| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2000;31:2431.)
© 2000 American Heart Association, Inc.
Original Contributions |
Stroke and Apolipoprotein E 
4 Are Independent Risk Factors for Cognitive Decline
A Population-Based Study
From the Institute for Research in Extramural Medicine (EMGO Institute) (M.G.D., D.J.H.D., L.M.B., C.J.) and Department of Psychiatry (D.J.H.D., C.J.), Vrije Universiteit, Amsterdam, Netherlands; Department of Clinical Chemistry, Academic Hospital Vrije Universiteit, Amsterdam, Netherlands (A.K.); and Center for Demographic Studies, Duke University, Durham, NC (E.H.C.).
Correspondence to M.G. Dik, MSc, Vrije Universiteit, Faculty of Medicine, LASA, Van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands. E-mail mg.dik.emgo{at}med.vu.nl
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Background and Purpose—Stroke and apolipoprotein E
4 (ApoE 4) are individually important risk
factors for cognitive decline, including Alzheimer disease. It
has been suggested that ApoE 4 multiplies the risk for cognitive
decline following stroke. In a population-based sample, using
well-defined sensitive cognitive measures, this study investigates
whether cognitive decline following stroke is worse for patients who
carry the ApoE 4 allele.
Methods—Subjects were participants in the Longitudinal Aging
Study Amsterdam (LASA). The sample consisted of 1224 subjects, aged 62
to 85 years, who participated in the 3-year follow-up examination and
for whom ApoE and stroke data were complete. We assessed cognitive
decline using the Mini-Mental State Examination, the Auditory Verbal
Learning Test (memory: immediate and delayed recall), and the Coding
Task (information processing speed). The effects of stroke and ApoE
4 on cognitive decline were evaluated with ANOVA and multiple
logistic regression analysis, adjusted for age, sex, education,
and baseline cognition.
Results—A synergistic effect modification for stroke and ApoE
4 on cognitive decline was not observed. Unexpectedly, instead,
stroke patients carrying the 4 allele demonstrated a
nonsignificantly lowered risk for Mini-Mental State Examination decline
(OR=0.3; 95% CI 0.1 to 1.1). ApoE 4 was associated with
declines in information processing speed (OR=1.5; 95% CI 1.1 to 2.1)
and small declines for immediate and delayed recall.
Conclusions—Stroke and ApoE 4 may impair cognition through
distinct nonsynergistic mechanisms. The slowing of information
processing speed for ApoE 4 carriers was more evident than
impairment in memory.
Key Words: apolipoproteins • cognition • longitudinal studies • population • stroke
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Stroke often results in cognitive impairment and decline.1 2 The relative risk for dementia within 4 years of ischemic stroke is 5.5, even after exclusion of patients who were demented within 3 months.3 Stroke affects many cognitive processes. General slowing in information processing and attentional deficits are prominent.4 The decline is sometimes progressive, leading to dementia with postmortem Alzheimer pathology.5
The established major genetic risk factor for cognitive decline in the
elderly and for late-onset Alzheimer disease is the 4
allele for the apolipoprotein E (ApoE) gene located on chromosome
19.6 7 The effects of ApoE 4 seem to be most prominent
on specific measures of memory function.8 9 Decline in
memory, especially delayed recall, is an early indicator of
Alzheimer disease, especially in patients with ApoE
4.10 11
Taken together, both stroke and ApoE 4 are associated with cognitive
decline. Furthermore, stroke and ApoE 4 may be related to cognitive
decline in a complex relationship, possibly similar to the relationship
that has been proposed between subclinical
cardiovascular factors, ApoE 4, and cognitive
decline.12 Slooter et al13 posit that the
risk of ApoE 4 on cognitive decline is independent and not mediated
via atherosclerosis. However, ApoE 4 seems to
modulate the effects of atherosclerosis on cognitive
decline. Haan et al12 showed that ApoE 4 increased the
risk of cognitive decline associated with subclinical
cardiovascular disease. They did not further explore
the modifying role of ApoE 4 on the association between stroke and
cognitive decline. Since many subclinical
cardiovascular factors are risk factors for
stroke,14 such modification is plausible. Synergy between
stroke and ApoE 4 in regard to cognitive decline, measured by the
Mini-Mental State Examination (MMSE), has been reported by Kalmijn et
al15 among 353 community-living elderly men but has not
been confirmed. Recently, Zhu et al16 did not find a
multiplicative effect for stroke and ApoE 4 on the risk of dementia
in 1301 subjects in the Kungsholmen cohort.
The purpose of this study is to examine the effect modification by ApoE
4 of the association between stroke and cognitive decline in a large
population-based study, with the use of specific measures sensitive to
cognitive decline.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Study Sample
Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA), a population-based study among 3107 subjects aged 55 to 85 years.17 The sampling and data collection procedures have been described elsewhere in detail.18 19 In summary, a random sample stratified by age and sex was drawn from the population registries in 3 geographic areas of the Netherlands. Sample selection was stratified by age and sex according to expected 5-year mortality to ensure sufficient sample sizes for longitudinal analyses within age and sex strata. Subjects were interviewed at home by trained interviewers. Approval for the study was given by the local medical ethics committee, and all respondents gave informed consent at the start of the study.
For the present study, the study design involved additional medical testing for subjects aged 62 years and older (n=2064). Follow-up measurements were completed for 1406 subjects (68.1%) after an average of 3.1 (SD 0.2) years. Of the 658 subjects who were lost to follow-up, 320 (15.5% of 2064 subjects) had died, 8 (0.4%) could not be contacted, 107 (5.2%) were too ill to be interviewed, and 223 (10.8%) refused.
For 167 of the 1406 subjects, ApoE could not be phenotyped because no blood was available from these subjects (ie, they did not agree to give blood). In addition, for 15 subjects information on whether a stroke had occurred was missing. Therefore, our present study sample consisted of 1224 respondents who participated in the follow-up measurement after 3 years and for whom the ApoE and stroke data were complete.
Cognitive Performance
Overall cognitive function was measured with the
MMSE.20 Memory was measured with an abbreviated version of
Rey’s Auditory Verbal Learning Test (AVLT).21 We used 3
learning trials instead of 5 trials in Rey’s AVLT to reduce the test
burden for the respondent. In each trial, the interviewer read aloud a
list of 15 words, after which the respondents recalled as many words as
they could. We noted the number of correctly recalled words (points).
Words mentioned by the respondent that were not on the AVLT word list
were not counted. Furthermore, words that were mentioned more than once
by the respondent were counted only once (each trial). After an
interval of approximately 20 minutes, during which a different
nonverbal task was performed, the respondents were asked to recall as
many words as possible (delayed recall). Immediate recall (score on the
third trial; range, 0 to 15) and delayed recall (range, 0 to 15) were
derived from this test. At follow-up, a parallel version of the AVLT
was used. The parallel versions, which are used in treatment
research,22 were validated and tested on
parallelism.23
Information processing speed was measured with the Coding Task.24 The task consisted of 3 identical trials, each lasting 1 minute, in which the respondent had to combine 2 characters according to a given example. The respondent was asked to work as quickly and accurately as possible. The score on each trial consisted of the number of completed characters. The mean score of the 3 trials (range, 4.7 to 43.0) was used in the analyses.
Apolipoprotein E
Serum samples were obtained and frozen at -80°C until
determination of ApoE phenotype. The ApoE phenotype was
determined by isoelectric focusing of delipidated serum samples,
followed by immunoblotting.25 The
distribution of the ApoE phenotypes was in Hardy-Weinberg
equilibrium (ApoE 2/2, 0.7%; 2/3, 11.1%; 3/3, 61.5%;
2/4, 2.7%; 3/4, 21.3%; 4/4, 2.7%). ApoE status was
classified as 4 carriers for subjects with the ApoE 4 isoform
(phenotypes 2/4, 3/4, 4/4) and as non-4 carriers
for subjects without the ApoE 4 isoform (phenotypes 2/2,
2/3, 3/3).
Stroke
History of stroke was obtained by diagnosis of the respondent’s
general practitioner (GP). Subjects who reported a stroke
although their GP did not report a stroke (n=26) were considered free
of stroke. The GP was thought to have better knowledge of the stroke
diagnosis, whereas inaccurate self-reports are possibly due to labeling
of symptoms such as dizziness or fainting as a cerebrovascular
problem.26 When information from the GP was not available
(n=211), stroke history was based on self-report. The agreement between
the patient’s self-report and the GP’s information was moderate
(
=0.56). The patient’s self-report was not dependent on cognitive
impairment.26
Our study included 53 subjects who had had a stroke before the start of our study and who participated at 3-year follow-up. Because the cognitive decline after stroke is thought to be a continuous process, we believed that it was important to also include the 22 stroke patients who had had a stroke during the follow-up period. This resulted in a total of 75 stroke patients available for longitudinal analyses.
Putative Confounders
Data on age and sex were derived from the population registries
at baseline. Education was assessed by asking the respondent for the
highest educational level completed, which was converted into total
number of years of education (range, 5 to 18 years).
Because depression is associated with both stroke27 and
cognitive decline,18 28 depression was considered a
putative confounder. Depression was assessed with the Center for
Epidemiologic Studies Depression Scale. This is a 20-item self-report
scale (range, 0 to 60) designed to measure depressive symptomatology in
the general population. We used the generally applied cutoff score 
16
to identify clinically relevant depressive
subjects.29 30
Stroke severity and time interval between stroke diagnosis and
cognitive testing may be related to ApoE 4.31 In
addition, it is likely that these stroke features influence the
cognitive decline.1 4 Therefore, we investigated whether
these stroke features differed for 4 versus non-4 carriers.
Stroke severity was assessed by asking the GP whether the patient was
limited in daily living because of the consequences of the stroke. If
data from the GP were not available (n=16), self-report data were used.
Response categories were on a 3-point scale, ranging from "not at
all" (1) to "severe" (3). Furthermore, additional information on
date of diagnosis was collected. The time interval between stroke
diagnosis and baseline cognitive testing was calculated and categorized
into <1 year, 1 to 3 years, and >3 years.
Data Analysis
Differences in baseline characteristics were evaluated between
stroke patients and subjects without stroke. Differences in ApoE
status, stroke features, and sex were evaluated with the
2 test. Differences in the continuous
variables age and education and each cognition score were tested
with the t test for independent samples.
Cognitive change was calculated for each subject as the difference
between baseline score and follow-up score. The effects of stroke and
ApoE 4 on cognitive change were evaluated with multiple
classification analysis by ANOVA, adjusted for age, sex,
education, and baseline cognition (ie, the score of the specific
cognitive test for which the change score was evaluated). The effect
modification was evaluated by the product term StrokexApoE 4 at
the 0.05 level of significance. If the product term was not
significant, we omitted the term from the model.
In addition, reliable cognitive change was calculated according to the
Edwards-Nunnally method, which takes into account the reliability of
the cognitive test and regression to the mean.32 The
change scores were dichotomized into "decline" and "no
decline," with P<0.10 as statistical cutoff score. The
analyses were performed with multiple logistic regression
models. We evaluated the effect modification by including the
product term StrokexApoE 4 in the model. As with ANOVA, the
product term was omitted from the model if the term was not
significant (P>0.05). The logistic regression models were
adjusted for age, sex, education, and baseline cognition score.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The 53 subjects with a stroke diagnosis at the time when first examined as part of the LASA cohort were significantly older and performed lower on each cognition test than the 1171 subjects without a diagnosis (Table 1
). The proportion of
ApoE 4 carriers among the stroke patients was higher than among the
nonpatients, but the difference was not significant. Stroke patients
with ApoE 4 had slightly lower baseline scores on MMSE and immediate
and delayed recall tests than stroke patients without ApoE 4 (data
not shown).
|
Table 2 shows that stroke patients with
(n=17) and without (n=36) the 4 allele for ApoE did not differ
significantly on stroke severity and time interval between stroke
diagnosis and cognitive testing. Since depression was not associated
with stroke (Table 1
) and stroke severity and time interval
since stroke diagnosis were not associated with ApoE status, these were
not included in the multivariate analyses as
putative confounders.
|
For the analyses of cognitive decline, the 22 incident stroke
cases (10 4+; 12 4-) were added to the 53 subjects with a stroke
diagnosis at baseline. This inclusion of incident stroke cases did not
influence the results because the results of only prevalent strokes
were comparable to the results with included incident strokes.
Furthermore, the rates of cognitive decline for prevalent and incident
stroke patients were comparable (data not shown).
Change in cognition over time is described in Table 3 for the 4 groups based on stroke and
ApoE status. The positive scores for the memory tests indicate
improvement, consistent with a training effect on repeated
testing.33 Except for the MMSE (P=0.01), the
interaction between stroke and ApoE 4 was not significant
(P=0.26 for immediate recall, P=0.06 for delayed
recall, P=0.82 for information processing speed). Contrary
to expectations, stroke patients without ApoE 4 had the lowest
changes in MMSE over time compared with the other groups.
Consistent with expectations, stroke patients with 4
showed greater declines in information processing speed than the other
groups (-2.1 points versus -0.8 unadjusted; -2.0 versus -0.8
adjusted). However, this large difference did not reach statistical
significance, possibly because of the small number of persons with both
stroke and 4.
|
When we considered the subjects unaffected by a stroke, the 300
carrying ApoE 4 tended, as expected, to have more decline (or less
improvement), as assessed by each cognitive measure, than the 849 who
did not carry an 4 allele. However, only the decline in
information processing speed (-1.4 points versus -0.8) was
statistically significant (P=0.01).
The odds ratios for cognitive decline over 3 years obtained from
logistic regression models are shown in Table 4. Comparable to the results for
continuous cognitive change (ANOVA), there was no interaction between
stroke and ApoE 4, except for the MMSE. Again contrary to
expectation, stratified analyses for stroke revealed a
nonsignificantly lowered risk for MMSE decline for 4 carriers in the
stroke group (OR=0.3; 95% CI 0.1 to 1.1). In the nonstroke group, the
risk of MMSE decline for 4 carriers was 1.3 (1.0 to 1.9). For
decline in recall and processing speed, instead, the 4 allele
for ApoE increased the risk of decline from 20% to 50% (30% to 50%
when estimated with adjustment for age and other potential
confounders). This was significant for information processing speed:
the odds of decline were 1.5-fold higher for 4 carriers (95% CI 1.1
to 2.1).
|
The complex pattern of risk for cognitive decline led us to further
examine mortality for 4+ and 4- stroke patients. We examined
mortality rates from baseline to 3-year follow-up and found that stroke
patients with and without 4 had about the same risk of death.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Our population-based longitudinal study supports independent effects for stroke and ApoE
4 on cognitive decline. This result
differs from that reported by Kalmijn et al15 in that they
found a multiplicative effect of stroke and ApoE 4 on cognitive
decline, measured by the MMSE. Their finding may be due to chance given
the small size of that study (6 stroke patients carrying the ApoE 4
allele, compared with 27 stroke patients with ApoE 4 in our
study). To account for differences in study design, we defined
cognitive decline as a drop in the MMSE of >1 SD (>2 points)
according to the definition in their study, but we found no
multiplicative effect of stroke and ApoE 4 either (data not shown).
Support for independent additive effects rather than a multiplicative
effect of stroke and ApoE 4 was found in the population-based study
on incident dementia by Zhu et al.16
It seems unlikely that the results found in our study derive from worse
mortality in the stroke patients with ApoE 4 because mortality was
not higher among stroke patients with ApoE 4 than in stroke patients
without ApoE 4. A higher mortality among ApoE 4 stroke patients
has been previously suggested in elderly subjects aged 75 years but
has not been confirmed in younger samples.31 34 Another
possible source of bias might have been introduced by differences in
stroke features between ApoE 4 and non-4 carriers. The severity
of the stroke and the time interval between stroke diagnosis and
baseline cognitive testing did not differ by ApoE 4 in our study and
therefore could not explain the lack of an synergistic effect
modification between stroke and ApoE 4 on cognitive decline.
Still, the finding that stroke patients without ApoE 4 showed faster
decline on the MMSE than the other groups requires consideration. Most
likely this is an artifact, possibly because of the skewed distribution
of the MMSE and the small number of subjects in this particular group.
In contrast, the rate of cognitive decline on information processing
speed is highest for stroke patients carrying the 4 allele
compared with the other groups.
Overall, ApoE 4 was also associated with decline in information
processing speed rather than with memory decline. Although memory
decline is known to be an early indicator of Alzheimer
disease,10 11 slowing of information processing may be an
even earlier indicator. This is supported by the processing-speed
theory of Salthouse,35 which postulates that slowing of
information processing results in impairments of higher-order cognitive
functions, such as memory and reasoning. Furthermore, the Coding Task
was shown to also measure components of memory, in addition to
information processing speed.36 In a previous
study9 we showed that ApoE 4 affected memory decline in
cognitively impaired elderly but not in cognitively normal elderly. The
proportion of cognitively normal elderly in the present study
sample may have masked the effect of ApoE 4 on memory decline.
Because the main interest of the present study was the effect of
ApoE 4 in stroke patients, we did not distinguish cognitively
impaired from cognitively normal subjects in this study. This would
have led to numbers that were too small for analysis.
The strength of this study is that we used longitudinal data from a
large population-based study. As a consequence, however, the stroke
patients in this population-based study may be more
heterogeneous than stroke patients in clinical studies.
Moreover, more severe and complex stroke cases are prone to nonresponse
and loss to follow-up because of a greater mortality of stroke patients
during the study interval. The stroke cases in our study are survivors
of stroke. Additional analyses showed, however, that the
association between ApoE 4 and baseline cognition did not differ for
nonsurvivors compared with survivors of stroke (data not shown).
A limitation of this study is that we do not have specific information
on the type, size, and location of the stroke. The majority of cases
will suffer from ischemic stroke.31
Size1 and side 4 of the stroke may
affect cognitive decline. However, the severity of the stroke, which
may be used as an indicator of stroke size, did not affect the
association between ApoE 4 and stroke regarding cognitive decline in
our study.
This population-based study could not confirm the suggestion that ApoE
4 modifies the effect of stroke on cognitive decline. Recently, Haan
et al12 reported that ApoE 4 increased the effects of
atherosclerotic disease on cognitive decline. Although vascular events
such as stroke are commonly seen as near the end stage of
atherosclerotic disease,37 the mechanisms in the brain
that cause cognitive decline after stroke may be different from the
mechanisms that cause cognitive decline during atherosclerotic disease.
ApoE 4 may affect cognitive decline in relation to atherosclerotic
disease, but it may not affect cognitive decline following stroke. Our
study suggests that stroke and ApoE 4 impair cognition through
distinct pathogenic mechanisms.
|
Acknowledgments |
|---|
LASA is funded by the Dutch Ministry of Health, Welfare, and Sports and the Vrije Universiteit. The study on ApoE and cognitive decline is supported by the Dutch Organization for Scientific Research (NWO). The contribution of Prof E. Corder, PhD, is supported by grant R37AG07198 from the National Institute on Aging (United States). We are grateful to the Immunochemisch Laboratorium of the Academic Hospital, Vrije Universiteit Amsterdam, directed by G.J. van Kamp, PhD, for ApoE phenotyping. We thank Prof P. Eikelenboom, MD, PhD, for his useful remarks on an earlier draft of this article.
Received April 4, 2000; revision received June 12, 2000; accepted July 3, 2000.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
-
Kase CS, Wolf PA, Kelly-Hayes M, Kannel WB, Beiser
A, D’Agostino RB. Intellectual decline after stroke: the Framingham
Study. Stroke. 1998;29:805–812.
[Abstract/Free Full Text] - Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD. Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer’s disease. Lancet. 1999;354:919–920.[Medline] [Order article via Infotrieve]
-
Tatemichi TK, Paik M, Bagiella E, Desmond DW, Stern Y,
Sano M, Hauser WA, Mayeux R. Risk of dementia after stroke in a
hospitalized cohort: results of a longitudinal study.
Neurology. 1994;44:1885–1891.
[Abstract/Free Full Text] - Hochstenbach J, Mulder T, Van Limbeek J, Donders R, Schoonderwaldt H. Cognitive decline following stroke: a comprehensive study of cognitive decline following stroke. J Clin Exp Neuropsychol. 1998;20:503–517.[Medline] [Order article via Infotrieve]
- Pasquier F, Leys D. Why are stroke patients prone to develop dementia? J Neurol. 1997;244:135–142.[Medline] [Order article via Infotrieve]
-
Strittmatter WJ, Saunders AM, Schmechel D,
Pericak-Vance M, Enghild J, Salvesen GS, Roses AD. Apolipoprotein E:
high-avidity binding to beta-amyloid and increased frequency of type 4
allele in late-onset familial Alzheimer disease. Proc
Natl Acad Sci U S A. 1993;90:1977–1981.
[Abstract/Free Full Text] - Henderson AS, Easteal S, Jorm AF, Mackinnon AJ, Korten A, Christensen H, Croft L, Jacomb PA. Apolipoprotein E allele epsilon 4, dementia, and cognitive decline in a population sample. Lancet. 1995;346:1387–1390.[Medline] [Order article via Infotrieve]
- O’Hara R, Yesavage JA, Kraemer HC, Mauricio M, Friedman L, Murphy GM Jr. The APOE epsilon4 allele is associated with decline on delayed recall performance in community-dwelling older adults. J Am Geriatr Soc. 1998;46:1493–1498.[Medline] [Order article via Infotrieve]
-
Dik MG, Jonker C, Bouter LM, Geerlings MI, Van Kamp
GJ, Deeg DJH. APOE-4 is associated with memory decline in
cognitively impaired elderly. Neurology. 2000;54:1492–1497.
[Abstract/Free Full Text] - Petersen RC, Smith GE, Ivnik RJ, Tangalos EG, Schaid D, Thibodeau SN, Kokmen E, Waring SC, Kurland LT. Apolipoprotein E status as a predictor of the development of Alzheimer’s disease in memory-impaired individuals. JAMA. 1995;273:1274–1278.[Abstract]
- Bondi MW, Salmon DP, Galasko D, Thomas RG, Thal LJ. Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer’s disease. Psychol Aging. 1999;14:295–303.[Medline] [Order article via Infotrieve]
-
Haan MN, Shemanski L, Jagust WJ, Manolio TA, Kuller L.
The role of APOE epsilon4 in modulating effects of other risk factors
for cognitive decline in elderly persons. JAMA. 1999;282:40–46.
[Abstract/Free Full Text] -
Slooter AJC, Cruts M, Ott A, Bots ML, Witteman JCM,
Hofman A, Van Broeckhoven C, Breteler MM, van Duijn CM. The effect of
APOE on dementia is not through atherosclerosis: the
Rotterdam Study. Neurology. 1999;53:1593–1595.
[Abstract/Free Full Text] -
Whisnant JP, Brown RD, Petty GW, O’Fallon WM, Sicks
JD, Wiebers DO. Comparison of population-based models of risk factors
for TIA and ischemic stroke. Neurology. 1999;53:532–536.
[Abstract/Free Full Text] -
Kalmijn S, Feskens EJM, Launer LJ, Kromhout D.
Cerebrovascular disease, the apolipoprotein e4 allele, and
cognitive decline in a community-based study of elderly men.
Stroke. 1996;27:2230–2235.
[Abstract/Free Full Text] -
Zhu L, Fratiglioni L, Guo Z, Basun H, Corder EH,
Winblad B, Viitanen M. Incidence of dementia in relation to stroke and
the apolipoprotein E 4 allele in the very old: findings
from a population-based longitudinal study. Stroke. 2000;31:53–60.
[Abstract/Free Full Text] - Deeg DJH, Westendorp-de Serière M, eds. Autonomy and Well-Being in the Aging Population I: Report From the Longitudinal Aging Study Amsterdam 1992–1993. Amsterdam, Netherlands: VU University Press; 1994.
- Van den Heuvel N, Smits CHM, Deeg DJH, Beekman ATF. Personality: a moderator of the relation between cognitive functioning and depression in adults aged 55–85? J Affect Disord. 1996;41:229–240.[Medline] [Order article via Infotrieve]
- Smit JH, de Vries MZ, Poppelaars JL. Data-collection and fieldwork procedures. In: Deeg DJH, Beekman ATF, Kriegsman DMW, Westendorp-de Serière M, eds. Autonomy and Well-Being in the Aging Population II: Report From the Longitudinal Aging Study Amsterdam 1992–1996. Amsterdam, Netherlands: VU University Press; 1998:9–20.
- Folstein MF, Folstein SE, McHugh PR. "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–198.[Medline] [Order article via Infotrieve]
- Rey A. L’ examen clinique en psychologie. Paris, France: Presses Universitaire de France; 1964.
- Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, Van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study. Lancet. 1998;351:857–861.[Medline] [Order article via Infotrieve]
- Jolles J, Houx PJ, Van Boxtel MPJ, Ponds RWHM, eds. Maastricht Aging Study: Determinants of Cognitive Aging. Maastricht, Netherlands: Neuropsychology Publishers; 1995.
- Savage RD. Alphabet Coding-Task 15. Perth, Western Australia: Murdoch University; 1984.
- Havekes LM, De Knijff P, Beisiegel U, Havinga J, Smit M, Klasen E. A rapid micromethod for apolipoprotein E phenotyping directly in serum. J Lipid Res. 1987;28:455–463.[Abstract]
- Kriegsman DM, Penninx BW, Van Eijk JT, Boeke AJ, Deeg D. Self-reports and general practitioner information on the presence of chronic diseases in community dwelling elderly: a study on the accuracy of patients’ self-reports and on determinants of inaccuracy. J Clin Epidemiol. 1996;49:1407–1417.[Medline] [Order article via Infotrieve]
- Beekman AT, Penninx BW, Deeg DJ, Ormel J, Smit JH, Braam AW, Van Tilburg W. Depression in survivors of stroke: a community-based study of prevalence, risk factors and consequences. Soc Psychiatry Psychiatr Epidemiol. 1998;33:463–470.[Medline] [Order article via Infotrieve]
-
Yaffe K, Blackwell T, Gore R, Sands L, Reus V, Browner
WS. Depressive symptoms and cognitive decline in nondemented elderly
women: a prospective study. Arch Gen Psychiatry. 1999;56:425–430.
[Abstract/Free Full Text] - Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385–401.
- Beekman AT, Deeg DJ, Van Limbeek J, Braam AW, De Vries M, Van Tilburg W. Criterion validity of the Center for Epidemiologic Studies Depression scale (CES-D): results from a community-based sample of older subjects in the Netherlands. Psychol Med. 1997;27:231–235.[Medline] [Order article via Infotrieve]
-
Basun H, Corder EH, Guo Z, Lannfelt L, Corder LS,
Manton KG, Winblad B, Viitanen M. Apolipoprotein E polymorphism and
stroke in a population sample aged 75 years or more. Stroke. 1996;27:1310–1315.
[Abstract/Free Full Text] - Speer DC. Clinical significant change: Jacobson and Truax (1991) revisited. J Consult Clin Psychol. 1992;60:402–408.[Medline] [Order article via Infotrieve]
-
Small SA, Stern Y, Tang M, Mayeux R. Selective decline
in memory function among healthy elderly. Neurology. 1999;52:1392–1396.
[Abstract/Free Full Text] -
Corder EH, Basun H, Fratiglioni L, Lannfelt L, Viitanen
M, Corder LS, Manton KG, Winblad B. Inherited frailty: APOE alleles
determine survival following a diagnosis of heart disease or stroke at
ages 85+. Ann N Y Acad Sci. 2000;908:295–298.
[Free Full Text] - Salthouse TA. The processing-speed theory of adult age differences in cognition. Psychol Rev. 1996;103:403–428.[Medline] [Order article via Infotrieve]
- Piccinin AM, Rabbitt PMA. Contribution of cognitive abilities to performance and improvement on a substitution coding task. Psychol Aging. 1999;14:539–551.[Medline] [Order article via Infotrieve]
-
Breteler MM, Claus JJ, Grobbee DE, Hofman A.
Cardiovascular disease and distribution of cognitive
function in elderly people: the Rotterdam Study. BMJ. 1994;308:1604–1608.
[Abstract/Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  Y. P. Jin, T. Ostbye, J. W. Feightner, S. Di Legge, and V. Hachinski Joint effect of stroke and APOE 4 on dementia risk: The Canadian Study of Health and Aging Neurology, January 1, 2008; 70(1): 9 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Rafnsson, I. J. Deary, F. B. Smith, M. C. Whiteman, and F. G. R. Fowkes Cardiovascular Diseases and Decline in Cognitive Function in an Elderly Community Population: The Edinburgh Artery Study Psychosom Med, June 1, 2007; 69(5): 425 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Borroni, S. Archetti, M. Ferrari, B. M. Cesana, A. Padovani, C. E. Regan, C. Katona, Z. Walker, and G . Livingston Relationship of vascular risk to the progression of Alzheimer disease Neurology, March 27, 2007; 68(13): 1083 - 1084. [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. de Frias, D. Bunce, A. Wahlin, R. Adolfsson, K. Sleegers, M. Cruts, C. Van Broeckhoven, and L.-G. Nilsson Cholesterol and Triglycerides Moderate the Effect of Apolipoprotein E on Memory Functioning in Older Adults J. Gerontol. B. Psychol. Sci. Soc. Sci., March 1, 2007; 62(2): P112 - P118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Snaphaan and F.-E. de Leeuw Poststroke Memory Function in Nondemented Patients: A Systematic Review on Frequency and Neuroimaging Correlates Stroke, January 1, 2007; 38(1): 198 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bartzokis, P. H. Lu, D. H. Geschwind, N. Edwards, J. Mintz, and J. L. Cummings Apolipoprotein E Genotype and Age-Related Myelin Breakdown in Healthy Individuals: Implications for Cognitive Decline and Dementia Arch Gen Psychiatry, January 1, 2006; 63(1): 63 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Melzer, M. G. Dik, G. J. van Kamp, C. Jonker, and D. J. Deeg The Apolipoprotein E e4 Polymorphism Is Strongly Associated With Poor Mobility Performance Test Results But Not Self-Reported Limitation in Older People J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2005; 60(10): 1319 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rowan, C.M. Morris, S. Stephens, C. Ballard, H. Dickinson, H. Rao, B.K. Saxby, A.T. McLaren, R.N. Kalaria, and R.A. Kenny Impact of Hypertension and Apolipoprotein E4 on Poststroke Cognition in Subjects >75 Years of Age Stroke, September 1, 2005; 36(9): 1864 - 1868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Ballard, C. M. Morris, H. Rao, J. T. O'Brien, R. Barber, S. Stephens, E. Rowan, A. Gibson, R. N. Kalaria, and R. A. Kenny APOE {epsilon}4 and cognitive decline in older stroke patients with early cognitive impairment Neurology, October 26, 2004; 63(8): 1399 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Dik, C. Jonker, H. C. Comijs, L. M. Bouter, J. W.R. Twisk, G. J. van Kamp, and D. J.H. Deeg Memory complaints and APOE-{epsilon}4 accelerate cognitive decline in cognitively normal elderly Neurology, December 26, 2001; 57(12): 2217 - 2222. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||