should improve all psychiatric symptoms in a patient with dementia, though evidently unrealistic, appears to have been the model of treatment of many clinical trials. We note that nonpharmacological treatments, though perhaps less widely used formally, also suffer from this deficiency in the evidence base. 1 Finally, we will note that some aspects of the treatment of people with dementia who live at home with others must also consider the impact on the suffering of caregivers. We will argue for scholarly inquiry into individual symptoms, how they arise, how they progress, how much they trouble patients and caregivers, and how likely they are to respond to treatment. Psychiatric complications of dementia are commonly referred to as behavioural and psychological symptoms of dementia, a loosely organized concept that incorporates various psychiatric symptoms in dementia. This is part of a syndromic approach to several psychiatric syndromes, 2 which is advancing to include diagnostic criteria in AD. 3 6 While syndromic approaches can improve diagnostic agreement, especially when used with a structured interview, they are especially valued for allowing etiological identification. 2 Even so, the history of psychiatric research shows that validating psychiatric syndromes is difficult. 7 For a syndrome to be valid, it should meet 1 of 2 criteria; it needs to be demonstrated to be an entity, separated from neighboring syndromes and normality by a zone of rarity. Alternatively, if the category s defining characteristics is more fundamental that is, if the category is defined by a physiological, anatomical, histological, chromosomal, or molecular abnormality clear, qualitative differences must exist between these defining characteristics and those of other conditions with a similar syndrome. 7, p 8 Despite decades of research, psychiatric syndromes have been neither demonstrated as being nonoverlapping, nor defined by something fundamental. 7 It would be hard to imagine that such an approach would yield more for most NPSs in dementia. Despite this, the syndromic approach in psychiatry has had the benefit of offering high clinical utility, a concept that Kendell and Jablensky 7 define as that which provides 398 W La Revue canadienne de psychiatrie, vol 56, no 7, juillet 2011

2 Psychiatric Complications of Dementia nontrivial information about prognosis and likely treatment outcomes, and (or) testable propositions about biological and social correlates. Reviewing psychiatric complications in dementia as syndromes in the context of clinical utility allows for a more comprehensive discussion of these complications and, in keeping with this approach, we will refer to these as NPSs, in keeping with recent practice. 2,8 The review is organized so that we first focus on NPSs that appear to have clinical utility, and then briefly review other psychiatric complications in dementia. Overview Psychiatric symptoms are relatively uncommon in elderly people without dementia; however, when they do occur, they can presage dementia. This applies both for late-onset psychotic 9 and for depressive symptoms. 10 Intriguingly, people who died by suicide in later life have been reported to have an increased rate of AD-related brain pathology, compared with age-matched control subjects, 11 although this relation has been questioned by a recent large study. 12 Psychiatric symptoms and signs are a frequent manifestation of dementias at all stages. They range the gamut of those seen in other ages from mood and anxiety symptoms to psychotic symptoms and agitation. Among people with dementia, 60% to 80% have psychiatric complications. 8 The rates differ in part owing to the definitions and measures used and in part owing to the setting. Unsurprisingly, rates are highest among people with dementia who are institutionalized (in excess of 80%), 13 while the lowest rates are found in people in population-based surveys Abbreviations ACCORD AD ADL BEHAVE-AD CAMI CIND DLB FTD MCI NPI NPS RBD REM VaD A Canadian Cohort Study of Cognitive Impairment and Dementia Alzheimer dementia activities of daily living Behavioral Pathology in Alzheimer s Disease Scale Cohen-Mansfield Agitation Inventory cognitive impairment, no dementia dementia with Lewy bodies frontotemporal dementia mild cognitive impairment Neuropsychiatric Inventory neuropsychiatric syndrome REM behaviour disorder rapid eye movement vascular dementia The Canadian Journal of Psychiatry, Vol 56, No 7, July 2011 W (62%). 14,15 Intermediate rates are observed in clinic-based populations. 16 While the overall prevalence of NPSs is similar in most dementias, some symptoms or syndromes may be more common in certain dementias. Indeed, for 2 types of dementias, DLB 17 and FTD, 18 psychiatric symptoms are part of the core diagnostic criteria. An understanding of such an association is important not only in aiding dementia diagnosis but also for management, as discussed below. NPSs generally increase with dementia progression but some features may progress variably and predict further complications. For example, apathy often increases with dementia progression and may predict more severe deterioration, functional decline, and depression. 19 Nearly two-thirds of NPSs persisted in 99 people who had a complete 2-year follow-up. 20 There may also be a complex relation between stage and type of dementia. This too can be useful in diagnosis and management if one starts with AD as the default diagnosis. In such a case, one can expect congruence between cognitive impairment, functional state, and psychiatric symptoms. 21 Stage incongruence, where there is a disparity between these domains, suggests dementia diagnostic possibilities other than AD. For example, relatively high Mini-Mental State Examination 22 scores, with psychotic symptoms and more than expected functional decline, may point to DLB rather than AD. NPSs in dementia are associated with excess disability 23 and worse quality of life both for patients and for their caregivers. 27 In other words, NPSs can lead to more disability than is expected for the stage of dementia, implying that, with treatment, it may be possible to reduce disability. 23 The economic burden of NPSs is considerable, making up about 30% of the cost of managing a person with dementia. 28 Indeed, a 1-point worsening of the NPI 29 score has been estimated to result in an annual increase of between US$247 and US$409 in total direct costs, depending on the value of unpaid caregiving. 28 Similarly, a recent Canadian study estimated about $30 per month for each 1-point increment in the NPI. 30 NPSs are nearly always associated with increased distress in caregivers and in treating physicians. The therapeutic desperation is perhaps reflected in the use of antipsychotics in Canadian nursing homes despite relatively poor benefitto-risk ratio. 31 Nearly one-third of residents (31.3%) of an Alberta long-term facility were on antipsychotics; the number increased for those relocating and following relocation (36.9%) to a new facility. 31 Other Canadian studies found rates of 17% 32 to 30%. 33 Antipsychotic medications are associated with risks, such as falls and tardive dyskinesia, that rise considerably in older people. 31,34 399

3 In Review Syndromic Approach to Psychiatric Complications in Dementia NPSs in dementia can be described by scholarly inquiry into naturally observable symptoms (bolstered by using validating criteria 2,35 ) or by statistical procedures that analyze how various symptoms cluster together. 4 Jeste and Finkel 3 have a work-in-progress proposal for diagnostic criteria for psychosis in AD. Likewise diagnostic criteria have been proposed for depression in AD 5 and sleep disturbance in AD. 6 In contrast to this approach, Lyketsos et al 4 argue, specifically regarding the Jeste and Finkel criteria, 3 that the degree of co-occurrence of psychotic with other NPSs is poorly addressed, especially as cooccurrence is the rule rather than the exception. Various scales, most commonly the NPI, 29 have been used to characterize psychiatric symptoms in dementia for statistically identifiable components. For example, using latent class analysis on psychiatric symptoms in AD in the Cache County Study, Utah, Lyketsos et al 15 propose 3 groups that account for 95% of the patients a small group with psychotic symptoms (13%), a larger group with predominantly affective symptoms (28%), and finally those with no, or a single, symptom (18%). The most consistently identified component in similar studies is psychosis, characterized by hallucinations and delusions, and a mood component, characterized by symptoms of depression, anxiety, and apathy. 20,36,37 In a recent study of late-onset AD, which used the NPI, 4 components were identified: behavioural dyscontrol, characterized by euphoria, disinhibition, aberrant motor behaviour, and sleep and appetite disturbances; psychosis characterized by delusions and hallucinations; mood by depression, anxiety, and apathy; and agitation consisting of aggression and irritability. 38 It is still too early to decide which of these approaches will prove more fruitful; however, it may be that these 2 approaches are complementary rather than contradictory. In this context, the next section will concentrate on a discussion of NPSs with clinical utility but not necessarily validity. Agitation Aggression Agitation defined as inappropriate verbal, vocal, or motor activity that is not an obvious outcome of the needs or confusion of the individual 39 can be classified as verbal or physical and aggressive or nonaggressive. 40 Verbal agitated behaviours include constant requests for attention, complaining, repetition of sentences or questions, and screaming. 41 People with verbal agitation are more likely to be women, cognitively impaired, have a greater number of medical diagnoses, higher levels of pain, and lower functional capacity than other institutionalized elderly people. 40 Verbal agitation is more likely to occur when these people are alone. In keeping with Cohen-Mansfield et al s proposal, 42 these patients are also more likely to be depressed, to have negative social interactions, and be socially isolated. 40 In contrast to verbal agitation, aggression in community-residing people with dementia is more likely to occur in men, in people with more cognitive impairment, in those with premorbid aggression and conflict with their caregivers, 43,44 and in those with severe depression. 44 In addition, agitation aggression can be a nonspecific indicator of other NPSs. 45 In clinical populations, both physical and verbal aggression have been associated with psychotic symptoms Agitation aggression is especially common in elderly people with dementia who are in institutionalized settings (ranging from 48% to 83%). 13 In community samples, the corresponding rates are lower (24% to 30%). 4,15 All types of agitation increase as dementia progresses and often persist. 20,49 Agitation and aggression are often the reason for use of psychotropic agents and for referral to specialist services. Cohen-Mansfield et al 42 propose that verbally agitated behaviours may be a form of help-seeking behaviour for residents with physical disease and depressed affect. In institutions, agitation aggression is also associated with assistance with ADLs, such as bathing, 13 and encompasses a wide range of troublesome behaviours. 50 Agitation commonly increases in the late afternoon and early evening, often as part of sundowning. 51 Agitation aggression has been most commonly measured by the CAMI 52 and items in scales such as the NPI and the BEHAVE-AD. 53 Using CAMI with informant data appears to correlate well with the more resource-intensive direct observation. 40 Antipsychotic medications can be useful, but have considerable risks, such as cerebrovascular disease, parkinsonian syndrome, and other movement disorders. 34,54 In consequence, it is important to identify proximal causes first and manage the proximal cause as a first step and use nonpharmacologic approaches where possible. 55 Apathy Apathy (Greek a- without pathos feeling) has historically been understood to mean lack of emotion or feeling. In dementia it is conceptualized as a motivational syndrome, defined as lack of motivation, relative to a person s previous level of functioning, and is manifested by diminished goaldirected cognition and behaviour. 56 Although apathy and depression have common symptoms, they are distinct syndromes. 56,57 In a study 57 of 154 patients with various neurodegenerative disorders, high rates of apathy with varying co-occurrence of apathy and depression were described. In a larger study 58 comparing AD and depression with normal control subjects, 58 apathy was diagnosed in 37% of 319 patients with AD, and, in 24% of the AD sample, apathy coexisted with a depressive disorder. Among patients with depression, 32% also had apathy, but apathy did not contribute to higher depression scores in those with AD. 58 Apathy in AD was significantly associated with severe ADL impairment and with impaired cognitive function, older age, and poor awareness of behavioural and cognitive changes. 58 Subsequent studies have confirmed 400 W La Revue canadienne de psychiatrie, vol 56, no 7, juillet 2011

4 Psychiatric Complications of Dementia the frequent co-occurrence and dissociability of apathy and depression and the association between apathy and dementia severity, impaired ADLs, and cognitive impairment. Apathy prevalence increases with dementia severity, and, in longterm follow-up, apathy appears to predict a more aggressive dementia, with faster decline on all domains. 19 Apathy in the patient causes considerable distress in caregivers, who may misinterpret the loss of motivation and engagement as oppositional behaviour. 62 Apathy appears to be the commonest psychiatric complication of dementia, with reported frequency varying from 28% to 80%. 63 Among NPSs, apathy has the most clearly identified neurobiological correlates. It is associated with a dysexecutive syndrome, correlating with lesions in the frontosubcortical circuitry. More specifically, a single photon emission computed tomography has found lack of initiative in AD to be associated with hypoperfusion of the right anterior cingulate area. 64 Chronic apathy was associated with anterior cingulate neurofibrillary burden. 65 Apathy has often been measured as an item in comprehensive scales, such as the NPI. More recently, specific scales and structured interview schedules have been developed to assess apathy. 66 The evidence for treatments for apathy is poor. Apathy in dementia can respond to psychostimulants, such as methylphenidate 67 or to cholinesterase inhibitors, 68,69 although this has been disputed. 70 Moreover, given the frequent co-occurrence of depression and apathy, a trial of antidepressant medications is also warranted, keeping in mind that selective serotonin reuptake inhibitors have been reported to cause apathy. 71,72 Psychosis Psychosis is defined in the International Classification of Diseases, 10th Edition, as simply indicating the presence of hallucinations, delusions or a limited number if several abnormalities of behavior, such as gross excitement and overactivity, marked psychomotor retardation and catatonic behavior. 73, p 3 Dementia is the commonest cause of psychotic symptoms in later life. 74 In recent studies 4,38 of NPSs in dementia, psychosis has consistently emerged as a grouping. Psychotic symptoms in dementia have been classified into 3 categories: delusions, hallucinations, and delusional misidentifications. 75 This has some support from principal components analysis of psychotic symptoms in dementia. 76 Even so, the phenomenology of psychotic symptoms in dementia is understudied. When delusions are examined in greater detail, paranoid misidentification and expansive delusions emerge as groupings that underlie delusions. 77 Paranoid misidentification includes paranoid delusions and delusional misidentification and is associated with anosognosia. 77 The Canadian Journal of Psychiatry, Vol 56, No 7, July 2011 W Most studies of psychotic symptoms in dementia have been in AD and have yielded operationalized diagnostic criteria. 2 Even so, the empirical basis for the criteria has been questioned especially as they do not account for co-occurrence of other NPSs, 4 such as depression and delusions, which are commonly seen together. 77,78 The prevalence of psychosis in dementia is substantial, with estimates for delusions in AD ranging from 9% to 63% (median 36%) and estimates for hallucinations ranging from 4% to 41% (median 18%). 79 Risk factors for developing psychosis in AD include severity of cognitive impairment, African-American ethnicity, and possibly lower educational level, extrapyramidal symptoms, and sensory impairments. 79 Delirium is an important differential diagnosis; often it is distinguished by its acuity of onset. Psychosis in dementia is often measured using scales such as the NPI or the BEHAVE-AD. Treatment of psychosis in dementia is not without controversy, given the risks of antipsychotic use. Recent meta-analyses suggest that atypical antipsychotic medications can be useful in psychosis in dementia but caution their routine use, given the risk of cerebrovascular disease and death. 54,80,81 A recently proposed criterion for using atypical antipsychotics in dementia is pragmatic: our focus should be upon those patients who either improve a lot following treatment or 82, p 24 those who deteriorate markedly. Depression Depression takes on many meanings, ranging from a symptom to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition defined syndromes such as major depression. Disagreement is expectedly higher when operationalized criteria are not used. Even so, diagnosing depression in later life, where depressed mood may be denied 83 or in dementia, where many symptoms co-occur, 84 can be difficult. Depressive symptoms are quite common in dementias one study estimated rates in excess of 80%. 85 Whether these represent a subsyndromal depression is a legitimate question. Nearly 10% of elderly people attending a clinic can have subsyndromal depression, defined as depressive symptoms that do not amount to major or minor depression, but which are associated with medical comorbidity, and which carry similar functional disability. 86 Although symptoms overlap between depression and dementia, a few items discriminate between the 2 disorders with high accuracy: sadness, diurnal variation of mood, and early or late insomnia. 84 Diagnostic criteria have been proposed for depression in AD to get better agreement between clinicians 5 but empirical validation is needed. In recent years, there has been considerable work in elucidating the relation between depression and dementia. 87 Late-onset depressive symptoms or syndromes often appear to be a prodrome to cognitive decline. 10 Likewise a recent history of depression is associated with an increased risk of AD. 87 More intriguingly, a lifetime history of depression 401

5 In Review appears to be associated with increased risk of AD and is a risk factor for VaD. 87 Depression can occur in up to 25% of patients with dementia, although it is thought to decrease in prevalence with dementia progression. Baldwin et al 88 recommend that for mild symptoms it is best to offer support to the patient and the caregiver and to review in 4 weeks. This allows for resolution of transient symptoms and assessment of potential placebo response. If treatment is indicated, then they recommend the following medications on the basis of evidence: meclobemide, citalopram, sertraline, and venlafaxine. They also stress the role of supportive therapy to the patient and caregiver. Sleep-related Disorders Dementias are associated with a range of nocturnal and daytime sleep disturbances. In AD, up to 44% of patients may suffer from sleep disturbances. 89 It significantly adds to the burden of family and caregivers when patients repeatedly get out of bed, wander, or talk in bed. 90 Sleep disturbances are also associated with increased physical and psychological morbidity in patients and caregivers. 90 Sleep disturbances typically become more severe with disease progression in AD. 89 In the initial stages of AD, sleep disturbances appear to be an exaggeration of the changes in sleep architecture seen in older adults, as well as reduced REM sleep. 6 Certain neurodegenerative disorders such as DLB, Parkinson disease with dementia, multisystem atrophy, and progressive supranuclear palsy are associated with RBD. RBD is a parasomnia characterized by dreamenacting behaviours, such as shouting, punching, and falling out of bed. 91 It is associated with excessive muscle tone (or loss of muscle, atonia) in REM sleep and related to unpleasant dreams. 92 About 45% of people with idiopathic RBD go on to develop neurodegenerative disorders (such as DLB and Parkinson disease) after a mean of 11.5 years. 93 Other sleep disorders, such as restless leg syndrome and obstructive sleep apnea syndrome, may complicate the clinical picture in dementia. 2 A recent randomized controlled trial has found behavioural interventions useful in treating sleep disturbance in AD. 94 Considering the cognitive and falls risk with benzodiazepines, behavioural interventions should be the first line of treatment. Anxiety Anxiety is only beginning to be studied in later life, so that there is a dearth of studies about anxiety in dementia. Based on larger community-based studies using NPI, nearly onequarter of elderly people with dementia have anxiety. 14,15,95 In clinic-based populations, the rates range from 10% to 36%. 16,96 One study 97 that specifically examined anxiety in dementias using the NPI found that anxiety was much more reported in patients with VaD and FTD, compared with those with AD and control subjects. 97 Behavioural Dyscontrol (Disinhibition; Stereotypic Repetitive Behaviours; Expansive Behaviours) Behavioural dyscontrol is less well studied in dementias in general than in specific dementias, such as FTD, as detailed below. Between 7% and 25% of patients with dementia may exhibit inappropriate sexual behaviours, often classified into sexual talk, sexual acts, and implied sexual acts. 98 As people commonly remain sexually active right into old age, any assessment of supposedly inappropriate sexual behaviour must account for the sexual needs of the older person being reviewed. Sensitive handling of the matter with patient and caregivers is important and, if found to be truly inappropriate, behaviour modification may be the first choice. 98 Psychiatric Complications by Dementia Stage Predementia Syndromes MCI 99 and CIND 100,101 have been conceptualized as transition syndromes between normality and dementia. MCI is considered to have 2 subtypes: amnestic and nonamnestic. 99 Amnestic MCI excludes people with other causes of cognitive impairment, such as depression. In contrast, the more inclusive CIND concept allows for impairment in all domains of cognition. 101 ACCORD, 16 a multicentre clinic-based study, found that nearly 75% of people with CIND reported at least 1 NPI item, especially depression, irritability, apathy, and sleep disturbance. However, a Brazilian study 95 reported both lower rates (36%) of NPSs in CIND and a different pattern of symptoms: anxiety and sleep disturbances were the commonest. Community studies 14,15 of MCI typically report lower rates, closer to the Brazilian study, ranging from nearly 29% to 50% of at least 1 NPI item. The commonest symptoms were similar to that found in ACCORD. 16 Dementia Stages The evolution of NPSs through dementia progression has been studied in cross-sectional studies and in longitudinal studies. In the former, NPSs are compared between people in various stages of dementia, but such a design is of course less helpful in improving our ability to predict the evolution of a symptom or syndrome. Later, longitudinal studies have addressed these issues. Most NPSs increase with dementia progression, with the notable exception of depression. 102 In an 18-month follow-up of participants in the Cache County Study, % of those with at least 1 NPS at baseline continued to have at least 1 symptom at followup. Moreover, in contrast to the notion that behavioural problems burn themselves out, two-thirds of people who at baseline had clinically important NPI scores (that is, 4 or more) continued to NPI scores equal to or greater than 4 at follow-up. Delusions were the most persistent symptoms, followed by depression and aberrant motor behaviour. In contrast, hallucinations and disinhibition were the least 402 W La Revue canadienne de psychiatrie, vol 56, no 7, juillet 2011

6 Psychiatric Complications of Dementia persistent. In a longitudinal follow-up study of apathy, the authors confirmed the increase in apathy with dementia progression: frequency of apathy increased from 14% in mild AD to 61% in severe AD staged by the Clinical Dementia Rating. 104 Psychiatric Complications by Dementia Diagnosis Compared with studies of NPSs in AD, fewer reports detail differences in NPSs by dementia type. Hence we will concentrate here first on a few notable points concerning NPSs in AD and then discuss other dementias. Alzheimer Disease The prevalence of NPSs clearly varies between samples, such that convenience samples report more NPSs than population-based samples. 4 Concepts of psychosis borrowed from mainstream psychiatry have not been fully useful in describing psychosis in AD. Of the 2 prominent types of psychotic symptoms, delusions and hallucinations, the former are by far the more common. Moreover, most patients with hallucinations also appear to have delusions. 77 In this large study, paranoid delusions and delusional misidentification were common. The commonest delusions were those involving stealing, grandiose delusions, and delusions that the house is not theirs. Delusions were significantly associated with depression, anosognosia, aggression agitation, and global cognitive deficits. The association of delusions and depression in AD has been also found in a previous study. 78 Apathy and depression frequently co-occur in AD, but rates can be lower than in other dementias, such as FTD. Anxiety in AD was most often associated with severe cognitive deterioration and early age of onset. 97 Vascular Dementia The overall prevalence of NPSs is not different from that of AD 105 ; however, the evolution of NPSs in VaD is unclear. Initial studies found patterns of NPSs to be different in VaD, compared with AD. For example, one study found the rates of anxiety and depression in VaD were nearly double that of in AD, and that depression in VaD was more likely to persist. 106 In this study the prevalence rates for psychotic symptoms was not significantly different between the groups. However, other larger studies have failed to show similar differences between the groups. 105,107 The first study 105 found a difference only in sleep disturbance and the other study 107 found only a trend toward VaD patients to be more depressed. 107 Dementia With Lewy Bodies Psychiatric symptoms are part of the core diagnostic criteria. 17 Unlike AD, hallucinations are very common, with visual hallucinations occurring in up to 77% of patients. Likewise, delusions are also quite common, with a reported prevalence of 46%. Recurrent visual hallucinations are present early in the course. 82 The Canadian Journal of Psychiatry, Vol 56, No 7, July 2011 W Frontotemporal Lobar Degeneration Various diagnostic schemas have been proposed to classify frontotemporal lobar degeneration. Most recognize a syndrome in which behavioural symptoms are prominent 108,109 and also recognize other subsyndromes with variably affected language and (or) other focal neurological syndromes, with variable behavioural problems 110 and overlapping neuropathological features, particularly abnormal tau and ubiquitin metabolism, affecting frontal and temporal structures. 111 We concentrate on the clinical syndromes of FTD, which is characterized by prominent behaviour changes, and which is by far the commonest. 108,109 Psychiatric symptoms are part of core diagnostic criteria. 18 Behavioural disturbance is more common in FTD than in AD 96,112,113 and can better discriminate between the 2 dementias than the cognitive profiles. 112 Patients with FTD tend to have more apathy, behavioural dyscontrol, aberrant motor behaviour, eating disorders, and sleep disturbances than AD 113 and have been replicated in another study. 96 Apathy can be twice as common in FTD as in AD or mixed dementia. 114 However, in an earlier, though smaller study, only stereotypic and altered eating behaviour and loss of social awareness reliably differentiated AD from FTD, with no effect of disease severity. 115 By contrast, executive dysfunction, poor self-care, and restlessness showed a significant effect of disease severity only, with the more impaired patients scoring more highly. Changes in mood were found to be equally prevalent in the 3 patient groups. Analysis of individual symptoms showed increased rates of mental rigidity and depression in the patients with semantic dementia, compared with those with frontal variant FTD. Conversely, the latter group showed greater disinhibition. Patients with FTD with normal magnetic resonance imaging results follow a more benign course than patients with atrophy at presentation. The substrate of the behavioural symptoms in such patients may differ from the neurodegenerative pathological features typically associated with FTD. 116 Conclusions Neuropsychiatric symptoms are very common accompaniments of dementias and associated with poorer prognosis. Our understanding is increasingly moving away from a broad grouping to a syndromic approach. Given that dementias have a clear and more fundamental neurobiological basis, it is hoped that a syndromic approach will yield clearer results regarding their validity. However, for the vast number of patients and their caregivers, including physicians, clinical utility is what one would hope to achieve with a syndromic approach, such that distress can be reduced by having a better understanding, leading to a more meaningful and less harmful management approach. 403

7 In Review Acknowledgements Dr Rockwood is supported by the Dalhousie Medical Research Foundation as the Kathryn Allen Weldon Professor of Alzheimer Research. Dr Rockwood has received speaking or consulting fees in the last 5 years from the Alzheimer Society of Canada, the Canadian Institutes of Health Research, Bristol Myers Squibb, Eisai, Glaxo, and Pfizer and consulting fees from Pharmacare programs in Newfoundland and Labrador, and British Columbia. He is Chief Scientific Officer and a shareholder in DementiaGuide Inc, which has developed individualized symptom tracking software and has contracts with several pharmaceutical companies. Dr Bhat undertook much of this review while on academic leave, studying at Dalhousie University, where he received travel and other support from the Fountain Innovation Fund of the QEII Health Sciences Foundation. The Canadian Psychiatric Association proudly supports the In Review series by providing an honorarium to the authors. References 1. 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Arch Neurol. 2006;63: Manuscript received August 2010 and accepted November Associate Professor, Rural Health Academic Centre, The University of Melbourne, Shepparton, Victoria, Australia. 2 Professor of Medicine (Geriatric Medicine and Neurology) and Professor of Alzheimer Research, Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia. Address for correspondence: Dr K Rockwood, Centre for Health Care of the Elderly, Veterans Memorial Lane, Halifax, NS B3H 2E1; Kenneth.Rockwood@Dal.ca 406 W La Revue canadienne de psychiatrie, vol 56, no 7, juillet 2011