Object naming and semantic fluency among individuals with genetic risk for Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY

Int J Geriatr Psychiatry 2005; 20: 128–136.

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/gps.1262

Object naming and semantic fluency among individualswith genetic risk for Alzheimer’s disease

Karen J. Miller*, Steven A. Rogers, Prabha Siddarth and Gary W. Small

Department of Psychiatry and Biobehavioral Sciences, the Neuropsychiatric Institute, the Alzheimer’s Disease Center, andthe Center on Aging, University of California at Los Angeles, Los Angeles, USA

SUMMARY

Objectives This study longitudinally examined the object naming and semantic fluency of individuals who are at risk fordeveloping Alzheimer’s disease (AD) by virtue of having APOE-4 or a family history of AD.Methods A total of 108 participants (40 with a family history of AD and 43 with APOE-4) completed the Boston NamingTest and the Animal Naming task at initial assessment and after two years.Results At baseline, object naming was significantly lower for those with both risk factors, F(2, 99)¼ 5.72, p< 0.01, butthose with either risk factor had significantly lower scores at follow-up, F(2, 99)¼ 3.41, p< 0.05. Semantic fluency (animalnaming) was reduced among subjects with the APOE-4 allele at baseline, F(1, 100)¼ 4.02, p< 0.05, but it was not asso-ciated with either risk factor at follow-up.Conclusions These deficits may be associated with a prodromal risk for AD and may serve as pre-symptomatic markersfor the development of AD. Copyright # 2005 John Wiley & Sons, Ltd.

key words— language; family history; APOE; Alzheimer’s disease

INTRODUCTION

For the millions of individuals who suffer fromAlzheimer’s disease (AD), few words can describethe fear and powerlessness that accompany their lossof recent memory, their changes in mood and person-ality, and their impaired skills in communication andlanguage. The physicians who treat these individualsoften experience feelings of frustration and futility,which often fuels an increased determination to use

research to alleviate the suffering in this population.Much of this research has been moving in the direc-tion of studying preclinical signs among those whohave not yet developed dementia. It has been discov-ered that the disease may be precipitated not merelyby declines in memory, but also by growing difficul-ties with language, particularly semantic skills likesemantic fluency and object naming (Jacobs et al.,1995). Much of this research has focused on thereduced levels of object naming and semantic fluencythat occur in the early stages of AD (Flicker et al.,1987; Monsch et al., 1992). However, little researchhas examined the language functioning of thosewho are currently asymptomatic, but at risk for devel-oping AD. This study longitudinally examined theobject naming and semantic fluency of asymptomaticindividuals who have preclinical risk for developingAD, either by virtue of their relation to patients withAD or their possession of the APOE-4 allele. It washoped that this would help determine the patterns ofobject naming and semantic fluency that are asso-ciated with the preclinical signs of AD as theydevelop over time.

Received 24 May 2004Copyright # 2005 John Wiley & Sons, Ltd. Accepted 28 September 2004

*Correspondence to: Dr K. J. Miller, UCLA NeuropsychiatricInstitute, 760 Westwood Plaza, Suite 88-201, Los Angeles, CA90024-1759, USA. Tel: 310-267-2663. Fax: 310-825-3910. E-mail:[email protected]

Contract/grant sponsor: National Institutes of Health; contract/grantnumbers: MH52453, AG13308, AG10123, MO1 RR00856-21.Contract/grant sponsor: Alzheimer’s Association; contract/grantnumber: IIRG94101.Contract/grant sponsor: California Department of Health Services;contract/grant number: 95-23330.Contract/grant sponsors: Montgomery Street Foundation; The Franand Ray Stark Foundation Fund for Alzheimer’s Disease Research;Judith Olenick Elgart Fund.

Preclinical signs and risk factorsof Alzheimer’s disease

Driven by the prospect of new treatments and the pre-vention of AD, researchers have demonstratedincreased interest in uncovering the preclinical mar-kers that indicate increased risk for AD (Hom et al.,1994; Fox et al., 1998). This includes identifying pro-dromal symptoms and risk factors, as well as a precli-nical phase that spans the time from disease inceptionto the time the disease becomes clinically sympto-matic (Jacobs et al., 1995; Small et al., 2001).One of the findings of this research is the discoverythat genetic patterns and genetic markers serve as sig-nificant risk factors associated with the disease.Among these genetic factors are a family history ofAlzheimer’s and the possession of the APOE-4 allele.

Regarding the former, it appears that AD may fol-low an autosomal dominant mode of inheritance(Martin et al., 1988). This suggests that those whohave relatives with AD are at increased risk for devel-oping the disease, particularly if their relatives hadearly- rather than late-onset of AD (La Rue et al.,1992; Hom et al., 1994; Silverman et al., 1994). Twinstudies reveal a concordance rate for developing ADthat is 40–50% among monozygotic twins and 8–50%for dyzygotic twins (Small et al., 1993). Even asymp-tomatic first-degree relatives of those with AD exhibitsignificant cognitive declines that are reflective ofAD, such as reductions in verbal memory, overallbrain function, performance IQ, and verbal learning(Hom et al., 1994; Fox et al., 1998). Hence, one’s sus-ceptibility to developing AD may be exacerbated by afamilial history of the disease.

In a similar fashion, it seems those who have a copyof the genetic marker APOE-4 are at increased riskfor developing AD. Apolipoprotein E alleles are poly-morphic proteins that direct lipid metabolism and thatare directly involved in transporting blood cholesteroland inducing synaptic plasticity. Any impairment intheir functioning may increase the risk for AD bydecreasing the amount of cholinergic activity in thebrain and increasing the density of senile plaques(Corder et al., 1993; Corder et al., 1994; Poireret al., 1995; Blass and Poirer, 1996). The APOE geneis found on chromosome 19 and comes in three com-mon alleles: APOE-2, APOE-3, and APOE-4. Ofthese, it is the APOE-4 gene that is often seen amongthose with sporadic AD and late-onset familial AD(Saunders et al., 1993; Poirier et al., 1995). Accordingto Ashford and Mortimer (2002), the APOE-4 geno-type may even account for as much as 50% of the riskfor developing AD.

Furthermore, the risk of developing AD increasesas the number of allele copies of the gene increase.Corder et al. (1994) estimated that each additionalcopy increases one’s risk by a factor of four. There-fore, both a family history of Alzheimer’s and the pos-session of the APOE-4 allele may serve as notablerisk factors that predate the expression of AD.

Object naming and semantic fluency

It may be that there are differences in the neuropsy-chological functioning between those who are at riskfor AD and those who lack these genetic risk factors.More directly, there may be neuropsychological defi-cits that are associated with these factors and that canalso represent prodromal signs of the disease. Manyof the previous studies examining the neuropsycholo-gical characteristics of preclinical AD have focusedon either global deficits in functioning or globalimpairments in memory, rather than particulardomains of functioning like language (Hom et al.,1994; Jacobs et al., 1995). This may be because mem-ory is often the most salient and painful loss for thosewith AD, and because the detection of global changesis first necessary to legitimize the pursuit of specificdeficits in a domain like language. However, a parti-cular assessment of language functioning may now beappropriate, especially considering the recent findingthat asymptomatic first-degree relatives of those withAD exhibit unique cognitive declines compared tocontrol groups (Hom et al., 1994, Jacobs et al., 1995).

The existence of preclinical deficits in object nam-ing and semantic fluency seems particularly likelyconsidering both the language impairments that oftenaccompany AD and their expression in the earlystages of AD. One of the characteristic complaintsamong those who suffer from AD is a difficulty nam-ing objects and finding words when provided withsemantic categories (Appell et al., 1982; Flickeret al., 1987; Monsch et al., 1992; Kessler et al.,1997). Moreover, these language difficulties havebeen increasingly demonstrated as a feature of theearly stages of AD (Binetti et al., 1995). Flickeret al. (1987) found those in the early stages of ADexhibited greatest impairment in object naming andsemantic fluency relative to normals, while Monschet al. (1992) discovered that the earliest stages ofAD were characterized by significant deficits insemantic fluency compared to normals.

Although object naming and semantic fluencyrepresent slightly different neural processes, theymay be conjointly affected because they share asemantic component involving the rapid production

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Copyright # 2005 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry 2005; 20: 128–136.

and retrieval of verbal information from semanticmemory. There is growing evidence that the structuresof semantic memory are among the regions thatexperience the earliest loss of differentiation andintegrity in AD (Appell et al., 1982). Some of thismay follow from the early deterioration that has beenseen in the parietal, temporal, and frontal lobes ofpatients with AD (Silverman et al., 1999; Famaet al., 2000; Pihlajamaki et al., 2000).

In this light, it appears that difficulties in objectnaming and semantic fluency are not only character-istic of AD in general, but also of the early stages ofAD in particular. This may implicate the deteriorationof object naming and semantic fluency in the preclini-cal phase of AD among those at risk for developingthe disease. It may be that those who are at risk forAD exhibit greater deficits in object naming andsemantic fluency when compared to controls whoare not at risk for AD.

This study therefore attempts to longitudinallyexamine the object naming and semantic fluency ofasymptomatic individuals who have preclinical riskfor developing AD, either by virtue of their relationto patients with AD or their possession of APOE-4.It was expected that those at risk for AD woulddemonstrate lower baseline scores and greaterdeclines over time on tests of object naming andsemantic fluency than those without this risk. Thisstudy also assessed differences in object naming andsemantic fluency according to the number of risk fac-tors that individuals’ possessed, including the possibi-lity of an interaction between family history andpossession of the APOE-4 allele.

METHOD

Participants

The participants were individuals who responded tomedia coverage, university-affiliated projects, ornewspaper advertisements for individuals with mem-ory complaints or family histories of dementia. Allparticipants received psychiatric and neuropsycholo-gical evaluation, as well as routine laboratory screen-ing tests, to assess cognitive performance and to ruleout treatable causes of cognitive impairment. Partici-pants were excluded from the study if they had a neu-rological, medical, or psychiatric condition that mightaffect memory or cognitive performance, includingsevere head trauma, current or past major psychiatricillnesses (e.g. Major Depression), or an active medicalillness (e.g. cancer). The participants were alsoexcluded if they scored less than 25 on the Mini-Mental Status Exam, which represented the criteria

used for participants to be ‘asymptomatic.’ Thesemethods of exclusion were based on a review of med-ical history, laboratory tests, and a psychiatric inter-view and evaluation.

A total of 147 individuals met inclusion criteria, butonly 108 had information available regarding both afamily history of AD and APOE-4. Family historywas defined as having a first-degree relative whowas diagnosed with probable AD, and APOE-4 geno-types were determined by standard genetic testingtechniques that obtained DNA from participants’blood samples. These procedures involved polymer-ase chain amplification and have been described pre-viously (Saunders et al., 1993). Of the final 108participants, 24 had both a family history of AD andwere either heterozygous or homozygous for theAPOE-4 allele, 16 had only a family history of AD,19 only had the APOE-4 allele, and 49 had neitherrisk factor. The number of participants in each cate-gory of risk factors is presented in Table 1.

Measures and procedures

Each participant completed the Boston Naming Test(BNT; Kaplan et al., 1983) and an animals namingtask as part of a full neuropsychological evaluationthat lasted approximately three hours. This evaluationincluded tests of attention, learning and memory,visuospatial function, cognitive flexibility, andselected language measures, including the BNT andthe animal naming task. However, it is these lattertwo language measures that are most salient to thepresent study.

The BNT is aimed at measuring object naming andinvolves having participants name the objects repre-sented in 60 ink drawings. If participants were unableto name the object, they were first provided a seman-tic cue, and if they were still unable to identify it, theywere then given a phonemic cue. The test was scoredby totaling the number of drawings that were

Table 1. Number of participants in each category of risk factors

Risk factors N Percent

None 49 45APOE-4

APOE-4 43 40Non-APOE-4 65 60

Family Hx.Family Hx. of AD 40 37No Family Hx. of AD 68 63

One risk factor 35 32Both risk factors 24 22

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correctly identified, either with or without a semanticcue. The analyses for this study did not assess thenumber of phonemic cues due to our particular inter-est in semantic deficits.

The Animal Naming task is a measure of semanticfluency and instructs participants to verbally generateas many names of different animals as possible withina one-minute period. Examiners wrote down each ani-mal name and kept track of the perseverative or intru-sion errors. This test was scored by totaling thenumber of unique animal names that were generated.

These tests were completed at a baseline occasionand then two years later to examine longitudinalchanges. These changes were calculated by subtract-ing baseline raw scores from scores at follow-up. Allof the examiners collecting neuropsychological datawere blind to participants’ family history of AD andthe results of genetic testing. Written informedconsent was obtained in accordance with the proce-dures set by the UCLA Human Subjects ProtectionCommittee.

Analytic strategy

Two complementary analytic strategies wereemployed to investigate the combined effects offamilial and genetic risk factors on object namingand semantic fluency. In one set of analyses,ANCOVA procedures were used to determine if therewere any differences in object naming and semanticfluency according to the number of risk factors thatparticipants possessed. Subjects were classified intothree groups: (a) those with both the APOE-4 alleleand a family history of AD (n¼ 24); (b) those witheither one of these risk factors (n¼ 35); and (c) thosewith neither risk factor (n¼ 49). Then, ANCOVAswere conducted with object naming/semantic fluencyas the dependent variable, subject group as the inde-

pendent variable, and age, gender and education ascovariates. These analyses were performed separatelyfor baseline and longitudinal change scores. T testswere used to make post hoc comparisons if resultswere significant.

In a separate set of analyses, ANCOVAs were usedto assess the effect of the interaction between familyhistory and APOE-4 on object naming and semanticfluency at baseline and two years follow-up. Theseanalyses used APOE-4 status, family history status,and their interaction as independent variables, withobject naming and semantic fluency as dependentvariables. These analyses also controlled for theeffects of age, gender, and education. If the interac-tion between APOE-4 status and family history wasnot significant, the main effect of these risk factorswas examined. All tests were two-tailed and consid-ered significant if p< 0.05. A correction for multiplecomparisons was not performed because all our ana-lyses were hypothesis-driven.

RESULTS

Demographic differences

As seen in Table 2, there were no significant differ-ences between the subject groups in their gender,age, or level of education. Table 3 presents means, teststatistics, and p values for the statistical analysesbetween the risk factors and object naming andsemantic fluency.

Object naming

At baseline, ANCOVA procedures revealed a signifi-cant difference in object naming for those with differ-ent levels of risk factors, F(2, 99)¼ 5.72, p< 0.01.Subsequent t test analyses showed that participantswho had both risk factors (M¼ 53.54, SE¼ 0.84),

Table 2. Demographic statistics by risk factors for AD

Demographics Overall No APOE-4 Family history of AD Either Both(n¼ 108) risk factors factors factor

APOE-4 Non-APOE-4 Family Hx. No Family Hx.

GenderMales (%) 51 22 22 29 17 34 19 10Females (%) 57 27 21 36 23 34 16 14

AgeM 64.19 63.67 64.42 64.03 64.65 63.91 64.80 64.33SD 5.85 6.14 5.64 6.03 5.91 5.84 5.28 6.16

Years of educationM 15.83 15.96 15.77 15.88 15.70 15.91 15.71 15.75SD 2.29 2.33 2.31 2.29 2.37 2.25 2.12 2.51

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namely a family history of AD and the APOE-4 allele,had significantly lower scores in object naming thanthose who had only one risk factor (M¼ 57.13,SE¼ 0.68) or no risk factors (M¼ 56.26, SE¼0.59), t(99)¼ 3.31 and 2.66, ps< 0.01, respectively.ANCOVA procedures also revealed that there wasan interaction between family history and APOE-4on object naming, F(1, 98)¼ 6.76, p< 0.05. As seenon Figure 1, those who had the APOE-4 marker anda family history of AD exhibited significantly lowerscores in object naming at baseline than all othergroups.

In the longitudinal analyses, an ANCOVA yieldeddifferences in object naming between those with dif-ferent levels of risk factors, F(2, 99)¼ 3.41, p< 0.05.Post-hoc t tests revealed that participants who had onerisk factor (M¼�2.16, SE¼ 0.59) had significantlygreater reductions in object naming over a two-yearperiod than those who had no risk factors (M¼�0.09, SE¼ 0.55), t(99)¼ 2.57, p< 0.05. Neitherrisk factor could be implicated as having a unique

effect on these changes in object naming, but therewas a trend for an interaction effect between the riskfactors on changes in object naming over time(p¼ 0.11). In particular, those who possessed theAPOE-4 marker and lacked a family history of AD(M¼�2.43, SE¼ 0.78) demonstrated notable reduc-tions in object naming compared to those who hadneither APOE-4 nor a family history of AD (M¼�0.11, SE¼ 0.56).

Semantic fluency

At baseline, an ANCOVA revealed that those with theAPOE-4 marker exhibited significantly lower scoreson semantic fluency than those without this risk fac-tor, F(1, 100)¼ 4.02, p< 0.05. A familial history ofAD did not have a significant effect on semantic flu-ency; there was no interaction between the risk factorson semantic fluency; and semantic fluency did not dif-fer according to the number of risk factors. Therewere no longitudinal differences in semantic fluencyfor those at risk for AD and those not at risk for ADby virtue of either risk factor.

DISCUSSION

This study investigated whether there are neuropsy-chological deficits in object naming and semantic flu-ency that are associated with a preclinical risk fordeveloping AD. The results suggest that those whohave genetic risk of AD, due either to a family historyof AD or the possession of the APOE-4 allele, mayexhibit cross-sectional and longitudinal impairmentsin object naming, as well as cross-sectional impair-ments in semantic fluency. In particular, those whopossess both risk factors may demonstrate a signifi-cantly reduced capacity for object naming comparedto those with either one or no risk factors. Over time,

Table 3. Means and significance tests for object naming and animal naming by subject group

Tests APOE-4 Family history Number of risk factors

M w/ M w/out F p M w/ M w/out F p M Zero M One M Two F p

BaselineBoston Naming Test 55.10 56.49 2.99 0.09 55.73 55.27 0.30 0.59 56.26 57.13 53.54 5.72 0.01Animal Naming Test 19.36 21.51 4.02 0.04 20.28 21.23 0.85 0.36 21.79 20.01 19.83 1.51 0.23

Longitudinal changeBoston Naming Test �1.60 �0.50 2.23 0.14 �1.64 �0.76 0.99 0.33 �0.09 �2.16 �1.57 3.41 0.04Animal Naming Test 1.10 �0.89 1.41 0.24 0.48 �1.09 0.63 0.43 �1.72 0.33 0.56 0.70 0.50

Note. All significance tests are controlling for age, gender, and education. Longitudinal changes were calculated by subtracting raw baselinescores from follow-up scores.

Figure 1. Interaction between family history and APOE-4 on themean scores of the Boston Naming Test (BNT) at initial assessment



however, even having one of these risk factors,regardless of which factor, may predispose indivi-duals to experience significantly greater reductionsin object naming than those who have no risk factors.Moreover, those who have the APOE-4 marker mayexperience reduced semantic fluency compared tothose without this marker. This suggests that one’sobject naming and semantic fluency may be compro-mised in part by individuals’ genetic susceptibility toAD. It also suggests that the deterioration of objectnaming and semantic fluency may be part of a precli-nical phase for the development of AD.

To illustrate the clinical significance of theseresults, it may be helpful to compare our findings withnormative data. At baseline, the group with both riskfactors had a mean of 53.54 out of 60 on the BostonNaming Test, whereas those with only one risk factorhad a mean of 57.13 and the group with no risk factorshad a mean of 56.26. According to normative data(Mitrushina and Satz, 1995), those with both risk fac-tors are performing significantly below their agepeers. This is evident because individuals who are63 to 64 years old, and therefore similar to the meanage of the people in this study, should obtain a scoreof 56.00 (SD¼ 3.30). As a result, those with both riskfactors are only performing at the 23rd percentilecompared to their age peers, whereas the other twogroups are performing at expected levels for theirage (above the 50th percentile). Those with multiplerisk factors therefore appear to demonstrate notabledeclines in object naming, which may significantlyshape their language functioning, quality of life, andthe way services are delivered.

Similarly, the findings from the longitudinal ana-lyses reveal that those with even one risk factor areexperiencing on average a two-point decline in theirtotal score. Compared to normative data, this indi-cates that individuals who had at least one risk factorat follow-up were performing below their age-matched peers (or below the 50th percentile).

Normative data reveals less clinical significance insemantic fluency when comparing those with andwithout APOE-4. However, there was a significanttwo- to three-point difference between the groups,which suggests that the at-risk group is decliningcompared to their age matched peers (Tombaughet al., 1999). Collectively, these comparisons withnormative data suggest that those who are at risk forAD may be experiencing a decline in semantic lan-guage functioning at baseline and follow-up thatmight be beyond normal aging, which strengthensthe possibility that these individuals are in the precli-nical phases of AD.

These findings are consistent with previous litera-ture that suggests that object naming and semanticfluency are most impaired among those who are inthe early stages of AD (Flicker et al., 1987; Monschet al., 1992). They also support the growing conten-tion that the associative networks of semantic mem-ory are compromised in the early stages of AD(Appell et al., 1982; Silverman et al., 1999; Famaet al., 2000; Pihlajamaki et al., 2000). This seemsparticularly true considering that both object nam-ing and semantic fluency share a word-finding fea-ture that involves the retrieval and production ofverbal material from semantic memory. This studyextends the foregoing literature, however, by show-ing how these word-finding difficulties and the dete-rioration of the semantic system exist not only in theearly stages of AD, but also among those who are atgenetic risk for developing AD. This may illuminatesome of the deficits that occur among those at riskfor developing AD, and it may enable object namingand semantic fluency to serve as preclinical markersof AD.

Taking each of our findings in turn, it appears thatboth object naming and category naming wereimpaired at first assessment for those at risk ofAD. Semantic fluency was reduced among thosewith the APOE-4 allele, whereas object namingwas more impaired for those with APOE-4 and afamily history of AD. This seems to change overtime, however, so that object naming is compro-mised by having only one of the risk factors, whilesemantic fluency does not appear to further declineover two years.

One way of understanding these findings might bethrough the structural regions implicated in the dete-rioration of object naming and semantic fluency. Thefinding that APOE-4 may have more of a direct effecton semantic fluency at initial assessment may be dueto its association with dysfunction of the parietal andtemporal lobes. According to recent studies that usedMRI scanning (Fama et al., 2000; Pihlajamaki et al.,2000) and SPECT indexing (Pasquier et al., 1995), theparietal and temporal regions are central to the pro-cesses involved in semantic fluency and are amongthose areas most affected in the early stages of AD.It is these regions that also show hypometabolismand decreased synaptic activity among those whocarry the APOE-4 allele (Small et al., 1995; Smallet al., 2000; Silverman et al., 1999). Hence, thosewho carry this allele may have more difficulty naminganimals because of the deterioration that is occurringin those regions that are most affected by APOE-4.Because this deterioration begins early and declines

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rapidly, any later changes may be more gradualthan abrupt. This means that the comparison of one’scapacity to name animals over a two-year period maybe less sensitive to differences within and betweenrisk factors. These interpretations have yet to betested, but it appears that semantic naming may bean early manifestation of the language deficits experi-enced by those with the APOE-4 allele.

The finding that family history did not have aunique effect on semantic fluency is somewhat sur-prising considering that family history often has agreater impact in the early stages of the AD(Silverman et al., 1994). However, it is difficult to linkthe effect of family history to a particular neuralregion that might affect semantic fluency, like the par-ietal and temporal lobes, so it may have more of a glo-bal effect on language functioning than a specificeffect on semantic fluency. It may be that semanticfluency is more directly affected by the APOE-4 allelethan by differences in family history.

In a somewhat different fashion, object namingmay be both an early and later deficit for those at riskfor AD. Its early expression may be of greatest con-cern for those who have both the APOE-4 allele anda family history of AD. However, this may be a matterof simply delaying the onset of later difficulties, forthe longitudinal analysis suggests that having eitherrisk factor is sufficient to jeopardize one’s object nam-ing ability after a two-year follow-up. This offers twosignificant implications.

First, it implies that it is the combined or aggre-gated effect of both risk factors that may lead to thedisintegration of object naming, at least early in thepreclinical phase of AD. There was a notable trendfor those with APOE-4 to have lower object namingscores at baseline, but the variability in object namingseems to be better explained by the presence of bothrisk factors. It may be that the level of initial impair-ment in object naming increases concurrent with thelevel of risk.

Second, these longitudinal findings may reflectthe spread of impairment that has been seen in theearly stages of AD. One of the hallmarks in thecourse of AD has been the spread of neuritic plaquesand neurofibrillary tangles from the posterior towardthe anterior part of the brain, particularly from theparietal and temporal regions to the frontal regions(Small and Leiter, 1998). Part of the deteriorationthat occurs in object naming has been traced to thebreakdown of the semantic networks in the frontallobes (Binetti et al., 1995; Flicker et al., 1987).Object naming requires access to this semantic net-work and its associations between pictures and

words. As neural deterioration compromises theparietal and temporal lobes and spreads toward thefrontal lobes, individuals may begin to lose greatercommand over their ability to name objects. Whilethe participants of this study did not demonstratememory impairment consistent with dementia, it ispossible that their declining performance on theobject naming tasks was associated with theirincreased risk for developing AD.

On a more general level, these findings suggest thatone’s neuropsychological risk for language difficul-ties may increase with one’s genetic risk for AD,regardless of whether or not they ever develop AD.APOE-4 and a family history of AD seem to representdifferent types of risks with different implications forlanguage. Moreover, these findings suggest thatobject naming and semantic fluency operate accord-ing to different neural pathways, even if they are partof the same semantic system and involve similarword-finding processes.

When viewing these findings, some importantcaveats may need to be considered. The sample sizewas substantial and lends support to the generalizabil-ity of our findings, but our subject groups were of dif-ferent sizes, which may be an artifact of conveniencesampling. Among those without a family history ofAD, we were unable to actually determine if partici-pants’ relatives actually suffered from AD. In its pre-sent state, AD can only be conclusively identifiedposthumously, although PET and MRI imaging areproviding some promising findings in the early detec-tion of the disease (Small and Leiter, 1998). More-over, this study provides important informationabout the factors and language deficits involved inthe preclinical course of AD, but it does not provideinformation about the course of the illness, or evenguarantee that those at risk will develop AD. Thereare a certain number of individuals who will notdevelop AD, even though they are positive forAPOE-4. More careful testing may be needed to com-pare the language deficits of those who share a risk forAD, but who differ in whether or not they actuallydevelop the disease.

Future research can address some of these limita-tions, as well as consider the dose-related effects ofboth APOE-4 and family history. It is not yet certainif the difference in participants’ object naming andsemantic fluency was due to simply having these riskfactors or due to different degrees of each risk factor.This may be a particularly important area of study inlight of recent findings that both types or risk factorshave a dose-related effect on AD (Corder et al., 1994;Martin et al., 1988).



CONCLUSION

This study may underscore the presence of languagedeficits that are associated with a preclinical risk fordeveloping AD. Among those who possess theAPOE-4 allele, there may be a greater likelihoodfor a loss in semantic fluency, and object namingmay be impaired if individuals have both APOE-4and a family history of AD. Over time, however,simply having one of these risk factors may compro-mise object naming, whereas the differences insemantic fluency seem to disappear. This suggeststhat the deterioration of object naming and semanticfluency may be preclinical neuropsychological mar-kers for the development of AD, especially whenthey accompany genetic risk factors. For those withthese risk factors, these findings may informtheir communication skills, their ability to nameobjects and respond to semantic categories ineveryday parlance, and their sense of self-esteem,which may be intimately tied to their language func-tioning. For clinicians and researchers, these find-ings may aid early identification and accuratediagnosis of AD, which highlights the importanceof a multidimensional approach to preclinicalassessment for AD. This assessment can includedocumenting family history, using neuropsycholo-gical tests of object naming and semantic fluency,and weighing the costs and benefits of genetic test-ing and neuroimaging. To the extent we accomplishthis, maybe we can contribute to the ongoing endea-vors to delay and prevent the onset of this debilitat-ing illness.

ACKNOWLEDGMENTS

This study was supported by grants MH52453,AG13308, AG10123, and MO1 RR00856-21 fromthe National Institutes of Health; IIRG94101 fromthe Alzheimer’s Association; 95-23330 from the Calif.Dept. of Health Services; the Montgomery StreetFoundation; the Fran and Ray Stark Foundation Fundfor Alzheimer’s Disease Research; and the JudithOlenick Elgart Fund for Research on Brain Aging.

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KEY POINTS

* Early Language Changes in those at risk forAlzheimer’s Disease

* Risk Factors for Alzheimer’s Disease* Family History and APOE

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Object naming and semantic fluency among individuals with genetic risk for Alzheimer's disease

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