PSYCHO-ONCOLOGY

Psycho-Oncology 12: 612619 (2003)

Published online 7 July 2003 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/pon.742

THE RELATIONSHIP OF APOE GENOTYPE TO

NEUROPSYCHOLOGICAL PERFORMANCE IN
LONG-TERM CANCER SURVIVORS TREATED
WITH STANDARD DOSE CHEMOTHERAPY
TIM A. AHLESa,*, ANDREW J. SAYKINb,c, WALTER W. NOLLd, CHARLOTTE T. FURSTENBERGa,
STEPHEN GUERINb, BERNARD COLEe and LEILA A. MOTTe
a

Department of Psychiatry and Center for Psycho-Oncology Research, USA

b
Department of Psychiatry (Neuropsychology Program), USA
c
New Hampshire Hospital, Concord, NH, USA
d
Department of Pathology, USA
e
Community and Family Medicine and the Norris Cotton Cancer Center, USA
SUMMARY
Purpose: The primary purpose of this study was to compare the neuropsychological performance of long-term
survivors of breast cancer and lymphoma treated with standard dose chemotherapy who carried the e4 allele of the
Apolipoprotein E (APOE) gene to those who carry other APOE alleles.
Patients and methods: Long-term survivors (mean=8.8
4.3 years post-treatment) of breast cancer (N 51,
age=55.9
8.8) or lymphoma (N 29, age=55.8
11.6) who had been treated with standard-dose chemotherapy
completed a standardized battery of neuropsychological and psychological tests. Survivors were also classied into
two groups based on the presence (N 17) or absence (N 63) of at least one e4 allele of APOE.
Results: Analysis of covariance, controlling for age, gender, education, diagnosis, and WRAT-3 reading subtest
(a proxy measure of baseline IQ), indicated that survivors with at least one e4 allele scored signicantly lower in the
visual memory (p50:03) and the spatial ability (p50:05) domains and tended to score lower in the psychomotor
functioning (p50:08) domain as compared to survivors who did not carry an e4 allele. No group dierences were
found on depression, anxiety, or fatigue.
Conclusions: The results of this study provide preliminary support for the hypothesis that the e4 allele of
APOE may be a potential genetic marker for increased vulnerability to chemotherapy-induced cognitive
decline. Copyright # 2003 John Wiley & Sons, Ltd.

INTRODUCTION
Increasing evidence supports the hypothesis that
high- and standard-dose chemotherapy can have a
negative eect on the cognitive functioning of
cancer survivors (Ahles et al., 2002; Ahles and
Saykin, 2001). The changes in cognitive functioning tend to be relatively subtle changes in memory,
concentration, and executive function. However,
these cognitive changes can aect attainment of
*Correspondence to: Department of Psychiatry, DartmouthHitchcock Medical Center, One Medical Center Drive, Lebanon,
NH 03756, USA. E-mail: tim.a.ahles@dartmouth.edu

Copyright # 2003 John Wiley & Sons, Ltd.

educational and vocational goals and have a

negative impact on the quality of life of cancer
survivors. The potential cognitive eects of chemotherapy have become an increasing concern
among cancer survivors and health-care teams that
care for them (Presidents Cancer Panel, 1999).
One critical question, among the many questions that remain to be answered in this area, is
whether all cancer patients who receive chemotherapy are at equal risk for chemotherapy-induced
cognitive decline. In a recent review of the
literature, Ahles and Saykin 2001 have suggested
that only a subgroup of survivors may be vulnerable to long-term cognitive decits associated with
chemotherapy. One potential risk factor for
Received 17 December 2002
Accepted 20 May 2003

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APOE AND NEUROPSYCHOLOGICAL PERFORMANCE

chemotherapy-induced cognitive decline is the presence of the apolipoprotein E e4 (APOE e4) gene.
The APOE gene is polymorphic and occurs in
three common alleles (APOE e2, e3, e4) which give
rise to six genotype combinations. The presence of
the APOE e4 allele has been associated with: (1)
increased risk for the development of Alzheimers
disease (Richard and Arnouyel, 2001); (2) neuropsychological decits following cardiac bypass
surgery (Tardi et al., 1997; Newman et al.,
1997), traumatic brain injury (Liberman et al.,
2002), repeated head trauma associated with
boxing (Jordan et al., 1997) and football (Kutner
et al., 2000); and (3) as a moderating factor of
other risk factors (e.g. diabetes) for cognitive
decline in the elderly (Haan et al., 1999).
If receiving chemotherapy is conceptualized as a
type of insult to the brain, then it is reasonable to
hypothesize that APOE e4 carriers will be more
vulnerable to chemotherapy-induced cognitive
decline. Therefore, the primary purpose of this
study was to compare the neuropsychological
performance of long-term survivors of breast
cancer and lymphoma, treated with standard dose
chemotherapy, who were categorized by the
presence or absence of the e4 allele of APOE.
PATIENTS AND METHODS
Study population
Cancer survivors treated with systemic chemotherapy (Breast cancer N 51, Lymphoma
N 29, 10 Hodgkins and 19 non-Hodgkins or
other lymphomas) were identied through the
Norris Cotton Cancer Center Tumor Registry.
Stage of disease for the breast cancer patients was
primarily 02 whereas, for the lymphoma patients,
all stages were represented (Table 1). Systemic
Table 1. Stage by diagnosis
Stage

Breast cancer
(n=51)

Lymphoma
(n=29)

Total
(n=80)

0
1
2
3
4
Unknown
Missing

2(4%)
14 (27%)
33 (65%)
1 (2%)
0 (0%)
0 (0%)
1 (2%)

10 (35%)
3 (10%)
4 (14%)
4 (14%)
4 (14%)
2 (7%)
2 (7%)

12 (15%)
17 (21%)
37 (46%)
5 (6%)
4 (5%)
2 (2%)
3 (4%)

Copyright # 2003 John Wiley & Sons, Ltd.

chemotherapy was dened as standard dose

chemotherapy regimens which are described in
Table 2. Additionally, survivors had to have been:
(1) a minimum of 5 years post-diagnosis; (2)
receiving no cancer treatment, except tamoxifen;
(3) disease free; (4) more than 18 years old when
Table 2. Chemotherapy regimens by diagnosis
Regimen

Number of
breast cancer
survivors

Cyclophosphamide/methotrexate/
5-uorouracil
Cyclophosphamide/doxorubicin/
5-uorouracil
Cyclophosphamide/doxorubicin
Cyclophosphamide/methotrexate/
5-uorouracil/vincristine/prednisone
Vinblastine/doxorubicin/thiotepa/halotestin
Cyclophosphamide/carboplatin
Taxol

22

Regimen

Number of
lymphoma
survivors

Cyclophosphamide/doxorubicin/
vincristine/prednisone
Mechlorethamine/vincristine/
procarbazine /prednisone
Oral cyclophosphamide
Doxorubicin/bleomycin/
vinblastine/dacarbazine
Mechlorethamine/vincristine/
doxorubicin/bleomycin/
vinblastine/dacarbazine/
procarbazine/prednisone
Cyclophosphamide/doxorubicin/
vincristine/etoposide/prednisone
Cyclophosphamide/vincristine/
procarbazine/prednisone
Cyclophosphamide/vincristine/
doxorubicin/methotrexate/
asparaginase/etoposide/mercaptopurine
Doxorubicin/etoposide/vinblastine
Vinblastine
Cyclophosphamide/doxorubicin/
methotrexate/etoposide/cytarabine/
bleomycin/vincristine/leucovorin/prednisone
Cyclophosphamide/bleomycin
Cyclophosphamide/doxorubicin/
vincristine/bleomycin/prednisone
Mechlorethamine/doxorubicin/
cyclophosphamide/vincristine/
bleomycin/prednisone

22
3
2
2
1
1

9
4
5
2
2

2
1
2

1
1
1

1
1
1

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614

T.A. AHLES ET AL.

diagnosed; and (5) uent in and able to read

English. Survivors were excluded if they had CNS
disease, treatment with CNS radiation or intrathecal therapy, neurobehavioral risk factors including
head injury with loss of consciousness, history of
neurological disorder, learning disability or an
Axis I psychiatric disorder (DSM-IV), specically
substance abuse, mood, anxiety based, or psychotic-spectrum disorders. All participating survivors
provided written, informed consent.
Procedures
Survivors who initially agreed to participate
received a call from a research nurse who
described the purpose and procedures of the study
and conducted a brief, standardized medical/
neurobehavioral screening designed to assess general medical and psychiatric status, with a
particular focus on neurobehavioral risk factors,
signs and symptoms of CNS disorder, and
medications that could potentially alter neuropsychological functioning. Survivors who were eligible following the medical screening and remained
willing to participate were scheduled for a time to
review and sign informed consent, complete the
assessment battery (approximately 2 h in duration), and provide a blood sample for APOE
evaluation. The neuropsychological examiners
were well-trained technicians who were supervised
by a board certied neuropsychologist (AJS). The
neuropsychology examiners were blind to
survivors treatment history and APOE status.
The conduct of this study was approved by the
Institutional Review Board of Dartmouth Medical
School.
One hundred and one survivors were approached who met the inclusion criteria described
above. Of the 101 survivors, 13 declined to
participate and eight agreed but could never be
scheduled; hence, the sample consisted of 80
survivors (80% recruitment rate).
The assessment battery included standardized
neuropsychological tests and measures of aective
variables and fatigue which may impact performance on neuropsychological tests (Ahles and
Saykin, 2000). The neuropsychological tests have
established utility in clinical neuropsychological
assessment and published normative data (Saykin
et al., 1995). Neuropsychological tests were
grouped into domains to reduce the number of
statistical comparisons based upon prior factor

Copyright # 2003 John Wiley & Sons, Ltd.

analyses in larger data sets and consensus of

experienced neuropsychologists (Gur et al., 1990).
Neuropsychological assessment battery
(1) Verbal Ability}Vocabulary (Wechsler Adult
Intelligence Scale,WAIS-III, Wechsler, 1997);
Reading subtest (Wide Range Achievement
Test, WRAT-3, Wilkinson, 1993), Boston
Naming Test (Kaplan et al., 1978), Controlled
Oral Word Association (Benton et al., 1978);
(2) Spatial ability}Block Design (WAIS III,
Delis et al., 1983a);
(3) Verbal learning}California Verbal Learning
Test (Delis et al., 1983b), Total number
correct on List A, Short and Long Delay Free
Recall, and Long Delay Recognition (minus
Total False Positives);
(4) Verbal memory}Logical Memory I, Stories A
& B and Logical Memory Multiple Choice
Story B (30 Delay), Wechsler Memory ScaleRevised (WMS-R, Wechsler, 1987);
(5) Visual memory}Visual Reproduction I and
Visual Reproduction II (30 Delay), WMS-R
(Wechsler, 1987) scales;
(6) Psychomotor function}Digit Symbol (WAIS
III, Delis et al., 1983a) and Trails A & B
(Reitan, 1971);
(7) Motor functioning}Finger Tapping (Reitan,
1979) and Thumb-Finger Sequencing (Saykin
et al., 1995);
(8) Attention (Accuracy)}Correct responses to
targets on the 6 min adult version of the
Vigilance and Distractibility subtests from the
Continuous Performance Test (CPT, Gordon
Diagnostic System, Gordon, 1986); and
(9) Attention (Reaction time)}Distractibility
and Vigilance Reaction Times scores from
the CPT (Gordon, 1986).
Psychosocial Assessment Battery
In order to control for the potential confounding eects of depression, anxiety and fatigue on
neuropsychological performance, participants also
completed the following measures:
(1) Center for Epidemiological Study}Depression
(CES-D, Radlo (1977))}The CES-D is a
20-item measure of depressive symptoms that
has been widely used in epidemiological
studies of depression. Patients are asked to

Psycho-Oncology 12: 612619 (2003)

615

APOE AND NEUROPSYCHOLOGICAL PERFORMANCE

rate how frequently they have experienced

each symptom on a four-point scale ranging
from Rarely or none of the time to Most or
all of the time. The CES-D has been widely
studied and has strong data supporting its
validity and reliability (Plutchick and Conte,
1989).
(2) Spielberger State-Trait Anxiety Inventory
(STAI, Spielberger et al., 1971)}The STAI
contains two 20-item forms which measure
state anxiety (the level of current anxiety) and
trait anxiety (the general level of anxiety
experienced). Extensive data on reliability
and validity support the utility of the test
(Spielberger et al., 1971).
(3) Fatigue Symptom Inventory (FSI, Hann et al.,
(1997))}The FSI is a 14-item measure designed to assess the intensity, frequency and
disruptiveness of fatigue experienced by cancer patients. Patients rate each item on an 11point scale ranging from 0 (not a problem) to
10 (an extreme problem). Evidence supports
the validity and reliability of the instrument in
a cancer population (Hann et al., 1997).
APOE evaluation
Ten milliliters of blood was drawn for APOE
testing. Genotyping was performed in the Molecular Genetics Diagnostic Laboratory at the
Dartmouth-Hitchcock Medical Center under the
direction of Dr Walter Noll using standard
techniques described by Hixson and Vernier
(1990) and modied by Reymer et al. (1995).
Briey, genomic DNA was isolated from peripheral blood lymphocytes. APOE specic primers
were used to amplify a fragment of the APOE
gene by PCR, and the PCR product was digested
using Hha1. The digested DNA was electrophoresed on an agarose gel and visualized under UV
light using ethidium bromide. Alleles were determined based on the size of the fragments, which
was determined by each alleles unique Hha1
restriction map.
Statistical analysis
The statistical analysis for this study was based
upon the methods used in our previous research
(Ahles et al., 2002). The nine neuropsychological
domain scores, described above, were calculated

Copyright # 2003 John Wiley & Sons, Ltd.

using z-transformed scores based on a larger

sample of cancer survivors (N 157) who had
completed the same battery of individual tests.
Analysis of covariance (ANCOVA) was then used
to evaluate the individual domain scores comparing groups dened by APOE status after
adjusting for age, gender, education, diagnosis,
and WRAT-3. Analysis of variance (ANOVA) and
chi-square were used to identify and evaluate
potential confounders of treatment and performance on neuropsychological testing.

RESULTS
Seventeen (21%) of the survivors carried at least
one e4 allele (e3/e4=15, e2/e4=1, e4/e4=1), a
percentage consistent with the population distribution (Jordan et al., 1997). The remaining 63
survivors (79%) had the following allele combinations: e3/e3=52, e2/e3=11. Table 3 displays the
demographic and psychological variables that
could be confounders of performance on neuropsychological testing by APOE status. No signicant dierences on the demographic or psychological factors emerged between the groups.
Table 4 describes the z-transformed domain
scores by APOE status. ANCOVAs were conducted with APOE status (presence or absence of
an e4 allele) as the independent variable, domain
score as the dependent measure, and age, gender,
education, diagnosis, and WRAT-3 reading subtest (an estimate of baseline IQ) as covariates. The
analysis indicated signicantly lower performance
for survivors with an e4 allele than survivors with
Table 3. Demographic
APOE status

and

psychological

variables

by

Variable

APOE e4+mean
(S.D.)
N=17

APOE e4+mean
(S.D.)
N=63

Age
Gender

58.0 (10.4)
12 female
5 male
14.5 (2.7)
9.5 (5.9)

55.3 (9.7)
52 female
11 male
13.6 (2.5)
8.7 (3.8)

12.7
36.0
38.0
3.7

11.1
32.5
34.9
3.8

Years of education
Years since last
treatment
CES-depression
State anxiety
Trait anxiety
Average fatigue

(8.0)
(12.4)
(10.9)
(2.2)

(8.9)
(9.8)
(9.5)
(1.9)

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616

T.A. AHLES ET AL.

Table 4. Z-Transformed domain means (S.D.) by APOE status

Domains

APOE e4
positive
mean (S.D.)

APOE e4
negative
mean (S.D.)

p-Valuen

Verbal ability
Verbal learning
Verbal memory
Visual memory
Psychomotor
functioning
Motor
Attention CR
Attention RT
Spatial ability

0.10
0.20
0.21
0.30
0.24

(0.68)
(1.16)
(0.90)
(1.12)
(0.80)

0.16
0.03
0.15
0.04
0.05

(0.86)
(0.94)
(0.89)
(0.81)
(0.66)

0.83
0.48
0.21
0.03nn
0.08

0.01
0.14
0.19
0.38

(0.72)
(0.97)
(0.69)
(1.17)

0.11
0.01
0.05
0.13

(0.73)
(0.87)
(0.67)
(0.97)

0.93
0.33
0.30
0.05nn

Controlling for age, gender, education, diagnosis, and

WRAT-3 (reading subset).
nn
p50.05.

no e4 allele in the visual memory (F1; 78 4:91,

p50:03) and the spatial ability (F1; 78 3:91,
p50:05) domains and a trend for the psychomotor
functioning (F1; 78 3.05, p50:08) domain.
Table 5 displays the unadjusted means for each
neuropsychological test by domain as well as
reference norms for each test. Examination of this
table reveals that the neuropsychological performance of survivors with the e4 allele and those
with no e4 allele were within the normal range of
performance when compared to the reference
norms.

DISCUSSION
The results of this study provide preliminary
support for the hypothesis that APOE is a genetic
marker for increased vulnerability to chemotherapy-induced cognitive decline. If only a subgroup
of patients treated with standard-dose chemotherapy are at risk for long-term cognitive problems,
APOE status may be one factor contributing to
this risk. The pattern of decreased functioning in
visual/spatial domains for e4 carriers has been
reported in previous human (Greenwood et al.,
2000) and animal (Raber et al., 1998) studies. The
potential mechanism for the interaction between
chemotherapy and APOE status is not clear, but
may be related to dierential microvascular or
neuronal repair processes following brain injury
(Nicoll, 1996) or pre-existing morphologic dierences (e.g. smaller hippocampal volume) in in-

Copyright # 2003 John Wiley & Sons, Ltd.

dividuals with the APOE e4 allele (Plassman et al.,

1997).
Interestingly, despite the pattern of dierences,
neuropsychological performance of survivors with
the e4 allele and those with no e4 allele were within
the normal range of performance as compared to
reference norms. This pattern of results is consistent with studies comparing the neuropsychological
performance of survivors treated with chemotherapy to survivors treated with local therapy (Ahles
et al., 2002; van Dam et al., 1998; Schagen et al.,
1999) reinforcing the hypothesis that chemotherapy does not cause cognitive decits in the
traditional denition of the term. Rather, the
impact of chemotherapy on cognitive functioning
tends to be relatively subtle as compared to decits
seen in Alzheimers disease or with moderate to
severe head trauma. Nevertheless, these subtle
changes can have important consequences in terms
of the attainment of educational and career goals,
daily functioning, and quality of life of cancer
survivors (Ahles and Saykin, 2001).
The interpretation of these results is limited by
the relatively small sample size and the lack of
pretreatment neuropsychological assessments. Additionally, although several studies have shown no
dierences in neuropsychological performance
between healthy adults with and without the
APOE e4 allele, other studies have reported lower
performance in healthy e4 carriers on certain
neuropsychological tests (Parasuraman et al.,
2002). Consequently, one possible interpretation
of the present data is that the cognitive diculties
are not related to chemotherapy, but to dierences
between carriers of the APOE e4 allele and carriers
of other forms of APOE. In order to adequately
examine the interaction of APOE e4 and chemotherapy, patients will need to be evaluated
pretreatment and followed over time and appropriate comparison groups (e.g. patients treated
with local therapy and/or healthy controls) will
need to be evaluated on a similar assessment
schedule. Accordingly, we are currently evaluating
the relationship between APOE status and
cognitive functioning in a larger, prospective
longitudinal study (including pretreatment neuropsychological assessment) of breast cancer and
lymphoma patients receiving treatment with standard dose chemotherapy or local therapy and
healthy controls.
In our previous study (Ahles et al., 2002),
dierences between survivors treated with chemotherapy and those treated with local therapy

Psycho-Oncology 12: 612619 (2003)

617

APOE AND NEUROPSYCHOLOGICAL PERFORMANCE

Table 5. Unadjusted, raw test means (S.D.) by domain and APOE status
Domain item

E4+(N=17)

Verbal ability
Vocabulary}scale score
Reading subtest of WRAT-3}standard score
Boston naming test}total raw score
Controlled oral uency}total raw score

11.9
103.9
55.9
41.1

Verbal learning}California verbal learning test

Total number correct list A
Total number correct short delay free recall
Total number correct long delay free recall
Long delay recognition}discrimination score

E4-(N=63)

Reference norms

(23.1)
(11.4)
(4.4)
(11.8)

10.0
95.4
55.4
44.3

(3.0)a
(11.6)b
(4.3)c
(10.2)c

47.5 (11.0)
9.9 (3.5)
10.9 (3.0)
0.27 (1.7)

49.3 (8.5)
10.7 (2.6)
10.8 (2.9)
0.02 (1.4)

61.2
13.1
13.3
0.0

(8.6)d
(2.5)d
(2.6)d
(1.0)d

Verbal memory
Logical memory I, stories A and B
Logical memory II, stories A and B (30 min delay)

24.2 (5.6)
20.6 (8.0)

22.3 (6.6)
17.2 (6.6)

23.5 (5.4)e
21.0 (5.4)e

Visual memory
Visual reproduction I, total
Visual reproduction II, total (30 min delay)

31.6 (6.8)
25.1 (11.2)

34.2 (4.4)
27.2 (9.3)

29.0 (5.2)e
25.4 (7.2)e

Psycho-motor
Digit symbol}scale score
Trails A}total time
Trails B}total time

10.5 (3.1)
33.4 (12.8)
87.9 (41.8)

11.5 (2.7)
30.1 (9.0)
78.0 (47.7)

10.0 (3.0)a
35.1 (10.6)f
77.7 (23.8)f

Motor
Max number of sequences achieved}right hand
Max number of sequences achieved}left hand
Average nger tapping score}right hand
Average nger tapping score}left hand

8.4
8.1
43.8
42.0

8.0
8.0
43.5
40.8

9.2
8.9
49.9
46.1

Attention CR
Distractibility}number correct
Vigilance}number correct

21.8 (10.1)
29.1 (1.6)

22.7 (8.0)
29.3 (1.9)

25.8 (5.2)c
29.7 (4.8)c

462.9 (105.0)
439.4 (67.4)

443.5 (63.6)
429.3 (90.6)

442 (88.0)c
402 (83.0)c

10.2 (3.1)

10.8 (2.6)

10.0 (3.0)a

Attention RT
Distractibility}reaction time (ms)
Vigiliance}reaction time (ms)
Spatial ability
Block design}scale score

(2.9)
(5.8)
(3.8)
(11.6)

(2.2)
(1.9)
(7.4)
(10.1)

11.0
99.7
55.7
38.2

(2.1)
(2.1)
(7.0)
(6.2)

(1.9)c
(1.8)c
(6.9)c
(6.8)c

Wechsler (1997).
Wildinson (1993).
c
Saykin (1995).
d
Paulo et al. (1997).
e
Ivnik et al. (1992).
f
Spreen and Straus (1991).
b

were primarily in the verbal memory and psychomotor domains. In the present genetic analysis,
although there was a trend for group dierences in
the psychomotor domain, the strongest results
were in the domains of visual memory and spatial

Copyright # 2003 John Wiley & Sons, Ltd.

ability. The dierences in pattern of results may be

related to the methodological issues outlined
above. An alternative hypothesis is that chemotherapy inuences verbal memory and psychomotor domains (i.e. seen in comparisons of

Psycho-Oncology 12: 612619 (2003)

618

T.A. AHLES ET AL.

patients treated with chemotherapy or local

therapy) and the performance in these domains
may not be worse in APOE e4 carriers treated with
chemotherapy. However, the presence of APOE e4
may interact with chemotherapy in the visual
memory and spatial domains. Armstrong et al.
(2002) have recently reported that late eects of
radiation therapy (>5 years post-treatment) were
seen in measures of visual memory, but not in
measures of other domains, including verbal
memory. The investigators hypothesize that this
eect may be caused by radiation damage to
cerebral blood vessels, particularly in areas of the
hippocampus that support visual memory. As
stated above, one explanation for the relationship
between APOE e4 and cognitive response to brain
insult is a reduced ability to repair the microvasculature. Therefore, a testable hypothesis for
future research is that the presence of the APOE e4
allele will interact with chemotherapy to inuence
functioning in visual memory and spatial domains,
but will not be associated with functioning in the
verbal memory domain.
In summary, this study provides preliminary
support for the hypothesis that the presence of the
APOE e4 allele may increase the vulnerability to
long-term cognitive decits associated with chemotherapy. Clearly, additional research that includes pretreatment assessments and appropriate
control groups is necessary to conrm this
association and to dene which cognitive domains
are aected by the interaction of chemotherapy
and the APOE e4 allele.

ACKNOWLEDGEMENTS
This research was supported by a supplement to the
Norris Cotton Cancer Center Core grant (P30 CA23108)
and RO1 CA87845 from the Oce of Cancer Survivors,
National Cancer Institute, Bethesda, MD.
We would like to acknowledge Dorothy R. Belloni
who conducted all of the APOE analyses and Tara
Mitchell and Sarah Bivins for administering the
neuropsychological testing.

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