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Semenza et al Neurocase 2003

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Semenza et al Neurocase 2003
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  This article was downloaded by: [Universita di Padova]On: 24 July 2012, At: 01:48Publisher: Psychology PressInforma Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,37-41 Mortimer Street, London W1T 3JH, UK Neurocase: The Neural Basis of Cognition Publication details, including instructions for authors and subscription information:http://www.tandfonline.com/loi/nncs20 Proper Names in Patients With Early Alzheimer’sDisease C. Semenza, S. Mondini, F. Borgo, M. Pasini & M. T. SgaramellaVersion of record first published: 09 Aug 2010 To cite this article:  C. Semenza, S. Mondini, F. Borgo, M. Pasini & M. T. Sgaramella (2003): Proper Names in Patients WithEarly Alzheimer’s Disease, Neurocase: The Neural Basis of Cognition, 9:1, 63-69 To link to this article: http://dx.doi.org/10.1076/neur.9.1.63.14370 PLEASE SCROLL DOWN FOR ARTICLEFull terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditionsThis article may be used for research, teaching, and private study purposes. Any substantial or systematicreproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form toanyone is expressly forbidden.The publisher does not give any warranty express or implied or make any representation that the contentswill be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses shouldbe independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims,proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly inconnection with or arising out of the use of this material.  Proper Names in Patients With EarlyAlzheimer’s Disease C. Semenza 1 , S. Mondini 2 , F. Borgo 1 , M. Pasini 2 and  M. T. Sgaramella 3 1 Department of Psychology, University of Trieste, Italy,  2 Department of General Psychology,University of Padova, Italy and  3 Ospedale S. Bortolo, Vicenza, Italy Abstract The objective of this study was to seek evidence of the particular sensitivity of proper name retrieval and to check theusefulness of proper names as diagnostic material in the early stages of Alzheimer’s disease (AD). Whether a generalizednaming deficit is an early symptom of AD it is not yet clear. Previous studies suggest that proper names might be thecategory of names that is indeed more sensitive to AD. Seventy AD patients (subdivided into ‘‘very mild’’, ‘‘mild’’ and‘‘moderate’’) and 47 control subjects participated in the study. The performances in two short distinct tests requiringproper name retrieval (Naming People on Definition and Naming Faces), one test of common name retrieval, short(MMSE, 3MS) and long (MODA) batteries for the detection of dementia were compared. Proper name retrieval testswere shown to be more sensitive to early AD than any other tests and batteries that failed to distinguish ‘‘very mild’’AD from controls. These findings suggest that proper name retrieval tasks might be profitably included in diagnostictools for the early diagnosis of AD. Introduction Proper names seem especially difficult to retrieve and are, bymost people, considered to make one experience temporaryfailures more often than other nouns (Cohen and Burke,1993). This difficulty has received several explanations(Semenza, 1997), all however related to the rather weak and arbitrary link that proper names entertain with theirreference. In the most recent theory (Semenza  et al .,1998), the basis of this fragility has been identified in thepeculiar organization of semantic information labeled byproper names. Unlike common names, that label categories,proper names designate individual (or groups of individual)entities. As a consequence, while, in the act of naming,common names are activated by attributes that have a highprobability of being linked to each other, proper names areactivated, via a different mechanism, by sets of attributes thathappen to be linked together only incidentally. Hence theparticular sensitivity of proper names to lack of cognitiveresources, as well as the difference between the two retrievalmechanisms, increase the possibility for the two categories toselectively dissociate after focal brain damage (Semenza andZettin, 1988, 1989; Semenza and Sgaramella, 1993). Thistheory makes, between common and proper name retrieval, adistinction that is clearly analogous to that between semanticand episodic memory mechanisms, but for an importantdifference: the name retrieval mechanisms are more periph-eral and operate at the lexical level. Both types of memorymechanisms are expected to undergo physiological changeswith age and, of course, to be sensitive to neurologicaldeterioration.Several studies are reported in the literature documenting aword finding difficulty with increasing age (Nicholas  et al .,1997). It is also widely accepted that proper names areparticularly sensitive to the age factor (Cohen, 1994),although convincing experimental support for this view issurprisinglysparse.Experimentalevidence,however,hasbeenrecently produced (Semenza  et al ., 1996), showing how anubiquitous, across-ages, proper name disadvantage in nounretrievalbecomes,innormalpeople,dramaticallygreaterfromthe age of seventy. The technique used in this study, learningof supra-span lists of names, allowed avoiding traditionaldifficulties (Cohen, 1994) entailed in diary studies (forgettinga proper name may be, in fact, less easy to compensate andsocially morerelevant than forgettingacommon name) and instudies comparing object naming with face naming (in thiscase perceptual difficulty is hard to balance). A series of factors like word frequency, length and phonological com-plexity were, in fact, controlled and could not be heldresponsible for such an effect. The same study showed thatin Alzheimer’s dementia (AD) the proper name disadvantageappeared earlier and in an even more striking fashion. Neurocase 1355-4794/03/0901–063$16.002003, Vol. 9, No. 1, pp. 63–69  #  Swets & Zeitlinger Correspondence to:  Sara Mondini, Dipartimento di Psicologia Generale, via Venezia 8, 35131, Padova, Italy. Tel:  þ 39 049 827 6616;Fax:  þ 39 049 827 6600; e-mail: Sara.Mondini@unipd.it    D  o  w  n   l  o  a   d  e   d   b  y   [   U  n   i  v  e  r  s   i   t  a   d   i   P  a   d  o  v  a   ]  a   t   0   1  :   4   8   2   4   J  u   l  y   2   0   1   2  Whether or not a generalized naming problem must beconsidered an early symptom of Alzheimer ’ s dementia (AD)is still a matter of debate: while some authors include a visualconfrontation naming problem in early symptoms, others donot consider it so typical in the early stages of the disease(Nicholas  et al ., 1997; Luzzatti, 1999). The above reported fi ndings suggest, however, that, of all names, propernames might be, indeed, those showing a typical sensitivityat the onset of progressive, generalized cortical damage.Further reasons for this hypothesis may be found in thepathology of AD, more typically starting in the temporaland the hyppocampal regions. The temporal lobe seemsmore involved in the retrieval of proper names with respectto other grammatical classes including common nouns(Semenza  et al ., 1995; Damasio  et al ., 1996; Gorno Tempini et al ., 1998) while the hippocampus is the keyarea in episodiclearning (see the above reported argument). The present studywas thus meant to seek further evidence of the particularsensitivity of proper name retrieval to cortical deterioration(on both confrontation and de fi nition) and to check theusefulness of proper names as diagnostic material in the earlystages of AD. Method Two distinct tests (henceforth  ‘‘ Proper Name tests ’’  whenreferring to both) requiring proper name retrieval were pre-pared: Naming Faces (15 items) and Naming People onDe fi nition (15 items) of very famous people (including con-temporary, e.g. Clinton, and a few historical personages, e.g.Napoleon); while some of these people were known world-wide (e.g. Queen Elizabeth), some others, like Italian TVcharacters or politicians, were only locally popular. A carefulselection brought to the choice of this testing material (seealso the corollary for principles inspiring the selection cri-teria). Only items where a preliminary investigation docu-mented success in 92 to 98 out of 100 subjects (50 to 70 y.o.)wereincludedinthe fi naltest.Asaresultofthisselection only fi ve famous people appeared in both Naming Faces andNaming People on De fi nition. Half of the experimental sub- jects was administered Naming Faces  fi rst, while the otherhalf started with Naming People on De fi nition. In order tominimize practice effects on the  fi ve common items the twoProper Name tests were never administered one immediatelyafter the other.A further naming on de fi nition of Common Name test (16items: 8 objects and 8 substances, see Appendix 1) was used,matched for dif  fi culty to the Proper Name tests (92 to 98%success for each items in the same 100 control subjects). Aconfrontation (picture) naming condition was not included inthe study because it turned out to be very dif  fi cult to selectitems according to criteria comparable to those used forProper Name tests. Typically, in fact, naming of pictures of objects either elicited, in normal subjects, 100% correct in theeasier items responses or a much worse performance (lessthan 80% correct) for the most dif  fi cult ones.These tests were administered together with the Mini-Mental State Examination (Folstein  et al ., 1975; ToumbaughandMcIntyre,1992;MitrushinaandSatz,1994)andanItalianversionoftheModi fi edMMSE(3MS),(TengandChui,1987).All AD patients (but not controls) also received the MODA(Milan Overall Dementia Assessment), an extensive andwidely used battery for the detection and assessment of dementia (Brazzelli  et al ., 1994). The MODA battery encom-passes two subsections: a  fi rst part concerning  ‘ Orientationability ’  (a series of questions about time, space and, familyinformation) and a  ‘ Testistic ’  part tapping cognitive abilities(attention, memory, learning, verbal  fl uency, visual percep-tion, copy and digital agnosia). Subjects Seventy patients referred as suspected AD (meetingNINCDS-ARDRA criteria, McKhann  et al ., 1984) and 47control subjects participated in the study. Controls wererecruited among non-neurological patients from the day carehospital and they were age- and education-matched with ADpatients [age: t (115) ¼ 1.1, n.s.; education: t (115) ¼ 1.69; n.s.].The AD subjects were subdivided on the basis of the MMSEscores in three groups: 15  ‘‘ very mild ’’  (range 30 – 26), 33 ‘‘ mild ’’  (25 – 21) and 22  ‘‘ moderate ’’  (20 – 16). MMSE scoresfor the controls were comparable to those of very mild AD[t (60) ¼ 0.313; n.s.]. The four groups did not differ from eachother in age and educational level. Table 1 summarizesdemographic information and MMSE scores of patientsand controls.A safe diagnosis of   ‘‘ very mild ’’  AD was made possibleonly by reassessing participants six months after the collec-tionoftheexperimentaldata.Thusthe ‘‘ verymild ’’ groupwasselected starting from a pool of 40 participants, who wereevaluated on formal request from their family physicianbecause of suspected AD. Their MMSE ranged between 26and 30 and on formal neuropsychological assessment they didnot meet NINCDS-ARDA criteria; these subjects would thusbelong, in all likelihood, to the Mild Cognitive Impairment Table 1.  Demographic information of AD patients and controlsAge Education MMSE(years)ControlsMean 69.53 8.47 27.85DS 10.47 5.43 2.17Very mild ADMean 68.00 7.40 27.67DS 5.90 4.32 1.23Mild ADMean 71.55 7.58 22.73DS 6.23 5.15 1.31Moderate ADMean 73.14 5.57 16.77DS 6.48 2.62 2.20 64 C. Semenza  et al.    D  o  w  n   l  o  a   d  e   d   b  y   [   U  n   i  v  e  r  s   i   t  a   d   i   P  a   d  o  v  a   ]  a   t   0   1  :   4   8   2   4   J  u   l  y   2   0   1   2  (Petersen  et al ., 1999, 2001) category, although all the diag-nostic criteria for inclusion in this category were not fullyconsidered. All these patients were nonetheless administeredthe experimental proper name tests and were given asecond assessment six months later. At this time 15 out of the initial 40 patients met unequivocally the NINCDS-ARDRA criteria and their MMSE scores had dropped to aclearly pathological level (25 patients received, instead, adiagnosis of pseudodementia, vascular disease and weredropped from the study). These 15 patients constituted the ‘‘ verymild ’’ ADgroupandtheirscoreintheProperNametestat the time of the  fi rst assessment entered the statisticalcomputations of this study. None of these patients have beentaking psychoactive medications at any time during thisinvestigation. Results The  fi rst group of analyses investigated the sensitivity of eachtest in discriminating controls and  ‘‘ very mild ’’  Alzheimerpatients. A series of non-parametric analyses were conductedusing either Mann-Whitney U Test for independent groups orWilcoxon test for dependent groups given the limited numberof subjects for each severity level. These analyses aimed tocompare the four groups of subjects in performing MMSE,3MS, Common names, Proper names and MODA. Table 2summarizes results of all groups in each test.The MMSE wasunabletodiscriminatebetweenthecontrolgroup and  ‘‘ very mild ’’  AD patients [U(47,15) ¼ 307.5,p ¼ .107], while it effectively distinguished the other groups[ ‘‘ very mild ’’  vs  ‘‘ mild ’’ : U(15,33) ¼ 0, p < .0001;  ‘‘ mild ’’  vs ‘‘ moderate ’’ : U(33,22) ¼ 0, p < .0001].The  3MS  was more sensitive but it could not yet discrim-inate between controls and  ‘‘ very mild ’’  AD [U(47,15) ¼ 245.5, p ¼ .078] but it only distinguished  ‘‘ very mild ’’  and ‘‘ mild ’’  [U(15,33) ¼ 41, p ¼ .0001] and  ‘‘ mild ’’  and  ‘‘ mod-erate ’’  [U(33,22) ¼ 134.5, p < .0001].The  Common Names  test could not discriminate controlsfrom  ‘‘ very mild ’’  [U(30,10) ¼ 92, p ¼ .072];  ‘‘ very mild ’’ vs. ‘‘ mild ’’  [U(10,22) ¼ 77.5, p ¼ .190],  ‘‘ mild ’’  vs.  ‘‘ moderate ’’ [U(22,14) ¼ 108, p ¼ .141], while distinguishing the othergroups. Table 2.  Results of control subjects and AD patients (very mild, mild and moderate) in MMSE, 3MS, Naming People on de fi nition, Naming Faces, Commonnames and MODAControls Very mild Mild ModerateMean C.I. SD Mean C.I. SD Mean C.I. SD Mean C.I. SDMMSE 27.85   0.64 2.17 27.67   0.68 1.23 22.73   0.46 1.31 16.77   0.98 2.203MS 97.74   2.19 7.44 91.87   4.1 7.41 74.79   3.32 9.36 61.59   6.86 15.47Naming People on de fi nition 13.32   0.64 2.19 8.60   2.26 4.08 6.00   1.26 3.55 3.86   1.39 3.14Naming Faces 14.17   0.34 1.17 8.80   2.5 4.52 7.85   1.25 3.53 4.62   1.72 3.77Common names 30.87   0.5 1.70 29.40   1.66 2.32 26.00   3.01 6.78 23.50   3.81 6.61MODA 90.08   4.08 7.07 80.14   2.65 7.49 67.38   5.10 11.50 Fig. 1.  Comparison between controls and very mild Alzheimer patients in the different tests. Proper names and Alzheimer ’ s disease 65    D  o  w  n   l  o  a   d  e   d   b  y   [   U  n   i  v  e  r  s   i   t  a   d   i   P  a   d  o  v  a   ]  a   t   0   1  :   4   8   2   4   J  u   l  y   2   0   1   2  Naming People on De fi nition was, instead, foundto discriminate between controls and  ‘‘ very mild ’’  AD[U(47,15) ¼ 115.5, p < .0001],  ‘‘ very mild ’’  vs  ‘‘ mild ’’ [U(15,33) ¼ 152.5, p < .05] and  ‘‘ mild ’’  vs  ‘‘ moderate ’’ [U(33,22) ¼ 224.5, p < .05].Naming Faces also discriminated between controls and ‘‘ very mild ’’  AD [U(47,15) ¼ 96, p < .0001],  ‘‘ mild ’’  vs. ‘‘ moderate ’’  AD [U(33,22) ¼ 183, p < .01], but notbetween  ‘‘ very mild ’’  and  ‘‘ mild ’’  AD [U(15,33) ¼ 212.5,p < .435].A practice effect on the  fi ve items that were common tothe two Proper Name Tests was not found. The patients ’ performance was then examined on a single case basis tolook for subjects who, reversing the general pattern, wouldbe signi fi cantly better at De fi nition than at Faces . No suchpatient was found. Fig. 1 shows the performance of controls and  ‘‘ very mild ’’ AD patients in the four tests (Naming Faces, Naming Peopleon De fi nition, MMSE, 3MS and Common Names). The rawscores of all tests were subject to linear transformation to therange (0 – 1).In order to further investigate the predictive value of each test, a logistic regression was performed on the scoresofnormalsandverymildADinMMSE,3MS,Commonnametests, Naming People on De fi nition and Naming Faces. Theresulting function correctly classi fi ed 87% of cases: the onlysigni fi cant predictor being the Proper Name tests (  p ¼ .003),see Table 3.The second part of the analysis investigated thesensitivity of MODA. AD patients ’  performances inthe MODA and in Proper Name Tests were compared.All AD patients, regardless of the severity level, showedmore dif  fi culties in naming proper names than in per-forming the MODA [Wilcoxon test: Naming People onDe fi nition, Z ¼ 7.016; p < .001; Naming Faces, Z ¼ 6.569;p < .001]. Proper Name tests were also much moresensitive than both the Orientation [Wilcoxon test: Nam-ing People on De fi nition, Z ¼ 7.08; p < .001; NamingFaces, Z ¼ 6.98; p < .001] and the Testistic [Wilcoxontest: Naming People on De fi nition, Z ¼ 5.67; p < .001;Naming Faces, Z ¼ 4.13; p < .001] sections of theMODA.Finally, an analysis was performed reclassifying thepatients according to MODA: 14 patients were stillwithin the normal limits (AD N), nine were classi fi edas  ‘‘ uncertain ’’  (AD U) and 47 were diagnosed asdemented (AD D). The Proper Name Tests, however,effectively discriminated not only between AD patients of different level of severity, but even AD N from controlsubjects [Naming People on de fi nition: U(47,15) ¼ 107,p ¼ .001; Naming Faces: U(47,15) ¼  60.5, p < .001], asshown in Fig. 2. Fig. 2.  Performance on Proper Name Tests (including Naming People on De fi nition and Naming Faces) of normal subjects and AD patients whose severity of disease is classi fi ed according with MODA (AD N ¼ Alzheimer patients whose MODA score identi fi ed a normal performance; AD U ¼ Alzheimer patients whoseMODA score identi fi ed an uncertain diagnosis of dementia; AD D ¼ Alzheimer patients whose MODA score identi fi ed a clear diagnosis of dementia. Table 3.  Logistic regression of analysis of Alzheimer diagnosis as a functionof each testB S.e. Wald df   p  Odds ratioMMSE .723 .649 1.242 1 .265 2.0613MS   .022 .176 .016 1 .899 .978 NP   .656 .223 8.645 1 .003 .519 NC .347 .466 .555 1 .456 1.415Constant   14.053 13.041 1.161 1 .281 .000 66 C. Semenza  et al.    D  o  w  n   l  o  a   d  e   d   b  y   [   U  n   i  v  e  r  s   i   t  a   d   i   P  a   d  o  v  a   ]  a   t   0   1  :   4   8   2   4   J  u   l  y   2   0   1   2

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