The Canadian Alzheimer · Darvesh is appropriate-ly cautious about pharmacotherapy, although in my experience—and here, in the absence of data from controlled trials, I use full

More to Dementia than AD 3Kenneth Rockwood, MD, MPA, FRCPC

Diagnosis and Management of Dementia with Lewy Bodies 4Ron Keren, MD, Psy, FRCPC

Practical Issues With Frontotemporal Lobar Degeneration 12Sultan Darvesh, BSc, MSc, PhD, FRCPC

Give Me A Chance: I Need More Time! 17France Cloutier, PhD

Personal Revelations, Experiences and Reflections of an AD Caregiver 20Roberta Bedard

Family Physicians Have an Important Role to Play in the Safely Home Program 22

The Alzheimer Society of Canada

The Canadian

Disease ReviewVolume 8, Number 2 June 2005

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Alzheimer

CHAIRMANPeter N. McCracken, MD, FRCPCGeriatric Medicine Staff,Glenrose Rehabilitation Hospital Part Director, Division of Geriatric Medicine and Professor of Medicine, University of Alberta Edmonton, Alberta

Paul J. Coolican, MD, CCFP, FCFP Family Physician, St. Lawrence Medical ClinicMorrisburg, Ontario Active Staff,Winchester District Memorial HospitalWinchester, Ontario

Shannon Daly, RN, MNClinical Nurse Specialist in GeriatricsGrey Nuns Community Hospital & Health CentreEdmonton, Alberta

Howard Feldman, MD, FRCPCProfessor of Medicine,Division of Neurology,University of British Columbia (UBC)Director, UBC Alzheimer Clinical Trials UnitVancouver, British Columbia

Steve Rudin, MEd, MSPHNational Executive DirectorAlzheimer Society of CanadaToronto, Ontario

Serge Gauthier, MD, CM, FRCPCProfessor of Neurology and Neurosurgery,Psychiatry and Medicine, McGill UniversityMcGill Centre for Studies in AgingMontreal, Quebec

Bernard Groulx, MD, CM, FRCPC Chief Psychiatrist, Ste-Anne-de-Bellevue HospitalAssociate Professor, McGill UniversityMcGill Centre for Studies in AgingMontreal, Quebec

Nathan Herrmann, MD, FRCPCAssociate Professor, University of TorontoHead of the Division of Geriatric Psychiatry,Sunnybrook Health Science CentreToronto, Ontario

Peter Lin, MD, CCFPMedical Director, University of TorontoHealth & Wellness Centre at ScarboroughScarborough, Ontario

Kenneth Rockwood, MD, MPA, FRCPCProfessor of Medicine,Kathryn Allen Weldon Professor of Alzheimer Research& Canadian Institutes of Health Research InvestigatorDalhousie UniversityGeriatrician, Queen Elizabeth II Health Sciences CentreHalifax, Nova Scotia

Copyright 2005 STA HealthCare Communications Inc.All rights reserved.The Canadian Alzheimer Disease Review is published by STA Communications Inc.The opin-ions expressed herein are those of the authors and do not necessarily reflect the views of the publisher. Physicians should take into account the patient’s individual con-dition and consult officially approved product monographs before making any diagnosis or treatment, or following any procedure based on suggestions made in thisdocument. Publications Agreement Number 40063348.

Publishing Staff

EDITORIAL BOARD

The editorial board has complete independence in reviewing the articles appearing in this publication and is responsible for their accuracy.Theadvertisers exert no influence on the selection or the content of material published.

We’d Like to Hear From You!The Canadian Alzheimer Disease Review welcomes letters from its readers. Address all correspondences to Letters, The Canadian Alzheimer Disease Review, 955 Boul. St. Jean, Suite 306, Pointe Claire, Quebec, H9R 5K3. The Reviewalso accepts letters by fax or electronic mail. Letters can be faxed to 514-695-8554 and address electronic mail [email protected]. Please include a daytime telephone number. Letters may be edited for length or clarity.

Paul F. BrandExecutive Editor

Russell KrackovitchEditorial Director,Custom Division

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Robert E. PassarettiPublisher

ON THE COVERThe Plan, by Renée ForestallRenée Forestall was Artist-in-Residence at the Memory Clinic, QEII Health Sciences Centre inHalifax, Nova Scotia when she produced The Plan. All of us plan, but an early deficit in patientswith Alzheimer’s disease is the loss of their ability to imagine themselves as competent futureagents. Here, the difference between planning for an unknown future and experiencing late-stagedementia are contrasted. Yet there is something unifying in the joy of the moment of an imaginedfuture, and the joy of an instant of pure pleasure without thought to the future, that shimmers inthe golden moment of the present.

2 • The Canadian Alzheimer Disease Review

E D I T O R I A L

From the past, when the term Alzheimer’s disease(AD) was underused, to the present, when it hasbecome part of the popular lexicon (i.e., “don’t mindmy forgetting your name, it’s just my Alzheimer’s act-ing up”), it is useful to remember that there is more todementia than AD. This point is well illustrated bythis issue of the Canadian Alzheimer Disease Review.

Dr. Ron Keren reminds us of the central impor-tance of dementia with Lewy bodies (DLB; page 4).DLB is a disorder in which there are things that weought to do (i.e., cholinesterase inhibition) and thingsthat we ought not to do (i.e., prematurely treatingwith antipsychotic medications) when encounteringhallucinations in an elderly person, especially onewith no prior history of a psychiatric disorder.Indeed, the benefits of cholinesterase inhibition canbe so dramatic, and the effects of antipsychotic med-ications (through the neuroleptic sensitivity syn-drome) so catastrophic, that elderly patients with hal-lucinations should probably be suspected of havingDLB until proven otherwise.

Dr. Sultan Darvesh takes us through what can bethe torturous characterization of frontotemporallobar degeneration (FTD; page 12). He usefully pro-poses three subtypes, although he recognizes thateven this will not fit the full spectrum of this fasci-nating group of disorders. FTD is clinically andpathologically heterogeneous and, depending on thepattern of degeneration, patients can fit competingprofiles. On one hand, patients can be withdrawn,with little initiative and slow motor behaviour. Onthe other hand, they can be loud, garrulous, disin-hibited and hyperactive. Dr. Darvesh is appropriate-ly cautious about pharmacotherapy, although in myexperience—and here, in the absence of data fromcontrolled trials, I use full editorial license—selec-tive serotonin reuptake inhibitors, especially citalo-pram or sertraline, commonly give good responses.

Also in this issue, Dr. France Cloutier reminds usthat our everyday experience can be helpful in under-standing disease expression in our patients (page 17).She describes her experience, as a native francopho-ne Quebecer, of doing a post-doctoral fellowship inEnglish—with me, actually. She is too modest topoint out that she won the AstraZeneca/CIHR prizeas the top awardee in the Alzheimer Society ofCanada competition, in which she was granted herpost-doctoral fellowship and, while I can attest that itdid not appear frustrating from the outside, I canreadily imagine the frustration she felt strugglingwith a relatively unfamiliar language. Last year, Igave a lecture in Montreal on delirium, a topic aboutwhich I care deeply, to a group of francophone col-leagues. Having gotten through the first several slidesin French, I had to beg their indulgence and switch toEnglish. As I told them, I cared about my subject andI could not stand talking like a child.

In the latest instalment of her remarkable serieson reflections as a caregiver, Roberta Bedard alsoshows us how our own experiences can help us atleast ask the right questions about AD (page 20).How is it that patients can have moments whenfacial recognition, language and judgment sudden-ly come together after each has apparently beenlost? These questions challenge how we haveunderstood disease progression in dementia.

But these are important questions to ask. DLBwas a clinical diagnosis before it was a neuro-pathological one, and FTD challenges us in whatis now its apparent heterogeneity. These demen-tias teach us the value of careful clinical observa-tion, and will do so for some time yet, as they willnever be entirely susceptible to animal modeling.The losses that they represent often reflect theassets that we most cherish as humans, remindingus of our special privilege to care for these people.

More to Dementia than ADby Kenneth Rockwood, MD, MPA, FRCPC

The Canadian Alzheimer Disease Review • 3


It took a long time from the firstdescriptions of Parkinson’s dis-ease (PD) in 1817, to appreciate thatthe same Lewy bodies, identified formany years in the brainstems ofpatients with PD, could be a leadingcause of dementia when found morediffusely in the cortex. Firstdescribed by Friederich Lewy in1912,1 these intracytoplasmic inclu-sion bodies were long known as thehistopathological hallmarks of PD.Interestingly, James Parkinson, whofirst described the illness that bearshis name, believed that cognitivedecline was not a part of PD.2 In1923, almost a century later,Friederich H. Lewy reported on 54of 70 PD patients with considerablemental disturbances, but did not dis-cuss a cause.3 In 1933, in his text-book, Diseases of the NervousSystem,4 Brain reported that whilePD patients do not necessarily expe-rience cognitive decline, thosepatients who have a more diffusepathological process, involving other

parts of the brain might experiencedementia. Finally, in 1961, Okazakiet al5 described two patients withdementia associated with behav-ioral and motor disturbances thathad inclusion bodies in the cere-bral cortex, indistinguishablefrom the Lewy bodies seen in PD.

Poorly visualized in the cortexwith traditional staining techniques,reports of cortical Lewy bodies wererare until the 1970s, when the devel-opment of new staining techniquesfor the protein ubiquitin led to theestablishment of cortical Lewy bod-ies as a cause of dementia. In 1989,Gibb stated “… Lewy bodies in thecerebral cortex may be associatedwith dementia more frequently thanrecognized.”6 Since then, a numberof different terms describing thecognitive decline caused by Lewybodies were coined, many of themdepicting on a relationship betweenLewy body and Alzheimer patholo-gy. Terms such as the Lewy bodyvariant of Alzheimer’s disease

Diagnosis and Management ofDementia with Lewy BodiesDementia with Lewy bodies (DLB) is a disorder with a mixture of complex cognitive,psychiatric and neurological features that can be challenging for patients, caregivers andclinicians alike. Considered to be the second-most common neurodegenerative dementia,DLB is an important diagnosis for clinicians to make and to treat. This article will reviewthe pathological and clinical features of DLB, as well as discuss its management.

by Ron Keren, MD, Psy, FRCPC

Dr. Keren is the clinical director ofthe University Health Networkand Whitby Mental Health Centrememory clinics and an AssitantProfessor at the University ofToronto.

(AD), AD with incidental Lewybodies, and AD with PD changes,suggested that AD was the predomi-nant pathology, while terms such assenile dementia of the Lewy bodytype, cortical Lewy body dementia,dementia with cerebral Lewy bodiesand diffused Lewy body diseaseimplied that cortical Lewy bodieswere the predominant pathology.

In 1996, an international consor-tium established the term “demen-tia with Lewy bodies” (DLB) anddeveloped consensus guidelines forits clinical and pathological diag-nosis.7 Today, DLB is generallyaccepted as the second-most com-mon cause of neurodegenerativedementia in older people.

The Synucleinopathies andLewy Body DisordersA-synuclein is a normal synapticprotein that has been implicated invesicle production. The synuclein-opathies are a subset of neuro-degenerative disorders that share acommon pathology where insolu-ble fibrillary aggregates of a-synuclein can accumulate in bothneurons and glia. In Lewy bodydisorders (DLB and PD), theaggregates accumulate in Lewybodies. In multiple system atrophy(MSA), aggregates are found inglial cytoplasmic inclusions. Inaddition to a-synuclein, Lewybodies are composed of neurofila-ments, crystallin and ubiquitin.8

Antibodies to a-synuclein used toimmunostain Lewy bodies have

helped to better visualize Lewybody pathology.

PDD and DLBParkinson’s disease dementia(PDD) and DLB share overlappingclinical symptoms and neuropathol-ogy.9 Patients with PD who live longenough are likely to develop PDD(Figure 1). Longitudinal studies ofpatients with PD10 show that 78% ofpatients meet DSM IIIR criteria fordementia after an average of adecade of motor symptoms. Most ofthese patients have fluctuating cog-nition and visual hallucinations sim-ilar to DLB, as well as extensivecortical Lewy bodies at autopsy.However, while validated diagnosticcriteria have been established forDLB, there are no such diagnosticcriteria for PDD, nor are there defi-nite pathological criteria that differ-entiate between the two. The con-sensus guidelines for DLB set anarbitrary “one-year rule” to separateDLB from PDD. Onset of dementiawithin 12 months of parkinsonismqualifies as DLB and more than

12 months of parkinsonism beforedementia qualifies as PDD.7 Giventhat PDD and DLB are likely differ-ent representations of the sameunderlying pathology, it has becomeincreasingly accepted that they aremore likely two points on a spec-trum of a disease rather than twoseparate diseases, as suggested bythe consensus guidelines.

DLB with AD PathologyThe pathological diagnosis of DLBdoes not exclude the presence ofplaques and tangles as seen in ADpathology. In fact, most patientswith DLB also have AD pathology.The degree of AD pathology, espe-cially neurofibrillary tangles, affectsthe clinical presentation of DLB andmay help explain why DLB is oftenclinically unrecognized. In a reviewby Merdes et al,11 89 of 98 patients(91%) with autopsy-proven DLBmet the criteria for AD set out by theConsortium to Establish a Registryfor Alzheimer’s Disease (CERAD).Patients with a low burden of ADtangle pathology (n = 24) were


Figure 1

Prevalence of Dementia in Patients with PD Increases with Time9

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much more likely to have visual hal-lucinations (66%) than patients witha high burden of AD tangle patholo-gy (33%, n = 66). Similarly, theclinical diagnostic accuracy forDLB was higher in subjects withlow tangle burden (75%) than thosewith high tangle burden (39%). Thestudy concludes that the degree ofconcomitant AD tangle pathologyhas an important influence on theclinical features of DLB as well asits diagnostic accuracy.

The Clinical Diagnosis of DLBIn 1996, an international meetingwas held to develop the consensuscriteria for the diagnosis of DLB.7

In addition to the central feature of

dementia, CERAD described threecore clinical features of DLB: recur-rent visual hallucinations, fluctuat-ing cognition and spontaneousmotor features of parkinsonism. Adiagnosis of probable DLB requiresthe presence of two core features,while the diagnosis of possible DLBrequires the presence of one corefeature. CERAD also described anumber of clinical features that sup-port a diagnosis of DLB, including:repeated falls, syncope, transientloss of consciousness, neurolepticsensitivity, systematized delusions,and hallucinations in other modali-ties. In 1999, a second consensusconference was held and addedsleep behavior disorder and depres-sion to this list.12 A history of stroke

or any other physical illness or braindisorder sufficient to interfere withcognitive performance would makea diagnosis of DLB less likely(Figure 2). Using these criteria, thespecificity of diagnosing DLB isquite high. However, the sensitivityis generally low, suggesting that thediagnosis can easily be missed usingthe consensus criteria (Table 1).McKeith et al12 suggest that diag-nostic accuracy may be improved bythe use of standardized methods foridentifying fluctuation and throughmeasuring medial temporal lobeatrophy on MRI, which is signifi-cantly less in DLB than in AD. Also,reduced dopamine transporter activ-ity in the striatum, visualized by FP-CIT-SPECT in DLB, but not in AD.

Clinical Features of DLB Age of onset ranges from 50 to 83 years, slightly favoring males.Mean survival time is similar to AD.However, some patients run a moreaggressive course, progressing todeath within one to two years fromthe onset of symptoms.13 The clini-cal features of DLB can be dividedinto three categories: cognitive, psy-chiatric and neurological.

Cognitive features. A decline incognitive function is almost alwaysthe presenting feature of DLB.Many studies have looked at theneuropsychological features thatmay help distinguish between thecognitive decline in DLB and thatin AD. A systematic review andmeta-analysis completed by


Figure 2

DLB: Clinical Diagnostic Criteria12

Central Features• progressive cognitive decline of sufficient magnitude to interfere with

normal social and occupational function• prominent or persistent memory impairment does not necessarily

occur in the early stages, but is evident with progression in most cases.• deficits on tests of attention and of frontal-subcortical skills and

visuospatial ability can be especially prominent.Core Features• fluctuating cognition with pronounced variations in attention and alertness• recurrent visual hallucinations that are typically well formed and detailed• spontaneous features of parkinsonismSupportive Features• repeated falls• syncope• transient loss of consciousness• systematized delusions• hallucinations in other modalities• REM sleep behavior disorder• depressionFeatures Less Likely to be Present• history of stroke• any other physical illness or brain disorder sufficient to interfere with

cognitive performance

Collerton et al,14 concluded thatDLB might be conceptualized as avisual-perceptual and attentional-executive dementia. Shimomura etal15 described a disproportionateimpairment of visuoperceptual andvisuoconstructive ability with rela-tive sparing of memory function inDLB. For clinical purposes, earlyimpairments in the drawing of theintersecting pentagons in contrast toperformance on tests of short-termmemory may be helpful in distin-guishing DLB and AD patients.16

Fluctuations in cognitive func-tion can vary over minutes, hours ordays, and occur in 50% to 75% ofpatients.12 Fluctuations are notexclusively found in DLB.However, compared to those foundin AD, the amplitude of fluctuationsin DLB appear to be more marked.Fluctuating cognition in DLB hasbeen described as having a sponta-neous, periodic, transient quality,appearing to be an interruption inthe ongoing flow of awareness orattention.17 The gold standard fordetermining fluctuation is “expertopinion” which has low inter-raterreliability.18 Resulting from this,fluctuations in cognitive functionmay be the most difficult of thethree core features for clinicians tocharacterize, likely contributing tothe low sensitivity in diagnosingDLB, using the current criteria. Theuse of questionnaires and diary-keeping by a reliable informant andthe use of specific psychometricprocedures, including computer-

based tasks that are sensitive toattention, were recommended in thereport of the second DLB work-shop.12 Ferman et al19 developed a19-item Fluctuations CompositeScale. The four distinguishing fea-tures of this scale that differentiatebetween patients with DLB and ADwere daytime drowsiness andlethargy, daytime sleep lasting atleast two hours, staring into spacefor long periods, and episodes ofdisorganized speed. Three or four ofthese features were present in 63%of patients with DLB and in 12% ofpatients with AD, resulting in a pos-itive predictive value of 83% for thediagnosis of DLB.

Psychiatric features. Early andprominent psychiatric features, espe-cially vivid visual hallucinations, butalso delusions, apathy and anxiety,occur early in the course of DLB.They tend to persist and help differ-entiate between DLB and otherdementias (Table 2). Approximatelytwo-thirds of patients report vivid,colorful and complex visual halluci-nations of mute images, often ofpeople or animals, similar to those

reported in PDD. Individuals mayrespond to their hallucinations withamusement, apathy or intense fear.13

The presence of visual or auditoryhallucinations in patients with Mini-Mental State Examination scoresgreater than 20 were found to beeven more suggestive of DLB.20

Evidence from the psychopathologyliterature suggests that hallucinationsare linked to a problem with realitymonitoring21 which may lead toconfusion between self-generatedmental images and perception.22

Delusional misidentification hasbeen found to be common in DLB.20

Depression has been found to be fre-quent in both DLB and PDD andmay be linked to the severity ofmotor symptoms.20 A better under-standing of the mechanisms underly-ing the various neuropsychiatric fea-tures of DLB will help in developingsafe and effective treatments.

Neurological features. Up to70% of patients have parkinsonism,with bradykinesia, limb rigidity andgait disorder being the most com-mon features.23 Extrapyramidalsigns are seen in 25% to 50% of


Table 1

Sensitivity and Specificity Using Clinical Consensus Criteria for Probable DLB13

Reference Sensitivity Specificity

Mega et al 75% 79%Holmes et al 22% 100%Luis et al 57% 90%Verghese et al 61% 84%McKeith et al 83% 95%Lopez et al 23% 100%

patients at the time of diagnosis andwhile most patients will developsome motor features during thecourse of the disease, up to 25%may not.23 Patients with DLB arethought to show greater posturalinstability and facial impassivity,with a tendency towards lesstremor.13 In a prospective clinico-pathological study, the absence ofextrapyramidal signs was the mostcommon reason for missing thediagnosis of DLB.24 The rate of pro-gression of motor symptoms inDLB is similar to that of PD.

RBD and DLBRapid-eye movement (REM) sleepbehavior disorder (RBD) is para-somnia characterized by loss ofnormal skeletal muscle atonia dur-ing REM sleep, resulting in vividand frightening dreams with simpleor complex motor behavior.13,25 Ithas been associated with DLB, PD,progressive supranuclear palsy(PSP) and MSA, but not with AD

or frontotemporal dementia.25

RBD may predate the developmentof parkinsonism or dementia inpatients with DLB, PD or MSA byyears or even decades.25 The asso-ciation between RBD and DLB isso strong, with a high specificity,that Boeve et al26 suggest that it beadded to the core features of DLB.

Autonomic Dysfunction in DLB Autonomic abnormalities are morecommon in patients with DLB thanin those with AD or in age-matchedcontrols.13 In a cohort of 30 patientswith DLB and 35 patients with AD,77% of the DLB patients and 55%of the AD patients were found tohave some form of neurovascularinstability, such as orthostatichypotension or carotid-sinus hyper-sensitivity.27 In a clinicopathalogiccohort of 29 patients with DLB, allbut one patient displayed someform of dysautonomia. Urinaryincontinence was the most frequent

(97%) symptom, with constipationoccuring the second-most frequent-ly (83%). Episodic hypotension andurinary retention occurred in 28%,hypotension without syncope in66% and slightly elevated tempera-ture in 72%.28

Neuroleptic SensitivityAll older patients are susceptible tothe extrapyramidal side effects ofneuroleptics. Patients with DLBhave been found to be especiallysensitive to these agents, includingatypical neuroleptics. McKeith etal29 reported that 50% of DLBpatients exposed to neurolepticsexperienced a severe sensitivityreaction which included cognitivedecline, parkinsonism, drowsiness,and features of the neurolepticmalignant syndrome (NMS): with athree-fold increase in mortality.These reactions were not dose-related. Similarly, Ballard et al30

reported severe sensitivity reactionsto neuroleptics in 29% of patients


Table 2

A Comparison of Clinical Symptoms in DLB and AD13

Dementia with Lewy bodies Alzheimer’s DiseaseAt presentation (%) Ever (%) At presentation (%) Ever (%)

Dementia 82 (40-100) 100 100 100Fluctuation 58 (8-85) 75 (45-90) 6 (3-11) 12 (5-19)Visual hallucinations 33 (11-64) 46 (13-80) 13 (3-19) 20 (11-28)Auditory hallucinations 19 (13-30) 19 (0-45) 1 (0-3) 4 (0-13)Depression 29 (7-75) 38 (12-89) 16 (9-38) 16 (12-21)Parkinsonism 43 (10-78) 77 (50-100) 12 (5-30) 23 (19-30)Falls 28 (10-38) 37 (22-50) 9 (5-14) 19 (11-24)Neuroleptic sensitivity 61 (0-100) 15 (0-29)

Figures show mean (range). Based on 261 cases of AD and 190 cases of DLB, with autopsy confirmation of diagnosis.


with DLB. All of the reactionsoccurred within two weeks of a newneuroleptic prescription or dosechange and 47% of patients receivedatypical neuroleptics. Open-labelstudies suggest that parkinsonism isleast likely to occur with clozapineor quetiapine and more likely withresperidone and olanzapine.31

Differential DiagnosisThe main differential diagnosesare AD, vascular dementia, PDD,PSP, MSA, corticobasal degenera-tion and prion disease.13

ManagementBarber et al32 describe a four-stepapproach to the management ofDLB: establishing an accurate andtimely diagnosis, identification ofthe severity and nature of keyproblem symptoms (cognitive,psychiatric and motor, includingtheir effect on caregivers), non-pharmacologic interventions andpharmacologic interventions.

Nonpharmacologic interven-tions have not been systematicallyreviewed. However, given the limit-ations of pharmacologic treatments,they are the mainstay of clinicalmanagement. Educating patients andtheir caregivers about the nature ofthe disorder and assisting with cop-ing strategies can be helpful. Motorimpairments may benefit frommobility aids and physiotherapy.32

ChEIs. Given the profoundcholinergic deficits in the cortex,brain stem and basal forebrain

nuclei, in addition to the relativesparing of post-synaptic corticalmuscarinic receptors, treatmentwith cholinergic agents wouldseem to benefit patients withDLB. Indeed, open-label studieswith cholinesterase inhibitors(ChEIs; donepezil, rivastigmineand galantamine) suggest a clini-cal benefit in cognitive and behav-

ioral domains.33-36 In a casereport of nine patients with DLBtreated with donepezil, there wasan improvement in hallucinationsin eight patients. However, therewas a worsening of motor symp-toms in three patients.37

A multi-centre, randomized,controlled trial of rivastigmine38

supported the findings of open-label studies, showing benefits incognitive and behavioral out-comes. Rivastigmine significantlyreduced the core psychiatricsymptoms of DLB (apathy, anxi-ety, delusions and hallucinations).Twice as many patients onrivastigmine as on placebo wereclinical responders, defined ashaving at least a 30% improve-ment from baseline with regard tobehavioral symptoms. Riva-stigmine also had a beneficialeffect on fluctuations in attentionas assessed using computerizedchoice reaction time tasks.39

There was no worsening of motorsymptoms, and safety and tolera-bility were judged acceptable.

Despite limited evidence in ran-domized, controlled trials, andbecause of the risk of severe sensi-tivity reactions to neuroleptics,ChEIs are viewed by some to befirst-line treatment for both the cog-nitive and psychiatric symptoms of

DLB. However, in addition to theknown gastrointestinal side effectsassociated with this class of drugs,clinicians should be aware of thepotential for worsening of motorand autonomic symptoms. Clearly,more randomized, controlled trialsare needed to further establish boththe efficacy and safety of thesedrugs in the treatment of DLB.

Other MedicationsEvidence for the treatment of parkin-sonism is limited. The effectivenessof levodopa (l-dopa) on motor symp-toms in DLB has not been estab-lished but is probably less than inPD.13 L-dopa has the potential toexacerbate hallucinations in patientswith DLB, challenging the clinicianto balance between increased func-tion and worsening psychosis.

Both clonazepam and mela-tonin have been suggested for thetreatment of REM sleep behaviordisorder.40

All older patients are susceptible to the extrapyrmidal sideeffects of neuroleptics. Patients with DLB have been found

to be especially sensitive to these agents, including atypicalneuroleptics.


References:1. Lewy FH. Paralysis agitans. I:

Pathologische anatomie. In: Handbuchder Neurologie III. Springer Press ,Berlin, Germany, 1912, 920–33.

2. Parkinson J. An essay on the shakingpalsy. Reprinted in: Critchley M(ed.): James Parkinson, 1755-1824:A Bicentary Volume of PapersDealing With Parkinson’s Disease.MacMillan Press, London,England,1955, p. 218.

3. Gibb WRG, Poewe WH. The cente-nary of Friederich H. Lewy 1885-1950.Neuropathol Appl Neurobiol 198;12217-221.

4. Brain R. The parkinsonian syndrome.In: Brain R (ed.): Diseases of theNervous System. Oxford UniversityPress, London, England 1933, 538–50.

5. Okazaki H, Lipkin LE, Aronson SM.Diffuse intracytoplasmic ganglionicinclusions (Lewy type) associated withprogressive dementia and quadrapare-sis in flexion. J Neuropathol ExpNeurol 1961; 20:237–44.

6. Gibb WRG, Luthert PJ, Janota I, et al.Cortical Lewy body dementia: clinicalfeatures and classification. J NeurolNeurosurg Psychiatry 1989; 52:185–92.

7. McKeith IG, Galasko D, Kosaka K, et al.Consensus guidelines for the clinical andpathologic diagnosis of dementia withLewy bodies (DLB): report of the consor-tium on DLB international workshop.Neurology 1996; 47:1113–24.

8. Marti MJ, Tolosa E, Campdelacreu J.Clinical overview of the synucleinopathies.Mov Disord 2003; 18(Suppl 6):S21-7.

9. McKeith IG, Mosimann UP. Dementiawith Lewy bodies and Parkinson’s dis-ease. Parkinsonism Relat Disord 2004;10(Suppl 1):S15-8.

10. Hughes TA, Ross HF, Musa S, et al. A10-year study of the incidence of andfactors predicting dementia inParkinson’s disease. Neurology 2000;54:1596-602.

11. Merdes AR, Hansen LA, Jeste DV.Influence of Alzheimer pathology onclinical diagnostic accuracy in demen-tia with Lewy bodies. Neurology 2003;60(10):1586-90.

12. McKeith IG, Perry EK, Perry RH. Reportof the second dementia with Lewybody international workshop: diagnosisand treatment. Consortium onDementia with Lewy Bodies.Neurology 1999; 53(5):902-5.

13. McKeith IG, Mintzer J, Aarsland D, etal. Dementia with Lewy bodies. LancetNeurol 2004; 3(1):19-28.

14. Collerton D, Burn D, McKeith I, et al.Systematic review and meta-analysisshow that dementia with Lewy bodiesis a visual-perceptual and attentional-executive dementia. Dement GeriatrCogn Disord 2003; 16(4):229-37.

15. Shimomura T, Mori E, Yamashita H, etal. Cognitive loss in dementia withLewy bodies and Alzheimer’s disease.Arch Neurol 1998; 55:1547-52.

16. Cormack F, Aarsland D, Ballard C, et al.Pentagon drawing and neuropsychologicalperformance in dementia with Lewy bod-ies, Alzheimer’s disease, Parkinson’s diseaseand Parkinson’s disease with dementia. Int JGeriatr Psychiatry 2004; 19(4):371-7.

17. Bradshaw J, Saling M, Hopwood M, et al.Fluctuating cognition in dementia withLewy bodies and Alzheimer’s disease isqualitatively distinct. J Neurol NeurosurgPsychiatry 2004; 75(3):382-7.

18. Mega MS, Masterman DL, Benson DF, etal. Dementia with Lewy bodies: reliabilityand validity of clinical and pathologic cri-teria. Neurology 1996; 47(6):1403-9.

19. Ferman TJ, Smith GE, Boeve BF, et al.DLB fluctuations: specific features thatreliably differentiate DLB from AD andnormal aging. Neurology 2004; 62:181-7.

20. Ballard C, Holmes C, McKeith I, et al.Psychiatric morbidity in dementia withLewy bodies: A prospective clinicaland neuropathological comparativestudy with Alzheimer’s disease. Am JPsychiatry 1999; 156(7):1039-45.

21. Bentall RP, Baker GA, Havers S. Realitymonitoring and psychotic hallucina-tions. British Journal of ClinicalPsychology 1991; 30:213-22.

22. Barnes J, Boubert L, Harris J, et al.Reality monitoring and visual halluci-nations in Parkinson’s disease.Neuropsychologia 2003; 41:565-74.

23. Mckeith IG. Dementia with Lewy bod-ies. Br J Psychiatry 2002; 188:144-7.

24. McKeith IG, Ballard CG, Perry R, et al.Prospective validation of Consensus crite-ria for the diagnosis of dementia with Lewybodies. Neurology 2000; 54(5):1050-8.

25. Schenck C, Mahowald M. REM sleepbehavior disorder: clinical, develop-mental, and neuroscience perspectives16 years after its formal identificationin SLEEP. Sleep 2002; 25:120–38.

26. Boeve B, Silber M, Ferman T, et al.Association of REM sleep behaviourdisorder and neurodgenerative diseasemay reflect on underlying synucleopa-thy. Mov Disod 2001; 16:622-30.

27. Ballard C, Shaw F, McKeith, et al. Highprevalence of neurovascular instabilityin neurodegenerative dementias.

Neurology 1998; 51(6):1760-2.28. Horimoto Y, Matsumoto M, Akatsu H,

et al. Autonomic dysfunctions indementia with Lewy bodies. J Neurol2003; 250(5):530-3.

29. McKeith IG, Fairbaim A, Perry FT.Neuroleptic sensitivity in patients withsenile dementia of Lewy body type.BMJ 1992; 305:673-78.

30. Ballard C, Grace J, McKeith IG.Neuroleptic sensitivity in dementiawith Lewy bodies and Alzheimer’s dis-ease. Lancet 1998; 351(9108):1032.

31. Jacoby R (ed.): Psychiatry in the Elderly,third edition. Oxford University Press,London, 2002, p. 550.

32. Barber R, Panikkar A, McKeith IG.Dementia with Lewy bodies: diagnosisand management. Int J GeriatrPsychiatry 2001; 16(Suppl 1):S12-8.

33. Minett TS, Thomas A, Wilkinson LM.What happens when donepezil is sud-denly withdrawn? An open label trial indementia with Lewy bodies andParkinson’s disease with dementia. Int JGeriatr Psychiatry 2003; 18(11):988-93.

34. Grace J, Daniel S, Stevens T, et al. Long-term use of rivastigmine in patients withdementia with Lewy bodies: an open-labeltrial. Int Psychogeriatr 2001; 13(2):199-205.

35. Samuel W, Caligiuri M, Galasko DR, etal. Better cognitive and psychopatho-logic response to donepezil in patientsprospectively diagnosed as dementiawith Lewy bodies: a preliminary study.Int J Geriatr Psychiatry 2000; 15:794.

36. Edwards KR, Hershey L, Wray L. Efficacyand safety of galantamine in patientswith dementia with Lewy bodies: a 12-week interim analysis. Dement GeriatrCogn Disord 2004; 17(Suppl 1):40-8.

37. Shea C, MacKnight C, Rockwood K.Donepezil for treatment of dementia withLewy bodies: a case series of nine patients.Int Psychogeriatr 1998; 10(3):229-38.

38. McKeith IG, Del Ser T, Spano, et al.Efficacy of rivastigmine in dementia withLewy bodies: a randomised, double-blind, placebo-controlled internationalstudy. Lancet 2000; 356(9247):2031-6.

39. Wesnes K, McKeith IG, Ferrara R, et al.Effects of rivastigmine on cognitivefunction in dementia with Lewy bod-ies: a randomized placebo-controlledinternational study using the cognitivedrug research computerised assessmentsystem. Dement Geriatr Cogn Disord2002; 13:183-92.

40. Boeve BF, Silber MH, Ferman TJ. Melatoninfor treatment of REM sleep behavior disor-der in neurologic disorders: results in 14patients. Sleep Med 2003; 4(4):281-4.


Frontotemporal lobar degener-ation is a group of disorderswhere patients display behavioralchanges and/or language function.Arnold Pick provided the firstdescription of a patient who hadlanguage impairment. On macro-scopic examination of the brain,there was atrophy of the frontaland temporal lobes.1 Upon micro-scopic examination, some neu-rons had intracytoplasmic inclu-sion bodies, that were named“Pick bodies,” and ballooned neu-rons that were named “Pickcells.”2,3 Onari and Spatz calledthis condition “Pick’s disease”(“Picksche Krankheit”).4 Thisentity was thought to be rare.However, the Manchester-LundGroup provided a clinical andpathological description of agroup of neurodegenerative disor-ders they called “frontotemporaldementia.”5 They suggested that

this disorder was relatively com-mon, particularly in patientsyounger than 65 years of age.Neary et al, provided consensuscriteria for frontotemporal lobardegeneration.6 They proposedthree subtypes, namely: fron-totemporal dementia, progressivenon-fluent aphasia and semanticdementia. They suggested thatfrontotemporal dementia wasclinically characterized by behav-ioral change. Progressive non-fluent aphasia was previouslydescribed under the name “pri-mary progressive aphasia.”7

Semantic dementia was previous-ly described as a disorder charac-terized by the loss of semanticknowledge.8 However, the nosol-ogy, clinical criteria and neuro-pathologic criteria need furtherrefinement. For example, it hasbeen suggested that all these dis-orders, including frontotemporal

Practical Issues WithFrontotemporal Lobar DegenerationFrontotemporal lobar degeneration is a group of neurodegenerative disorders whose clinicalpresentations and neuropathologic features are heterogeneous. There are three subtypes offrontotemporal lobar degeneration, namely: frontotemporal dementia, progressive non-fluentaphasia (primary progressive aphasia) and semantic dementia. Some have suggested thatthese subtypes may be distinct entities. Several genetic mutations, particularly onchromosome 17 in the tau gene, have been associated with this disorder.

by Sultan Darvesh, BSc, MSc, PhD, FRCPC

Dr. Darvesh is a neurologist in theDepartments of Medicine(Neurology and GeriatricMedicine), and Anatomy andNeurobiology, as well as anAssistant Professor at DalhousieUniversity in Halifax, Nova Scotia.

dementia, progressive non-fluentaphasia, semantic dementia,corticobasal degeneration andother diseases have overlappingclinical, neuropathological andgenetic aspects, and hence theyshould fall under the rubric of“Pick Complex”.9,10 Furthermore,it has been suggested that the useof the term “frontotemporaldementia” as a common designa-tion for frontal lobe dementia andprimary progressive aphasia maybe too inclusive and should beseparated because of the presenceof distinct signs and symptoms.11

Nonetheless, current consensuscriteria provide a reasonableframework for assessment andmanagement of these patients.

Characteristics ofFrontotemporal LobarDegeneration as a GroupIt has been suggested that about25% of individuals with dementiaunder age 65 years have fron-totemporal lobar degeneration.12

It affects men and women aboutequally, and the mean duration ofthe illness is about eight years. Itis estimated that up to half ofthese cases have a first degree rel-ative with this disorder.13

Characteristics ofFrontotemporal DementiaPatients with frontotemporaldementia can be categorized intothree subgroups. Patients in thefirst subgroup predominantly

exhibit disinhibition, inattentionand overactivity. Those in the sec-ond subgroup predominantly dis-play apathy and social withdraw-al. Patients in the third subgroupshow ritualistic, stereotypedbehavior. In addition to this, somepatients may have a change indietary habits. For example, theymay show hyperorality and pref-erence for certain foods, such assweets. They may also exhibit a

decline in personal hygiene, rest-lessness, impulsivity, irritability,aggression, hypersexuality andsexual disinhibition. A small per-centage of these patients also hasmotor neuron disease.

From a neuroimaging perspec-tive, there may be atrophy of thefrontal and/or temporal lobe onMRI scanning. It is reported thatSingle Photon Emission ComputedTomograghy (SPECT) scanningmay show hypoperfusion in thefrontal and/or temporal regions.14

Neuropathologically, those withdisinhibited, impulsive, antisocialbehavior and stereotypical featuresusually have involvement of theorbitofrontal cortex. Those withdeficits in planning and organiza-tion primarily have involvement ofthe dorsolateral prefrontal cortex,and those with apathy have

involvement of the medial frontaland anterior cingulate gyrus.15

Characteristics of Non-fluentProgressive Aphasia (Primary Progressive Aphasia)Although progressive aphasiawas described approximately100 years ago,16,17 Mesulamdescribed this disorder in moredetail under the name of “pri-mary progressive aphasia” and

provided further diagnostic crite-ria.7,11,18 For the first two years,these patients display insidiousonset and gradual progression offluent or non-fluent speech,anomia, agrammatism, phone-mic paraphasic errors and theymay have some comprehensiondeficit. They have difficulty withrepetition, reading and/or writingover the course of the disease.They do not have significant apa-thy or disinhibition. They havepreserved recent memory andvisuospatial function. They may,however, have acalculia, ideomo-tor apraxia and perserveration.After two years, all cognitivedomains can be affected, but lan-guage remains prominent anddeteriorates faster. Most of thesepatients have focal involvement ofthe left frontal lobe.


It has been suggested that about 25% of individuals withdementia under 65 years have frontotemporal lobar

degeneration. It affects men and women about equally, andthe mean duration of the illness is about eight years.


The most common neuropatho-logic features of this disorder areneuronal loss, gliosis, and spongio-sis of the superficial layers of thecortex, although Pick bodies and

Pick cells have also been describedin some cases.19 In very few cases,pathology of Alzheimer’s disease(AD) has been observed.20

Characteristics of Semantic DementiaSemantic dementia was firstdescribed by Warrington.8 Thesepatients lose the meaning ofwords. They have difficulty withnaming and comprehension. Inaddition, they have problemswith object recognition. Theymay have preserved repetition,particularly single words. Theymay also have preserved abilityto read and to write to dictation.They may have idiosyncraticusage of words. There is anabsence of phonemic paraphasicerrors (e.g. “cope” for “coat”)but these patients do exhibitsemantic paraphasias (e.g. “pen-cil” for “pen”). They generallyhave insight into their difficul-ties. This disorder is thought tobe due to a loss of semantic

memory. In addition to this,these patients may exhibit diffi-culty recognizing faces(prosopagnosia) and/or associa-tive agnosia, whereby they have

impairment in object recogni-tion. In contrast to AD, patientswith semantic dementia havepreserved episodic memory.They are usually oriented and areable to relate to recent events,although they may have difficul-ty recalling more distant events.

From a neuroimaging per-spective, there may be hypoper-fusion in one or both temporallobes on SPECT scanning.21

Temporal lobe atrophy is muchmore significant and there isusually an asymmetric involve-ment, with the left temporal lobebeing more involved.

Genetic Aspects of Frontotemporal Lobar DegenerationIt has been reported that as muchas 38% to 45% of all the fronto-temporal lobar degeneration casesare hereditary,13 and that 80% to90% of these cases can have anautosomal dominant pattern ofinheritance. Mutations in the tau

protein gene, located on chromo-some 17, have been described.22

The tau protein is found in the nor-mal brain and is thought to beimportant in the maintenance ofneuronal cytoskeleton and axonaltransport. In families with a taumutation, the phenotypic expres-sion of the disease has variedamong family members. Forexample, different family membersmay exhibit psychiatric disorders,behavioral disturbances (such associal withdrawal, alcoholism,hyperreligiosity and hyper-sexuality), dementia, parkinsonismand amyotrophy.23,24 In addition,some members may have predom-inant language disturbance, whileothers may have parkinsonism.25

Neuropathologic Aspects ofFrontotemporal Lobar DegenerationNeuropathologic changes arefound predominantly in thefrontal and temporal lobes, sym-metrically or asymmetrically.There can be neuronal loss, glio-sis and spongiosis in the superfi-cial layers of the cerebral cor-tex.26-28 In those with Pick’s dis-ease, there are ballooned neu-rons (Pick cells) and intraneu-ronal argyrophilic ubiquitin-positive and tau-positive neuronalinclusion bodies (Pick bodies).From a neurochemical perspec-tive, the involvement of both sero-tonergic and catecholinergic sys-tems have been observed.29

The most common neuropathologic features of non-fluent progressive aphasia are neuronal loss, gliosis,and spongiosis of the superficial layers of the cortex,although Pick bodies and Pick cells have also beendescribed in some cases.


Pharmacologic Treatment of Frontotemporal Lobar DegenerationSerotonergic systems areinvolved in some behavioral syn-dromes, such as apathy, depres-sion and impulsivity. As a conse-quence, drugs such as fluvoxam-ine, fluoxetine, paroxetine andsertraline, that enhance the sero-tonergic tone, have been used.These drugs have exhibited vari-able effects on these symp-toms.30-32 Low dopaminergictone has been suggested.Cconsequently, bromocriptine, aD-1 and D-2 dopaminergic ago-nist, has been tried. However, therole of selective serotonin reup-take inhibitors (SSRIs) anddopaminergic agonists need to beexamined further.

Because of cholinergic deficitin AD, cholinesterase inhibitorsare currently used to treat thesymptoms of this disease.33

Although deficits in cholinergicmarkers have been observed infrontotemporal lobar degenera-tion,34 there is no evidence thatcholinesterase inhibitors are bene-ficial in the treatment of this disorder.

NonpharmacologicManagement ofFrontotemporal Lobar DegenerationSince behavioral disturbances inthese dementias include environ-ment exploratory behavior,

disinhibition, aggression, hyper-orality, loss of personal hygiene,and poor judgement, managementof these patients includes behav-ioral strategies directed at educat-ing the caregivers to adopt strate-gies that can help deal with thesebehavioral symptoms. An essen-tial component of planning behav-ioral management is to ask care-givers to keep a log of behavioraldisturbance, including the type of

disturbance, the severity and thepossible circumstances that mighthave triggered the problem. Thisallows individualized interven-tions and the setting of realisticgoals, which can be key to effec-tive non-pharmacological man-agement.35,36 These targetedstrategies may include provisionsof structured environments orremoval of environmental cuesthat could potentially triggerbehavioral disturbance. Further-more, safety issues must beaddressed. This may include ces-sation of driving and makingimportant financial decisions, eachof which can put a great burden oncaregivers. In this regard, caregiv-er education and support groupsare vitally important. Managementof these patients, like other chron-ic illnesses, is best provided by a

multidisciplinary approach. Thisincludes physicians, nurses, occu-pational therapists, physiothera-pists, social workers, speech-lan-guage pathologists and other alliedhealth professionals.

ConclusionFrontotemporal lobar degenera-tion refers to a heterogeneousgroup of disorders in which thereis a range of impairments, from a

dysexecutive syndrome to impair-ment of semantic knowledge tolanguage disturbance. The clini-cal impairments and neuropatho-logical manifestations of fron-totemporal lobar degenerationcan overlap with many other dis-orders, such as motor neuron dis-ease. Genetic factors, such asmutations in the tau gene on chro-mosome 17, appear to show somebiologic basis for these disorders.There is, however, difficulty inattributing a mutation in one geneto the varied clinical manifesta-tions seen in these disorders.Careful clinical, neuropathologi-cal and genetic profiles need to beundertaken to further refine ourunderstanding of this disorderand to provide satisfactory diag-nostic criteria to improve man-agement thereof.

It has been reported that as much as 38% to 45% of all thefrontotemporal lobar degeneration cases are hereditary,13

and that 80% to 90% of these cases can have an autosomaldominant pattern of inheritance.


References:1. Pick A. Uber die Beziehungen der

senilen Hirnantropie zur aphasie.Prager Medizinishe WochenscrifT1892; 17:165-7.

2. Alzheimer A. Uber eigenartigeKrankheitsfalle des spateren Alters.Zeitscrift fur die GesamteNeurologie und Psychiatrie 1911;4:356-85.

3. Altman E. Uber die umschriebeneGehirnatrophie des spateren Alters. ZNeurol Psychiatr 1923; 83:610-43.

4. Onari K, Spatz H. AnatomischeBeiträge zur Lehre von der Pickschenumschriebene-Grosshirnrinden-Atrophie (‘Picksche Krankheit’).Zeitschrift für die Gesamte Neurologieund Psychiatrie 1926; 101:470-511.

5. The Lund and Manchester Groups.Clinical and neuropathological criteriafor frontotemporal dementia. J NeurolNeurosurg Psychiatry 1994; 57:416-8.

6. Neary D, Snowden JS, Gustafson L, etal. Frontotemporal lobar degeneration:a consensus on clinical diagnostic cri-teria. Neurology 1998; 51:1546-54.

7. Mesulam MM. Slowly progressiveaphasia without generalized dementia.Ann Neurol 1982; 11:592-8.

8. Warrington EK. The selective impair-ment of semantic memory. Q J ExpPsychol 1975; 27:635-57.

9. Kertesz A, Munoz D. Pick’s disease,frontotemporal dementia, and pickcomplex: emerging concepts. ArchNeurol 1998; 55:302-4.

10. Kertesz A. Pick’s complex and FTDP-17. Mov Disord. 2003; Suppl 6:S57-62.

11. Mesulam MM. Primary progressiveaphasia. Ann Neurol 2001; 49:425-32.

12. Mann DMA, Neary D, Snowden JS.Chromosome 17 and frontotemporaldementia. In: Gauthier S andCummings JL (eds.): Alzheimer’sDisease and Related Disorders Annual.Martin Dunitz Ltd, United Kingdom,2000, pp. 27-55.

13. Chow TW, Miller BL, Hayashi VN, et al.

Inheritance of frontotemporal dementia.Arch Neurol 1999; 56:817-22.

14. Miller BL, Ikonte C, Ponton M, et al.A study of the Lund-Manchesterresearch criteria for frontotemporaldementia: clinical and single-photonemission CT correlations. Neurology1997; 48:937-42.

15. Cummings JL. Principles of neuropsy-chiatry: towards a neuropsychiatric epis-temology. Neurocase 1999; 5:181-8.

16. Sérieux P. Sur un cas de surdité verbalepure. Rev Med 1893; 13:733-50.

17. Rosenfield M. Die partielleCrosshirnatrophie. J Psychol Neurol1909; 14:115-30.

18. Mesulam MM. Primary progressiveaphasia—a language-based dementis.N Engl J Med. 2003; 349:1535-42.

19. Kertesz A, Hudson L, Mackenzie IR, etal. The pathology and nosology of pri-mary progressive aphasia. Neurology1994; 44:2065-7202.

20. Galton CJ, Patterson K, Xuereb JH, etal. Atypical and typical presentations ofAlzheimer’s disease: a clinical, neu-ropsychological, neuroimaging andpathological study of 13 cases. Brain2000; 123:484-98.

21. Garrard P, Hodges JR. Semanticdementia: clinical, radiological andpathological perspectives. J Neurol2000; 247:409-22.

22. Wilhelmsen KC, Lynch T, Pavlou E, etal. Localization of disinhibition-dementia-parkinsonism-amyotrophycomplex to 17q21-22. Am J HumGenet 1994; 55:1159-65.

23. Lynch T, Sano M, Marder KS, et al.Clinical characteristics of a familywith chromosome 17-linked disinhibi-tion-dementia-parkinsonism-amyotro-phy complex. Neurology 1994;44:1878-84.

24. Rosen HJ, Lengenfelder J, Miller B.Frontotemporal dementia. Neurol Clin2000; 18:979-92.

25. Foster NL, Wilhelmsen K, Sima AA, etal. Frontotemporal dementia and

parkinsonism linked to chromosome17: a consensus conference. AnnNeurol 1997; 41:706-15.

26. Brun A. Frontal lobe degeneration ofnon-Alzheimer type: I.Neuropathology. Arch Gerontol Geriatr1987; 6:193-208.

27. Brun A. Frontal lobe degeneration ofnon-Alzheimer type revisited.Dementia 1993; 4:126-31.

28. Mann DMA, South PW, Snowden JS, etal. Dementia of frontal lobe type:Neuropathology and immunohisto-chemistry. J Neurol NeurosurgPsychiatry 1993; 56:605-14.

29. Anderson IM, Scott K, Harborne G.Serotonin and depression in frontallobe dementia. Am J Psychiatry 1995;152:645.

30. Hope RA, Allman P. Hyperphagia indementia: fluvoxamine takes the bis-cuit. J Neurol Neurosurg Psychiatry1991; 54:88.

31. Hoehn-Saric R, Lipsey JR, McLeod DR.Apathy and indifference in patients onfluvoxamine and fluoxetine. J ClinPsychopharmacol 1990; 10:343-5.

32. Swartz JR, Miller BL, Lesser IM, et al.Frontotemporal dementia: treatmentresponse to serotonin selective reup-take inhibitors. J Clin Psychiatry 1997;58:212-6.

33. Rockwood K, Darvesh S. Cholinergicdrugs for Alzheimer’s disease. In: GrayJ, (ed.): Drug Advances. RemedicaPublishing, London UK, 2003, pp.159-77.

34. Sparks DL, Markesbery WR. Alteredserotonergic and cholinergic synapticmarkers in Pick’s disease. Arch Neurol1991; 48:796-9.

35. Gordon J, Powell C, Rockwood K.Goal attainment scaling as a measureof clinically important change in nurs-ing home patients. Age Ageing 1999;28:275-81.

36. Talerico KA, Evans LK. Responding tosafety issues in frontotemporal dementias.Neurology 2001; 56(11 Suppl 4):S52-55.

Suggested Reading:1. Constantinidis J, Richard J, Tissot R. Pick’s

disease. Histological and clinical correla-tions. Eur Neurol 1974; 11:208-17.

2. Edwards-Lee T, Miller BL, Benson DF, etal. The temporal variant of frontotempo-

ral dementia. Brain 1997; 120:1027-40.3. Hodges JR, Patterson K, Oxbury S, et a.

Semantic dementia. Progressive fluentaphasia with temporal lobe atrophy.Brain 1992; 115:1783-1806.

4. Neary D, Snowden JS, Mann DM. The

clinical pathological correlates of lobaratrophy. Dementia 1993; 4:154-9.

5. Rahman S, Sahakian BJ, Hodges JR, etal. Specific cognitive deficits in mildfrontal variant frontotemporal dementia.Brain 1999; 122:1469-93.


Ihave been in English immer-sion for the last year. My expe-rience of learning a second lan-guage—French being my mothertongue—has made me realizethat, in struggling with that sec-ond language, I am experiencingthe kind of frustration and senseof reduced self worth that peoplewith Alzheimer’s disease (AD)may experience, as well.

First of all, you cannot imaginehow hard it is sometimes to expresswhat I want to say. Words get stuckin my mouth and, when I finally doget them out, they seem to me to belike a staccato rhythm and not at allharmonious. I notice that when I amtired, words come even more slowlyto my mind and I say them moreslowly as well. I often use circum-locution to express myself. I knowthe word I want in French, of course,but I do not know, or do not remem-ber, the word in English. So I startexplaining what I want to say usingother, less exact words. This is aprocess we notice in people withAD. Circumlocution takes moretime to explain what I want to say,rather than using the exact wordright away. For whoever is listening,it also takes longer to find out exact-ly what I mean. Please give me timeto explain myself. It is not that I amstupid—although I do feel like thatat times—it is just that the word Iam looking for does not come to mymind so easily. I can now imagine

how hard it must be for people withAD to express themselves.

I remember going to the grocerystore and asking: “Could I havesome coleslaw, please?” The clerkasked me to repeat my request. I didso and he asked again, because hewas confused by my accent. “Didyou say coleslaw?” That made me soupset. I can smile at it now, but Icould not at the time and, to be hon-est, I do not feel that smile now. Iwould say to myself: “What iswrong with what I am saying?” Iguess it was a question of a strongFrench accent. If we draw a parallelwith people with AD, we can realizehow frustrating it must be for them tobe asked to repeat themselves. As weoften do not understand what theysay, we keep asking them: “What didyou say? Can you say that again?”Just as my request seemed obviousand clear to me, requests made byAD patients may seem just as clearto them. I know my problem was myaccent; imagine how frustrating itmust be for AD patients when they

Give Me A Chance: I Need More Time!The difficulty a patient with Alzheimer’s disease (AD) faces in communicating with thosearound them is perhaps not so different from the challenge of learning a new language. Dr. France Cloutier makes this comparison, reminding us to treat AD patients with the careand understanding they deserve.

by France Cloutier, PhD

Dr. Cloutier works in the GeriatricMedicine Research Unit ofDalhousie University in Halifax,Nova Scotia.


do not know the reason for our con-stant questioning.

Another thing: when people askme questions, it takes more time forme to answer. It is as if words gettyped into my brain and then I haveto consciously decode them. I slow-ly get my answer ready and, after allthat, I have to struggle to pronouncethe words correctly. By this time, theperson has gone on to another ques-tion. Be patient! It is not that I amstupid, it is just that I need more time

to go through that complex process.Give me a chance as someone who isstruggling to learn English and donot forget to do the same for peoplewith AD who are struggling to com-municate. By the way, I can feelwhen people are less patient with mewhen I am slow in expressingmyself, but what can I do? Somedays are better than others. Is it notthe same for people with AD? Theyhave good days and days where theyare more confused. Almost certainlythey can feel our impatience in thetone of our voice or in our gestures.

When I am tired from strug-gling to use English all day, mybrain truly cannot register anyadditional information. I just can-not take any more of what peopleare saying. Then it is as if a cur-tain dropped or a door shut firmly.I just turn off the power to mybrain. Again, I am experiencing

some of what people with ADmay go through.

I believe that problems expressingourselves can easily lead to isolation.This happens to me as a languagelearner, for example, when peoplearound me speak too fast or usewords that I am not used to hearing.Sometimes they laugh, but I do not,as I simply do not “get” the humor. Ina way, I do not feel like I am part ofthem. My world is simply some-where else. It might be the same for

people with AD. They must frequent-ly be living in another world and,surely, this is as close as we can get tothe experience of people with AD.

Finally, I am often not at my bestbecause of the language barrier. Ithink I could say so much more andget much more involved in what isgoing on if only I could do sospeaking French. It is hard toexpress how frustrating it is and,once again, I can draw a parallelwith people with AD. They too havedone so much more with their livesand with their language. We shouldnot forget to go beyond what we seeand hear and remember to take theirlife story into account.

As strange as it seems, my expe-rience with English immersion hasmade me feel closer to people withAD. They experience complexproblems in communicating. It isnot that they lack intelligence; it is a

matter of not being able to expressor communicate, for reasons differ-ent than my own. As a healthcareworker, this experience makes memore sensitive to the way I relate topeople with AD. Do I give themenough time to decode what I amsaying? Do I speak too quickly? DoI use words they can understand?Do I take into account their physicalcondition? For example, are they toohungry or, especially, are they tootired? Do I get annoyed or impatientbecause they are slow in answering?Do I think, “Why should I bother?They don’t understand anyway!”Do I understand their unhappiness atnot being understood? Do I reallygive them a chance?

In my first weeks using English,I remember being so tired and sofrustrated at the end of the day. Ihope I will never forget how I feltand always be compassionate aboutwhat people with AD go through.As we have seen, it is possible thatsome feelings I have experiencedare similar to what people with ADexperience. However, the major dif-ference is that I have improved withtime and I am even proud of myself.My experience is temporary; theirsgets constantly worse and they donot merely lose a sense of pride,they forget about pride itself.

The author is grateful toBob Johnston for his helpfulcomments on earlier versionsof this paper.

I believe that problems expressing ourselves can easilylead to isolation.

20 • The Canadian Alzheimer Disease Review • May 2002

Dr. Lorem Ipsum is Duis autemvel eum iriure dolor in hendreritin vulputate velit esse molestieconsequat, vel illum dolore eufeugiat nulla facilisis.

Unsettling ExperienceI don’t know how to start this arti-cle, but something happenedtoday that unnerved me, and hasled me to ask questions to which Idon’t know the answers.

There is a sweet lady who is aresident at the care centre. She isvery old, very thin, very short, andcompletely adorable. Her skin hasthe fine down that age sometimesbrings. I don’t feel right aboutusing her real name. So, for thisarticle, she will be known asSarah Jane. Her large blue eyeshave cataracts, so sometimes shewill say, “Is that you, Roberta?”When I say it is I, she responds,“Good, will you tell me what todo?” So, depending on which wayshe is facing, I say to her that sheshould go to the dining room, orthat she should go to her room.She will obligingly push her

walker to wherever I have told herto go, and is content.

Sometimes, Sarah Jane and Ichat. She and her husband were mis-sionaries in a northern province, andshe has interesting stories to tell. Ifind her an interesting conversation-alist, and enjoy spending time withher when my husband is asleep.

Every day when I come infrom the elevator she says, “Hello,Roberta.” In the dining room atmealtimes she will ask me whatshe should do.

“Should I stay here and wait?Will they bring my lunch soon? Willthey give me coffee, do you think?”And she relies on my answers.“Thank you, Roberta,” she will say.

Today at dinner time, her daugh-ter, whom I had never met, and anurse were leading her to her table.“There’s Roberta,” said Sarah Jane.

Jaws dropped.

I didn’t know that she didn’trecognize anyone, not even herown family members. That shehadn’t recognized anyone forquite some time. That she doesnot recognize any of the nurses oraides, nor does she remember thatshe has seen them before.

“You must have made quite animpression,” her daughter said, “shedoesn’t know anybody anymore.”

Yet she knows me, asks aboutmy husband Ray by name, and car-ries on quite reasonable conversa-tions with me. I knew she wasimpaired, and made allowances. ButI had no idea that she wasn’t relatingto others the way she was relating tome. Somehow she and I have tappedinto something that allows us to con-nect. To others she is “not in there”and, of course, they have been deal-ing with her accordingly—with lov-ing care and respect and kindness—

Roberta Bedard is a caregiver for her husband who has Alzheimer’s disease (AD). She haswritten many humorous and touching vignettes about her personal experiences in dealingwith the development of the disease, and has graciously agreed to feature these vignettes asa series in the Canadian Alzheimer Disease Review. Roberta’s writings enable readers toshare in her journey with AD caregiving, provide valuable insight on the human aspect ofdisease and stimulate contemplation on the deeper meanings of life and love.

In this feature...In “Unsettling Experience,” Roberta writes about how her experience with a new friend has raisedmany questions that she cannot answer.P

er

spec

tiv

es

Chapter 7by Roberta Bedard

Personal Revelations, Experiences andReflections of an AD Caregiver


but not engaging her in conversa-tion, because she “couldn’t.”

Now come the questions. Is itpossible that there are otherAlzheimer patients who are “inthere” and no one knows? This isa frightening thought to me. Howthey must suffer in their inabilityto be recognized by those wholove them. How hard it must be tobe trapped. Is this a one-off? Wasit a complete fluke that Sarah Janeand I connected? Is this a uniquesituation? Why does she recog-nize me and no one else? Whatdid I inadvertently do that allowedthe breakthrough? Can this flukebe extrapolated to others?

So many questions and noanswers. My mind is scurrying,trying to find something to hold onto. I don’t want to know that somepatients would be responding ifwe could only find the key. I wishI had the kind of mind that wouldallow me to back away from thethought. But I don’t. Now what?

This evening, as I was leavingthe care centre, I stuck my head inher door and said, “I’m heading outnow. I’m going to make my supperand go to bed.” She held out herarms to me from her bed. “I want ahug.” I bent over her bed, and herfragile arms encircled my necklightly. “I’ll pray for you tonight,my dear,” she said, “I love you.”

Please look for Chapter 8:Losing Him in the next issue ofthe Canadian Alzheimer DiseaseReview.

Third Canadian Colloquium on DementiaOctober 27 – 29, 2005The Westin OttawaOttawa, Ontario

The Third Canadian Colloquium on Dementia brings togetherleading experts in dementia research to engage in a multidisciplinary,international exchange of ideas. The two-and-a-half day meeting willconsist of a number of plenary, workshop and poster sessionsdesigned to encourage delegate participation and interaction.

The Third Canadian Colloquium on Dementia is sponsored by theCanadian Academy of Geriatric Psychiatry, the CanadianNeurological Society, the Canadian Geriatrics Society and theConsortium of Canadian Centres for Clinical Cognitive Research.

Program Highlights

• A Beta directed therapies for Alzheimer’s diseaseDr. Peter St. George-Hyslop (University of Toronto)

• Debate: Treatment of Behaviour in Dementia withAtypical Antipsychotics: Benefits Outweigh RisksDr. Nathan Herrmann (University of Toronto), Dr. Jiska Cohen-Mansfield (George Washington University)Dr. Clive Ballard (University of Newcastle upon Tyne)

• Caregiver Interventions in Dementia Dr. Mary Mittelman (New York University School of Medicine)

• What is Vascular Dementia?Dr. Gustavo Roman (University of Texas)

Call for Abstracts!

Share your research with colleagues by submitting abstracts forposter presentations to the Third Canadian Colloquium onDementia. Guidelines for submission can be found on the ThirdCanadian Colloquium on Dementia website: www.ccd2005.ca

For more information and for registration, please visit:www.ccd2005.ca

The Third Canadian Colloquium on Dementia is thankful toJanssen-Ortho Inc., Novartis Canada, Pfizer Canada andLundbeck Canada for their support through the provision of anunrestricted educational grant.

Don’t miss out on this important event! Register today!!


Ten years ago, the Alzheimer Society of Canada(ASC) developed a much-needed program for peo-ple with Alzheimer Disease and related dementias(ADRD). In collaboration with the Royal CanadianMounted Police (RCMP), Health Canada and theSolicitor General, ASC created a registry to identifypeople at risk of becoming lost outside the home.

Ten years later, the Alzheimer WanderingRegistry—now called Safely Home™—is an estab-lished, effective program that provides a worthwhileservice to Canadians.

“Safely Home is as relevant today as it was 10 years ago and perhaps even more so due toincreasing numbers of people with ADRD,”explains Stephen Rudin, executive director of theAlzheimer Society of Canada. “Until we find a cureor a way of preventing the symptoms, Canadianswill appreciate the peace of mind that the registryprovides.”

In recognition of the 10th anniversary of SafelyHome—Alzheimer Wandering Registry, and thanksto new funding, the registry has a new name, a newlook and enhanced resources to assist healthcarefacilities, police, and search and rescue personnel inworking with people with ADRD who are lost.

New MaterialsThe enhanced materials include two trainingresources: Alzheimer Disease: A Resource for

Police & Search and Rescue Personnel, whichconsists of a DVD and a corresponding facilita-tor’s guide and participant’s guide; and SEARCHis an EMERGENCY, a manual for organizationslike long-term care facilities that care for peoplewith ADRD. The materials were created in col-laboration with the police and search and rescuecommunity across the country. The DVD andaccompanying material will help prepare policefor their interactions with people with ADRD.The manual will assist healthcare professionalsin the event that people in their care get lost.

According to Ontario Police College directorRudy Gheysen, “the Ontario Police College isproud that it has been afforded the opportunityto assist the Alzheimer Society in developmentof its training and awareness materials support-ing the Safely Home project. Safely Home is aninvaluable tool for police officers everywhere. Itwill enable police officers to perform theirduties more effectively and ultimately be ofgreater assistance to a very vulnerable segmentof society.”

Role for Family PhysicansWhile new materials have been created for SafelyHome to make it more effective and useful for itsusers, family physicians (FPs) can play a role in thesuccess of the program.

Family Physicians Have an Important Role to Play

in the Safely Home Program

News from the Alzheimer Society of Canada


FPs are usually the first point of contact for afamily learning about ADRD. The estimated420,000 Canadians older than 65 years who haveADRD should be encouraged to register with SafelyHome. Approximately 20% to 60% of those peoplewill become lost outside the home at some point,and research indicates that it is vital to locate a lostperson as quickly as possible to reduce the chanceof injury or death. Currently, 18,500 Canadians areregistered in the program.

The ASC encourages you to talk to your patientsand their family members about Safely Homeand/or provide them with a free brochure about theregistry. Let them know about the benefits of theprogram.

"Safely Home is an extremely helpful programthat is a Canadian success story,” says Dr. CaroleCohen, clinical director of Sunnybrook andWomen’s Health Sciences Centre. “It is appropriatefor individuals with any type of dementia who are atrisk of getting lost outside their place of residence.The enrolment process is easy and should beencouraged as part of the planning process for any-one with dementia."

How the Program WorksBecause people with ADRD sometimes lose theability to recognize familiar places and to remembertheir own name or address, people registered in theprogram wear a bracelet indicating that they havememory problems and that police should be con-tacted. If a registrant is disoriented or confused,police are able to identify him or her through thenumber marked on their bracelet and the informa-tion stored in a confidential police database.

The registry lists names and other pertinent, per-sonal information in a database that can be accessedonly by police in Canada and the U.S.

The one-time fee to register is $25 (whichincludes the bracelet, a Caregiver Handbook and ID

cards) so, while registrants have relatively nothingto lose by adding their name to the database, theyhave everything to gain if they require the servicesome time in the future.

To obtain brochures for your patients or for moreinformation on the Safely Home AlzheimerWandering Registry, contact the Alzheimer Societyin your area, or call 1-800-616-8816 or visitwww.alzheimer.ca.

The Alzheimer Society of Canada is a not-for-profithealth organization dedicated to helping people affect-ed by Alzheimer Disease. The Society provides supportand educational programs for people with AlzheimerDisease and their caregivers. The Society also fundsresearch into finding the causes and cure of the dis-ease, and into improved methods of caregiving. TheSociety consists of a national office, 10 provincialorganizations and more than 140 local groups acrossthe country.

For more information on Alzheimer Disease andrelated dementias, Alzheimer Society programs andservices, and how you can help, contact your localAlzheimer Society or visit the Society’s website atwww.alzheimer.ca or call 1-800-616-8816.

Documents

The Canadian Alzheimer · Darvesh is appropriate-ly cautious about pharmacotherapy, although in my experience—and here, in the absence of data from controlled trials, I use full