(Stroke. 2001;32:1678.)
© 2001 American Heart Association, Inc.
Original Contributions |
Lipoprotein(a) and Cognitive Performances in an Elderly White Population
Cross-Sectional and Follow-Up Data
From the Department of Neurological and Psychiatric Sciences (C.S., L.P., G.P., P.V., D.I.), University of Florence, Italy; and National Research Council of Italy (A. Di C.), Progetto Finalizzato Invecchiamento.
Correspondence to Leonardo Pantoni, MD, PhD, Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Firenze, Italy. E-mail pantoni{at}neuro.unifi.it
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Abstract |
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Background and Purpose—Elevated lipoprotein(a) [Lp(a)] serum levels have been associated with an increased risk of vascular diseases, and preliminary observations suggest that they are a risk factor for vascular dementia. The relationship between Lp(a) levels and cognitive performances in the general population has never been investigated. Our aim was to evaluate the effect of elevated Lp(a) levels on cognitive functions in the elderly.
Methods—Cognitive performances were assessed by means of the Mini-Mental State Examination (MMSE), the Babcock Short Story, and the Matrix Test in a population sample of 435 white subjects aged 65 to 84 years who were evaluated at baseline and after 3 years. Lp(a) levels were determined by ELISA.
Results—No statistically significant difference was found in neuropsychological test scores between subjects with and without elevated Lp(a) levels, although subjects with elevated Lp(a) levels had slightly better cognitive performances. This difference reached a statistical significance level only in a subscore of the Matrix Test (number of correct responses) when adjusted for age, sex, education, smoking, and history of stroke. At follow-up, no statistically significant difference was found in cognitive performances between subjects with and without elevated Lp(a) serum levels in either univariate or multivariate analyses. Subjects with and without elevated Lp(a) showed a similar decline rate during follow-up.
Conclusions—In this sample of elderly white subjects, elevated Lp(a) levels were not associated with poorer cognitive performances or with an increased rate of cognitive decline. Elevated Lp(a) levels do not appear to be a major determinant of cognitive impairment in the elderly.
Key Words: aging • cognitive disorders • lipoproteins • neuropsychological tests
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Lipoprotein(a) [Lp(a)] is a molecule formed by an LDL bound to a glycoprotein called apolipoprotein(a) [apo(a)].1 Although the physiological function of Lp(a) is still unknown, elevated Lp(a) serum levels have been found to be associated with an increased risk of coronary,2 3 4 5 6 7 peripheral artery,8 9 and cerebrovascular10 11 12 13 14 15 16 diseases. This association is presumably mediated by the procoagulant17 and the proatherogenic18 effects of Lp(a).
Because cardiac and cerebrovascular diseases are recognized risk factors for dementia,19 20 the study of Lp(a) in relation to cognitive functions seemed worthy of investigation. Although preliminary data from 2 controlled series of hospitalized patients have indicated that Lp(a) is a possible risk factor for vascular dementia,21 22 the effect of Lp(a) levels on cognitive functions has never been investigated in large population-based surveys.
As part of a study aimed at evaluating the effect of elevated Lp(a) serum levels on the prevalence of vascular diseases in an elderly (65 to 84 years old) white population cohort,23 we were able to study the relationship between Lp(a) levels and cognitive performances assessed at baseline and after 3 years.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The study was conducted in Impruneta, Florence, which is 1 of the 8 centers participating in the Italian Longitudinal Study on Aging (ILSA).24 25 ILSA is a population-based, longitudinal study of the health status of Italians aged 65 to 84 years. The main objective of ILSA is the study of prevalence and incidence rates of age-related diseases in the elderly Italian population and the identification of their risk and protective factors. ILSA is also aimed at assessing age-associated physical and mental functional changes. All individuals from 65 to 84 years of age who were living at home or institutionalized and residing in the study areas at the start of the prevalence study (March 1, 1992) were eligible for inclusion. In each of the participating centers, a random sample of 704 individuals, stratified by age and sex, was selected from the demographic records of the registry office of each municipality according to an equal allocation strategy: 88 subjects of each sex from 4 age groups (65 to 69, 70 to 74, 75 to 79, and 80 to 84 years).
Cross-Sectional Study
The prevalence survey was conducted from March 1,
1992, to June 30, 1993. Cases of a given disease were identified in the
study cohort by way of a 2-phase design. In the screening phase, a
questionnaire and a series of brief tests to identify suspect cases for
further investigation were administered to each subject in the sample.
In the confirmation phase, suspect cases were clinically confirmed, and
a differential diagnosis of specific disorders within a syndrome was
formulated. A detailed protocol of the study has been published
elsewhere.24 25
As part of the screening phase, a short battery of neuropsychological tests was administered by a physician. The tests assessed global cognitive functions (Mini-Mental State Examination [MMSE]),26 selective attention [Matrix Test],27 and episodic memory [immediate and delayed recall of the Babcock Short Story]28 ). The Matrix Test (scores range from 0 to 60) has a basic format with 3 different matrices made up of 13 strings of 10 digits (0 to 9 in random sequence); each line includes 0 to 5 targets, and digits must be crossed out within a time limit (45 s/matrix). Through a 21-unit story, the Babcock Short Story (scores range from 0 to 16) measures immediate and delayed (10 minutes) recall and their sum; an event-weighed, hierarchical scoring system was used that rewarded the degree of organization of the subject’s oral recollection.
The presence of cognitive impairment/no dementia (CIND) was assessed in all the subjects who scored <24 on the MMSE in the screening phase. In the ILSA Study, a diagnosis of CIND was made on the basis of a clinical and neuropsychological examination, informant interview, and assessment of the subject’s functional activities. The details of the method are reported elsewhere.29 The CIND definition is consistent with a more recent one of mild cognitive impairment.
Characteristics of Subjects Investigated in the
Cross-Sectional Study
The original study cohort was a random population
sample, selected according to the above sampling design in the
municipality of Impruneta, a hilly area on the outskirts of Florence,
Italy, that has 15 237 inhabitants, most of whom are engaged in
agricultural, handicrafts, and tertiary activities. On March 1, 1992,
the percentage of persons >65 years of age in this municipality was
16.7%. Of the total of 704 subjects in the original randomized cohort,
6 died before the start of the survey and 154 refused (refusal rate
22.06%) to participate. Due to a delay in starting the Lp(a)
assessment, Lp(a) serum levels were determined in only 446 of the 544
subjects who had agreed to
participate.23 Because the
survey was to start with examination of the oldest subjects first,
those who, because of this delay, missed Lp(a) determination were
mainly in the 80- to 84-year-old age group. The mean age of subjects
with (n=446) and without (n=252) Lp(a) determination was 74.5±5.7 and
75.4±5.8 years, respectively
(t test
P=0.035), with no significant
difference in sex distribution [among subjects with and without Lp(a)
level assessment, 51.8% and 46.4% were men, respectively;
2
P=0.173]. In addition, the
subjects who refused to participate in the ILSA survey were mainly
those in the oldest age groups. These exclusions led to a younger mean
age of this study cohort compared with the original one. We were unable
to explore whether further selection biases occurred in regard to
subjects who were lost due to their refusal to participate in the
population survey, because apart from age and sex, we had no other
information related to either determinants or outcomes. On the other
hand, we were able to analyze the differences in the prevalence
of risk factors between participants with Lp(a) determination (n=446)
and those who, although participants of the survey, did not have a
Lp(a) determination (n=98). No substantial differences were observed in
the prevalence of stroke, myocardial infarction, angina, or diabetes
(2
P 0.163 to 0.694). There was
only a significant difference in smoking [36.9% versus 20.4% in
subjects with and without Lp(a) assessment, respectively;
P=0.002] and a trend
difference in hypertension [68.5% versus 58.4% in subjects with and
without Lp(a) assessment, respectively;
P=0.068].
Four hundred thirty-five of 446 subjects with Lp(a) assessment and 97 of 98 subjects without Lp(a) assessment underwent neuropsychological testing. The 97 subjects scored worse than the 435 subjects. As expected, because the subjects without Lp(a) determination were older, these differences were no longer significant after correction for age.
Lp(a) Assessment
A blood sample was taken after a 12-hour fast for
several laboratory investigations to determine baseline values. Serum
concentration of Lp(a) was quantified with an ELISA
(Biopool).
Normal values of Lp(a) levels are not known for the general population >65 years of age. Given that a number of studies have suggested that the risk associated with Lp(a) is confined to the upper quartile,2 30 31 we chose the 75th percentile as a cutoff to define subjects with elevated Lp(a) levels. As in another population-based study,31 in our cohort the 75th percentile differed significantly between male (310 mg/L) and female (400 mg/L) subgroups; therefore, the subjects were considered as having elevated Lp(a) concentration when the level exceeded the 75th percentile for their sex.
Follow-Up Study
The follow-up survey of the ILSA Study was started on
September 1, 1995. Screening and confirmation procedures were the same
as those for the cross-sectional survey. Of the 435 patients with a
Lp(a) determination and a complete neuropsychological examination at
baseline, 49 died before the follow-up neuropsychological evaluation;
we were unable to make a comparison between follow-up and baseline
cognitive assessment for an additional 73 subjects who either were not
assessable (n=24) or refused to actively participate in the follow-up
study (n=49). Thus, 313 subjects were available for cognitive
reexamination.
Statistical Analysis
To examine the effect of Lp(a) on cognitive function,
we analyzed the score differences for each of the 3 tests
(MMSE, Matrix Test, Babcock Short Story) administered in the 2 study
phases and compared the subgroups of subjects within each of the 4
quartiles of Lp(a) and the 2 subgroups of subjects with and without an
elevated (
75th percentile) Lp(a) level. The significance was tested
by means of ANOVA and t test
for independent samples, respectively. Because age, educational level,
history of stroke, and smoking were the factors that had been found to
alter cognitive functions in the total ILSA
population,29 we examined
the possible confounding or modifying effect of these factors used as
covariate variables in the ANOVA. We defined as a smoker each
subject with a pack-year index of >10 (pack-years was defined as packs
of cigarettes per day multiplied by the number of years the subject
smoked). The relationship between Lp(a) levels and baseline
neuropsychological test scores was analyzed by means of
Pearson’s correlation.
Baseline neuropsychological test scores of the total sample were compared with the follow-up results, and the statistical significance of the differences was analyzed by t test for independent samples. All the scores were also corrected for age, educational level, history of stroke, smoking, and baseline score (ANOVA).
For the 66 subjects who were unable to complete the MMSE test at baseline due to motor, visual, or hearing deficits or illiteracy, a ratio was calculated between the score obtained and the maximum score obtainable. This ratio was then multiplied by 30 to normalize it with the scores of other subjects.
The relative prevalence of CIND in subjects with and without
elevated Lp(a) levels was examined, and the statistical significance
assessed by 2 test.
Version 9.0 of SPSS software for Windows was used for these analyses.32
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The demographic characteristics and educational level of the study cohort are given in Table 1
.
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No statistically significant difference was found in
neuropsychological test scores between the 2 groups of subjects with
(75th percentile) and without (<75th percentile) elevated Lp(a)
levels, although subjects with elevated Lp(a) levels had slightly
better cognitive performances in all the tests
(Table 2). This difference reached statistical
significance in the number of correct responses in the Matrix Test
after control for age, sex, education, smoking, and history of stroke
(Table 2). No correlation was found between Lp(a) levels and
the neuropsychological test score (Pearson’s correlation
P 0.364 to 0.625).
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The rate of subjects with elevated Lp(a) levels was equally
distributed in the group of subjects available and in the group of
subjects lost at follow-up (24.9% of available subjects versus 24.6%
of lost subjects). No statistically significant difference in sex
distribution was found (for men, 52.1% of available subjects versus
53.3% of subjects lost at follow-up, 2
P=0.453). Compared with the 313
available subjects, the 122 subjects lost at follow-up were older (mean
age 76.3±5.8 versus 73.7±5.6 years,
t test
P=0.0001) and at the
cross-sectional assessment had significantly higher rates of dementia
(17.2% versus 2.2%, 2
P<0.001), myocardial
infarction (13.9% versus 7.4%,
P=0.029), and heart failure
(10.7% versus 1.9%, P<0.001)
and nonsignificantly higher rates of stroke (7.4% versus 3.8%,
2
P=0.100) and intermittent
claudication (8.6% versus 5.5%, 2
P=0.208).
Table 3 shows the mean test scores among the subgroups
of subjects classified according to the 4 quartiles of Lp(a)
determination. No statistically significant difference was found in
score variations between baseline and follow-up assessments in each
Lp(a) class level.
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At follow-up, the neuropsychological test scores showed no
statistically significant difference between subjects with and without
elevated Lp(a) levels at baseline in either the univariate
or the multivariate analysis
(Table 4).
Table 4 also shows the differences between the
neuropsychological test scores at baseline and at follow-up assessment.
The cognitive performances of subjects with and without
elevated Lp(a) levels worsened over the follow-up period with a similar
trend.
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In our sample, a CIND diagnosis was made in 25 subjects. No
significant difference was found in the prevalence of CIND between
subjects with and without elevated Lp(a) serum levels (4.9% versus
6.6%, respectively; 2
P=0.533).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In our population cohort of elderly white subjects, we did not detect any significant difference in the cognitive performances between the groups of subjects with and without elevated Lp(a) levels. Overall, the slightly better cognitive profile of subjects with elevated Lp(a) levels detected at baseline was nonsignificant from a statistical and, in our opinion, a clinical point of view. Moreover, the significant difference seen at baseline in a subscore of 1 of the 3 neuropsychological tests was not confirmed at follow-up. Thus, we conclude that in our population sample, the serum level of Lp(a) did not influence a subsequent rate of cognitive decline.
Because elevated Lp(a) levels have been reported to be associated with an increased risk of coronary artery and cerebrovascular diseases, our original hypothesis was that an elevated Lp(a) level could also be a risk factor for poorer cognitive performances. Although a previous study on the same population did not disclose any association between elevated Lp(a) levels and vascular diseases,23 we decided to analyze the effect of elevated Lp(a) levels on cognitive functions for the possibility that silent cerebrovascular disease (not assessable because the ILSA protocol does not include a neuroimaging evaluation) might be found in this population. There are at least 2 studies that show an association between elevated Lp(a) levels and silent cerebral infarction33 or subcortical vascular encephalopathy.34 The results of our study on an aged (>65 years) cohort do not support the original hypothesis. One should bear in mind, however, that the association between vascular diseases and elevated Lp(a) has been found mainly in subjects <60 years of age35 36 37 38 and that elevated Lp(a) levels alone did not represent, as in our cohort, a risk factor for vascular diseases.23 Thus, the putative detrimental effect of Lp(a) on cognitive performance could be similarly undetectable in older subjects of the general population. Because apo(a) molecular weight has been recently regarded as the main determinant of the harmful effect of Lp(a),39 it could be hypothesized that subjects with elevated Lp(a) levels who survive to older age carry a less risky type of Lp(a) and thus are protected from its deleterious effect.
To the best of our knowledge, this study is the first to have evaluated the effect of Lp(a) levels on cognitive performances in the general population. In 2 Japanese studies,21 22 elevated Lp(a) levels were found to be a risk factor for dementia. In the first study, higher Lp(a) levels were observed in patients with vascular dementia and large artery stroke compared with patients with Alzheimer’s dementia, cerebral hemorrhage, and lacunar infarcts.21 In the second study, the Lp(a) levels of patients with cerebrovascular disease and dementia were higher than those of age-matched control subjects.22 Both studies focused on vascular dementia and used hospital-based patient series. In our population study, Lp(a) levels did not appear to influence the prevalence or subsequent rate of dementia, but we had a very small number of cases and we chose not to present these data. In our sample, only 1 of 6 subjects with a diagnosis of vascular dementia had an elevated Lp(a) level.
On the other hand, the influence of Lp(a) levels on cognitive performances in whites has not been previously investigated. As shown in a biracial population study,40 41 the effect of elevated Lp(a) serum levels on vascular diseases may be dissimilar in different races: compared with whites, blacks have twice as high mean Lp(a) levels but carry the same or even a lower disease risk. One can assume that the effect of Lp(a) on cognition may also vary according to race.
Concerning the methodological issues of our study, Lp(a) was not assessed in nonresponders (the nonresponse rate of 20% can be considered acceptable for such population-based surveys) and in the previously mentioned group of individuals because of the delay in Lp(a) determination. Both these circumstances lowered the mean age of the study cohort due to the exclusion of older subjects but probably did not result in a systematic selection bias. In fact, apart from age and smoking, there was no difference in the prevalence of the diseases and risk factors being investigated between the group of subjects with and without Lp(a) level determination. The multivariate analysis showed that the worse neuropsychological performances of subjects without Lp(a) determination were mainly due to their older age.
We arbitrarily chose the 75th percentile to separate subjects with and without an elevated Lp(a) level. This was supported by data showing that the vascular risk associated with Lp(a) is confined to the upper quartile.2 30 31 The 75th percentile for Lp(a) level in our study was slightly higher than that of previously quoted studies, and therefore it is unlikely that it could be below a putatively dangerous level. A repeat of the same analyses with the 70th, 80th, and 90th percentile cutoff limits or with a common 75th percentile for men and women did not change the significance of the results.
The battery of neuropsychological tests used to evaluate cognitive performances in this population sample originated from the general protocol of the ILSA Study.24 This protocol included the MMSE along with the Babcock Short Story and the Matrix Test to screen subjects in this population suspected of having mental decline. The MMSE was chosen because it is the test most widely used and validated for the neuropsychological screening of large population-based studies. The choice of the other 2 tests was dictated by the need to expand the exploration of cognitive functions omitted by the MMSE and by these tests being rather easily administered in terms of time and compliance by the subjects under investigation (also in consideration of the low educational level of this Italian 65- to 84-year-old age group). Although the screening battery of tests used in the ILSA Study cannot be regarded as comprehensive (information regarding selective dysfunction related to age such as language and planning capacity is lacking), the Matrix Test and the Babcock Short Story are highly focused in finding alterations in attention and episodic memory, respectively. However, we cannot exclude that the use of a more comprehensive battery of neuropsychological tests and a longer follow-up period would have led to different results.
In conclusion, according to our data, elevated Lp(a) levels cannot be considered among the factors that influence cognitive performances in elderly whites. Future longitudinal observation studies should be aimed at evaluating the role of Lp(a) in relation to cognitive performances in younger age groups and in different racial groups.
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Acknowledgments |
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This work was supported by the National Research Council of Italy (C.N.R., Rome, Italy). Monia Salvi and Patrizia Trallori provided excellent secretarial support during the population-based study.
Received November 24, 2000; revision received March 23, 2001; accepted March 23, 2001.
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References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. Howard GC, Pizzo SV. Lipoprotein(a) and its role in atherothrombotic disease. Lab Invest. 1993;69:373–386.[Medline] [Order article via Infotrieve]
2.
Rhoads GG, Dahlen
G, Berg K, Morton NE, Dannenberg AL. Lp(a) lipoprotein as a risk factor
for myocardial infarction.
JAMA. 1986;256:2540–2544.
3.
Bostom AG, Gagnon
DR, Cupples LA, Wilson PWF, Jenner JL, Ordovas JM, Schaefer EJ,
Castelli WP. A prospective investigation of elevated lipoprotein(a)
detected by electrophoresis and cardiovascular disease
in women. The Framingham Heart Study.
Circulation. 1994;90:1688–1695.
4.
Bostom AG, Cupples
LA, Jenner JL, Ordovas JM, Seman LJ, Wilson PWF, Schaefer EJ, Castelli
WP. Elevated plasma lipoprotein(a) and coronary heart disease
in men aged 55 years and younger: a prospective study.
JAMA. 1996;276:544–548.
5.
Stein JH, Rosenson
RS. Lipoprotein Lp(a) excess and coronary heart disease.
Arch Intern Med. 1997;157:1170–1176.
6. Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for coronary artery disease. Am J Cardiol. 1998;82:57U–66U.[Medline] [Order article via Infotrieve]
7.
Nguyen TT, Ellefson
RD, Hodge DO, Bailey KR, Kottke TE, Abu-Lebdeh HS. Predictive value of
electrophoretically detected lipoprotein(a) for coronary heart
disease and cerebrovascular disease in a community-based cohort of 9936
men and women. Circulation. 1997;96:1390–1397.
8. Widmann MD, Sumpio BE. Lipoprotein(a): a risk factor for peripheral vascular disease. Ann Vasc Surg. 1993;7:446–451.[Medline] [Order article via Infotrieve]
9. Sutton-Tyrrell K, Evans RW, Meilahn E, Alcorn HG. Lipoprotein(a) and peripheral atherosclerosis in older adults. Atherosclerosis. 1996;122:11–19.[Medline] [Order article via Infotrieve]
10.
Zenker G,
Költringer P, Bunè G, Niederkorn K, Pfeiffer K, Jürgens G.
Lipoprotein(a) as a strong indicator for cerebrovascular disease.
Stroke. 1986;17:942–945.
11.
Woo J, Lau E, Lam
CWK, Kay R, Teoh R, Wong HY, Prall WY, Kreel L, Nicholls MG.
Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors
for stroke in the Chinese.
Stroke. 1991;22:203–208.
12.
Pedro-Botet J,
Senti M, Nogués X, Rubiés-Prat J, Roquer J, D’Olhaberriague L,
Olivé J. Lipoprotein and apolipoprotein profile in men with
ischemic stroke: role of lipoprotein(a),
triglyceride-rich lipoproteins, and apolipoprotein E
polymorphism. Stroke. 1992;23:1556–1562.
13.
Shintani S,
Kikuchi S, Hamaguchi H, Shiigai T. High serum lipoprotein(a) levels are
an independent risk factor for cerebral infarction.
Stroke. 1993;24:965–969.
14. Nagayama M, Shinohara Y, Nagayama T. Lipoprotein(a) and ischemic cerebrovascular disease in young adults. Stroke. 1994;25:74–78.[Abstract]
15.
Jürgens G,
Taddei-Peters WC, Költringer P, Petek W, Chen Q, Greilberger J,
Macomber PF, Butman BT, Stead AG, Ransom JH. Lipoprotein(a) serum
concentration and apolipoprotein(a) phenotype correlate with
severity and presence of ischemic cerebrovascular disease.
Stroke. 1995;26:1841–1848.
16. Hiraga T, Shimada M, Okubo M, Nakanishi K, Kobayashi T, Murase T. Lipoprotein(a) is an independent risk factor for multiple cerebral infarctions. Atherosclerosis. 1996;122:29–32.[Medline] [Order article via Infotrieve]
17. Hajjar KA, Gavish D, Breslow JL, Nachman RL. Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature. 1989;339:303–305.[Medline] [Order article via Infotrieve]
18. Scanu AM, Lawn RM, Berg K. Lipoprotein(a) and atherosclerosis. Ann Intern Med. 1991;115:209–218.
19. Skoog I. Status of risk factor for vascular dementia. Neuroepidemiology. 1998;17:2–9.[Medline] [Order article via Infotrieve]
20. Nyenhuis DL, Gorelick PB. Vascular dementia: a contemporary review of epidemiology, diagnosis, prevention, and treatment. J Am Geriatr Soc. 1998;46:1437–1448.[Medline] [Order article via Infotrieve]
21. Urakami K, Wada-Isoe K, Wakutani Y, Ikeda K, Ji Y, Yamagata K, Kowa H, Okada A, Adachi Y, Nakashima K. Lipoprotein(a) phenotypes in patients with vascular dementia. Dement Geriatr Cogn Disord. 2000;11:135–138.[Medline] [Order article via Infotrieve]
22. Matsumoto T, Fujioka T, Saito E, Yasugi T, Kanmatsuse K. Lipoprotein(a) as a risk factor for cerebrovascular disease and dementia. Nutr Metab Cardiovasc Dis. 1995;5:17–22.
23. Pantoni L, Sarti C, Pracucci G, Di Carlo A, Vanni P, Inzitari D. Lipoprotein(a) serum levels and vascular diseases in an older Caucasian population cohort. Italian Longitudinal Study on Aging (ILSA). J Am Geriatr Soc. 2001;49:117–125.[Medline] [Order article via Infotrieve]
24. Maggi S, Zucchero M, Grigoletto F, Baldereschi M, Candelise L, Scarpini E, Scarlato G, Amaducci L, for the ILSA Group. The Italian Longitudinal Study on Aging (ILSA): design and method. Aging Clin Exp Res. 1994;6:464–473.
25.
The Italian
Longitudinal Study on Aging Working Group. Prevalence of chronic
diseases in older Italians: comparing self-reported and clinical
diagnoses. Int J Epidemiol. 1997;26:995–1002.
26. 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]
27. Spinnler H, Tognoni G. Standardizzazione e taratura italiana di test neuropsicologici. Ital J Neurol Sci. 1987;8(suppl):47–50.
28. De Renzi E, Faglioni P, Ruggini C. Prove di memoria verbale di impiego clinico per la diagnosi di amnesia. Arch Psicol Neurol Psichiatr. 1977;3:303–308.
29. Di Carlo A, Baldereschi M, Amaducci L, Maggi S, Grigoletto F, Scarlato G, Inzitari D. Cognitive impairment without dementia in older people: prevalence, vascular risk factors, impact on disability. The Italian Longitudinal Study on Aging. J Am Geriatr Soc. 2000;48:775–782.[Medline] [Order article via Infotrieve]
30.
Dahlen GH, Guyton
JR, Attar M, Farmer JA, Kautz JA, Gotto AM Jr. Association of levels of
lipoprotein Lp(a), plasma lipids, and other lipoproteins with
coronary artery disease documented by angiography.
Circulation. 1986;74:758–765.
31. Simons L, Friedlander Y, Simons J, McCallum J. Lipoprotein(a) is not associated with coronary heart disease in the elderly: cross-sectional data from the Dubbo study. Atherosclerosis. 1993;99:87–95.[Medline] [Order article via Infotrieve]
32. Norusis MJ. SPSS for Windows: Advanced Statistics: Release 6.0. Chicago, Ill: SPSS Inc; 1993.
33.
Kario K, Matsuo
T, Kobayashi H, Asada R, Matsuo M. "Silent" cerebral infarction is
associated with hypercoagulability, endothelial cell
damage, and high Lp(a) levels in elderly Japanese.
Arterioscler Thromb Vasc Biol. 1996;16:734–741.
34. Mielke O, Fassbender K, Bertsch T, Aufenanger J, Hennerici M. Lipoprotein(a) in subtypes of cerebrovascular disease: evidence for a role as an independent factor in subcortical vascular encephalopathy (SVE). Cerebrovasc Dis. 1998;8(suppl 4):103.
35.
Ridker PM,
Hennekens CH, Stampfer MJ. A prospective study of lipoprotein(a) and
the risk of myocardial infarction.
JAMA. 1993;270:2195–2199.
36.
Ridker PM,
Stampfer MJ, Hennekens CH. Plasma concentration of lipoprotein(a) and
the risk of future stroke.
JAMA. 1995;273:1269–1273.
37.
Jürgens G,
Költringer P. Lipoprotein(a) in ischemic cerebrovascular
disease: a new approach to the assessment of risk for stroke.
Neurology. 1987;37:513–515.
38.
Sunayama S, Daida
H, Mokuno H, Miyano H, Yokoi H, Lee YJ, Sakurai H, Yamaguchi H. Lack of
increased coronary atherosclerotic risk due to elevated
lipoprotein(a) in women 55 years of age.
Circulation. 1996;94:1263–1268.
39.
Kronenberg F,
Kronenberg MF, Kiechl S, Trenkwalder E, Santer P, Oberhollenzer F,
Egger G, Utermann G, Willeit J. Role of lipoprotein(a) and
apolipoprotein(a) phenotype in atherogenesis: prospective
results from the Bruneck Study.
Circulation. 1999;100:1154–1160.
40. Schreiner PJ. Lipoprotein(a) as a risk factor for preclinical atherosclerotic disease in a biracial cohort: the Atherosclerosis Risk in Communities (ARIC) Study. Chem Phys Lipids. 1994;67/68:405–410.
41.
Schreiner PJ,
Heiss G, Tyroler HA, Morrisett JD, Davis CE, Smith R. Race and gender
differences in the association of Lp(a) with carotid artery wall
thickness. The Atherosclerosis Risk in Communities
(ARIC) Study Arterioscler Thromb Vasc
Biol. 1996;16:471–478.
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