Copyright
Blackwell Munksgaard 2006

Acta Neurol Scand 2006: 114: 8490 DOI: 10.1111/j.1600-0404.2006.00597.x

ACTA NEUROLOGICA
SCANDINAVICA

Relation between vascular risk factors and

cognition at age 75
Fischer P, Zehetmayer S, Bauer K, Huber K, Jungwirth S, Tragl K-H.
Relation between vascular risk factors and cognition at age 75.
Acta Neurol Scand 2006: 114: 8490.
Blackwell Munksgaard 2006.
Objective Recent trends in dementia research emphasize that not only
cerebrovascular events but also vascular risk factors induce, favour or
cause cognitive impairment and Alzheimers disease. Material and
methods We evaluated vascular risk factors (blood pressure, LDL
cholesterol, HDL cholesterol, triglycerides, HbA1c, homocysteine,
lipoprotein(a), brinogen, C-reactive protein and smoking habits) in a
community-based cohort of 75-year-old individuals of two districts in
Vienna (247 men, 359 women) and correlated these risk factors with
overall cognition. Results Pathological vascular risk factors were
found frequently in the age cohort. However, the expected associations
between the Mini-Mental State Examination and any cardiovascular
risk factors were missing. Only individuals with a positive history of
smoking showed lower cognitive capacities. Conclusions We assume
that cognitive dysfunction in old age is connected to factors other than
the known classical and novel risk factors for the development of
cardiovascular disease.

P. Fischer1, S. Zehetmayer2,
K. Bauer3, K. Huber3,
S. Jungwirth4, K.-H. Tragl4
1
Ludwig Boltzmann Society, L. Boltzmann Institute of
Aging Research & Department of General Psychiatry,
Medical University of Vienna, Vienna, Austria; 2Institute
for Medical Statistics, Medical University of Vienna,
Vienna, Austria; 3Ludwig Boltzmann Society, L.
Boltzmann Institute of Molecular Genetic Laboratory,
Danube Hospital, Vienna, Austria; 4Ludwig Boltzmann
Society, L. Boltzmann Institute of Aging Research,
Vienna, Austria

Key words: vascular risk factors; cognition; dementia;

smoking
Peter Fischer, Psychiatrische Klinik AKH, Waehringer
Guertel 18-20, A1090 Wien, Austria
Tel.: +43 1 40400 3543
Fax: +43 1 40400 3099
e-mail: peter.fischer@meduniwien.ac.at
Accepted for publication January 17, 2006

Atherosclerotic vascular changes are responsible

for cardiovascular events such as myocardial
infarction and stroke. Cerebrovascular lesions
cause cognitive dysfunction, and vascular risk
factors favour cognitive decline by favouring the
occurrence of cerebrovascular lesions. But vascular
risk factors such as hypertension, hypercholesterolaemia, diabetes mellitus, elevated levels of homocysteine and C-reactive protein, or smoking
habits are reported to directly promote the cognitive decline with ageing and the development of
dementia, including Alzheimers disease (AD) (1
12). However, the role of vascular risk factors in
reducing cognitive function in old age is not
conclusive (13). One possible reason for this
uncertainty is the examination of individuals with
high variability of age, although the associations
between vascular changes and cognitive decline are
age dependent.
The Vienna Transdanube Aging (VITA) study is
primarily designed as a community-based cohort
study for the early prediction of AD, but also
permits epidemiological research concerning the
relation of vascular risk factors to cognitive function (14). The present study investigated the
84

community-based age cohort (n 606) of the

VITA at baseline, that is at a mean age of
75.7 years.The aim of the study was to survey the
frequency of vascular risk factors, conventional
and novel, in a cohort of 75-year-old people in two
neighbouring districts of Vienna and to examine
the associations of these vascular risk factors with
cognitive dysfunction cross-sectionally.
Methods

The VITA is an interdisciplinary, community-based

cohort study of all 75-year-old inhabitants of the
Floridsdorf and Donaustadt district of Vienna
and is designed for the early detection of AD.
A total of 1505 citizens born between May 1925
and April 1926 were ofcially registered in both
districts and were contacted by personal letter or
by up to four telephone calls either at home or in
an institutional setting. The recruitment has been
described in detail previously (14). Six hundred
and six individuals ensured complete participation
in the VITA study at baseline, and a further 91
participated without blood donation. The mean age
of the 606 individuals was 75.77 years with a

Vascular risk factors and cognition

standard deviation of only 0.45 years, which minimized age-associated changes of variables within
the cohort.
The standardized survey of causes of refusal to
participate showed lack of interest in 52%,
somatic diseases in 25%, negativism in 8%,
obvious aective problems in 7% and rare other
causes. For obtaining information about persons
refusing participation, data on current medication
of refusers were compared with that of participants
in a series of refusers (n 52): we found no
signicant dierence between the rate of medication concerning dierent types of medication.
There was a trend towards higher intake of
benzodiazepines in refusers and a trend towards
higher intake of lipid-lowering drugs (LLD), antihypertensives and antithrombotic treatment in
participants of the VITA. This could be interpreted
in the way that vascular risk factors were rather
less prevalent in non-participants.
After obtaining written consent, venous puncture and blood pressure were recorded after a
5-min rest before breakfast with the subjects in a
sitting position. The following vascular risk factors
were measured: systolic blood pressure (sBP) at
rest, diastolic blood pressure (dBP) at rest, total
cholesterol (CHOL), LDL cholesterol (LDL),
HDL cholesterol (HDL), triglycerides (TGL),
HbA1c as an indicator of the carbohydrate metabolic state, homocysteine (HCY), lipoprotein(a)
(Lp(a)), brinogen (FIBR), C-reactive protein
(CRP) and smoking history.
Laboratory analyses were performed as follows:
Total cholesterol (mg/dl), HDL (mg/dl), TGL (mg/
dl) and CRP (mg/l) were analysed with a Hitachi
917 analyser (Roche, Basel, Switzerland) using
reagents from the same manufacturer and LDL
(mg/dl) was calculated. HbA1c (% of total haemoglobin) was measured on a Roche Integra
Analyser (Roche) with reagent from the same
manufacturer. Lipoprotein(a) (g/l) was measured
with a BN II Nephelometer (DADE Behring,
Marburg, Germany) with reagents from the same
manufacturer. HCY (lmol/l) was measured with
an Abbott IMX analyser using the reagents from
Abbott Laboratories (Abbott Park, IL, USA).
FIBR (mg/dl) was measured with an AMAX 400
analyser (Amelung- Trinity; Bray, Ireland) using
appropriate reagents from DADE Behring. All
methods were performed according to the manufacturers recommendations. The laboratory performs permanent internal and external quality
control programmes.
People under treatment for arterial hypertension
(BP-treated) or under LLD were described separately. For the evaluation of cognitive function, the

individuals were tested with the Mini-Mental State

Examination (MMSE) from the CERAD battery
(German version; 15) by a clinical psychologist
experienced in the investigation of old probands
and blind to the results concerning vascular risk
factors.
The statistical analysis was performed using the
statistic programs SAS and SPSS (SPSS Inc.,
Chicago, IL, USA). Group comparison was made
by comparison of mean ranks (U-test) or by
comparison of frequencies (chi-square test). Linear
regression analyses (backward selection of all main
eects, P < 0.05) with MMSE as the dependent
variable, and all vascular risk factors, gender, LLD
(yes/no) and antihypertensive drugs (yes/no) as the
independent variables were also calculated. In
addition, a second model was calculated with all
signicant variables from the rst model and all
interactions of the signicant variables.

Results
Vascular risk factors in the examined population

Without antihypertensive treatment, blood pressure (BP) was similar for men and for women
(Table 1). 63.7% (385 of 604) individuals took
antihypertensive treatment (63.2% of men and
64.1% of women). Of 219 subjects without antihypertensive treatment, 144 had elevated BP in a
sitting position after at least 5 min rest applying
the threshold of hypertension of 140/90 mmHg of
the Joint National Committee (16).
Treatment of hyperlipidaemia with either
brates or statins was found in 17.8% of the 75year-old cohort (18.8% of men and 17.2% of
women). Blood levels of the parameters of lipid
metabolism (CHOL, LDL, HDL and TGL) in
individuals without antihyperlipidaemic treatment
revealed slightly elevated values with blood levels
of CHOL and LDL signicantly higher in women
than in men. Blood levels of HDL were signicantly higher in women than in men and were
higher overall than the levels reported to be
connected to increased vascular risk. Antihyperlipidaemic treatment was accompanied by blood
levels of CHOL and of LDL below the levels
of untreated people. Under LLD, blood levels of
HDL were signicantly lower, while blood levels
of TGL were signicantly higher than without
antihyperlipidaemic treatment.
Concerning HbA1c, men and women of the
cohort were divided into three groups: the total
population (c), the group of individuals receiving
oral antidiabetics without insulin (d), and the
diabetics with insulin treatment with or without
85

Fischer et al.
Table 1 Vascular risk factors (mean
SD) in men vs women at age 75: (a)
individuals without respective treatment; (b) individuals with respective treatment;
(c) receiving antidiabetics, no insulin; (d) receiving insulin with or without antidiabetics
Risk factor
sBP
(a)
(b)
dBP
(a)
(b)
CHOL
(a)
(b)
LDL
(a)
(b)
HDL
(a)
(b)
TGL
(a)
(b)
HbA1c
(c)
(d)
HCY
Lp(a)
FIBR
CRP
MMSE
Smoker
No
Yes
BP-treated
No
Yes
LLD
No
Yes

Men (n 247)

Women (n 359)

P-value (U-test)

91 (147.12
22.62)
156 (146.51
19.49)

128 (144.60
20.08)

229 (148.23
20.80)

0.549
0.490

91 (82.97
9.95)
156 (81.24
11.08)

128 (82.62
10.32)

229 (82.06
10.70)

0.786
0.647

199 (222.92
42.99)

46 (192.83
39.28)

294 (247.80
43.22)

61 (215.90
40.29)

0.000
0.007

198 (144.16
39.53)

46 (112.63
32.65)

292 (158.19
37.35)

61 (125.95
35.65)

0.000
0.080

199 (53.36
14.29)

46 (49.26
8.93)

294 (63.58
15.38)

61 (59.57
13.31)

0.000
0.000

199
46
244
31
10
245
239
243
244
246

(130.48
62.01)
(154.78
74.80)
(5.78
0.96)
(6.96
1.31)
(7.61
1.76)
(14.74
4.89)
(0.153
0.127)
(376.47
89.70)
(4.45
7.62)
(27.8
1.7)

294
61
354
32
9
355
348
347
355
359

(131.54
72.82)
(151.85
73.60)
(6.09
3.15)
(7.69
1.48)
(7.89
1.66)
(14.00
6.01)
(0.190
0.186)
(396.84
86.60)
(4.62
6.61)
(27.8
1.9)

0.945
0.970
0.024
0.046
0.391
0.002
0.023
0.001
0.028
0.676
Chi-square test
0.000

84
163

260
99

91
156

128
231

0.765

194
53

284
75

0.867

sBP, systolic blood pressure; dBP, diastolic blood pressure; CHOL, total cholesterol;
LDL, low-density lipoprotein; HDL, high-density lipoprotein; TGL, triglycerides;
HbA1c, % of total haemoglobin; HCY, homocysteine; Lp(a), lipoprotein(a); FIBR,
fibrinogen; CRP, C-reactive protein; MMSE, Mini-Mental State Examination; LLD,
lipid-lowering drugs.

antidiabetics. HbA1c was signicantly higher in

women than in men and was also signicantly
higher in female diabetics treated orally than in
male diabetics who took oral antidiabetics without
insulin treatment. HbA1c was highest in the
patients with insulin treatment.
Smoking habits were reported in 163 of 247 men
(66.0%) but only in 99 of 359 women (27.6%).
Sixty-six subjects had smoked for 115 years, a
further 88 between 16 and 30 years, and 107
subjects had smoked for more than 30 years.
According to the age of the cohort, blood levels
of homocysteine were high in general. Homocysteine levels were found to be signicantly higher in
men than in women. Lp(a) in serum, brinogen
86

Table 2 Linear regression (backwards) for MMSE in 606 individuals from the age
cohort of the VITA study. Possible predictors: sBP, dBP, LDL, HDL, TG, HbA1c, HCY,
Lp(a), FIBR, CRP, smoking (0, 115, 1530 and >30 years), on antihypertensive
drugs, on lipid-lowering drugs, body mass index and gender. (a) First model with
selection of all relevant main effects without interactions (R2 0.03). (b) Second
model with all significant variables from the first model and all possible interactions (R2 0.03)
Variable
(a)
Intercept
DBP
BP treatment
Smoking
(b)
Intercept
Smoking
Smoking dBP

Parameter estimate

SE

Type II SS

F-value

P>F

25.92
0.02
0.31
0.19

0.61
0.01
0.16
0.06

5718.28
21.37
21.90
28.86

1806.6
6.8
4.1
9.1

<0.0001
0.010
0.044
0.003

27.63
)1.04
0.01

0.09
0.37
0.00

285138
24.72
33.48

89301.7
7.74
10.49

<0.0001
0.006
0.001

MMSE, Mini-Mental State Examination; VITA, Vienna Transdanube Aging; sBP,

systolic blood pressure; dBP, diastolic blood pressure; LDL, low-density lipoprotein;
HDL, high-density lipoprotein; TGL, triglycerides; HbA1c, % of total haemoglobin;
HCY, homocysteine; Lp(a), lipoprotein(a); FIBR, fibrinogen; CRP, C-reactive protein;
SE, standard error.

and C-reactive protein levels were found to be

signicantly higher in women than in men.
Relation of cognitive function to vascular risk factors

Linear regression analysis with vascular risk factors as independent predictors explained only 3%
of variance of the MMSE (R2 0.03) (Table 2).
The linear regression calculated without inclusion
of possible interactions resulted in three signicant
variables (Table 2a). Subjects taking antihypertensive drugs, subjects with higher dBP and subjects
with a positive history of smoking showed better
cognitive performance. When all interactions of the
signicant variables were added to the model
(Table 2b), dBP and antihypertensive medication
were no longer signicant and the parameter
estimate of smoking had a negative sign, i.e.
people who smoked for many years had signicantly lower MMSE scores. Moreover, the interaction between smoking and dBP showed
signicance, indicating that the subgroup of smokers with high dBP at age 75 had no impairment of
cognition. No other vascular risk factors [sBP,
HbA1c, LDL, HDL, TGL, HCY, FIBR, CRP,
Lp(a), gender or body mass index (BMI)] inuenced the global cognitive functioning of the
community-based age cohort.
Discussion

In our cohort of 75-year-old individuals no association of either conventional or novel vascular risk
factors with global cognitive function could be

Vascular risk factors and cognition

detected cross-sectionally. This result was irrespective of the psychometric test used, as similar
calculations using other tests of the CERAD also
found associations explaining only 12% of variance of the tests. This is interesting because recent
trends in dementia research brought back the
concept of vascular cognitive impairment, supposing that not only cerebrovascular events but also
vascular risk factors per se induce, favour or cause
cognitive impairment and AD (11, 17). It has been
stated that even sporadic AD is a vascular
disorder (10). On the contrary, we did not detect
any of the expected direct associations between
vascular risk factors and cognitive dysfunction in
our cohort at age 75.
We found a mild association between antihypertensive treatment and better cognition, and an
inversely mild association between higher dBP and
better MMSE scores in the total population before
including possible interactions into the model.
Therefore, arterial hypertension may be a certain
risk factor for cognitive dysfunction in the elderly
as has been described previously (13, 5, 18). The
fact that antihypertensive treatment prevents
dementia has been shown in the Syst-EUR Trial
(19), but this has been interpreted as an effect of
calcium antagonists used in this trial (13). Some
longitudinal studies showed no association
between arterial hypertension or antihypertensive
treatment and AD (8, 13, 20). On the other hand,
longitudinal studies such as the Framingham study
or the Honolulu Aging study described cognitive
impairment preceded by high sBP, but blood
pressure declined during the years prior to dementia onset (1, 21, 22) which would explain the lack of
associations between sBP and cognition in our
cross-sectional data.
Results of some previous studies were replicated
when only main eects and their interactions in the
regression analysis were regarded: low dBP was
associated with a higher risk of dementia in elderly
individuals (13, 23, 24). But this positive effect of
higher dBP on MMSE scores was signicant only
for heavy smokers in the second regression model
including interactions of the main effects.
Smoking habits, which revealed the expected
association with cardiovascular events in our
population, showed a positive relationship to
higher scores of global cognition in the rst
regression model of our data. In the early 1990s,
results from small casecontrol and family studies
suggested a protective eect of smoking on dementia, but that had been explained by selection
artefacts (13, 25, 26). Recent results from large
longitudinal studies found no evidence of a protective effect of smoking (27, 28) or an increased

risk for dementia in smokers (5, 29). Smoking was

associated with a signicantly increased risk of AD
in population-based studies with a high prevalence
of smoking: 64% of the individuals of the EURODEM pooled analysis from Europe (5) and 61% of
participants in the Honolulu Aging study (29) ever
smoked compared with 66% of men and 28% of
women in the VITA cohort. A lower overall rate of
smoking was reported in the Scandinavian Kungsholmen Project where 32% of non-demented
participants but only 23% of participants with
AD smoked or had smoked (28). This difference
could be explained by poorer survival of demented
smokers in the latter study.
Inclusion of interactions between smoking and
other vascular risk factors in our nal multivariate
model showed a signicant association between
dBP and smoking, which reversed the direct
association between smoking and better global
cognition towards a signicant association between
smoking and poor cognition. Our data indicate
that heavy smoking is associated with lower
cognitive abilities except in male subjects with
high dBP at age 75. According to these ndings,
clinico-pathological data from one populationbased longitudinal study found that the number
of neuritic plaques increased with amount smoked
(29).
Controversial eects of diabetes mellitus on
cognition have been described (13, 30, 31). We
did not nd any inuence of elevated HbA1c and
diabetes mellitus on cognition in our communitybased population at age 75. The only association in
the VITA cross-sectional data were signicantly
lower memory scores in the 19 probands of the
VITA cohort who were treated with insulin. This
might reect rather an inuence of insulin and
insulin-degrading enzyme on AD pathology (32,
33) than a direct inuence of diabetes mellitus on
cognition. Comorbidities, in particular with hypertension, may increase the probability of diabetes to
support cognitive decline (34) as is the case with
cardiovascular diseases. However, we found no
association of cognitive dysfunction even in hypertensive subjects with diabetes mellitus in the VITA
cohort. An impact of diabetic microangiopathy to
cognition in old age seems plausible but may be
currently overinterpreted following our database.
Plasma levels of HCY were not at all associated
with cognitive dysfunction in the VITA community
in contrast to some literature (35). Some studies
comparing cognition between subjects with very
high and very low HCY levels reported signicant
correlations between high HCY levels and low
global cognition (9, 36). A direct comparison of
MMSE scores in 101 subjects of the VITA with
87

Fischer et al.
HCY levels below 10 lmol/l (mean MMSE
27.6, SD 1.7) and 191 subjects with HCY levels
higher than 15 lmol/l (mean MMSE 27.7;
SD 2.0) was not signicant (T-test: t )0.302,
d.f. 290; P 0.763).
Similar to others (37), we did not nd an
inuence of plasma cholesterol or treatment with
LLD on MMSE scores in the age cohort investigated cross-sectionally. Some prospective longitudinal studies found no relation between previous
cholesterol levels and AD (13, 38, 39). Serum
cholesterol levels might decrease before the onset
of clinical manifestations of AD and previous high
serum cholesterol level might be associated with
later AD after controlling for age (40). Whether
there is a protective effect of therapy with LLD or
statins on cognition (41) is under investigation in
the longitudinal setting of the VITA. We found no
inuence of overweight (BMI) on cognition crosssectionally, neither in the total cohort, nor in the
male or female subgroups, but some previous
studies did (42, 43). The latter studies did not
investigate an age cohort and did not include the
metabolic sequelae of elevated BMI such as
CHOL, HbA1c, etc. into their models.
The lack of association between vascular risk
factors and cognition cannot be explained by low
frequencies of any vascular risk factor in the VITA
cohort. The dimensions of conventional and of
novel vascular risk factors were in accordance with
previous reports for individuals of similar age from
industrialized countries (4446). Other factors may
contribute to this lack of association. Possibly,
individuals who are most affected by high-risk
factors have passed away before the age of 75 years
which leads to the selection of low-risk people. In
addition, survivors of cardiovascular events may
present with a drug- or disease-related decrease of
vascular risk factors. They may have changed their
lifestyle, thus not accurately reecting their previous status of BP, lipid metabolism and diabetes
control in later life. Another important factor is the
decrease of some of the risk factors in prevalence
and in efcacy within the process of aging with the
reduction and even with loss of association with
cognitive decline and cardiovascular diseases in
cross-sectional studies of elderly people (5, 7, 8,
2123, 30, 31, 45, 47, 48).
Our study has several potential limitations. One
is the limited geographical area. Another is the low
participation of 606 (40.26%) out of 1505 contacted and invited individuals. However, because the
age group is limited, the sample size is less
troublesome than it might rst appear. The reasons
for non-participation (14) exclude a selection of
our cohort that would seriously limit the results of
88

the study concerning vascular risk factors. Indeed,

we found all risk factors in high frequency. The
possibility remains that cognitively impaired or
depressed individuals did not participate, but this
bias would also decrease the load of degenerative
factors on cognition. Moreover, the analysis of the
frequency of medication in a consecutive series of
refusers showed no signicant differences compared with participants of the VITA. Reliance on
the personal statement of the individuals concerning smoking behaviour, LLD therapy and therapy
with antihypertensive drugs is a further limitation
of the study. Furthermore, we can only present
cross-sectional data as the longitudinal part of the
VITA study is currently under way. The advantage
of investigating a large birth cohort is that the
covariate of age is extinguished. The standard
deviation of age in the 606 community-based
individuals is only 0.45 years.
The ndings in our 75-year-old cohort can be
taken as a contribution to those reports which
claim that the cognitive decline within this age
group has only low association with vascular risk
factors. In our cohort vascular risk factors did not
contribute to the process of cognitive decline. More
than 95% of the variance of cognition at age 75
seems to rely on other factors, probably on the
degenerative changes of Alzheimer type and Lewy
body type. We cannot support the concept that
sporadic AD of the elderly should be classied as a
vascular disorder (10). Nevertheless, vascular
pathology, like lacunes or infarcts, resulting from
events closely linked to vascular risk factors, may
lower the threshold for the clinical presentation of
dementia at a given level of AD-related pathology
(49).
Acknowledgements
This work was supported by the Ludwig Boltzmann Society
and conducted at the Ludwig Boltzmann Institute of Aging
Research.

References
1. Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The
association between midlife blood pressure levels and latelife cognitive function. The Honolulu-Asia Aging Study.
JAMA 1995;274:184651.
2. Skoog I, Lernfelt B, Landahl S et al. 15-year longitudinal
study of blood pressure and dementia. Lancet
1996;347:11415.
3. Skoog I. Status of risk factors for vascular dementia.
Neuroepidemiology 1998;17:29.
4. Diaz-Arrastia R. Hyperhomocysteinemia: a new risk factor
for Alzheimer disease? Arch Neurol 1998;55:14078.
5. Launer LJ, Andersen K, Dewey ME et al. Rates and risk
factors for dementia and Alzheimers disease: results

Vascular risk factors and cognition

6.
7.

8.

9.

10.
11.
12.

13.

14.

15.

16.

17.
18.

19.

20.

21.

22.

23.

24.

25.

from
EURODEM
pooled
analysis.
Neurology
1999;52:7884.
Schmidt R, Schmidt H, Fazekas F. Vascular risk factors in
dementia. J Neurol 2000;247:817.
Simons M, Keller P, Dichgans J, Schulz JB. Cholesterol and
Alzheimers disease. Is there a link? Neurology
2001;57:108993.
Posner HB, Tang MX, Luchsinger J, Lantigua R, Stern Y,
Mayeux R. The relationship of hypertension in the elderly
to AD, vascular dementia, and cognitive function. Neurology 2002;58:117581.
Seshadri S, Beiser A, Selhub J et al. Plasma homocysteine
as a risk factor for dementia and Alzheimers disease. N
Engl J Med 2002;346:47683.
De La Torre JC. Vascular basis of Alzheimers pathogenesis. Ann NY Acad Sci 2002;977:196215.
OBrien JT, Erkinjuntti T, Reisberg B et al. Vascular cognitive impairment. Lancet Neurol 2003;2:8998.
Teunissen CE, Van Boxtel MPJ, Bosma H et al. Inammation markers in relation to cognition in a healthy aging
population. J Neuroimmunol 2003;134:14250.
Breteler MM. Vascular risk factors for Alzheimers disease: an epidemiological perspective. Neurobiol Aging
2000;21:15360.
Fischer P, Jungwirth S, Krampla W et al. Vienna Transdanube Aging VITA: study design, recruitment strategies
and level of participation. J Neural Transm 2002;62:105
16.
Berres M, Monsch AU, Bernasconi F, Thalman B, Stahelin
HB. Normal ranges of neuropsychological tests for the
diagnosis of Alzheimers disease. Stud Health Technol
Inform 2000;77:1959.
Joint National Committee. The seventh report of the Joint
National Committee on prevention, detection, evaluation,
and treatment of high blood pressure. JAMA
2003;289:256072.
Bowler JV. Vascular cognitive impairment. Stroke
2004;35:3868.
Int-Veld BA, Ruitenberg A, Hofman A, Stricker BH,
Breteler MM. Antihypertensive drugs and incidence of
dementia: the Rotterdam Study. Neurobiol Aging
2001;22:40712.
Forette F, Seux ML, Staessen JA et al. The prevention of
dementia with antihypertensive treatment: new evidence
from the Systolic Hypertension in Europe (Syst-Eur)
study. Arch Intern Med 2002;162:204652.
Dibari M, Pahor M, Franse LV et al. Dementia and disability outcomes in large hypertension trials: lessons
learned from the systolic hypertension in the elderly program (SHEP) trial. Am J Epidemiol 2001;153:728.
Farmer ME, Kittner SJ, Abbott RD, Wolz MM, Wolf PA,
White LR. Longitudinally measured blood pressure, antihypertensive medication use, and cognitive performance:
the Framingham study. J Clin Epidemiol 1990;43:47580.
Elias MF, Wolf PA, Dagostino RB, Cobb J, White LR.
Untreated blood pressure level is inversely related to cognitive functioning: the Framingham study. Am J Epidemiol 1993;138:35364.
Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ.
Low blood pressure and the risk of dementia in very old
individuals. Neurology 2003;61:166772.
Qiu C, Von Strauss E, Fastbom J, Winblad B, Fratiglioni L.
Low blood pressure and risk of dementia in the Kungsholmen Project. Arch Neurol 2003;60:2238.
Riggs JE. Smoking and Alzheimers disease: protective effect or dierential survival bias? Lancet 1993;342:7934.

26. Brayne C. Smoking and the brain. Br Med J 2000;22:1087

8.
27. Doll R, Peto R, Boreham J, Sutherland I. Smoking and
dementia in male British doctors: prospective study. Br
Med J 2000;320:1097102.
28. Wang HX, Fratiglioni L, Frisoni GB, Vitanen M, Winblad B.
Smoking and the occurrence risk of Alzheimers disease:
cross-sectional and longitudinal data in a populationbased study. Am J Epidemiol 1999;149:6404.
29. Tyas SL, White LR, Petrovitch H et al. Mid-life smoking
and late-life dementia: the Honolulu-Asia Aging Study.
Neurobiol Aging 2003;24:58996.
30. Gregg EW, Yae K, Cauley JA et al. Is diabetes associated
with cognitive impairment and cognitive decline among
older women? Study of Osteoporotic Fractures Research
Group. Arch Intern Med 2000;160:17480.
31. Hassing LB, Johansson B, Pederse NL, Nilsson SE, Berg S,
Mc Clearn G. Type 2 diabetes mellitus and cognitive performance in a population based sample of the oldest old:
impact of comorbid dementia. Aging Neuropsychol Cognit
2003;10:99107.
32. Galasko D. Insulin and Alzheimers disease: an amyloid
connection. Neurology 2003;60:8867.
33. Watson GS, Peskind ER, Asthana S et al. Insulin increases
CSF Abeta42 levels in normal older adults. Neurology
2003;60:1899903.
34. Hassing LB, Hofer SM, Nilsson SE et al. Comorbid type 2
diabetes mellitus and hypertension exacerbate cognitive
decline: evidence from a longitudinal study. Age Ageing
2004;33:35561.
35. Budge MM, De Jager C, Hogervorst E, Smith AD. Total
plasma homocysteine, age, systolic blood pressure, and
cognitive performance in older people. J Am Geriatr Soc
2002;50:20148.
36. Rins ND, Den-Heijer T, Hofman A et al. Homocysteine and
cognitive function in the elderly. Neurology 2002;59:1375
80.
37. Reitz C, Ctang MX, Luchsinger J, Mayeux R. Relation of
plasma lipids to Alzheimer disease and vascular dementia.
Arch Neurol 2004;61:70514.
38. Romas SN, Tang M-X, Berglund L, Mayeux R. APOE
genotype, plasma lipids, lipoproteins, and AD in community elderly. Neurology 1999;53:51721.
39. Im J-M, Stewart R, Shin I-S, Yoon J-S. Low cholesterol,
cognitive function and Alzheimers disease in a community
population with cognitive impairment. J Nutrition Health
Aging 2002;6:3203.
40. Notkola I-L, Sulkava R, Pekkanen J et al. Serum total
cholesterol, apolipoprotein E(e4) allele, and Alzheimers
disease. Neuroepidemiology 1998;17:1420.
41. Wolozin B, Kellman W, Rousseau P, Celesia GG, Siegel G.
Decreased prevalence of Alzheimer disease associated with
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;57:143943.
42. Nourhashemi F, Andrieu S, Gillette-Guyonnet S et al. Is
there a relationship between fat-free soft tissue mass and
low cognitive function? Results from a study of 7,105
women. J Am Geriatr Soc 2002;50:1796801.
43. Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I. A
18-year follow-up of overweight and risk of Alzheimer
disease. Arch Intern Med 2003;163:15248.
44. Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for
systemic atherosclerosis. A comparison of C-reactive protein, brinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral
arterial disease. JAMA 2001;285:24815.

89

Fischer et al.
45. Bohmer F, Lapin A. What are normal laboratory
parameters in elderly patients when examined on rst
admission to a geriatric hospital? A pilot study. Eur J
Geriatr 2003;5:8693.
46. Elim AJ, Berlowitz DR, Fincke G et al. The health status of
elderly veteran enrolees in the Veterans Health Administration. J Am Geriatr Soc 2004;52:12716.
47. Franklin SS, Gustin W, Wong ND et al. Hemodynamic
patterns of age-related changes in blood pressure. The
Framingham Heart Study. Circulation 1997;96:30815.

90

48. Khot UN, Khot MB, Bajzer CHT et al. Prevalence of

conventional risk factors in patients with coronary heart
disease. JAMA 2003;290:898904.
49. Iekse RG, Leverenz JB, Mc Cormick W et al. Eect of
vascular lesions on cognition in Alzheimers disease: a
community-based study. J Am Geriatr Soc 2004;52:
14428.