Series Editor: Gr. eme J Hankey, MO, FRACP 11: Disorders of memory and intellect John D G Watson Development of effec tive treatments for dementia is a major challenge L\IPAIRED IJIo'TELLECTUAL FUKCTlOS has profound effects on pati ents, th eir famil ies and society, b ut medical and community services are far fro m optimal. Dementia is mo re commo n with advancing age . In childhood, gene tic disorders acco u nt for a number of co gn itive problems. In young and middle-aged adults, traumatic brain injury is a m ajo r ca use; hypoxic/hypot en sive brain damage (often associat ed with traumatic in jur y) also accounts for a number of cases. In olde r adults, acquired d em entia is th e major cause of disordered int ellect . At th e age of 60 year s, the prevalence is about 1%; 3%--1 1% of all comm uni ty-living adults old er than 65 years are affected ; by th e age of 85 , between 20 % and 50% are affected . M ore tha n 50 cau ses of demen tia hav e been identified ; the m ost com mo n is Alzheimer's di sease (AD), followed by vascular d ementias (VAD) . The current chall enges are early detection of patient s with demen tia, ide nti fication of th e causes of d em en tia, and th e development of major th era peu tic agents. As our po p ulatio n ages, demen tia will incre asingly account for m edical, social and finan cial p roblems. Cognitive functions and neuroanatomy Within the b rain, cognitive functions may be localised or dis- tributed. C urrent th inking is th at th e brain has a gre at d eal of distributed organisation, with many functions more specifically located to one part of th e br ain . Cognitive ab ilities d epend on on e another, to some extent in a hierarchical manner. Attention, conce ntra tio n, alertness and moo d are card inal. People with attentional d isorders may appear to have m ore specific defects (a false localising sign), suc h as word-finding difficulties. However, pa tients without overt art entional problems often pr esent beca use of concerns about m em ory impairm en t. One can ofte n diagnose the cause as anxiety, d epression, or sleep d ep rivation . The se are very ame nable to tre atment, especially in comparison with true d em entia . f.ocallS6(f brain functIons: Most researchers beli eve th at th e brain has co mplex, overlap ping sets of connections th at follow both parallel and hiera rch ical organisation. Some regions in th ese connections are so cr ucial th at a fun cti on is attributed to th em (ie, th e fun ctions arc relatively localised). Roy. 1 PrInce Alfred Hospit.ill, Sydn e y, NSW, John C G W, tl on , OPhil. MBBS. FRACP. D,rector . Neuropsychology UIlII. and Associate Professor 01 Med 'c,ne, University of Sydney Repronts will oct be availab le from me author Corr espondence Associate Professor J D G ....atson , Neurop sychology Unit. Royal Prince Allred Hosp'tal . Missenden Road , Camperdo wn. NSW 2050, iwatsonO mail.usyd,edu.au MJA Vol175 15 October 200 1 : . . • The clinical approach to the patien t with a suspect ed disorder of memory and intellect is to establish whether it is dementia. which parts of the brain are affected. what is the cause, what is the prognosis, and wha t can be done about it. • The diagnosis of demen tia usually requ ires the involvement of memory and at least one other cognitive system. Delirium and depression are important differentia l diagnoses . • Patient s with dementia should usually have some simple investigations afte r a careful history-taking and examinat ion to identify "reversible" caus es. • The commonest ca use of dementia is Alzhe imer's disease, in which short-term memory disturbance is usually prominent. Other causes of dementia include cereb rovascular disease, t ewv-ooov disease and Pick's disease . There is now hope for patients with Alzhei mer's disease (which can be treated with some success with cholinesterase inhibitors) and patients with vascular demen tia. in whom aggressive control of caus al risk factors may retard progression . The classical exam ple is of left inferi or frontal dama ge cau sing language di sorders. Other localised functions include vision (occipita l lobe) and praxis (th e ability to form in th e mind th e steps needed to carry out a task), visuospatial ability and na vigat ional skills (non- d ominant parietal lobe) . Dis tributed function s: These arc an atom ically less well-defined cognitive processes than langu age or vision. Attention and memor y are the two m ost impo rt ant exam ples. Di sturbed atten tion lead s to distra ctibility and inability to perform the task. at hand. Pa tients may pe rsist inappropriately with actio ns or respo nses, not ch anging their mental set to new requiremen ts (perseveration) . D isordered attentio n leads to disorientation in time an d oft en in place . Delirium or the CKll U confusWnal SUl U is the corres po ndin g clinical syndrome. Consciousness m ay also be im pai red or cloudy, but th is is not th e prima ry prob lem. The fun ctional anatomy of th e anentional system includes the brains tem , th alamus and fronta l cortex, with some righ tsid ed emphasis for the latter. Focal or diffuse brain in jury may cause att entional probl em s. The causes can be metabolic, toxic, pharmacological o r st ru ctu ral; th e first thr ee arc more com mon . I Gathering an accurate history is the be st 433 MJA Pract ice Essentials approach to such patients. Investigations may be useful, includ ing brain scanning (CT or MRI), electroencepha lography (EEG) and lum bar puncture . There are vario us conc epts of memory, but all agree that there is mo re tha n one type. This is of practical benefit, as differ ent diseases have different effect s on memor y.a-s For example, patien ts with Alzheim er 's disease ma y recall how to d rive a car, but no t where they left the keys or the route. Box I shows a diagno stic approach based on pattern of memory loss. We do not know the cau se of AD . About 2% of cases are dependent on a single gene mutation, involving chromosome 2 1, 14 or 1. Families with these mutations have early-onset AD and are much studied in the hope of finding the underlying path ological mechanisms. There is recent evidence that genes on chromosom e 10 may be risk fact ors for the more common late-onset AD. ~ ·6 On chromos ome 19 lies the apolipoprotein E (APOE) gene, which has a number of allelic forms. The APO EE~ allele confers an increased risk of develop ing late-onset AD (heterozygotes have a two- to fourfold increas e in risk, homozygotes four- to eightfold). This allele ma y affect the general tendency to neuronal damage rather th an the specifics of developing AD; it may also increase the risk of poorer outcome after acute head injury." Risk factors for AD are increasing age and family history. Significant head injury may confer a slight increase in risk (say, twofold), but there are conflicting studies. Possible protective facto rs include higher levels of educ ation, oestrogen ingestion , non-steroidal anti-inflamm atory drug use, and viramin E. Pathogenesis proba bly depends on predisposition and environmental factors. This will have therapeutic implications, as it seems unli kely tha t tr eatm ent ta ken after AD onset will reverse the damage. If an agent is developed to be taken for many years by tho se at risk of AD, precise screening will be ne eded and Costs are likely to be high . Causes of dementia Alzheimer's disease This dis ease is defined by its neuropathology of extraneuronal senile plaq ue s, containing a core of am yloid protein, and neurofibrillary tangles, conta ining paired filaments in a helix formation. It is believed that cells containing tangles are degenerating and will subs equently die . T heir loca tion and numbers are likely relat ed to the type and severity of cogniti ve dysfunction. Major sites are the pyramidal cells of association cortex and in the hippocam pu s. They are also found in a number of subcort ical nuclei with diffu se projections to the cor tex, such as the nucleus basalis of Me yner t, the proje ction of which is cho linergic. This is the rationale for using centr ally act ing cholinergic medi cations. 1 : Al gorithm of decision processes In diagnosing non-d elirious pat ients with memory problem s I Mild mem ory pr ob lem s Psychological factors , stress ere. I Mod era te m emory p ro blems No Sudden psychological factors Temporal Seve re me mory p roble m s Poor test co nsistency or I PSyc!lological I anxiefy, depression , etc. Mal inge ring sub trontal palllOlogy (eg, stroke or lumo ur) ex~anafion: Memory probl am in prcooruon 1001ilE/r cogn itive problems Sudden Gradual Temporal or sub!ron la l pathology (eg. small stroka or lumour) oerscaterer or parieta l lumour, Parkinson's disaasa , mull iple scle rosis Memory problam not in proportion to omer cogni tive problems Long dueane n Gradual Tho ught disorder or hall oo natio ns Psychosis Fronl al lumo ur wilh CSF obs truction NO thought ersoreer Hunlingl on's d isease , Pick's disease, vascular Lossot demen~a Personal ide ntify intact personal idenlity Shan history Long hislory BiITonlalor temporal lumour Alzheimer s dise ase or simjlar Transien t globa l amnesia . herpes s imp~x erlCepha lilis , c aetererposienor c ere bral arte ry jntarc lion Hysteria or tugue state Note mat the dec ision pat hs and examples of illnesses are not exhaustive. Adapted and much simpljlied Iro n Kap ur 198 8 , Fig ure t.t 434 MJA Vol 175 15 Octobe r 2001 ~' _ \ Practice Essentials Vascular dementias Al though th ere i s acceptance tha t cerebrovascular disease causes deme ntia, there is less agreement on it s definition and preval ence. Vascul ar d em entia (VA D ) o ften coexists wi th other for ms of dem entia , especiall y A D. There is overlap in the risk factors for bo th AD an d VA D, and trying to di stinguish ri gi dl y between th e two m ay be ccunte rp ro ducrive.s VAD pr ob ably accounts for up to 20% o f d ementia in West e-n society. The clinical p icture differs between pati ents w-rth multiple larg e-vessel infarc ts (m ulti -in f ar ct dementia) and those wi th sm all-vessel disease affecting the wh ite m atte r . The clin ical cou rse is often one of flu ctua ti on , and st ep wi se deterior ation i s a hallmark , oft en with evidence o f stroke. O cher suggestive features include early gait disorder, urinary difficulties and parkinsonism. Diseases oth er than stro ke can cau se VA D, including vasculitis. recurrent sm all emboli, recurrent haemorrhages, and infections suc h as syphilis and L ym e disease. 'Whi t e ma tte r changes on computed t omography (CT) and m agn etic resonance i m agin g (.\t Rl) are com mo n ly th ought to indicate cereb ral isch aem ic di sease, b ut they al so occur i n n or ma l agei ng. A recen t study showed th at th e prevalence and d egr ee o f white m atter lesions in crease wi th age; at any age wom en have m ore lesions, particul arly i n the fron tal lobes." The aut hors sp ecu late that th is m ay explain the h igher incidence of dem entia in women tha n men , especially at l at er ages. A t pr esent , m ost au thoriti es wou ld suggest that cer ebrova scula r r i sk factor m anagem ent is the correct app roach to VAD, but the evidence i s not stro ng. There i s on ly one me thodol ogicall y sound trial, i n a group o f 3 7 patient s who received 325 mg o f aspirin daily. Compared ....ith 33 controls, th e r at e of cogniti ve decl ine slowed. w Another observational stud y found that patients older than 50 years taking sta tin s arc less li kely to have d ementia , with th e effect seem i ngly rela te d to the m edications per se, and not the ch olester ol level.'! Large multicent re, r and om i sed , d ouble-blind, pla cebocontrolled trials would be best in assessing the effect of 2 : Criteria for e1in'ul d iaenosis of probal* AD C.se history: ProC.....lve eocnitt'te chances A ez-veer-oro man presented bec ause of worsening memory. One 01his adult children had suddenly separated. so the pat ient had more responsibility for . ing atter his grandchildren. He was thought to be depressed. Antidepressants caused some improvement in mood. but had little effect on memory. The patient still vcrkeo part time in an unskilled jOb he had held for many rears and drove a car without getting lost His father had displayed some features of dementia at about the age of 80. He was slow and vague in conversation and scored 14/30 on the Fclstein MMSE," well below the cut-off for likely severe co gnitive impairment. There were no primitive reflexes or focal neurological finding s. The gail was a little slow and stooped, with poor arm swing. A CT scan of the brain was normal. Neuropsychological assessment demonstrated severe constructional apraxia, impaired semantic memory, executive dysfunction , with some impairment of recent memory, A positron emission tomography scan of brain metabolism'Sdemonstrated impairments in the pari etal and temporal lobes, consistent with dementia of the Atzneener type. Within a year he had to give up work, Repeat nevoc svcnocarcat assessment showed worsening function, now with impaired ep isodic memory. He was commenced on ooneoezn. but could only tolerate a dose of 5 mg per oav His rate of cognitive dec line slowed over the ensuing three years. Comment: This case is not unusual. There is some family history, but not especially strong . Depression was considered and treated . The constant pattern 01the patient's daily life probably enabled him to continue at work for longer Ihan might have been expected . His presentation in normal conversation was slow and vague, but only when he was ch allenged by a lormal cognitive assessment did the severity of the prob lem become evident MJA Vol 175 15 October 2001 Gener al • Onset between 40 and 90 years • Dementia established by clinic al examination and/or cognitive tests • Deficits in more than one area of cognition • Prcqressive worsening of cogn itive state • No evidence of d elirium (at least initially) • Absence of general Of neurologic al disease that could account for the progressive cognitive deficits Supporting l eatur es • Progressive deterioration of spec ific functions such as language, praxis and percept ion • Impaired activities of daily living • Altered behaviour • Similar family history • Progressive cereb ral atrophy· on computed tomography or magnetic resonance imaging: normal lumbar puncture: electroencephalog ram normal or nonspecific chang es Features c onsIstent with diagn o sis • Plateaus in progression • Associa ted symptoms: depre ssion, insomnia, incontinence, delusions, illusions, hallucinations, behavioural outbursts, sexual disorders, weight loss • Certain neurological signs: increased muscle tone, myoclonus, gail disorder, seizures • Structura l brain scanning normal for age· Featur es that make dIag nosis uncert etn or un likely • Sudden onset • Foca l neurological signs , especially if early in the course • Seizures or gait disturbance early in the course AOap!l!'CIlrom McK haM et ai " ,ge,. ." " Espec lllllV initially !her e are otten no (itagnosbC features on S!l'uCIU'a1 ornag.ng....m C T Of MRI . aIIhougn hn::bonaI sc anr>ing tecIYliques . in parbcular QU8ntJl allve POSItron emoSSIQfl ItllTlOg-"raphy . may be very helptvl 435 MJA Practice Essentials 3 : Fe atures di s tin guishing d elirium, d ementia an d d epre ssion Feature Delirium Dementia Depression Onset Acute Insid ious Ac ute or subacu te Time cou rse Fluctua tes dur ing single day Worsens over lengthy time ; cognit ive loss precedes depression; behaviour worse at night Depression precede s co gnitive loss Weeks to mont hs; otten prior history Duration Hours to weeks Months to years Attention Impaired Little affected; impaired in later stages Unimpaired Orientation Usually impaired in time, often p lace, sometimes person Impaired in later stages Unimpaired Alertness Abnorma l: low or high Normal, at least initially Norma l or low Cons istency of performance Variab le Consistent Variable and slow Sleep-wake cycle Always affected Affected in later stages Difficu lty sleepi ng . early morning wakening Short-term memory Always impaired Not affected initially Poor effort may lead to variable impairment Lonq-term ep isod ic Impaired memory Impaired; recent loss e xceeds remote Equal recent and remote loss Perception Otten visual illusions and halluc inations Commo nly impai red in later stages Normal , unless psychotic de pression Cogniti ve loss Unaware or den ied Minimised by patient Maximised by patient Word-find ing d ifficulty, though ts of deat h and dying Suicidal thoughts "Near miss' frequent "Don't know" freq uent Speech and thought Disorganised , deluded, slow or rap id Ramb ling , impersistent Answers given Partly adap ted from Feinberg and Goodma n. 1984.'· ,.- z aspmn, sratins and other treatments. H owever, there are many technical issues, such as which cognitive, be havioural and global domains to assess. Because vascular risk modification benefits p atients in other ways, there wou ld be et hical difficulties in administering a placebo to pa tients with a diagnosis ofVAD, or with vascular risk factors. Other causes of dementia T h ere are many other causes of d em entia, so me less ra re th an previously thought. F or exa mple, Lewy bod ies are found in the b rains of2%-9% of elde rly p eop le, an d de mentia with Lewy bodies (D LB) accounts for 12%- 27% of cases previou sly diagnosed as AD. 12 D L B has the features of fluetuating cognition with m arked va riation in attention and ale rtness, visual hallu cin ation s and p arkinsonism (u su ally without response to L-dopa) . N eurolep tic agents, presc ribe d for the hallu cin ations , often considerably worsen patients with DLB. As with VAD, DLB overla ps co ns ide ra bly with AD . Another condition, Pick's disease, is strictly d efined by the presence of characteristic neuropatho logy, but the rubric is now often used clinically for dementia of th e frontal-lob e type, an d frontotemporal dementia.'? Some cases are fa milial. In its complete form , patients d isp lay diso rdere d executive fu nction (goal-sett in g, plan ni n g), disi nhibited behaviour and lan guage dysfunction. Cogni tive p rob lems usualIy seen in AD , such as visuospatial diffic ulties and ap raxia, are not common early in Pick's disease. Box 1 conta ins some other causes to be co nsidered. 436 Dia gnosi s Do es the patient wi th cognitive impairmen t have dementia? In deme ntia, th ere is acq uired cognitive loss in an alert p er son, interferin g with daily living, soc ial an d occ u pational ab ilities. The d iagnosis is m ad e on history and/or cog nitive testing . T he usual d efinitions require th at at least two areas of cog nit ion (me mory, prax is, langu age, visual percep tion, visuospatial abilities, and executive skills) be affected, one of th em m em o ry. Simple cogn itive sc reen ing tests that cover a n um ber of cognitive domai ns (and take about five mi nutes) can help d etect pa tients with dernentia.v-" Some kind of form al testing is important, as m any patients with mi ld to m oderate dementia do not p resent too badly in no rmal co nversation (Case histo ry). Box 2 outlines the features needed for a diagn osis of AD, th e m ost common d ementi a. Fam ily m em bers are ab le to ma ke the d iagnosis: a meta-an alysis of studies co m paring infor m an t questio nnaires with brief co gnitive tests fou nd that the for mer were a litt le more sen sitive with the same specificity, and d eserved to be u sed m ore widely." T h e m ajor di fferential di agnoses ar e de lir ium an d d epressio n (Box 3) . When a pa tient's confusion leads to florid behavioural disturbance, the dia gnosis of d eliri um is usually sim p le. M ore problematic is th e patien t with quie t delir ium: the impai rment of co nsciousness is sub tle and the behavio ural ch ang e ofte n n egative rat h er than di srup tive, so the d isord er may be mi ssed. A me ta- analysis of me thods to disMJA Vol 175 150cl ober200 1 I'U A Pract ice Essentia ls nnguish de pression and dem entia also concl u ded th at info rmant questionnaires performed as we ll as co gnitive scree ning rests .w Sub cortical demen tia m ay be found in H u nt ington 's and Parkinson 's d iseases, AIDS en ceph alopath y, mu lt iple sclerosis and cereb rova scu lar disease, alt hou gh the latt er ofte n causes a mixed pictu re. What part of th e brain is affected ? It helps p ractically and theoretically to di vid e d em entia according to what p art of th e brain is affected : cort ical o r subcortical. AD and C reutzfel dt-jakob disease are examples of the former. Lo ss of co rt ical grey matter lead s to co rresponding cognitive d efects; th us, dist urbed m em ory, lan guage, praxis an d visu ospa tial abi lities arc th e pr ed omi nant featu res in AD, wh ile attention and frontal-e xecu tive fu nctions are well p reserved , at least in itially. In subcortic al de ment ias, the cogn it ive d efects ari se from the loss of sub cort ical regu lat ion o f cortex, espe cially p refrontal. Typically, the re is slowin g o f cognition and responses, p er son ality change, and mood di sturba nce. Patients are oft en uninterested in th e world and m ent ally inert. Reduce d attent ion leads to p oor encod ing and th us poor memory. Recogn ition mem ory is b ett er than free recall. Whom to r efer Box 4 outlines th e diagn ostic ap p roach in a p atient with d em entia. O n e co u ld argu e that if syste ma tic enquiry an d exa mina tion provid e eno ug h infor mation to d iagnose AD with out any u n usu al fea tures, th en spec ialist referral is no t n eeded. H owever, the d iagn osis is so serio us for all con cerned that patients, relatives an d G Ps often feel more comfort abl e if it is su ppo rted by a specialist, usually a general physician , neurologist, geriatrician or psychiatr ist. O ther factors det er mining referral inclu de regi on al var iat ion in th e o rgan isation of assessm ent services, access to C T and M R scannin g, and requirements for access to subs idised d ementia med ication s and subs id ised nu rsing home care . 4: Dementia: c li nical approach and Inves tig at ions History Obtain the history from a reliable informant as well as from the patient. Key points are the areas of cognit ion affected , especially compa red with previous funct ion and skills, and the mode of onset and progression. Actual examples of cog nitive impairment are very usetot Becoming hopelessly lost in previously familiar territory is significant. Forgetting how to use familiar household objects or appliances sugg ests apra xia; not recognising objects for what they are suggests agnosia. Not being able to plan and prepare a meal sugges ts a d isorder of execut ive func tion (often related to frontal lobe problems) . Neurolog ical and ph ys ical exa mi nation Carry out genera l and neurological examinations. For example , left ventricu lar hype rtrophy, hypertension, and other vasc ular risk factors, when co upled with foca l neurolog ical features, suggest vascu lar d ementia. Parkinsonian features sugg est Parkinson's disease or dementia with Lewy bodies . Brief co gni t ive test s The Mini Mental State Examination (MMSE) and similar short instruments are only screening tests." The lower the score the more likely is dement ia to be prese nt. Early demen tia, espec ially in a patient with bette r education and intellect, is unlikely to be picked up by these tests, Labo rato ry tests and " reversi b le" dementia Lists of laboratory tests have been suggested for detecting "reversible" dementia. Recent evidence suggests that such gene ral screening is unlikely to c hange outcomes. If the case is typica l of Alzheimer's disease , then there is lilli e ind ic ation tor a wide range of tests. Patients with "reversible" dementias , even if identified and treated , rarely improveet.ee Appropriate laboratory tests include standard haematology and biochem istry (includ ing serum calcium), thyroid function, vitamin 8 '2 levels, and syphilis serology. If history and examination are sug gestive , other tests may be valuab le, such as immunological tests, erythrocyte sediment ation rate, toxico logical and heavy metal screens, cerebrospinal fluid examination, and HIV tests, Rarer cause s of dementia are possib le: later Investigations may include tests for Whipp le's and coel iac d isease, and genetic tests. Occasionally even a brain biopsy is done, especially in rapid ly prog ressive dement ia in a younge r person . Neuroimagi ng In the absence of conclusive evidence as to the utility of computed tomog raphy (CT) sc anning, I believe this should be done on all patients to rule out certain causes ot cogn itive c eclin e such as subdu ral haematoma. Magnetic resonance imagi ng (MRI) may be more useful, at least in a subset of patients. In c ases of dementia, CT and MRI may be co mpletely normal, may show focal or general atrophy, or may show other relevant abno rmalities. In the tertiary referral setting, funct ional imag ing , especially glucose uptake as measured by pos itron emission tomogra phy. can be very helpf ul in early or atypical cases. Neurop sy c ho lo gical test s Dementia present for some l ime may not need specia lised neuropsycholog ical assessmen t. However, formal neuropsychological testing is valuab le early in the cours e of dementia, or if there are unusual features, with dementia in a younger perso n, or when there is the possibility of depression or similar. MJA Vol 175 15 October 2001 437 MJA Practice Es s e n tj a ~ s Pro gno sis The p rogn oses of AD an d VAD d o n ot differ mu ch . Progression rate before the tim e of d iagnosis in fluences subsequent p rogress. If two pa tient s ha ve similar cognit ive diffic ult ies at d iagnosis, th e one with th e lon ger time to th at point will do better than the othe r. T he estimated med ian su rviva l after onset varies fro m five to n ine years. A recen t Canadian study has readd ressed this issue, arguing that there has been failure to cons ide r pa tients who progresse d and d ied too rap idly to be included in studies (length bias).H F or both AD and VAD, the un adjusted med ian survi val was in accordance with other stu d ies at 6 .6 years. T he ad justed median su rvival was much less at 3 .1 years for prob able AD , and 3 .3 years for VAD . The two-year su rvival rate for pa tients in the co mmun ity is about 50% more th an for th ose in nu rsing homes.w M anagement There are no speci fic tre atments for most causes o f dementia. M any therap ies have been tried (Box 5) . T he effect iveness of most h as not bee n well pr oved or disp roved. It is important to expla in to th e p atient and family the featu res of the de me nt ia an d p rognosis, and to d iscuss th e m ajor cognitive prob lem s. Review of m edications that m ay worsen matters is nee ded, an d advice on minimising alcohol in take. T reat m en t of coexisting con ditions, such as d epres. sion or poor hearing, can h elp many. M anagement of behavioural and psychiatr ic m anifestations is very ch allenging, especially agit ation and wandering. Simple beh aviou ral techniques, environmental manipula tion and a stron gly structured routine may help. M ed ications are ofte n used , but their safety and efficacy are n ot well demonstra ted . As mo re b asic activi ties of da ily living are lost, the level of ca re n eed ed in creases, eventually requ iring nursing home care. I d iscuss this with the family early to initiate steps to ident ify op tions an d costs. I recomm en d early contact with the Alzheim er 's Associatio ns, and discussion of financial, estate and gu ardia nship issu es. Driving sho u ld be d iscussed. Earl y in the illne ss it may be possible to drive, with geogr aphical or diurnal licence rest rictions. I often refer for an on-road d riving assess ment. Caregiver distr ess, fatigue, de press ion, physical illness, and subs tance m isuse are ofte n serious problem s. For fami lies of those wit h m ild to moderate AD, counse lling and supp ort may delay the tim e to n ursing home placement by a year." Respite care is likely to be useful, but is often h ard to obtain. In Australia, there are strong Alzheimer's Associations. Th ey organise semina rs and education programs for carers and he alth profession als, an d provid e publications and video- 5 : Treatments that have been tried for dementia Acetyl chOline manipulation s Certain acetylcho linesterase inhibitors (donepe zil, rivastig mine. galantamine) cente r modest improvements in patients with Alzheimer's d isease (AD) in the areas of cognition, behaviou r and activities of daily liVing (El ),h Z! There is no evide nce that nicotine is a useful treatment for Alzheimer's disease (E3z),2lI Extra cons umption 01lecithin. a major dietary source of cho line, is hypothesised to increase the production of acety lch oline and reduce symptoms of dementia, but randomised trials do not support its use (El), 29 Neuroprot ectlon Vitamin E may benefit peop le with AD, but cu rrently there is insuffic ient evidence of efficacy (E2).30 There is promising evidence for a benefic ial effect of seleg iline in AD, but not enough to recommend its routine use (El ).31 Hormonal t he rapy A meta-analysis of obse rvational studies on hormone replacement therapy and cogn ition sugges ted a decre ased risk of dementia, However, better, larger studies are needed (E3~) . 32 There is no p resent evidence for any benefit 01oebvdroeptandrosterone (El),33 Anti -Inflamm ato ry drugs There is no evidence that aspirin is effect ive in treating patients with vascula r dementia (E3 ~) . Jo< Obse rvational studies in patients with arthritis suggest that NSAIDs may have a protect ive effect on the incidence and onset 01 AD. Prospective, double-blind , placebo-controlled studies are needed to determine their role (E3z),35 Antipsy chotIc medication Classica l neuroleptic s have little efficacy over p lacebo in behav ioural diso rders associated with dement ia, with efficacy rate eq uivalent to side effect rate (Et ).36 However, thioridaz ine, one of the most commonly presc ribed drugs because it is thought to produce less frequent motor side effec ts, has marked anticho linergic propert ies that could have a detr imental effect on cognition. A meta-analysis showed that, com pared with placebo, its only positive effect is in the reduction of anxiety, and it has equal or higher rates of adv erse effects than p lacebo , other neurolep tics and othe r sedatives (El),37 Risperidone may be more r eiofur and safer (E2).36 Oth er th erap ies Reality orientation (the presentation of orientation information (eg . time. plac e and person-related] to provide patients with a greater understand ing of their surround ings) has some benefits on both cogn ition and behaviour. A continued program may be needed to sustain potential benefits (E1).39 No firm conclusions are possible regarding the effect iveness of reminiscence therapy (the vocal or silent reca ll of events in a person's life, either alone , or with another person or group ot people). The trials are of poor quality (El) .40 43. MJA Vol 175 15 October 2001 MJAPrad ice Essentials tapes. There is a strong co mmitme nt to ca rer support : in New South Wales alone there are more th an 160 de mentia carer support gro ups . Understanding of dementia and its progression, help in man aging difficult behaviour, and advice on other co mm unity support opti ons can all be obtai ne d. The Alzheimer's Association of Austra lia can be contacted at PO Box 108 , Higgins, ACT 26 15. Phone: (02) 6254 4233. Fax: (02) 6278 7225 . Web: . Evidence-based guidelines • Certain acetylcholinesterase inhibitors can benefit people with Alzheimer's dtseese.e-" (E1) • Hormone replacement therapy may reduce risk 01 oemenue.» (E32) • Non-steroidal anti-inflammatory drugs may have a protective effect on incidence and onset of Alzheimer's oteeeee.» (E32) New medications for dementia If, Febr uary 2001, the Commonwealth subsidised, unde r strict conditions, donepezil and rivastigmine for use in mild to moderately severe AD. These drugs increase brain acetylcholine concentrations, thus modestly helping m em ory difficulries and oth er cognitive or behavioura l problems (see E0X 5). They are not cures, and at present th eir continued subsidy will require evidence of improveme nt (not just stabilisation) after six mon ths' use . Other medications are appearing on the market, incl ud ing galan tam ine. It is hoped that effective agen ts will emerge for th e treatll• ent of th e various form s of dementia. The difficulty of this task cannot be overstated. Basic knowledge of the mechanisms of de m ent ia, th e ident ification of th ose at risk, good study design , eth ical issues, cost and side effect pro files are ali factors th at make thi s a challenging endeavour. References Rummans TA. Evans JM. Krahn LE. et al. ()(!Iirium in elde rly patients; evaluation and manage ment. Mayo Cion Proc 1995; 10, 989·998 2 HQdges JA. COgmtive assessment lor clinicians Oxford: O.ford University Press. "" 3 BunefS N. 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