Embed Doc
Copy Link
Readcast
Collections

CommentGo Back

Download

1550 CORRESPONDENCE Journal of the National Cancer Institute, Vol. 97, No. 20, October 19, 2005

CORRESPONDENCE CORRESPONDENCE

Re: Cancer as a Risk Factorfor Dementia: A House Builton Shifting Sand

Our recent article

( 1 )

reported that,in a population-based sample of twins,there was increased risk for cognitivedysfunction in long-term cancer sur-vivors relative to their cancer-free co-twins. Cognitive dysfunction was foundin 14.5% of cancer survivors and in8.7% of twins who had not had cancer.Although clinically diagnosed dementiawas twice as frequent among cancer survivors as in their co-twins, this dif-ference was not statistically signi

ﬁ

cant.In an associated editorial, Wefel andMeyers

( 2 )

raised several concerns. In particular, they criticized use of telephone interviews to assess cognitivedysfunction. Although they did not stateso explicitly, they seemed concerned both that the method was too insensitiveto detect subtle cognitive sequelae

( 3 )

and that not everyone who scored poorlywas suf

ﬁ

ciently impaired to meet criteriafor dementia.In our assessment of cognitive func-tion, errors that classi

ﬁ

ed an individualas having cognitive dysfunction includedinability to remember three commonwords for 90 seconds, to know the day of the week, or to explain how two familiar items were similar to each other. Classi-

ﬁ

cation as having cognitive dysfunctionfurther required that an informant con-

ﬁ

rm that the individual’s daily function-ing (e.g., managing personal

ﬁ

nances,living independently) was impaired dueto problems of memory or cognition.The telephone assessment was not de-signed to identify subtle differences incognitive functioning but to locate indi-viduals whose cognition was obviouslycompromised. The fact that we founddifferences in rates of cognitive dysfunc-tion between cancer survivors and their cancer-free co-twins indicates that theassessment was sensitive to importantdifferences.They also noted the “ poor diagnosticaccuracy” associated with the telephoneinterview. The telephone interview wasnever intended to be a measure of clinicaldementia. Moreover, it is highly sensi-tive. Those who have dementia are de-tected

( 4 )

. In any event, we do not think that concerns about cognitive sequelaein cancer survivors should be limited tofrank dementia.They urged consideration of the alter-native hypothesis that cancer patientshad poorer cognitive functioning beforetheir cancer treatment. We agree with thevalue of longitudinal information. How-ever, even if some cognitive problemsexisted prior to the cancer, it seemsunlikely that the level of dysfunctionobserved in long-term survivors (14years postdiagnosis on average) wouldhave been present to any large extent before the cancer diagnosis.Finally, they question whether re-call error or interviewer bias might explain our

ﬁ

ndings. In our study, cancer

Journal of the National Cancer Institute, Vol. 97, No. 20, October 19, 2005 CORRESPONDENCE 1551

diagnoses were taken from the na-tional cancer registry, and cognitivescreening was conducted independentlyfrom establishing cancer history andin a context where interviewers were blind to future use of the data to studylate adverse health effects of cancer patients. Thus, we cannot see recallerror or interviewer bias affecting theresults.The increasing number of cancer survivors makes studies of late adversehealth effects important. Future individ-ualized treatment regimens, built on better prognostic and therapy predictivemarkers, will most likely reduce thenumber of unnecessarily treated patientsand thus late treatment-related sequelae.If future research con

ﬁ

rms long-term or late effects on cognition following can-cer treatment, patients and their healthcare providers deserve to have thisinformation.L

ARA

H. H

EFLIN

ETH

E. M

EYEROWITZ

ALL

AUL

ICHTENSTEIN

OHANSSON

ANCY

L. P

EDERSEN

ARGARET

ATZ

EFERENCES

(1)

ﬂ

in LH, Meyerowitz BE, Hall P, Lichtenstein P,Johansson B, Pedersen NL, et al. Cancer as a risk factor for long-term cognitive de

ﬁ

-cits and dementia. J Natl Cancer Inst 2005;97: 854 – 6.

(2)

Wefel JS, Meyers CA. Cancer as a risk factor for dementia: a house built on shifting sand.J Natl Cancer Inst 2005;97:788 – 9.

(3)

Meyers CA, Wefel JS. The use of theMini-Mental State Examination to assess cog-nitive functioning in cancer trials: no ifs, ands, buts, or sensitivity. J Clin Oncol 2003;21: 3557 – 8.

(4)

Gatz M, Reynolds CA, John R, Johansson B,Mortimer JA, Pedersen NL. Telephone screen-ing to identify potential dementia cases in a population-based sample of older adults. IntPsychogeriatr 2002;14:273 – 89.

OTES

ﬁ

liations of authors:

Department of Psy-chology, University of Southern California, LosAngeles, CA (LHH, BEM, NLP, MG); Depart-ment of Medical Epidemiology and Biostatistics,Karolinska Institutet, Stockholm, Sweden (PH, PL, NLP, MG); Department of Psychology, GoteborgUniversity, Goteborg, Sweden (BJ).

Correspondence to:

Beth E. Meyerowitz, PhD,Department of Psychology, University of SouthernCalifornia, Los Angeles, CA 90089-1061 (e-mail:meyerow@usc.edu).DOI: 10.1093/jnci/dji331© The Author 2005. Published by Oxford Univer sityPress. All rights reserved. For Permissions, pleasee-mail: journals.permissions@oxfordjournals.org.

RESPONSE

We commend He

ﬂ

in et al. for recog-nizing that the assessment of frank dementia is insuf

ﬁ

cient and that identi

ﬁ

-cation of subtler cognitive dysfunction isof great importance. The comprehensive,interdisciplinary approach utilized toidentify and subsequently diagnose casesof frank dementia is also laudable

( 1 )

.However, using a screening measure toidentify subtler cognitive dysfunctionremains problematic.He

ﬂ

in et al. themselves emphasizedthat the telephone assessment “was notdesigned to identify subtle differences incognitive functioning but to locate in-dividuals whose cognitive function wasobviously compromised.” From their study data

( 1 )

, more than 50% of in-dividuals identi

ﬁ

ed as evidencing obvi-ous impairment by telephone screeningwere not found to have impairmentconsistent with dementia on formal eval-uation. Furthermore, it is well acceptedthat mental status screening measures areinadequate for assessing and diagnosingsubtler cognitive dysfunction

( 2 ,3 )

andmay in fact be misleading. For instance,Cullum et al.

( 4 )

selected a sample of healthy elderly community-dwelling participants who performed within theaverage range on a rigorous, standard-ized, 16-word neuropsychological meas-ure of verbal memory. They subsequentlyadministered three-word memory teststhat paralleled the procedure used on theMini-Mental State Exam

( 3 )

and foundthat approximately 33% – 60% of participants recalled zero of three or one of three words. Such studies clearly demon-strate the fallibility of mental statusscreening approaches when assessingindividuals without frank cognitivedysfunction. Thus, we again encourageHe

ﬂ

in et al. to review the test resultsfrom the comprehensive neuropsycho-logical evaluations performed on their study sample to determine the incidenceof subtler cognitive dysfunction.If cancer survivors are at increasedrisk of evidencing cognitive dysfunction,the etiologic rationale provided by He

ﬂ

inet al. is but one of several com peting ex- planations. In our related editorial

( 5 )

, welisted several possible mechanisms bywhich cognitive function may be differ-entially affected in co-twins with a his-tory of cancer, including the presence of secondary cancers, other organ systemdamage, the development of other neuro-logic diseases, or per sistent cognitivedysfunction secondary to treatment- related neurotoxicities. Although the presence of impaired cognitive function prior to treatment has been demonstratedfor a variety of cancer patients

( 6 ,7 )

, wenever asserted that any potential differ-ences observed between co-twins withand without a history of cancer were duesolely to possible cognitive de

ﬁ

cits mani-fested prior to their cancer treatment.We agree that information about persistent or late cognitive dysfunctionassociated with cancer and cancer treat-ments should be made available to cancer patients and their health care providers.The increased incidence of dementia inco-twins with a history of cancer is inter-esting and warrants further investigation.We also share the concern of He

ﬂ

in et al.that cancer patients may suffer from anincreased incidence of cognitive dysfunc-tion, although we feel that the etiologyand mechanisms still need to be elucidated.Given the importance of this issue andthe complex nature of cognitive function,we remain steadfast in our conviction thatappropriate methodologic designs usingmeasures appropriate for the measure-ment of subtler cognitive dysfunction re-main critical to provide patients and practitioners with accurate information.J

EFFREY

S. W

EFEL

HRISTINA

A. M

EYERS

EFERENCES

(1)

Gatz M, Fratiglioni, Johansson B, Berg S,Mortimer JA, Reynolds CA, et al. Completeascertainment of dementia in the Swedish TwinRegistry: the HARMONY study. NeurobiolAging 2005;26:439 – 47.

(2)

Meyers CA, Wefel JS. The use of the Mini-Mental State Examination to assess cognitivefunctioning in cancer trials: No ifs, ands, or buts,or sensitivity. J Clin Oncol 2003;21:3557 – 8.

(3)

Lezak MD. Neuropsychological assessment,3rd Ed. New York (NY): Oxford UniversityPress; 1995.

(4)

Cullum CM, Thompson LL, Smernoff EN.Three-word recall as a measure of memory.J Clin Exp Neuropsychol 1993;15:321 – 9.

(5)

Wefel JS, Meyers CA. Cancer as a risk factor for dementia: a house built on shifting sand.J Natl Cancer Inst 2005;97:788 – 9.