J7ournal of Neurology, Neurosurgery, and Psychiatry 1994;57:1451-1456 NEUROLOGICAL MANAGEMENT Management of neurological disorders: dementia M N Rossor (7 Neurol Neurosurg Psychiatry 1994;57:1451-1456) Dementia Research Group, Department of Neurology, St Mary's Hospital, Praed Street, London, W2 INY, UK and National Hospital for Neurology and Neurosurgery, Queen Square, London WC1 3BG, UK M N Rosser Correspondence to: Dr M N Rossor, Dementia Research Group, Department of Neurology, St Mary's Hospital, Praed Street, London, W2 INY, UK. Dementia is the clinical syndrome of impair- ment in multiple domains of cognitive func- tion occurring in an alert patient. Some definitions of dementia demand that the cog- nitive impairment is progressive but for the clinician the static cognitive impairment aris- ing after an encephalitic illness or head injury shares many of the problems of management encountered with the progressive dementias such as Alzheimer's disease. The dementias as a group constitute one of the commonest problems presenting to neurologists and psy- chiatrists and comprise the third leading cause of death. The commonest causes of dementia- namely, Alzheimer's disease and vascular dementia-are predominantly diseases of elderly people. Recent epidemiological stud- ies suggest a low prevalence of dementia in populations below the age of 70, being in the region of 1 % in those aged between 50 and 70 years with a dramatic rise to about 50% in very elderly people. 1-3 Because dementia by definition means that cognitive impairment is sufficient to result in a loss of previous skills to the extent that the patient's normal, social, or work activity is compromised the dement- ing illnesses represent a major burden on society. With an ageing population the number of patients with dementia is expected to rise. Based on demographic trends of those above the age of 80 in the United States it is antici- pated that there may be 10-15 million people affected by Alzheimer's disease by the middle of the next century.4 Estimates that include the rapidly ageing population in Japan and other Asian countries give global figures that may exceed one hundred million.5 The same trend can be anticipated in the United Kingdom; there are currently over half a million people predicted to have Alzheimer's disease and a larger total with dementia. It should, however, be recognised that about 18 000 people below the age of 65 are believed to have Alzheimer's disease and if one considers the number of neurological ill- nesses in which cognitive dysfunction may also feature, such as multiple sclerosis or the extrapyramidal diseases, then the figure is clearly far higher. A recent systematic cost of illness analysis of Alzheimer's disease in England has been undertaken.6 This included estimates of inpatient/outpatient day care as well as resi- dential care costs and arrived at a total figure of 1144 million pounds for 1992. Com- parison with other burden of illness analyses and adjustment for overall United Kingdom costs makes Alzheimer's disease more expen- sive than epilepsy although less than stroke if community and non-NHS care costs are excluded. If these are included then the com- parable figures are 1373 million pounds for Alzheimer's disease and 838 million pounds for stroke. Moreover, this analysis did not include the indirect costs to family carers over and above the benefits they received from Government agencies. The burden of infor- mal care from family members is substantial. Diagnosis Published definitions of dementia all include the involvement of multiple domains of cog- nitive impairment with intact arousal mecha- nisms to distinguish the patient with dementia from one with a confusional state. Moreover, the cognitive impairment should be of sufficient severity to result in the loss of previously acquired skills such that this inter- feres with normal social or employment func- tion. The most widely used criteria are those of the American Psychiatric Association Diagnostic and Statistical Manual of which the latest (DSM IV) has just been published.7 Such criteria can provide a useful guide to the identification of the syndrome but not to the cause. The syndrome of dementia is of grave significance, as it usually reflects progressive degenerative disease that threatens the very integrity of the patient. Moreover, dementia occurs in the setting of many neurological disorders necessitating a broad differential diagnosis and wide ranging investigations. In this group, the clues to the diagnosis and direction of subsequent investigations are usually provided by the additional neurologi- cal abnormalities, although some disorders- for example, multiple sclerosis-can present as cognitive impairment with little else to find on examination. Alzheimer's disease is the comm.onest of the degenerative dementias (table). Charac- teristically, the disease starts with impairment 1451 on August 20, 2020 by guest. Protected by copyright. http://jnnp.bmj.com/ J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.12.1451 on 1 December 1994. Downloaded from
Transcript
J7ournal ofNeurology, Neurosurgery, and Psychiatry 1994;57:1451-1456
NEUROLOGICAL MANAGEMENT
Management of neurological disorders: dementiaM N Rossor
(7 Neurol Neurosurg Psychiatry 1994;57:1451-1456)
Dementia ResearchGroup, Department ofNeurology, St Mary'sHospital, PraedStreet, London, W2INY, UK and NationalHospital forNeurology andNeurosurgery, QueenSquare, London WC13BG, UKM N RosserCorrespondence to:DrM N Rossor,Dementia Research Group,Department of Neurology,St Mary's Hospital, PraedStreet, London, W2 INY,UK.
Dementia is the clinical syndrome of impair-ment in multiple domains of cognitive func-tion occurring in an alert patient. Somedefinitions of dementia demand that the cog-nitive impairment is progressive but for theclinician the static cognitive impairment aris-ing after an encephalitic illness or head injuryshares many of the problems of managementencountered with the progressive dementiassuch as Alzheimer's disease. The dementiasas a group constitute one of the commonestproblems presenting to neurologists and psy-chiatrists and comprise the third leadingcause of death.The commonest causes of dementia-
namely, Alzheimer's disease and vasculardementia-are predominantly diseases ofelderly people. Recent epidemiological stud-ies suggest a low prevalence of dementia inpopulations below the age of 70, being in theregion of 1% in those aged between 50 and70 years with a dramatic rise to about 50% invery elderly people. 1-3 Because dementia bydefinition means that cognitive impairment issufficient to result in a loss of previous skillsto the extent that the patient's normal, social,or work activity is compromised the dement-ing illnesses represent a major burden onsociety.With an ageing population the number of
patients with dementia is expected to rise.Based on demographic trends of those abovethe age of 80 in the United States it is antici-pated that there may be 10-15 million peopleaffected by Alzheimer's disease by the middleof the next century.4 Estimates that includethe rapidly ageing population in Japan andother Asian countries give global figures thatmay exceed one hundred million.5 The sametrend can be anticipated in the UnitedKingdom; there are currently over half amillion people predicted to have Alzheimer'sdisease and a larger total with dementia. Itshould, however, be recognised that about18 000 people below the age of 65 arebelieved to have Alzheimer's disease and ifone considers the number of neurological ill-nesses in which cognitive dysfunction mayalso feature, such as multiple sclerosis or theextrapyramidal diseases, then the figure isclearly far higher.A recent systematic cost of illness analysis
of Alzheimer's disease in England has beenundertaken.6 This included estimates ofinpatient/outpatient day care as well as resi-dential care costs and arrived at a total figureof 1144 million pounds for 1992. Com-parison with other burden of illness analysesand adjustment for overall United Kingdomcosts makes Alzheimer's disease more expen-sive than epilepsy although less than stroke ifcommunity and non-NHS care costs areexcluded. If these are included then the com-parable figures are 1373 million pounds forAlzheimer's disease and 838 million poundsfor stroke. Moreover, this analysis did notinclude the indirect costs to family carers overand above the benefits they received fromGovernment agencies. The burden of infor-mal care from family members is substantial.
DiagnosisPublished definitions of dementia all includethe involvement of multiple domains of cog-nitive impairment with intact arousal mecha-nisms to distinguish the patient withdementia from one with a confusional state.Moreover, the cognitive impairment shouldbe of sufficient severity to result in the loss ofpreviously acquired skills such that this inter-feres with normal social or employment func-tion.The most widely used criteria are those of
the American Psychiatric AssociationDiagnostic and Statistical Manual of whichthe latest (DSM IV) has just been published.7Such criteria can provide a useful guide to theidentification of the syndrome but not to thecause. The syndrome of dementia is of gravesignificance, as it usually reflects progressivedegenerative disease that threatens the veryintegrity of the patient. Moreover, dementiaoccurs in the setting of many neurologicaldisorders necessitating a broad differentialdiagnosis and wide ranging investigations. Inthis group, the clues to the diagnosis anddirection of subsequent investigations areusually provided by the additional neurologi-cal abnormalities, although some disorders-for example, multiple sclerosis-can presentas cognitive impairment with little else to findon examination.
Alzheimer's disease is the comm.onest ofthe degenerative dementias (table). Charac-teristically, the disease starts with impairment
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Differential diagnosis of patients presenting with dementia orprogressive isolated cognitive deficits on a degenerative basis.It is not exhaustive and does not include diseases in whichdementia is not commonly the presenting feature.
of memory, at which time, if this is an iso-lated cognitive impairment, the patient wouldnot fulfil the dementia criteria of multipledomains of cognitive dysfunction. Languageimpairment with both word finding and
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Figure 1 (A) Beta A4 immunohistochemistry illustrating a senile plaque and vascular
amyloid in a case ofAlzheimer's disease. (B) Anti-tau immunohistochemistry illustratinga neurofibrillary tangle in the same case (courtesy ofDr T Revesz, Institute ofNeurology,London).
comprehension difficulties and visuospatialdysfunction, however, soon emerge. Neuro-pathologically, the disease is identified bysenile plaques and neurofibrillary tangles (fig1). The plaques consist of dystrophic neuritesclustered around a core of ,B amyloid protein,which is derived from a larger precursor pro-tein, the amyloid precursor protein (APP).8Neurofibrillary tangles are derived from themicrotubule associated protein tau, which isin an abnormally hyperphosphorylated state.9The definitive diagnosis of Alzheimer's dis-ease depends on histological confirmation,usually at necropsy, although as the histologi-cal abnormalities of senile plaques and neuro-fibrillary tangles are also found to a lesserextent in aged normal subjects, neuropatho-logical quantitative criteria have been devel-oped for the diagnosis.'0
Criteria for the clinical diagnosis have beenpublished by the National Institutes ofNeurological and Communicative Disordersand Stroke and Alzheimer's Disease andRelated Disorders Association (NINCDS/ADRDA). 1 Three levels of diagnostic cer-tainty are provided by these criteria: definiteAlzheimer's disease requires histological con-firmation in a patient who fulfils the criteriafor dementia; probable Alzheimer's diseasecan be diagnosed without histology in thepresence of a typical history and dementia;possible Alzheimer's disease is reserved forthose patients with atypical features or inwhom additional potential causes for demen-tia, such as vascular disease, are present.These criteria have been assessed against sub-sequent neuropathology and in some studieshave provided very high rates of accuracy.'2 13
Tiemey et al assessed the clinical criteriaagainst various neuropathological criteria andderived figures of 064-086 for sensitivity(cases clinically diagnosed as Alzheimer's dis-ease with histopathological confirmation as aproportion of all cases with histologicallyproved Alzheimer's disease) and of 089-09for specificity (cases clinically diagnosed asnot Alzheimer's disease without Alzheimerhistopathology as a proportion of all non-Alzheimer cases). '4
Within the degenerative dementia groupclinical diagnoses are becoming more refinedalthough there is still a poor correlationbetween histology and phenotype. Thusalthough identification of regional patterns ofdeficits can define a group of patients withfrontal lobe dementia,'5 the underlying histol-ogy can include a non-specific mild cell losswith white matter change, Pick's disease,plaques and tangles, or spongiform change.
Similarly, the focal degenerations such asprogressive dysphasia can be associated witha variety of histopathologies such as occur inPick's disease, Alzheimer's disease, neuronalachromasia, and focal spongiform change.'6The other main group is vascular disease,
usually due either to multiple cortical infarcts,to small vessel disease, or both. 17
Occasionally, a discrete small infarct-forexample, in the paramedial thalamus-cancause appreciable cognitive impairment. '8
The criteria developed by Hachinski et al'9provide a relatively poor guide when assessedagainst neuropathology, with an accuracy ofonly about 60%.20 Recently, more detailedcriteria, which utilise additional informationfrom neuroimaging, have been published.202'
Diseases with subcortical pathology, suchas Parkinson's disease, progressive supranu-clear palsy, and hydrocephalus are associatedwith cognitive slowing, referred to as subcor-tical dementia.22 Although the concept hasbeen challenged, the pattern of pronouncedslowing of cognition is useful clinically toidentify with relatively low error a group ofpatients, some of whom (for example, thosewith hydrocephalus) can be amenable totreatment.
History and examinationIt is essential to obtain a history from an inde-pendent carer, usually the spouse, as well asfrom the patient, particularly as anosognosiafor cognitive impairment occurs often inAlzheimer's disease and frontal lobe demen-tias. This should be done when the patient isnot present as carers are often unwilling to beopen in front of the patient. Details of thehistory that suggest deficits in specific areas ofcognition should be explored and enquiriesabout activities of daily living such as shop-ping, cooking, housework, and householdadministration must be included. A usefulclue is a change in the role of a patient withinthe family although this may be due to factorsother than cognitive impairment, and featuresof a depressive illness causing a pseudode-mentia should be excluded. Pseudodementiashould be suspected if the patient complainsmore of the memory impairment than thespouse, although depressive symptoms are acommon accompaniment to early Alzheimer'sdisease.23 Changes in sexual behaviour shouldbe sensitively discussed as this is an area thatcan cause considerable distress but is rarelymentioned by the spouse.A general medical history must be obtained
including current and previous medications.A family history of dementia is often presentif carefully and specifically sought as most ofthe degenerative dementias can occur asautosomal dominant as well as sporadic dis-ease. With the younger patient it is necessaryto enquire about employment and all patientsshould be asked about driving, not onlybecause it gives a guide to cognitive functionbut also because of the medicolegal implica-tions (see later). It is important to emphasisethat whereas dementia is defined by the pres-ence of multiple domains of cognitive impair-ment, patients will often start with a singledeficit and this may not always be memory;Alzheimer's disease may occasionally presentwith visuospatial dysfunction, visual disorien-tation, dysphasia, or dyspraxia. A focal pre-sentation may be characteristic of otherdementias such as Pick's disease.
Examination should ensure adequateexploration of the major domains of cognitivefunction and must involve some simple tests
of function of the non-dominant hemisphere.The mini mental state examination24 is a briefbedside test of cognitive function that is nowwidely used and although not designed toprovide any detail of neuropsychologicalfunction it is easy and rapid to give to outpa-tients.25 The clinical dementia rating scaleprovides an overall staging of the functionaldeficit.26 CAMDEX and its associated cogni-tive assessment CAMCOG, provide a morecomprehensive diagnostic assessment,27 buttake time and can be inflexible. The USConsortium to Establish a Registry ofAlzheimer's disease (CERAD) has attemptedto develop a battery of tests useful for theearly diagnosis of Alzheimer's disease28 butthese are more appropriate to the detailedinvestigation of neuropsychological functionthan as simple bedside tests.On general neurological examination the
presence of pyramidal signs, extrapyramidalfeatures, or peripheral neuropathy maysuggest a diagnosis other than a simpledegenerative dementia. Many patients withAlzheimer's disease may have extrapyramidalfeatures, however, most commonly rigiditybut occasionally bradykinesia, which mayrelate to additional Lewy body formation.2930A careful general medical examination isessential as this may provide important cluesto secondary causes of dementia-for exam-ple, cardiac murmurs in vascular dementia orcytomegalovirus retinitis in a young patientwith cognitive impairment due to HIV infec-tion.
InvestigationIdeally all patients should undergo formalneuropsychological assessment to determinethe extent and severity of the cognitive deficit.Routine investigations of haematology andbiochemistry should also include treponemalserology, thyroid function, vitamin B12 andred cell folate, chest radiograph, and neuro-imaging. Scanning by CT will exclude spaceoccupying lesions and hydrocephalus andmay also indicate changes in white matterassociated with demyelination or vascular dis-ease. Special orientation of the plane of CTcan show medial temporal lobe atrophy inAlzheimer's disease.3' Magnetic resonanceimaging is of greater value than CT andregional volumetric studies may increasinglyaid the diagnosis of specific degenerativedementias (fig 2).32 It is recognised that inelderly demented patients routine neuro-psychology and neuroimaging may not bepractical; nevertheless, this is the ideal thatshould be sought. An EEG can be valuable;early slowing would favour Alzheimer's dis-ease by contrast with a normal EEG com-monly found with Pick's disease and otherfrontal lobe dementias; periodic complexesmay be important in the diagnosis of priondisease.
In some patients a wider range of investiga-tions is necessary. Specific blood tests mightinclude screening for metabolic disorderssuch as Wilson's disease, metachromatic
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Figure 2 (A) MRI showing bilateral hippocampal and temporal lobe atrophy in a case ofAlzheimer's disease. (B) MRI showing asymmetric anterior hippocampal, amygdala, andtemporal lobe atrophy in a case of Pick's disease (courtesy ofDrN Fox, St Mary'sHospital, London).
leucodystrophy, and GM2 gangliosidoses;Tests for HIV should always be considered inunexplained cognitive impairment, particu-larly in young patients. Examination of CSFis often carried out in patients with preseniledementia but is usually normal in degenera-tive dementia: a raised protein or cell countwould suggest the possibility of a vasculitis or
other inflammatory disorder and, in view ofthe potential treatable nature of these dis-eases, may be an important finding. It is nev-
ertheless uncommon to find an abnormal
CSF in the presence of a normal MRI.Muscle biopsy may be indicated to look forragged-red fibres in association with mito-chondrial cytopathies. Very occasionally abrain biopsy may be indicated if a treatablecause such as cerebral vasculitis is suspected.In hereditary disease appropriate geneticscreening for the Huntington mutation, amy-loid precursor protein mutations, and prionprotein gene mutations are all available;whether apolipoprotein e4 allele genotypingwill prove to be of use in diagnosis and man-agement remains to be seen.33 Functionalimaging with PET is still largely a researchinvestigation, but single photon emissioncomputed tomography (SPECT) is now morewidely available and may be valuable in show-ing a posterior (common with Alzheimer'sdisease) as opposed to anterior pattern ofhypometabolism. 34
PreventionAt present there are few causes of dementiathat are preventable. Control of hypertensionmay prevent some of the cases of vasculardementia although there is no simple relationbetween the development of dementia andvascular risk factors. With the discovery ofthe Huntington's mutation, amyloid precur-sor protein mutation, and prion proteinmutations, prenatal testing is likely to becomemore important in young onset dementias.
PrognosisThe diagnosis of dementia carries a graveprognosis. Prompt treatment of some under-lying diseases such as neurosyphilis, cerebralvasculitis, and metabolic disturbances canresult in stabilisation and even reversal.Unfortunately most follow a relentless pro-gression. This may vary from the devastat-ingly rapid deterioration measured in monthsin some cases of sporadic Creutzfeldt-Jakobdisease to a deterioration measured in 10-15years for some of the focal degenerations.The median survival from diagnosis inAlzheimer's disease is in the range of seven to10 years, although some patients may have aprolonged mild stage. 35 Average rates ofdecline are in the order of 3-4 points on themini mental state examination per year.
Communication and counsellingAlthough grave and tragic information oftenhas to be imparted a frank discussion whenthe diagnosis and prognosis are known isessential. Commonly, however, the diagnosismay be unclear in the early stages. Thus whenfirst seen the patient may show only mildchanges in cognition and in the absence of aspecific clinical test there is a natural reluc-tance to make a diagnosis such as Alzheimer'sdisease: inevitably there is a burden of uncer-tainty that has to be shared between thepatient, the family, and the doctor.Nevertheless, there is still a reluctance to dis-cuss Alzheimer's disease and its implications
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that is comparable with that associated with adiagnosis of cancer 10 to 20 years ago. Earlydiscussion of the implications and how helpcan be offered, together with appropriatecounselling, is vital. The disease affects notonly the patient but the entire family: inyoung onset dementia the illness can be dev-astating for the children and in older patientsdisruption of the shared plans for retirementcan present a considerable sense of loss.Memory clinics can provide diagnosis,
counselling, and advice but most longer termsupport is provided in the community by thesocial work and community psychiatric ser-vices. The Alzheimer's Disease Society pro-vides additional information and support.Some smaller patient support groups are nowbeing established for some of the rarer disor-ders such as Pick's disease and Creutzfeldt-Jakob disease (see appendix).
Neurological follow up of cases of demen-tia is indicated when the diagnosis is unclearor when specialist advice is needed for someof the rarer diseases. In general, however,management is shared between the generalpractitioner, hospital, and community psychi-atric services.
ManagementThe specific treatment of dementia relates tothe underlying condition. There are the rareinstances of reversible dementia such as thoseassociated with hydrocephalus, hypothyroid-ism, cerebral vasculitis, neurosarcoid, orneurosyphilis. For most, there are no specifictreatments although there is now the emerg-ing prospect of symptomatic treatment.Where there is any doubt about the diagnosisor the presence of depressive symptoms,patients should be given a trial of an antide-pressant, commonly one of the selective sero-tonin uptake inhibitors that avoid theanticholinergic side effects of tricyclic antide-pressants and are better tolerated. This willhelp to identify patients with depressive pseu-dodementia and may also improve cognitivefunction in depressed patients early in thecourse of Alzheimer's disease.
Attention has recently been directedtowards enhancing cholinergic transmission,which is reduced in Alzheimer's disease dueto disruption of the subcorticocortical cholin-ergic projection. Most attention has beendirected towards the acetylcholinesteraseinhibitors after the report of a beneficial effectof tetrahydroaminoacridine (tacrine). Recentstudies have confirmed this. The study ofFarlow et al using a parallel design with 468Alzheimer patients given tacrine in doses of20-80 mg or placebo for 12 weeks showedimprovement both on a global clinicalimpression of change and the cognitive subsetof the Alzheimer's Disease assessment scale(ADAS-COG).6 About half the patients onthe highest dose had an improvement of 4points on the ADAS-COG, which is equiva-lent to about six months of normal sponta-neous decline. The most recent study37comprised 653 patients on treatment for 30
weeks with doses of tacrine up to 160 mg perday and improvement was seen at the higherdose in about 40% of patients who were ableto complete the study with an improvementof more than 4 points on the ADAS-COG;however, 43% withdrew due to cholinergicside effects. Changes in transaminases reflect-ing the hepatotoxicity of the drug are com-monly seen, with 29% of patients developingabnormal transaminases of more than threetimes the upper limit of normal and abouthalf showing some abnormality. This is nor-mally reversible on cessation of the drug andpatients can often be successfully rechal-lenged.
Tacrine (Cognex) has received a licencefor use in Alzheimer's disease in the UnitedStates and more recently in France, but notin the United Kingdom. Further acetyl-cholinesterase inhibitors are likely to becomeavailable over the next few years and there isintense activity within the pharmaceuticalindustry to develop other symptomatic treat-ments for Alzheimer's disease and, in thelonger term, drugs that may alter the underly-ing disease process. Thus efforts are beingdirected towards drugs that might inhibit thehyperphosphorylation of protein tau, whichleads to neurofibrillary tangle formation andthe deposition of /3 amyloid protein associatedwith senile plaques.As well as these exciting developments in
Alzheimer's disease, treatment of behaviouraldisturbance is important and is common tomany of the dementias. Hallucinations,aggressive behaviour, and psychoses can bedifficult to treat as many patients are verysensitive to the effects of neuroleptics, partic-ularly patients with diffuse Lewy body diseasein whom rapid deterioration in motor andcognitive function can occur. The judiciousand closely monitored introduction of a neu-roleptic drug, however, particularly one withless extrapyramidal side effects, may be bene-ficial. Sleep disturbance is also common butcan respond to small doses of a rapidly actingbenzodiazepine such as temazepam.
LiaisonIn the United Kingdom neurologists tend tosee younger patients presenting with preseniledementia or cases of dementia with additionalneurological abnormalities. Most cases ofdementia that occur in elderly people andwhich are due to Alzheimer's disease are seenby psychiatrists and geriatricians. By contrast,in the United States and in many Europeancountries, Alzheimer's disease is predomi-nantly seen by neurologists. Dementiaencompasses many disciplines and good man-agement will involve care by neurologists,psychiatrists, and geriatricians as appropriate,together with neuropsychologists and special-ist nurse counsellors. Liaison with generalphysicians, surgeons, and other professionalsis also important to ensure that the patientgets appropriate care for other medical prob-lems. Untreated or inadequately managedconditions can often exacerbate confusion
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and behavioural disturbance, yet there issometimes reluctance to treat if there hasbeen a diagnosis of dementia.
As well as medical and paramedical liaisonother agencies are important, particularlywhen patients are still in employment. Wehave clear guidelines for employment of thosewith epilepsy or cardiac disease who are air-line pilots, public service vehicle drivers, etc.For those with cognitive impairment theopportunities for harm are far greater but theguidelines fewer. Even for driving the infor-mation is unclear.38 Once a diagnosis ofdementia has been made then the Driver andVehicle Licensing Authority should beinformed by the patient but there are fewguidelines as to whether the patient is able todrive or not. Unfortunately for many patientsdriving is seen as important for maintainingindependence in society and self esteem.
Although the ideal is for, seamless carefrom the initial neurological assessment anddiagnosis through the longer term manage-ment within the community and on to longterm hospital care, this is often not achievedand one is faced with crisis management ofthe patient who is unable to be managed athome. This makes the early diagnosis, expla-nation, and prognosis all the more important.
AppendixAlzheimer's Disease Society (Creutzfeldt-JakobGroup), Gordon House, 10 Greencoat Place,London, SW1P 1PH, UK.
Pick's Disease Self Help Group, National Hospitalfor Neurology and Neurosurgery, Queen Square,London, WC1N 3BG, UK.
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