Journal of Gerontology: MEDICAL SCIENCES

2003, Vol. 58A, No. 4, 372377

Copyright 2003 by The Gerontological Society of America

Association of Alzheimers Disease Onset With

Ginkgo Biloba and Other Symptomatic Cognitive
Treatments in a Population of Women Aged 75 Years
and Older From the EPIDOS Study
Sandrine Andrieu,1,2 Sophie Gillette,1,2 Karine Amouyal,1 Fati Nourhashemi,1,2 Emma Reynish,1
Pierre Jean Ousset,1 Jean Louis Albarede,1 Bruno Vellas,1 and Hele`ne Grandjean2
1

Department of Internal Medicine and Clinical Gerontology, Acute Unit for Alzheimers Patients, Toulouse, France.
2
Institut National de la Sante et de la Recherche Medicale (INSERM) U558, Toulouse, France.
Background. Peripheral C4A treatment (cerebral and peripheral vasotherapeutics) and especially Ginkgo biloba
extracts are prescribed for a number of symptoms, particularly memory impairment, in elderly patients. It is postulated that
because of its pharmacological actions, this treatment could prevent the decline of cognitive function, but no studies have
been published to date to test its efficacy in prevention of Alzheimers disease. The potential association between use of
C4A treatments, in particular EGb 761 (standardized Ginkgo biloba extracts), and dementia of the Alzheimer type was
investigated.
Methods. A case-control study was nested in a cohort of 1462 community-dwelling elderly women aged over 75 years.
Sixty-nine women with Alzheimer-type dementia were compared with 345 paired women whose cognitive function
remained normal. This study involved women whose cognitive function was evaluated at baseline by use of Pfeiffers test
and whose medication history was taken. The onset of cognitive impairment was investigated over a 7-year follow-up
period. In order to study the factors associated with the onset of dementia, the data concerning women with a score of >8
on Pfeiffers test at inclusion, indicating normal cognitive function, were analyzed.
Results. A multivariate analysis including potential confounding factors showed that fewer women who developed
Alzheimers dementia had been prescribed C4A treatment (including EGb 761) for at least 2 years (odds ratio 5 0.31,
95% confidence interval 5 0.120.82, p 5 .018). Figures for EGb 761 alone were similar but did not reach statistical
significance (odds ratio 5 0.38, 95% confidence interval 5 0.081.76, p 5 .22).
Conclusion. These results suggest that C4A treatment may reduce the risk of developing Alzheimers dementia in
elderly women. The potential preventive effect of C4A treatments, including EGb 761, requires further examination. To
establish a causal relationship, these findings have to be confirmed with prospective studies.

LZHEIMERS disease (AD) is the most prevalent form

of dementia, affecting 5% of people over 65 years old
and nearly 30% of people over 80 (1). It is essential to develop
treatments that are effective in preventing the onset of the
disease. C4A treatments (cerebral and peripheral vasotherapeutics), including Ginkgo biloba extracts, are widely used
in Europe and in the United States, particularly for memory
impairment in elderly persons. These medications are well
tolerated and could have potential for preventing cognitive
decline. Research in this field is particularly important today
because of the relationship between cognitive decline and
increased risk of AD in elderly people (2).
A number of studies have investigated the efficacy of
standardized Ginkgo biloba extracts (EGb 761) in patients
with altered cognitive function or AD. In a review of the
literature, Oken and colleagues identified four trials of
rigorous design (double blind, placebo controlled). After
meta-analysis, they concluded that treatment with EGb 761
had a moderate but significant effect on cognitive function
(3). More recently, two double-blind, randomized, placebocontrolled clinical trials reported conflicting results concerning the efficacy of EGb 761 in the treatment of AD (4,5).

372

In addition to its vasodilator properties (6), Egb 761 is

also an antioxidant. Oxidative stress is well recognized as
one of the mechanisms involved in the development of AD
(7,8), and because EGb 761 has antioxidant properties, it
could have a preventive effect on the onset of this disease.
Prospective large-scale long-term randomized studies are
necessary to establish this effect. Prior to planning such
studies, we had the opportunity to examine this hypothesis
in an ongoing study, the EPIDOS (EPIDemiology of
OSteoporosis) study. In this multicenter study, women
(>75 years) were assessed cognitively at baseline and were
then followed for 4 years, during which the history of their
prescribed drugs was recorded. At the end of the EPIDOS
study the cognitive function of the participants from one
center, Toulouse, was reassessed, allowing us to perform
a case-control study in this cohort.
METHODS

The EPIDOS Study

The EPIDOS study was a prospective multicenter study
with the aim of investigating the risk factors for femoral

C4A TREATMENT AND RISK OF ALZHEIMERS DISEASE

Table 1. Peripheral Treatments Coded as C4A

1. Ginkgo biloba extracts
2. Other C4A drugs
Naftidrofuryl
Vinburnine
Raubasine-Almitrine
Nicergoline
Ergot alkaloids
Piribedil
Ifenprodil
Buflomedil
Cinnarizine
Pentoxifylline
Vincamine
Moxisylyte
Cyclandelate
Papaverine

neck fracture. From January 1992 to January 1994, 7598

ambulatory women aged 75 years and over in 5 French
cities (Amiens, Lyon, Montpellier, Paris, and Toulouse)
volunteered to participate in this study. The protocol has
been described in detail elsewhere (9).
At baseline, women were assessed for physical and
functional capacities. Autonomy was assessed by three
items concerning basic activities of everyday life (dressing,
washing, and mobility) and Lawtons Instrumental Activities of Daily Living (IADL) scale (10). Cognitive function
was determined by Pfeiffers test (short portable mental
status questionnaire), which yields scores ranging from
0 to 10, with 10 representing the best performance (11). This
test has good sensitivity and specificity for detecting cases
of dementia compared with diagnosis by a clinician (12).
Demographic data (age, education, family situation, and
income), medical history, life habits (social support,
activities, lifestyle, accommodation, etc.), and treatments
were recorded. As a way to assess treatment, subjects were
asked to bring their prescribed medications to the visit. All
peripheral treatments coded as C4A in the European Pharmaceutical Marketing Research Association (EphMRA) classification, from which the Anatomical Therapeutic Chemical
(ATC) system originated (http://www.ephmra.org).
The study was approved by the local ethics committees,
and all participating women signed informed consent forms.
Every 4 months, participants completed a questionnaire
about falls, fractures and other new conditions. At yearly
intervals, they also listed the medications they were taking.

Toulouse Cohort Study

The Toulouse cohort (n 5 1462) was followed-up at the University Hospital and all cases of dementia of the Alzheimer
type were recorded. All participants were invited to take part
in an additional follow-up study. Those who had given informed consent were assessed either at home or at the Department of Internal Medicine and Clinical Geriatrics. During
this visit, demographic data and information on medical
conditions and prescribed drugs were recorded. Instrumental
activities of daily living (IADL) and cognitive function were
reassessed. Cognitive function was tested by use of Pfeiffers
test (11), Folsteins Mini-Mental State Examination (13),
and the test from Grober and colleagues (14).

373

This information was analyzed independently by

a geriatrician and a neurologist from the Department of
Internal Medicine and Clinical Geriatrics, who had
expertise in AD and were unaware of medication taken.
Diagnostic and Statistical Manual, 4th edition (DSM-IV)
criteria were used to establish a clinical diagnosis of
dementia. AD was diagnosed according to the criteria of
the NINCDS-ADRDA work group (15). When the two
assessors disagreed on a diagnosis, a joint decision was
reached after additional information was obtained from the
general practitioner. Subjects were then classified into four
groups: normal cognitive function, mild cognitive impairment according to Petersens criteria (16), AD, and other
types of dementia.
Initially, 1462 women were included in the EPIDOS study
in Toulouse. During the initial 4-year follow-up, 72 women
were diagnosed with dementia of the Alzheimer type. Of the
642 women who were followed up for 7 years, 450 were
considered as normal, 38 had dementia of the Alzheimer
type, and 154 had other disturbances of cognitive function
(mild cognitive impairment or another type of dementia,
including mixed dementia). Thus, at the end of the study, data
on cognitive status were available for 714 women (48.8% of
the initial cohort), of whom 110 had dementia of the
Alzheimer type. Of the other 748 women, whose cognitive
status remained undetermined, 25.8% (n 5 193) died during
follow-up, 54.7% (n 5 414) were lost to follow-up, and
18.9% (n 5 141) withdrew from the follow-up study.

Statistical Analysis
Analysis was performed with SAS software (SAS Version
8.0; SAS Institute, Inc., Cary, NC). Bivariate analyses were
based on conventional tests comparing means for quantitative variables (analysis of variance), and frequency distributions for qualitative variables (chi-square test or Fisher exact
test, according to sample size). Comparisons were made
between AD patients and a control group consisting of five
controls for one case. For all cases, medication history was
available from six follow-up consultations: baseline (T0),
each year of follow-up study (T1, T2, T3, and T4), and at the
final examination (T7). For the cases diagnosed as AD
during follow-up and for their five corresponding controls,
only data preceding the diagnosis were used. In order to
study the factors associated with the onset of dementia, only
data for women with a score >8 on Pfeiffers test at baseline
(17,18), who were thus considered as cognitively normal,
were used. The analysis included 69 women with AD of the
110 women who were diagnosed with AD, and 345 controls
with normal cognitive evaluation.
To account for potential confounding factors, the
variables statistically related to AD and those related to
exposure to C4A treatment, with a value of p , .25, were
included in the logistic regression model, with Alzheimers
dementia as a dependent variable. The model was fitted by
using the HosmerLemeshow test (19).
RESULTS
Those patients lost to follow-up were initially in worse
health than those included in the study. However, there were

ANDRIEU ET AL.

374

Table 2. Characteristics of Women With and Without ATD

Baseline Parameters
Age
<80 y
8185
.85 yr
End of primary school certificate
No (,5 y)
Yes (.5 y)
Income (euros/mo)
.915
457915
,457
Unknown
Perceived health
Good
Poor
Marital status
Married
Widowed
Divorced
Single
Washing, dressing, & walking
Independent
Dependent
IADL
0 incapacity
>1 incapacity
Depression
No
Yes
Hearing problem
No
Yes

Non-ATD
No. (%)

ATD
No. (%)

OR

95% CI

247 (71.6)
79 (22.9)
19 (5.5)

40 (57.9)
20 (29.0)
9 (13.1)

.0292

.1401
.0145

1
1.56
2.93

0.862.83
1.246.92

29 (8.4)
316 (91.6)

11 (15.9)
58 (84.1)

1
0.48

0.231.02

173
80
9
83

17
26
4
22

1
2.70
4.52
3.31

1.365.35
1.2616.25
1.706.44

(50.1)
(23.2)
(2.6)
(24.1)

(24.6)
(37.7)
(5.8)
(31.9)

284 (85.5)
48 (14.5)

46 (66.7)
23 (33.3)

100
190
20
35

14
41
7
7

.0531
.0005

.0045
.0207
.0004

1
2.96

1.655.32

(20.3)
(59.4)
(10.1)
(10.1)

.0002
.3125

.1942
.0802
.4781

1
1.54
2.50
1.43

0.802.96
0.907.00
0.533.83

329 (95.4)
16 (4.6)

60 (87.0)
9 (13.0)

.0219

1
3.08

1.307.30

315 (91.3)
30 (8.7)

56 (81.2)
13 (18.8)

.0117

1
2.44

1.204.96

309 (89.8)
35 (10.2)

59 (85.5)
10 (14.5)

.2934

1
1.50

0.703.19

158 (45.8)
187 (54.2)

37 (53.6)
32 (46.4)

.2345

1
1.73

0.441.22

(29.0)
(55.1)
(5.8)
(10.1)

Notes: ATD 5 Alzheimers-type dementia; OR 5 odds ratio; CI 5 confidence interval; IADL 5 instrumental activities of daily living. Non-ATD = 345
(83.33%); ATD 5 69 (16.67%).

no differences concerning C4A prescription between the

748 women lost to follow-up and the 714 women for whom
follow-up data were available (38.8% vs 39.0%).

Exposure to C4A Medications

In the study population, 50.7% (n 5 210) of women
reported having taken a C4A medication (Table 1); 32.9%
(n 5 69) of this subgroup had been given EGb 761, 55.7%
(n 5 117) had been given another C4A medication, and
11.4% (n 5 24) had been given both types of treatment.
Factors Associated With AD
Women diagnosed with AD during follow-up were
considerably older at inclusion than nondemented subjects
(80.8 6 4.1 years vs 79.2 6 3.4 years; p 5 .02). They
generally had lower financial status and level of education,
and poorer perception of their health with difficulty
performing activities of daily living (ADL) (Tables 2 and 3).
They also performed slightly less well on the Pfeiffer test
(8.9 6 0.9 vs 9.3 6 0.7; p 5 .03). Analysis of the medication histories of patients with AD showed they were less
likely to have taken C4A treatments for three consecutive
periods, but there were no other significant differences regarding other treatments (aspirin, calcium channel blockers,

mineral supplements, or nonsteroidal anti-inflammatory

drugs).

Factors Associated With C4A Treatment

Women who had received C4A treatment were older at
inclusion (79.8 6 4.0 years vs 78.9 6 3.0 years; p 5 .01),
but they were otherwise not significantly different from the
untreated group (Table 4).
Logistic Regression
Table 5 shows the results of the final model. Three
variables were excluded, using the stepwise process model
(ADL, IADL, and education level). Logistic regression
showed that women with dementia appeared to have been
regularly exposed to C4A treatment less often than had
others (odds ratio 5 0.31, 95% confidence interval [CI]
0.120.82, p 5 .018). In an additional analysis, the variable
C4A exposure was replaced with EGb or Ginkgo exposure. The results were similar but did not reach statistical significance with odds ratio 5 0.78, 95% CI 5 0.32
1.91, and p 5 .59; odds ratio 5 0.51, 95% CI 5 0.112.51,
and p 5 .41; and odds ratio 5 0.38, 95% CI 5 0.081.76,
and p 5 .22 for at least one exposure, two consecutive
exposures, and at least three consecutive exposures, respectively.

C4A TREATMENT AND RISK OF ALZHEIMERS DISEASE

375

Table 3. More Characteristics of Women With and Without ATD

Treatment
Estrogens
No
Yes
Mineral supplements
Not exposed
Nonconsecutive exposure(s)
2 consecutive exposures
>3 consecutive exposures
Calcium antagonist
Not exposed
Nonconsecutive exposure(s)
2 consecutive exposures
>3 consecutive exposures
Aspirin
Not exposed
Nonconsecutive exposure(s)
2 consecutive exposures
>3 consecutive exposures
NSAIDs
Not exposed
Nonconsecutive exposure(s)
2 consecutive exposures
>3 consecutive exposures
C4A treatment
Not exposed
Nonconsecutive exposure(s)
2 consecutive exposures
>3 consecutive exposures
EGb or Ginkgo
Not exposed
Nonconsecutive exposure(s)
2 consecutive exposures
>3 consecutive exposures

Non-ATD
No. (%)

ATD
No. (%)

342 (99.1)
3 (0.9)

68 (98.6)
1 (1.4)

249
77
12
7

(72.2)
(22.3)
(3.5)
(2.0)

50
14
4
1

(72.5)
(20.3)
(5.8)
(1.4)

242
23
31
49

(70.1)
(6.7)
(9.0)
(14.2)

49
8
6
6

(71.0)
(11.6)
(8.7)
(8.7)

232
62
25
26

(67.2)
(18.0)
(7.2)
(7.5)

44
15
5
5

(63.8)
(21.7)
(7.2)
(7.2)

270
43
14
18

(78.3)
(12.5)
(4.1)
(5.2)

51
11
6
1

(73.9)
(15.9)
(8.7)
(1.5)

169
57
39
80

(49.0)
(16.5)
(11.3)
(23.2)

35
16
12
6

(50.7)
(23.2)
(17.4)
(8.7)

264
37
20
24

(76.5)
(10.7)
(5.8)
(7.0)

57
8
2
2

(82.6)
(11.6)
(2.9)
(2.9)

OR

95% CI

.5192
.8006

.2181
.9240
.2743
.3634

.2181
.9240
.2743
.9078

.4625
.9181
.9785
.1811

.4134
.1091
.2387
.0289

.3689
.2959
.0280
.5254

.9973
.3086
.2046

1
1.68

0.1716.4

1
0.91
1.66
0.71

0.481.73
0.515.36
0.095.91

1
1.72
0.96
0.61

0.734.06
0.382.41
0.251.49

1
1.28
1.06
1.01

0.672.44
0.382.90
0.372.78

1
1.35
2.27
0.30

0.662.80
0.836.18
0.042.25

1
1.36
1.49
0.36

0.702.63
0.713.12
0.150.90

1
1.00
0.46
0.39

0.442.27
0.112.04
0.091.68

Notes: ATD5 Alzheimers-type dementia; OR 5 odds ratio; CI 5 confidence interval; NSAIDs 5 nonsteroidal anti-inflammatory drugs; C4A 5 cerebral and
peripheral vasotherapeutics; EGb 5 standardized Ginkgo biloba extracts.

DISCUSSION
Alzheimers dementia is a neurodegenerative disease with
long-term evolution before definitive lesions. With an
unprecedented demographic change in the Western population, prevention and effective treatment of age-dependent
disease is a public health priority. Many elderly people
worried about cognitive impairment are requesting therapy,
and millions of people in Europe and the United States are
regularly taking Ginkgo biloba extracts. The value of this
treatment deserves study.
Our objective was to investigate the potential association
between use of C4A treatments, in particular EGb 761
(standardized Ginkgo biloba extracts), and Alzheimers
dementia onset in elderly women. We found that women
regularly taking C4A treatment were three times more
numerous in the group without dementia than in the group
with dementia. The odds ratio for EGb 761 was similar but
did not reach statistical significance.
Women participating in the EPIDOS study were volunteers and therefore not representative of the general population. Cognitive status was evaluated in only 50% of the
initial population, so we could not study the relative risk of
AD associated with C4A prescription. However, our study
was prospective and could precisely determine the cognitive

status of the women (normal or AD). Therefore, a casecontrol study nested in the cohort was possible. One of the
strong points of the study is the fact that the population had
cognitive assessments at the outset by the Pfeiffer test and
only those with scores of 8 or more were included. Because
C4A treatments are physician prescribed, we could be sure
that all patients received the standardized extract of Ginkgo
biloba. The medication history was recorded each year, so
we assumed patients who had three consecutive recordings
of C4A medication received the treatment long term. It was
this group of patients who showed significant results.
However, in the early stages of dementia, women could
have forgotten whether they had taken specific medication.
We postulate that they were not more likely to have forgotten
their C4A treatment than their other treatments, and yet there
was no difference in the two groups for any other type of
medication (aspirin, calcium channel blockers, mineral
supplements, nonsteroidal anti-inflammatory drugs).
Epidemiological studies should help to identify risk factors
for AD. Our study has once again identified age attained as an
independent risk factor. It has not, however, shown any
relationship between aspirin or nonsteroidal anti-inflammatory treatment and risk for AD. This may be due to the relatively infrequent use of these drugs in the study population.

ANDRIEU ET AL.

376

Table 4. Bivariate Analysis: Characteristics of Women According to Exposure to C4A Treatment at the Time of Diagnosis
C4A Treatments
Baseline Parameters
Age
<80 y
8185
.85 y
End of primary school certificate
No
Yes
Income euros/mo)
.915
457915
,457
Unknown
Perceived health
Good
Poor
Marital status
Married
Widowed
Divorced
Single
Washing, dressing, & walking
Independent
Dependent
Binary IADL
0 incapacity
>1 incapacity
Hearing problem
No
Yes
Depression
No
Yes

Not Exposed
No. (%)

1 Exposure
No. (%)

>3 Exposures
No. (%)

2 Exposures
No. (%)

p
.01

154 (75.5)
44 (21.6)
6 (2.9)

43 (58.9)
21 (28.8)
9 (12.3)

37 (72.6)
10 (19.6)
4 (7.8)

53 (61.6)
24 (27.9)
9 (10.5)

16 (7.8)
188 (92.2)

12 (16.4)
61 (83.6)

5 (9.8)
46 (90.2)

7 (8.1)
79 (91.9)

29
23
3
18

23
12
0
16

47
17
4
18

.20

.50
91
54
6
53

(44.6)
(26.5)
(2.9)
(26.0)

(39.7)
(31.5)
(4.1)
(24.7)

(45.1)
(23.5)
(0.0)
(31.4)

(54.7)
(19.8)
(4.7)
(20.9)
.25

163 (82.7)
34 (17.3)

54 (76.1)
17 (23.9)

39 (79.6)
10 (20.4)

74 (88.1)
10 (11.9)

63
110
13
18

17
43
5
8

15
32
1
3

19
46
8
13

.42
(30.9)
(53.9)
(6.4)
(8.8)

(23.3)
(58.9)
(6.8)
(11.0)

(29.4)
(62.7)
(2.0)
(5.9)

(22.1)
(53.5)
(9.3)
(15.1)
.17

194 (95.1)
10 (4.9)

67 (91.8)
6 (8.2)

45 (88.2)
6 (11.8)

83 (96.5)
3 (3.5)

183 (89.7)
21 (10.3)

65 (89.0)
8 (11.0)

45 (88.2)
6 (11.8)

78 (90.7)
8 (9.3)

108 (52.9)
96 (47.1)

33 (45.2)
40 (54.8)

23 (45.1)
28 (54.9)

31 (36.1)
55 (63.9)

177 (86.8)
27 (13.2)

69 (94.5)
4 (5.5)

47 (94.0)
3 (6.0)

75 (87.2)
11 (12.8)

.97

.07

.18

Notes: C4A 5 cerebral and peripheral vasotherapeutics; not exposed, n 5 204 (49.3%); 1 exposure, n 5 73 (17.6%); 2 exposures, n 5 51 (12.3%); >3 exposures, n 5 86 (20.8%). IADL 5 instrumental activities of daily living.

Conclusion
In conclusion, our study including 414 patients over 75
years old showed that women with diagnosed dementia had
been less frequently exposed to chronic use of C4A
treatment. This effect remained significant after adjustment
for potential confounding effects. Although these results
should be interpreted with caution because of the study
design, the evidence for the protective effects of other
treatments was not stronger than that shown for C4A
treatment. Primary prevention trials should be undertaken to
confirm these findings. In fact, large interventional studies
are ongoing with EGb 761 in North America and Europe to
determine the preventive effect of these treatments, but
results will not be available for 6 to 7 years. A recent study
with Ginkgo extract treatment has shown no effects on
memory (20); however, this study was done in younger
people (68.5 years) with no cognitive complaints and with
only 6 weeks of treatment. The effect of Ginkgo on
oxidative stress and on vascular function will require much
longer time review to be effective. Following our long-term
observational study, some long-term placebo-controlled
studies are on the way over a 1-year period to prevent
dementia in older elderly persons (more than 75 years) with
cognitive complaints.

However, a preliminary study of the effect on memory of

6 weeks of treatment with Ginkgo gave negative results
(20). If the protective effect of C4A treatment is confirmed,
this class of medication is a strong contender for widespread
Table 5. Multivariate Analysis (Logistic Regression)
Model
Variable to be Explained
Pfeiffer test in 1992
Age (y)
Income (ref: .915 euros)
457915
,457
Unknown
Perceived health (poor vs good)
Hearing problem
C4A treatment (ref: not exposed)
Nonconsecutive exposure(s)
2 consecutive exposures
>3 consecutive exposures
Adequacy of the model
(HosmerLemeshow test)

OR

95% CI

.0082
.0004
.0063
.0033
.0168
.0106
.0333
.0765
.0698
.7261
.4915
.0180
.7175

0.60
1.16

0.410.87
1.071.26

2.91
5.56
2.62
2.02
0.58

1.435.94
1.3622.70
1.255.47
1.063.86
0.321.06

0.87
1.34
0.31

0.411.86
0.593.04
0.120.82

Notes: For variable to be explained, dementia of the Alzheimers type

(n 5 69) is versus dementia not of the Alzheimers type (n 5 332). OR
5 odds ratio; CI 5 confidence interval.

C4A TREATMENT AND RISK OF ALZHEIMERS DISEASE

preventive treatment use because of its minimal side effects

compared with others such as nonsteroidal anti-inflammatory drugs or estrogens.
ACKNOWLEDGMENTS
This work was part of the EPIDOS study supported by an Institut
Nationale de la Sante et de la Recherche Medicale (INSERM)/MSDChibret contract. Additional follow-up was supported by an INSERM/
Beaufour Ipsen contract. EPIDOS study participants included coordinators
G. Breart, P. Dargent-Molina, P. J. Meunier, A. M. Scott, D. Hans, and P.
D. Delmas, and principal investigators C. Baudoin and J. L. Sebert
(Amiens), M. C. Chapuy and A. M. Scott (Lyon), F. Favier and C. Marcelli
(Montpellier), C. J. Menkes, C. Cormier, and E. Hausherr (Paris), and H.
Grandjean and C. Ribot (Toulouse).
The authors thank Ms. Christelle Cantet for her collaboration in this
study.
Address correspondence and to Sandrine Andrieu, MD, PhD, Department of Internal Medicine and Clinical Gerontology, Acute Unit for
Alzheimers Patients, 170 Chemin de Casselardit, 31059 Toulouse Cedex
03, France. E-mail: sandrieu@cict.fr

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Received May 15, 2002
Accepted October 18, 2002