Downloaded By: [University of Alberta] At: 23:30 21 September 2007 nated by profoundamnesia(Kopelman,1995; the WEstate, chronic phase of KS is domi- (ophtalmoplegia, ataxia) peripheral Whereas 1989). (Victor,Adams,&Collins, encephalopathy (WE) Wernicke of ceded byasudden-onsetepisode alcoholic Korsakoffsyndrome(KS),oftenpre- the excessive alcoholconsumption is chronic and most devastating clinicalpathologies causedby bances andsignificantbrain damage. One of the abuse canleadtocognitive–behavioraldistur- alcohol societies. Long-termexcessive modern Alcoholism isamajorpublichealthproblemin Edmonton, AB T6G 2R7, Canada Canada 2R7, T6G AB Edmonton, records. therapeutical the ex arranging for Köln) (TPR Mendt Markus and Germersheim), in Korsakoff Functions Cognitive NCEN i 2007, JOURNAL OFCLINICALAND http://www.psypress.com/jcen DOI: 10.1080/13803390701557271 DOI: http://www.psypress.com/jcen Cognitive performanceofdeto Address correspondence to Esther Fujiwara, Department of Psychiatry, Rm 1E1 Walter Mackenzie Centre, University of Alberta, of University Centre, Mackenzie Walter 1E1 Rm Psychiatry, of Department Fujiwara, Esther to correspondence Address We wouldto like thank Martina Konrad(Haus Grefrath), Sabine Kühn (Haus Eller),Andrea Schwerdt(Therapiezentrum cognitivedecline ordementia-like onset of symptoms over twoyears. fewer detoxifications in the past. In this sampleof detoxi come occurred more frequently in men thanand womenassociated was with higherpremorbid education and still remained within pathological range. Comparing most improved and most deteriorated patients, better out- general knowledge, visual long-term memory, and verbal fluency improved slightly after two years, though they mal subjects. Comparing T1 and T2 revealed no significan within thetwo-year period. Atboth sessions,majority the of theKSpatients’ results were inferiorthoseto ofnor- disease-related parameters, drinking history, additional pathologies, as well as psychosocial and cognitive therapy spatial abilities. Surveys with caregivers and medical records provided information about current and previous long-termand memory, workingmemory, basicexecutive functions, language, general knowledge, andvisual– follow-up1 (T1)witha two aftertime ne years (T2).The syndrome (KS). Therefore, we assessed neuropsychological performance in 20 detoxified chronic KSinpatients at However, little is known about the time course of cognitive functions in patients with chronic alcoholic Korsakoff dementia. the riskof increasingdecline,promote eventually cognitive to is assumed Excessive alcoholconsumption First syndrome patientsremainsstableovertwoyears , 1–12 Hans J.Markowitsch 3 2 1 Esther Fujiwara, University ofAlberta,Department Haus Remscheid,Soziotherapeutisches Remscheid,Germany Zentrum, University Psychology, Physiological © 2007 Psychology Press, an imprint of theT INTRODUCTION and confusionprevail in EXPERIMENTAL NEUROPSYCHOLOGY EXPERIMENTAL neurological symptoms Emi:[email protected]). (E-mail: 1,3 MatthiasBrand, 1 Psychiatry, Edmonton, Alberta, Canada Alberta, Psychiatry,Edmonton, of Bielefeld, Bielefeld, of Bielefeld, Germany 1 aylor & Francis Group, aylor & uropsychological tests assessed verbal and visual short- fied KS patients therewas no SabineBorsutzky, t decline in any of the investigated functions. Instead, Victor etal., 1989). Furt contribute to the pathology (Homewood & (Homewood pathology the to contribute itself further alcohol of effects 2004). Neurotoxic vulnerability (Heapetal., 2002; Pitkin & Savage, is probably facilitated by KS for factor etiological from severe malnutrition is regarded as themajor below). see executive dysfunctions(Joyce&Robbins,1991; and 1990) & Denes, Cipolotti, Barba, (Dalla accompaniedbyconfabulations1965), sometimes and depressivemood(Talland, tive oragitation, such apathy,lackofinitia- motivational changes as pati ofKS disturbances aminationthe of patients and valuablehelpwith medical and xified alcoholicKorsakoff Thiamine (vitamin B1) deficiency resulting deficiency B1) (vitamin Thiamine an Informa business 1 Hans-P.Steingass, her cognitive and behavioral indication ofaccelerated ents concern emotional– ents concern and WE; this deficiency a geneticorage-related 2 and Downloaded By: [University of Alberta] At: 23:30 21 September 2007 not derived within the groups (classical acute groupsnot derived within the changes was of cognitive time course the actual for the nonimproved group only. From these data, available assessment was formal cognitive alone”; ableto live such as“returntowork” or “being dementia. Improvement wasmeasured by criteria patients withgradual onset KS and alcoholic admission, the latterof whichcorresponding to associated symptoms for a longer time priorto duration ofdrinking history, and, having had KS- shorterthe groupofolderfemaleindividuals, tors intermsofoutcome included: belonging to in morethan60%ofthe nounced deficits(“alcoholic dementia”) improved and 11 patientswithawider range of more pro- gradual-onset KSpatients 14% ofthecases,12 with classical, acute onset KS improved in only 21 patients and followedupfor6.5years.Whereas 50 patients recruited from hospital admission lists differential outcomes of the disease in asample of (1978)identi 1989). Cutting through50% (Malamud &Skillicorn,1956) however, show aconsiderable rangefrom0% 1993). Reported recoveryratesinKSpopulations, generally regardedNixon, aspoor(cf.Parsons & of theKSis the chronicphase 1995), prognosisof Huber, Trabert,Betz,Niewald, & et al.,1997; (Mann, Mundle,Strayle,&Wakat,1995;Nicolas reversible afterprolonged phases of abstinence associated cognitive dysfunctions arepartially 1998). Stanhope Robbins, 1991; (Brand etal.,2003; Brokate2003; etal., Joyce & functions in frontal-lobe-associatedexecutive seen areconsistently disturbances memory severe exceed that patients ofKS deficits neuropsychological additional Svoboda,Cartwright & Wang, Fowler,& Rajaram, 2001;Kril, Halliday, affects frontal lobe regi alcohol-related brain damage predominantly (Hardingal.,KS patients2000). et cits of Further defi- memory pronounced to the related closely 1989). Damage tothediencephalon is most Kopelman,1995; Mair, Warrington, & 2000; bodies (Harding,Halliday,& Kril, Caine, medial/paratenial nucl mediodorsal andanterior thalamic nuclei, the grey periventricular and periaqueductal stem, brain- upper cerebellum, affect usually patients and metabolicalcoholicin changesof brains KS Bond, 1999; Lishman, 1990). Resulting structural FUJIWARA ETAL. 2 (Siebert, 1933) tomorethan75%(Victoretal., (Siebert, 1933) Weiskrantz, 1979; Reed et al., 2003; Victor et al.,Weiskrantz,Reed etal., 1979;Victor 2003; asthe such regions diencephalic and matter, Although alcohol-induced cerebral atrophy and the often overwhelmingly ei, andthemammillary cases. Mostfavorablefac- ons (Goldstein, Volkow, (Goldstein, ons , Guinan, & Kopelman, , 1997). Accordingly, fied KSsubtypeswith potential cognitive changes. for would account factors time period,and which dementia-related symptoms woulddevelopinthis interested whetheraccelerated cognitivedecline or Specifically, wewere effects—change overtime. probable neurotoxic intake ofalcohol with viduals who werepreviouslyexposedtoexcessive indi- patients—i.e., of detoxifiedchronic phaseKS whethercognitiveabilities we aimedtoinvestigate but noresultingneurological disorder. Therefore, nervous diseases,includingthose with alcoholism without previoushistoryofalcohol-relatedcentral tion and/orsteeperdeclinethanalcoholabusers deteriora- even earlieronsetof show viduals might indi- be reasonedthatthese system. Itcan nervous to thecentral alcohol-related damage experienced cognitive functions in individuals whodefinitely the timecourseof about known population; littleis consumption within normalrangesin the normal derived fromstudyingalcohol findings are similar faster thandidthoseofnonabusers. Theseand alcohol abusers droppedover fivepointsper year Alzheimer dementia patientswhowere of scores notedthatMini-M (1990) hol abuse.For instance, Teri,Hughes,andLarson former alco- of cognitivedeclinemaybealteredby Rockwood, 2001).Also,thetimecourse Thomas & etal.,1991; Saunders al.,2003; et Mukamal 2004; mild cognitiveimpairment(Anttilaetal., of heavydrinkers to later develop dementiaor showna 1993), others have heightened probability Rosenetal., Mann, 2000; ease (Cervilla,Prince,& tion and cognitive impairment or Alzheimer’s dis- found noassociationbetween alcohol consump- mixedresults.Whereas somehave studies revealed impairment anddementia, although previous cognitivepossible riskfactorfor as a posed consumptionsive alcoholhas likewise been pro- Exces- depression (Modrego&Ferrandez,2004). or al., 2004), cerebrovascular diseases(Riekseet 2001), (Jellinger, Paulus,Wrocklage,&Litvan, nervousas traumaticbraininjuries diseasessuch (Meyer et al.,1998;Satz, 1993), history ofcentral of dementia such as low premorbid education cognitive decline andeventuallyincreasetherisk developmentto promotethe are known of tors decline (cf.Ryback,1971). A number ofriskfac- general toacceleratedcognitive vulnerability of severealcoholabuse leadstoa history that a dementia altogether(Victo or invalidating the concept ofprimary alcoholic Horvath,1975;Lishman, tia (Cutting, 1978; 1990) eral subtypes,separatingalcoholic itfrom demen- Beyond thediscussion whether KSconsists ofsev- and potential deteriorations were not evaluated. onset KS,gradualKS, alcoholiconset dementia) ental State Examination ental State r, 1994), itseemslikely r, 1994), Downloaded By: [University of Alberta] At: 23:30 21 September 2007 to the criteria of Oslin, Atkinson,Smith,and criteria of to the and thereforealcohol-relatedaccordingdementia Patients did notexhibit typicalsignsof dementia, not includeneuroradiologicalinvestigation. did and data clinical from derived were diagnoses following DSM–IVcriteria(291.1: American “Alcohol-Induced Persistin or Organization, 1994) 10.6: WorldHealth (F to ICD–10 according Syndrome” Amnesic Induced alcoholic KSwasformallydiagnosed as“Alcohol- phrenic psychosis. Inthe remaining39patients, ouslyschizo- sufferedastroke andonehada two patients wereexcluded: one patienthad previ- basis oftheseexaminations the institutions. On the differentcooperatingductedby physiciansin ive neurological and psychiatricexamination, con- Brand et al.(2003).Allpatientsunderwent extens- Thesepreviouslyhave patients been described in individuals. multi-impaired alcohol-addicted which specializedthe in treatment ofchronically meine Hospitalgesellschaft (AHG) (Germany), socio-therapeutical nursinghomes of the Allge- Patientsre werepermanent 41 patientswithalcoholicKSwere recruited. At thefirsttestsession(T1:Mayto August 2000), Subjects overtime. performance cognitive damage on study effects of prior alcohol-induced brain consumption could be excluded,allowingusto both sessions,theinfluenceofongoingalcohol highly controlledclinicalenvironmentbetween consecutive testsessions.Asthepatientslivedina the sameKSpatientsontwo test performancein er feuain97 .5981.44 9.8 1.45 9.75 Note background Professional education of Years g tT 97 .25.06.46 59.30 5.72 59.70 Gender T2 at Age Psychiatric Association,1994),respectively.The cdmc13 5 12 11 9 1 7 12 14 6 Academic Apprenticeship Unskilled Male Female For this purpose, we studiedneuropsychological . SD =standard deviation. METHODS Demographic variables of KS Demographic variablesof sidents in four different DNMS Significance SD M N SD M N g AmnesticDisorder” oskf ains( 0 Comparison subjects(N 20) = Korsakoff patients (N= 20) TABLE 1 1 TABLE patients and comparison subjects and patients and the comparison group (CG) were well matched the comparison group(CG)werewell and participation. financialincentivefor any received sent. Neither patients norcomparison subjects the procedure ofthe studyand gave writtencon- were informedabout participants examination, all Bielefeld and their relati the Universityof of cafeteria at the bers ofstaff consistedpersonnelof administrative andmem- ropsychologicalgroup status.Thecomparison for evaluatingthe patients’a basis neu-general group was testedon oneoccasion only toprovide the study.Thecomparison in history participated son subjects without neurological orpsychiatric compari- etc.). Asacomparisongroup,20healthy at time oftest,hadvisitorsonthetesting day, sons (e.g., were working outside thenursing home ate,patients and wereunavailableforotherrea- 4 declinedto particip- 2 patients of T2, on theday individualsthe from finaldataset.Furthermore, was incomplete,wh patients’ medical andaddiction history (see below) work after discharge. them returnedto relatives. None of by care of professional ambulant ca discharged were women; one received subsequent had beendischarged.All5patientswho admitted to other nursing homes, and5patients out for the followingreasons: 5patientshad been patients who did not participateinT2dropped The August 2002). to May (T2: after twoyears available forthesecondtestsession jects were in anyofthepatients.Of39patients,20sub- (eyesigns, encephalopathy neurological symptomsfromtheWernicke patient with unilateral amblyopia, no residual state of the Korsakoff pathology. Except forone a Wernicke episode, which preceded the chronic patients. Allpatientshadadocumentedhistoryof Hendrie (1998)wasnotdiagnosed inanyofthe As can beseeninTable1,the20KSpatients ONTV UCIN NKRAOF3 KORSAKOFF IN FUNCTIONS COGNITIVE ich led to the exclusion of these Documentationof 2 re, the otherswere taken ves and friends.Before ataxia) werereported ataxia) χ χ 2 2 t t = 1.33 = ( 0.96 = ( = = 0.21 = ( − 0.11 ( p p p p =0.51) =0.33) =0.84) = 0.91) Downloaded By: [University of Alberta] At: 23:30 21 September 2007 tion (mean =10.25, tion and 17 years at thetimeofsecond investiga- abstinently inthe nursing homes for between 2 four nursing homes. The KSpatients had lived completed bythe personnel and directors ofthe medical and addiction history via questionnaires course ofthe disease. consisted of individualsmore withfavorable a improbablethatgroup the ofdischarged patients all variables; ground, Mann-Whitney of these variables ( no signif Results indicated T2. the sampleat female patientswhostayedin 6 who were dischargedthe homethat of with test performance atT1ofthe 5female patients demographic variablesneuropsychological and sional background. on gender,age,yearsofeducation,andprofes- FUJIWARA ETAL. 4 questionnaires: All 20 patients participated in patients All 20 questionnaires: the from we obtainedthe following details T2, respect With to thetimeperiod between T1 and homes. atthenursing stay entire their during ment test sessions. taking tricyclic antidepressantsthe timeofboth at at T2(6pertensivesat were marize: 9patients antihy- being treatedwith suffered fromtheir symp other patients with additionaldiseases had all having their complaints betweenT2; T1and started with cardiacproblems,3 9 patients the Of had patient concomitant depressivesymptoms. 1 hadrecovered1 patient from anorexia,and 2 patientshadcancer(gastrointestinal,prostate), high blood pressure, heart rhythm disturbances), reported tosufferfrom cardiac problems (e.g., symptoms ofKS,at T29of the 20patients were ment for KSsymptomatology. Additionally to received medical treatment or nutritional supple- stage KSatbothtestsessions,noneofthem the patientsenrolledinth between 0 and10 (mean = 2.05, menteddetoxifications prior toadmittance was 19 patients had no relapse. The number of docu- 20 patientstwo relapses, had eachaday; lasting SD been between10 and 46 years (mean =25.83, tion ofalcohol addiction before admittance had We obtainedcharacteri group KS the of Characteristics In ordertoavoidselection effects,wecompared All patients received socio-therapeutical treat- All patientsreceived socio-therapeutical Socio-therapeutical treatment = 10.07 years). Between T1 andT2,one of the p s > .05). Therefore,> s itseems χ SD 2 testfor professional back- = 5.19 years); their dura- = 5.19years); T1) and 1 patient was and 1 T1) toms before T1. To sum- is study were in chronic U icant differences in any stics ofthepatients’ stics Testsforall other SD =2.37). As oedte 64 39.8 23.2 2.48 36.47 1.65 34.25 6.63 4.4 a 48.59 Note 93.74 Totalnumber of hours of supervisedactivities training Neuropsychological Occupational therapy Training indailylivin duties Home Group meetings (Osterrieth, 1944). Speed (Osterrieth, 1944). Speed recall of theRey–Osterrieth Complex Figure memory wasmeasured bya30-minutedelayed Test after15–20minutes, andvisuallong-term the Memo a delayedrecall of withwas measured Härting et al., 2000). Verbal long-term memory assessed with“DigitSpan Reversed” (WMS–R; & Fink,1992). Verbal workingmemorywas task (Schaaf,Kessler,Grond, selective reminding Recall” ofwordsfrom the MemoTest,a verbal “Immediate and 2000) etal., (WMS–R; Härting Scale–Revised Wechsler Memory the sion of with SpanForward”from ver- “Digit the German 1975). Verbal short-term memorywasassessed tion (MMSE) (Folstein, Folstein,&McHugh, StateExamina- ofthe Mini-Mental Denzler, 1990) the Germanversion (Kessler, & Markowitsch, screenedby cognitive state was tery: Thegeneral and T2,weadministeredbat- following the test patients. activities calculated for theentire groupof20 supervised ofper organizedand month hours h/month). ropsychological training onceortwiceaweek(4–8 h/month). Finally,16patientshadsessionsofneu- (6–64 activities and similar work, garden painting, tional metalwork,woodwork, therapy comprising Almost allofthepatients( short leisure trips, andthelike (4–46 h/month). training, whichincluded ofdaily living in activities patients participated 15 or laundry(37–128h/month); the kitchen in instance,shifts for worked, duties—they related additionally involvedinmoreextensivehome- private rooms(4–6 h/month); 10patients were their such ascleaning duties carried outbasichome group meetings (4–12 hours per month) and See text for median and range. and for median text See Average number of hours per m Average numberofhoursper To compare neuropsychologicalstatus atT1 Neuropsychological testbattery of summarizes the averagenumber 2 Table . SD =standard deviation. treatment between T1 andT2 betweenT1 treatment ciiis1. 12.43 12.0 g activities TABLE 2 TABLE of information of information processing going shopping, biking, going shopping, n onth of socio-therapeutical onth of =18)receivedoccupa- Mean a SD a Downloaded By: [University of Alberta] At: 23:30 21 September 2007 breaks were given on demandofthe patient. were given breaks measure. Index” servesas a rough approximationof this crepancy betweenMWT–IQ andour “Memory limited selectionoftestsemployed here, the dis- Lewis, Cermak,&Goodglass, 1973).Giventhe absence ofgeneralButters, cognitive decline(cf. to illustrate the specificity of amnesia in the KS patients Quotient (MQ);theyhavebeenusedin andWechsler MemoryScale WAIS–IQ ference measuresarederivedfromFullScale assessed at T2.Usually,thesekindsofIQ–MQdif- Index” wasthensubtractedfrom MWT–IQ and dividedthe result theirsum, IQ-scaled standard scores, calculated into ComplexFigure recall of theRey–Osterrieth delayed and ofwordsfromtheMemoTest recall purpose, wetransformedtheresults in delayed Forthis was calculated. measures memory term estimated MWT–IQandthetwoassessedlong- and intellectualabilities,thedifference between trate discrepanciesbetweenmemoryperformance To illus- 1991). Lehrl, Merz,Burkhard, & Fischer, (“Mehrfachwahl-Wortschat National AdultReadingTest(Nelson,1982) the of adaptation German a with intelligence functions.executivebasic subsets of we concludethat assessedatleast our testbattery Therefore, and Pantelis(1996). Andrewes, Smith, with executive dysfunctions inthe study of Hanes, nated between controls andseveral patient groups executive functions. Bothsuccessfully discrimi- interferenceof realms canwellbeseeninthe of tions. Forinstance,verbalfluency andinhibition employed testscoversubsets ofexecutive func- as planning and decision-making, some of the tests didnot assess higherexecutive functions such knowledge.of Although ourselectioneral verbal Tewes, tomeasureRevised 1991) gen- (WAIS–R; version of the Wechsler Adult Intelligence Scale– tered thesubtest“Information”Germanof the Figure.Finally,weadminis- Complex Osterrieth oftheRey– abilities weremeasuredbycopying verbal fluencywasadministered.Visual–spatial Naming (FAS) Task (Spreen &Strauss,1998)of abilities,theWord ive functionsandlanguage (Oswald &Fleischmann,1997).Toassess execut- Interference Test Trial” oftheWordColor ference wasexaminedwiththe“Interference Stroop Test(Stroop,1935) Fleischmann, 1997), developed on the basisofthe (Oswald& Nürnberger–Alters-Inventar the of Interference Test Trial” oftheWordColor was studiedwithreadingspeedofthe“Word Each test session lasted about 1–1.5 hours; Each test lasted 1–1.5 session about weadditionallyassessedpremorbid At T2, by two.This “Memory z-Intelligenztest”, MWT: . Susceptibilitytointer- parameters by were analyzed parameters for pairwise comparisons. Differencesinnominal Whitney Mann– used thecorrespondingnonparametric by theKolmogorov–SmirnovTest, the normaldistribution(indicated from deviations Memo Testin T1 ( z rangingdown to measures in memory long-term Index”. “Memory and MWT–IQ between total performance scores and discrepancies summarizes comparisons parison subjects’ results or normativedata. Table4 tests were ance score, all raw scores in neuropsychological 13.22) astested atT2.Toderive atotalperform- (average IQestimatedbyMWT=104.83, also showed a normal pr of dementia-related deterioration.patients The sessions andnonindicative both test at mal range Mini-MentalExamin State subjectsor normative populations.However, to ances wereinferior KS patients’perform-ropsychological teststhe T1. at comparison group(CG) ropsychological statusat T1 and T2andofthe Table 3givesanoverviewoftheKSgroup’sneu- Neuropsychologicalstatus and atT1 T2 not betweentests. Trial oftheStroopTestweredividedbythree) but andInterference with the Color Trial, Word Trial, rected within scoresofthesametest (e.g., statistics were multiple comparisons, results Bonferroni-cor- parametric methods ( parametric methods normally distributed data were conducted with Chicago: SPSS Inc.). Statistical comparisonsof for Windows (Release12.0.0,4September2003; SciencesStatistical PackagefortheSocial (SPSS) out withthe carried were All statisticalanalyses Statistical analyses Figure in T1 ( Figure inT1 Rey–Osterrieth Complex delayed recallofthe the WAIS–R was likewise inferior to that of waslikewise inferiortothat the WAIS–R ledge asassessedfrom withsubtest “Information” General know- 4). individuals (seeTable to healthy (e.g., verbalfluency, working memory) compared executive functions in some lower performance both test sessions patients showed significantly = –2.61 indelayed recallofwords from the –2.61 = The group showed most pronounced deficits pronounced most showed group The testAt both sessions, majority inthe ofthe neu- U ONTV UCIN NKRAOF5 KORSAKOFF IN FUNCTIONS COGNITIVE z Tests, or WilcoxonSignedRank Tests -transformedon thebasis ofthe com- z = –2.30 in T2). Additionally, at Additionally, inT2). =–2.30 z = –2.58in T2) and RESULTS t Incaseofsignificant tests). those ofthecomparison emorbid intelligence level between KS and CG, ation was within nor- χ 2 tests.Toadjustfor p <.05), we z = –2.62 in SD = Downloaded By: [University of Alberta] At: 23:30 21 September 2007 iiMna tt xmnto 5017 5521 > 26 104.83 2.12 — 25.5 1.73 25.0 MWT Mini-Mental StateExamination Note Wechsler Adult Inte Adult Wechsler A et2. .63.01.64.510.90 43.25 11.76 30.70 3.19 8.36 17.20 24.5 4.24 13.8 Scale–Revised. Intelligence Adult Wechsler WAIS–R; 1991); 4.27 Note Test FAS 16.75 12.4 Trial) (Word Stroop Information (WAIS–R) ceptibility measured with theceptibility StroopTest werein measured and interferencesus- test sessions, reading speed both tothecomparisonsubjects’ At similar results. Complex Figurewere of theRey–Osterrieth copy the with as measured abilities visuo-constructive population. Short-termmemoryand entire the formance in anonpathological rangecomparedto show patients the KS the lattertestsdid that innoneof Note in bothtestsessions. comparison subjects a a FUJIWARA ETAL. 6 z FAS Test (Interference) Stroop (delayed) Figure Osterrieth Rey (delayed) Test Memo Memo Test (immediate) Digit Spanreversed forward Span Digit Rey–Osterrieth Figure (copy) tests; tests; eoTs dlyd .514 .012 . 1.97 1.21 0.83 1.24 5.47 6.0 4.75 7.05 6.41 16.21 3.79 1.24 0.80 0.72 0.84 4.02 31.0 1.10 3.89 5.05 5.57 4.08 4.96 1.47 0.97 0.95 0.80 2.68 29.20 30.03 1.05 3.75 5.05 5.70 2.45 5.80 (Interference) Stroop Rey Osterrieth Figure (delayed) 29.78 Memo Test (delayed) (immediate) Test Memo Digit Spanreversed forward Span Digit Rey–Osterrieth Figure (copy) MWT–IQ minus “Memory Index” “Memory minus MWT–IQ Stroop (Word Trial) (Word Stroop (WAIS–R) Information derived from normative data (Oswald &Fleischmann, 1997); score; IQ-scaled -total score -total . . SD = standard deviation. KS . SD= deviation. standard c SD “Memory Index”: sum of Memo Test (delayed) and Rey Osterrieth Figure (delayed)divided by two; z -scores lower than -scores lowerthan =standard deviation.Unless othe b b time in seconds. in time lligence Scale–Revised. Neuropsychological status of KS patients at patients of KS status Neuropsychological z = –0.84, indicating per- indicating =–0.84, c patients atT1an patients 45.11 − − − − − − − − − − − enS enSD Mean SD Mean .70.57 1.37 .00.68 0.52 1.60 0.80 0.24 1.13 2.62 0.85 2.61 0.66 2.36 1.59 0.84 0.54 0.40 .51.41 0.35 1.75 Raw scores in the neuropsychological testbattery scoresintheneuropsychological Raw rwise stated,results aregiven as d a a MSD SDMSD M Sptet tT KS patients at T2 KS patientsat T1 1T 1T2 T1 T2 T1 b b 43 43.71 14.32 1.03 0.88 Sptet Comparison group –KS KS patients d T2, comparison groupat d T2,comparison − − − − − − − − − − − .405 — — 0.57 1.24 .909 – 0.95 0.78 1.09 0.68 0.86 2.30 0.71 2.58 0.69 2.35 1.36 0.72 0.65 0.34 0.85 0.58 .91.43 1.29 36 32.65 23.65 .316.45 3.73 TABLE 3 3 TABLE TABLE 4 4 TABLE b d a a sum of all neuropsychological test results divided by the number of number the by divided results test neuropsychological all of sum T1 and T2 contrasting comparison group data contrastingcomparison andT2 T1 20 — — 12.04 z total tests revealed formance across data. Summarizingtheneuropsychological per- the tonormative low averagerange compared sample. Furthermore, although somepatientshad inour abilities preservedintellectual relatively performanceand highly deterioratedmemory 40 IQ-scaledstandard scoresbetween ancy ofover discrep- Index” differencemeasurerevealed alarge The MWT–IQ “Memory ance atbothtestsessions. .7—— — — 0.97 — 1.13 = –1.0,indicating = belo z -scores. T1. MWT:Mehrfachwahl-Worts U U ttsi significance statistic t t t t t t ======10.5 =99.5 = t/U t/U b b a − − − − − − 5.91 10.0 2.66 0.91 4.53 7.0 p p p p p p p p 15 — 21.55 — 13.22 <.0 – < .001 < .001 = .01 = .37 < .001 < .001 = .16 < .001 .8— 2.98 w-average overall perform- d IQ-scaled score; WAIS–R; score; IQ-scaled U U ttsi significance statistic t t t t t t ======7.0 = 86.5 = = t/U t/U chatztest (Lehrl et al., et (Lehrl chatztest − − − − − − Comparison group group Comparison 3.54 7.56 7.91 2.42 0.80 3.30 z -scores below at T1 at p p p p p p p p = .001 = .001 < .001 < .02 = .44 = < .001 < .09 = = .002 = Downloaded By: [University of Alberta] At: 23:30 21 September 2007 ences (zdiff) showedan positivemean average of revealednosignificant and T2 differences, Comparison ofMini-Mental betweenthe two testsessions Changes in neuropsychological performance diagnosesof of theclinical additional validation gives and 1995) Kopelman, forKS(e.g., Butters et 1973; characteristic al., be expected on the basis of their IQ.Thispatternis was disproportionatelylowerthanwould Index” their“Memory scores, somewhat lowMWT–IQ Memo Test (immediate) Digit Spanreversed forward Span Digit Rey–Osterrieth Figure (copy) Trial) (Word Stroop (WAIS–R) Information Stroop (Interference) Stroop Rey–Osterrieth Figure (delayed) (delayed) Test Memo Adult Intelligence Scale–Revised. Adult Intelligence Wechsler WAIS–R: T2; T1 from to improvement *Significant z FAS Test and With ameanscoreof recall oftheRey–Oste three tests:Information, p transformed total scores of T1 and T2, significantly higher overall performancethein remained stablebetweente Table 5. shown in are two sessions cal testperformancebetweenthe p vidual between T1andT2perpatientbysubtractingindi- of the testsbetween two sessions. drop observe anysignificant session (cf.Table 4).Most notably,not wedid within thepathological range also atthe second test –3.21, 2.52, -total score -total Changes of the patients’ ofthe Changes = .047. This was mostly duetoimprovement on = .29. Pairwise comparisons in neuropsychologi- comparisons = .29.Pairwise Whereas the majority of the individual testresults the of Whereas themajority Additionally, we performance calculated changes z p = –1.24 ( =–1.24 = .02, andverbal fl p z =.005.However, theseimprovements were -total scores of T2 from T2 of scores -total between test sessions T1 andT2 testsessionsT1 between SD = 0.57) atT2,the = 0.57) TABLE 5 TABLE rrieth ComplexFigure, neuropsychological performance z = –1.37 ( =–1.37 t uency in the FAS Test, = –2.41, = our sample (see Table 4). Table oursample(see st sessions, weobserved State Examination in T1 in performance in any in performance in -ttsi significance z-statistic t/Wilcoxon performances at T1 and T2 and T1 at performances z z t t t t t t t t t = =0.86 ======1.69 = = = z -total scores of T1. of scores -total − − − − − − − − − SD Comparisons of of Comparisons 0.49 0.44 0.24 0.41 2.41* 0.12 2.52* 2.13* 3.21* p = 0.57) at T1 =0.57)at = .03, delayed = .03, z -score differ- t p p p p p p p p p p p t =.63 =.67 =.81 =.69 =.03 =.91 =.41 =.02 =.05 =.11 =.005 = –2.13, =–1.1, t =– t = z - either session (T1:zdiff patients (zdiff scoresferencetop thirdof andcontrastedthe group into three subgroups according totheirdif- deteriorationbetween T1andT2,wedivided the to compare extremegroups ofimprovement or tive abilitylevelacrosstestsessions.Nevertheless, of patients eitherimproved orretained their cogni- 1.62, range=–2.18to–0.82; observed in the zdiff observed inthe in Figure1). per group bars (see firsttwo those in the othergroup deteriorated across sessions the factthat individuals in one groupimproved and ance of both groups in either testsession, despite cognitive perform- similarlevelsof general indicates = –0.96, range = –2.42 to –0.27; zdiff to–0.27; =–2.42 range = –0.96, significantly from each other intheir 6.0, change change in thezdiff negative of magnitude the to compared higher in in patients (zdiff patients in thezdiff patients the6 whereas 3 of of6 male subjects, consisted group median =0.5, range =0–1; zdiff zdiff to0.54; =0.32 range 0.39, = median 2.1 to–0.47; = –2.75 to–0.81;zdiff = –2.75 p (mean zdiff=0.33, substantial positive change between testsessions patientsindicated zdiff scoreofthe11improved –0.05, zdiff = in thisgroup did not showmajorchange (mean (mean zdiff =–0.22, withnoticeabledeteriorationonly 4patients a scorespatients consistedof zdiff withnegativeof sessi change betweentest patients, whereas9 patientsshowednegative observedimprovement in 11 betweenT1 andT2 zdiff =0.12( 9.0–13.0 years;zdiff range =0–6; cations before admittance. bution, years of education, were differences These groups. related parameters were significant differences in rioration (seethirdbar dete- of themagnitude T2exceeded and T1 between of observedimprovement magnitude the Therefore, = 0.15, range =0.08 to0.35; level ofeducation (zdiff before admittancetoth = .049). The zdiff Moreover, Moreover, the magnitudeofpositivechange Probably duetothe small sampleProbably sizes,few onlya z p -total scores between T1 andT2:zdiff between T1 -total scores = .021), and fewer documented dexociations ONTV UCIN NKRAOF7 KORSAKOFF IN FUNCTIONS COGNITIVE U U low high = 16.0, SD = 6.0, SD ; N=6).The groupsdid notdiffer ; N=6)withthe bottomthird of = 0.03). In contrast, the mean Incontrast,the =0.03). low high low low = 0.26). Arithmetically, we =0.26).Arithmetically, SD SD low group (magnitude ofchange (magnitude group p group werefemale ( : median = 9.0, rangemedian =9.0,: 9.0; high group, further, hadahigher further, group, p per groupinFigure1). =.046). Otherdemographic =0.13).Thus,themajority high = .82; T2: zdiff T2: = .82; =0.10),whereas5patients high e nursing homes (zdiff demographic and disease- : median=–1.42,range– shown betweentwo the ons. However, the group groupwassignificantly and number ofdetoxifi- number and : median = –1.42, : median=–1.42, range Indetail,thezdiff : median11.5, range = U seen ingender distri- = 12.0, 12.0, = U low = 2.0, =2.0, : median= 2.5, low z -total score in p : median=– high = .39).This low p =.027). χ : median : median 2 =4.0, high high U high = : : Downloaded By: [University of Alberta] At: 23:30 21 September 2007 of change in the zdiff the in change of the zdiff the means); for intervals confidence be considered critically. First, generalization of our generalization First, critically. be considered history. tion andfewerdetoxificationsinthedrinking and wasassociated withhigher premorbid educa- men thaninwomen frequently in occur more to riorated patients,bettercognitive outcometended with the mostdete- comparing themostimproved range, exceeded thatofthedeteriorations. Directly though improvements, still icantly after two The ofthese years. magnitude Instead, threemeasuresimprovedsignif- observed. betweentestsessions were significantdeclines attent memory, (e.g., tions years. In none oftheinve two koff syndromeinpatientsstableover remain detoxified chronic-phasealcoholicKorsa- ties of thatcognitiveabili- is ofthisstudy The main result between the two cal interventions wereno variables, disease-related parameters, or therapeuti- riorated (zdiff dete- most of groups extreme in T2 T1 and between differences Figure 1. FUJIWARA ETAL. 8 Two characteristics ofour investigationhaveto Two high z -total scores at T1and T2andmagnitude of absolute group was significantly higher than the magnitude the than higher significantly was group low ) and most improved (zdiff extreme groups. low DISCUSSION group ( U ion, executive functions)ion, executive *: themagnitude change of in stigated cognitivefunc- = 2.0, =2.0, t statisticallydifferent within the pathological within the p =.027). high ) patients (95% ) patients (Brandt, Butters, Ryan,&Bayog,1983; Mann, (Cutting, 1978; Victoret patients more acute KS abstinence in longed can bepartiallyreversed afterpro- dysfunctions ous longitudinal studiesshowing that cognitive artefacts. due toretest functions stabilityorimprovement observed in cognitive tive topracticeeffects, shown onmeasuresknowntoberelativelyinsensi- in normalpopulations, and improvement was also exceeds thosecoveredby studies of practice effects densely amnesic, the test–retest intervalhere Taken together,giventhatourpopulationis tial practiceeffects seemunlikelyinoursample. Sedlak, andAwad(1993) Lüders, Chelune, Naugle, in interval test–retest retest interval was used in Dikmen etal. (1999)— fluency. Accountingforthe factthata shorter test– effectsforverbal practice andonlymoderate sures, mea- intelligence verbal and memory long-term effectsinvisual reportedsmallpractice (1999) Heaton, Grant,andTemkin 11 months, Dikmen, studies, overanaver tive previous norma- which weobservedchangeswith in domains Comparing theneuropsychological level. an explicit on least test session—at the first test, no patient rememberedhavingparticipated in our patientsaredenselyamnesic.Atthesecond Most importantly, study. this in unlikely are effects we arguethat,foranumberofreasons,retest on comparisonsubjects, retest data of the absence effects. In ments couldbeaconsequenceofretest sider thepossibility that improve- the observed with chronic-phasealcoholicKS. patients course ofcognitivefunctions in time to the size, our can results nevertheless add clarification sample duetothesmall pite limitedgeneralizability we healthy individuals. believeTherefore, thatdes- points in timeand do notinvolve comparisons to based oncomparing thesameindividualsattwo However, themain conclusions ofour study are patients. have beensomewhatbiasedagainstthe between patients and comparison subjects may comparisons patients), ofthe orfriends relatives originate fromthepatients’environments (i.e. not formance. Also, since our comparisongroup did in turn, has negatively impacted on cognitiveper- likelihood ofadmission tonursinghomes, which, higher led toa have thismay Potentially, sive. already lower before theirdrinkingbecame exces- functioning was patients’ premorbidcognitive the stillbepossiblethat it mal range, might Although the overall estimated IQwasinthenor- results islimited due to samplesize. our small Our findingsarecompatible withthoseofprevi- con- in thisdatasetitisimportantto Secondly, al., 1989) and alcoholics al., 1989)and it is thatwe unlikely itis age test–retest intervalof was6months—substan- Downloaded By: [University of Alberta] At: 23:30 21 September 2007 retrieval in retrieval KS might result concomitant from memory that disturbed remote suggested tions. He executive func- frontal-lobe-associated testsof to deficits inKSpatientsarehighly related memory reportedthat remote Kopelman(1991) 1999). & Levin, 1979; Kopelman,Stanhope, &Kingsley, affected retrogradememory the generallyless Semantic knowledgeispart of 2002). ilde, Videbech,Gjedde,&Gade, Rosenberg, roimaging studies of healthy individuals (Ravnk- lesions (Stuss and et 1998) in functional neu- al., brain frontal well documentedinpatientswith tal-lobe-associated componentofverbal fluency is tions controlledbyfrontalbrainregions. Thefron- measures lies intheirrecruitmentof executive func- be speculated thatthecommon basis ofthesetest stayed within the highly deteriorated range. Itcan memory visual long-term healthy subjects,whereas twomeasuresapproachedtheresultsof former subjects, the patients’ performance atT2 on the cantly inferior to theperformance of comparison Though stillsignifi- the Rey–OsterriethFigure). of and avisual long-termmemorytest(delayed recall test (subtest“Information”fromtheWAIS–R), functions test(FASTest),asemanticknowledge over thesessions comprised alanguageexecutive and course ofcognitiveperformance inKS. designed foramorecompletecoverage of the time investigation fromwhichfuturestudiesmaybe of chose therefore,bemust, regarded a starting point The follow-upoftwoyearsthat we might emerge. an acceleratedonsetofdementia-likesymptoms investigation norspeculateabouttheageatwhich forour neither identifyanidealtest–retestinterval we could 1979), etal., see Mair (but KS patients neuropsychological studieswithchronicalcoholic Nevertheless, due tothe scarcity of longitudinal mate time courseof cognitive functions inKS. theulti- forcharacterizing be suited might more Also, retestingperformanceatolderageranges inovert behavior. would manifest which changes not havecoveredthecriticaltime range during here thatourtest–retestinterval of two years might chronic stagesof the disease.It has to be noted might slight cognitive remain even improvement at the possibilityof system duetoalcohol.Instead, experience ofseveredamagetothecentralnervous even after indicate acceleratedcognitivedecline, not do MMSE, Table3).Therefore,ourresults cation ofbeginningdementiaaftertwo years(cf. and therewas noindi- ropsychological measures, further deteriorationneu- observe onanyofthe ment wasnotreversedinour sample, wedidnot impair- the Though & Sullivan,Pfefferbaum, 2004). Gunther, Stetter,&Acke Neuropsychological measures that improved Neuropsychological measuresthat rmann, 1999;Roseribloom, inKS (Albert, Butters, damage, the femalepatients includedhere may to alcohol-induced brains female nerability of ahigher vul- Assuming parameters. disease-related other number ofdetoxifications, or history, drinking in their the men did notdiffer from group results ofCutting(1978), tothe Contrary 2003). but seeHommer, 2004; degree a greater than itdoes men (Prendergast, ity aswellthiamine deficiency affects women to Alternatively, itmightbethatalcoholneurotoxic- effect might, indeed, be one of education only. had lesseducationthan did men. Thus, the gender gender andeducation areconfoundedsince women since thesamplesizesareverysmall. Furthermore, has tobe treatedcautiously, men only.Thiseffect group whichconsistedof thatimprovedthe most, thanthe composed most was of more women behavioral level.Thegroupthatdeterioratedthe after which disturbances become apparent atthe to beexceeded damage threshold ofneural the neural connections,orraises higher redundancyin education maypromote a reasonedthat higher it canbe (Satz, 1993), capacity nitive reserve tive functionsalsoinoursample. In terms of a cog- higher education wasabeneficial factorforcogni- Bherer, Colcombe,Dong,& Greenough, 2004), aging (cf.Kramer, normal as well pathologies cientsecond inthe as well since the overall level of performance was highly defi- be regardedhas to cautiously,long-term memory in our sample. The observed improvement in visual in verbal fluencyandsemantic retrieval of knowledge nence,be reflectedin may pathology, partially reversi & Andersson, 2001).Taken together, frontallobe and severelearning impairme correspond tothelong-lasting brain regions and ceding KSmaypermanentlyaffectdiencephalic In contrast,thethiamine deficiency typically pre- changes that are partly hol aremost likely tobe reflected byfrontallobe thatdirectne argued (1990) frontal lobedamage.Inthesamevein,Lishman assumed sensitiveto of thesetests subjects inone functions, andalcoholics differedfromhealthy mon impairmentonly on study, KSpatientsandalcoholicsshowedacom- their hol offrontal-lobe-associatedfunctions.In suggested (2003) a restrict only in In KS patients. this Brokateetal. regard, memoryfunctions bility infrontal-lobe-associated patients, Squire(1982)reportedaspecificvulnera- icits ofKSpatientswiththoseotheramnesic comparingmemory def- Similarly, cephalic lesions. frontal lobeinvolvementratherthan from dien- Similar to previousinvestigations in other ONTV UCIN NKRAOF9 KORSAKOFF IN FUNCTIONS COGNITIVE reversible with reversible abstinence. as the firsttest session. the female patients inour the femalepatients therelativeimprovement ble afterlong-termabsti- ed vulnerability to alco- ed vulnerability urotoxic effectsof urotoxic alco- measures ofexecutive nt inKS (see also Brun Downloaded By: [University of Alberta] At: 23:30 21 September 2007 bilitative efforts evenin bilitative efforts this population. neuropsychological testmeasures encouragereha- we slight improvements observed insome of the the meantime, the alcoholicKS.In with to patients might bedifferentinhealthy individualscompared slope ofcognitivedeterioration,onceinitiated, allow generalization of our findings. Also,the and longertest–retestintervalsisnecessaryto samples oflarger the assessment Furthermore, age. older decline in antedated onsetofcognitive an age rangetodetermine wh the courseofcognitive functions overabroader In future studies, it maybe worth while studying cognitive declineandthedevelopmentofdementia. extensive alcoholism inevitably leadstoaccelerated was small,itcastsdoubt on the hypothesis that has to be treatedcautiouslysinceourstudy sample vious excessive alcohol a drome, asevereneurologicalconditionduetopre- pati indetoxified years two of period over atime ated cognitivedecline Errico, King,Lovall Collie (Duka, Townshend, previ of number the with associated cognitive performance lower reporting patients patible withafewstudiesinalcoholic com- are results our detoxifications, previous more with ofpatients thegroup in deterioration for the responsible pathology exact underlying ofthe less Regard- records. inmedical not appear may seizures attempts towithdrawan unsupervised thepatients’ since be underestimated might variable this sample, our in reported not was mingsen, &Bolwig, 1988). Thoughseizure activity Hem- Ingvar, (Clemmesen, regions brain limbic and incortical dysregulation metabolic general with &Blow brain damage(Booth tosecondary leading potentially theamygdala), in alcohol withdrawal can kindl can withdrawal alcohol inrats fear conditioning withdr ofalcohol lations corre- positive (2004) reported Stephens and Lyons, Borlikova, Ripley, Moreover, 1999). Gonzalez, & Veatch 2001; Knapp, & Ali, Braun, (Crews, of alcohol supply alternating with abstinence followingwithdraw alcohol subgroup. Animalstudiesreported brain damage detoxifications comparedto the most deteriorated improved subgrouphad had a smaller number of counterparts. Finally,themost male than their disproportionatrepresent a FUJIWARAETAL. 10 To conclude, ourstudydid not revealacceler- Original manuscript received 13 December 2004 December 13 received manuscript Original Revised manuscript accepted 23 March 2005 March 23 accepted manuscript Revised First published online day month year o, & Parsons, 2002). ents withKorsakoffsyn- . Apart from the fact that d potentially undiscovered potentially d buse. Althoughthisresult awals and impairment in impairment and awals ous alcohol withdrawals ous alcohol ether therestillmaybe ely more affected group ely more affected als or repeated periods als or repeated r, &Stephens,2003; e seizure acti e seizure , 1993), it is associated vity (e.g., Dikmen, S.S.,Heaton, R. K., Grant, I., & N. Temkin, R. Dalla Barba, G., Cutting, J.(1978).Therelationship between Korsakov’s Brokate, B.,Hildebrandt,H. Crews, F. T., Braun, C. J., Ali, R., &Knapp, D. J. & Bolwig, R., Hemmingsen, M., Ingvar, L., Clemmesen, Chelune, G. 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