Alzheimer’s & Dementia 3 (2007) 341–347

General risk factors for dementia: A systematic evidence review

Christopher Pattersona,*, John Feightnerb, Angeles Garciac, Chris MacKnightd
a
Division of Geriatric Medicine, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
b
Department of Family Medicine, Faculty of Medicine, University of Western Ontario, London, Ontario, Canada
c
Department of Medicine (Geriatrics), Queen’s University, Kingston, Ontario, Canada
d
Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia, Canada

Abstract This review identifies and quantifies general (ie, nongenetic) risk factors for all-cause dementia,
Alzheimer’s disease, and vascular dementia specifically.
© 2007 The Alzheimer’s Association. All rights reserved.
Keywords: Dementia; Alzheimer’s disease; Vascular dementia; Risk factors

1. Background reason, the present systematic review focuses solely on

longitudinal cohort studies.
Since the Canadian Consensus Conference on Demen-
We posed the question “What modifiable risk factors are
tia was convened in 1999, many advances have been
associated with dementia, Alzheimer’s disease, or vascular
made in the understanding of dementing disorders. One
dementia?” A comprehensive electronic literature search
area that was considered worthy of further investigation
was performed on Medline and EMBASE from 1966 to
was that of risk factors for dementia, because knowledge
December 2005. The search string is listed in the Appendix.
of these risk factors has direct relevance to the primary
This search identified 3,424 articles. It was possible to reject
prevention of these disorders. The topic of preventing
1,705 of these as obviously irrelevant. The remaining 1,719
dementia was previously addressed at the Canadian Con-
references with their abstracts were reviewed by a single
sensus Conference on Dementia [1], and an update on
primary prevention appears as a companion piece to the reader (C.P.), who identified possibly relevant articles and
present article [2]. set aside the remainder. These latter references and abstracts
were then reviewed by three other readers (J.F., A.G., C.M.)
to ensure that no possibly relevant articles had been dis-
2. Methods carded. The following criteria were used for relevance: (1)
longitudinal cohort studies; (2) a population broadly repre-
The identification and relative importance of risk factors
sentative of Canadian demographics; (3) dementia, Alzhei-
are best addressed through longitudinal cohort studies. Al-
mer’s disease, or vascular dementia as outcome; and (4)
though case-control studies can be used to explore risk
general risk factors identified (eg, hypertension, educational
factors for disease, significant differences have been ob-
status, occupation, chemical exposure.) Articles addressing
served when conclusions of case-controlled studies are
genetic risk factors were excluded.
compared with longitudinal studies. An example of differ-
After assembling all possibly relevant publications, the
ent conclusions is found with tobacco, where case-control
full articles were obtained, and each was assessed indepen-
studies have suggested that tobacco is associated with a
dently by two reviewers for quality. Additional articles from
lower risk of dementia, whereas numerous longitudinal
personal files and those identified by scrutiny of bibliogra-
studies have shown that the risk is increased [3]. For this
phies of retrieved articles were added to the pool for quality
assessment. After consulting several key references on ap-
praisal of risk factor literature, the following criteria were
*Corresponding author. Tel.: (905) 521-7931; Fax: (905) 521-7905. chosen to determine whether an article was good, fair, poor,
E-mail address: pattec@hhsc.ca or ineligible.
1552-5260/07/$ – see front matter © 2007 The Alzheimer’s Association. All rights reserved.
doi:10.1016/j.jalz.2007.07.001
342 C. Patterson et al. / Alzheimer’s & Dementia 3 (2007) 341–347
2.1. Population characteristics
Inclusion criteria were defined, including ages, locations,
dates; exclusion of dementia at inception; and population
broadly representative of Canadian demographics.
2.2. Follow-up
All participants were accounted for at end of follow-up,
without excessive “preventable” losses. No differences in
follow-up were found between those developing dementia
and those with no dementia.
2.3. Exposures (risk factors)
List of risk factors was considered. Exposures were mea-
sured in the same way for those with and without dementia.
2.4. Outcomes
Dementia and subtypes were defined by standardized
criteria. Ascertainment of outcome was independent of ex-
posure status.
2.5. Analysis
Important confounders were included in analysis (age,
sex, education at minimum). Statistical analysis was appro-
priate (ie, multiple logistic regression). Specific measures of
risk are stated (eg, relative risk).
The overall quality rating was determined as good (all
criteria fulfilled adequately); fair (most criteria fulfilled ad-
equately, no fatal flaw); or poor (fatal flaw or multiple minor
inadequacies). Each article was reviewed for quality inde-
pendently by two readers, and a consensus was reached if
disagreement occurred. Articles graded as good or fair were
then submitted for data abstraction by two independent
reviewers.
3. Results
Risk factors are either immutable (eg, age, gender, eth-
nicity) or potentially modifiable. This article deals only with
potentially modifiable risk factors. A total of 60 articles of
single longitudinal studies were identified to be of good or
fair quality. In addition, eight systematic reviews of good or
fair quality also addressed relevant risk factors. Table 1
summarizes risk factors and their relative risk (RR) for
dementia of different types. Other measures of risk (eg,
odds ratio [OR], hazard ratio [HR]) are indicated where
necessary.
4. Potentially modifiable risk factors
4.1. Blood pressure
The relationship between blood pressure and subsequent
development of dementia is somewhat confusing. Both
higher and lower systolic (SBP) and diastolic blood pressure
(DBP) levels have been implicated in increased risks of
subsequent dementia. For example, from the Kungsholmen
project, SBP in excess of 180 mm Hg is associated with an
increased RR of all-cause dementia (ACD) of 1.6 and for
Alzheimer’s disease (AD) of 1.5 after 6 years [4]. However,
in the same study population, a SBP of less than 140 mm Hg
was also associated with increased risk of ACD (RR, 1.9)
and AD (RR, 2.2) [5]. From the combined results of the
Rotterdam and Gothenberg H-70 studies in individuals who
are taking antihypertensive agents, each increase of 10
mm Hg in SBP appears to lower the RR of ACD (0.93) and
AD (0.89) [6]. A longitudinal study in Finland reported an
increased relative risk of AD of 2.3 in the long term after
elevated SBP [7]. However, a decline in SBP of 15 or more
mm Hg appears to predate the onset of both ACD and AD,
according to data from the Kungsholmen project [8]. From
the same study group a DBP of less than 65 mm Hg is also
associated with a RR of 1.54 for ACD and 1.7 for AD, as
does a pulse pressure of less than 70 mm Hg [9]. Thus, it
would appear that increased SBP increases the risk of sub-
sequent ACD, AD, and vascular dementia (VaD) in women,
but so apparently does reduced systolic, diastolic, and pulse
pressure below normal levels, overall a somewhat contra-
dictory and confusing situation.
4.2. Diabetes mellitus
Several studies have linked the presence of type 2 dia-
betes mellitus to subsequent development of dementia.
Analysis of data from the Canadian Study of Health and
Aging (CSHA) concluded that diabetes increased the risk of
ACD and AD, although the increased risks did not reach
statistical significance. For VaD, however, the RR was 2.03
[10]. Diabetes in midlife was shown to increase the subse-
quent risk of ACD (OR, 2.83) in a stratified sample of civil
servants from Tel Aviv [11]. From the Kungsholmen Study
in Sweden, Xu et al [12] concluded that there was an
increased risk of ACD and VaD (HR, 1.5 and 2.6, respec-
tively), although the increased risk for AD did not reach
statistical significance. Data collected within a large ran-
domized controlled trial of raloxifene suggested an in-
creased risk of ACD in those with diabetes mellitus, but the
increased OR of 2.38 did not reach statistical significance
[13]. Thus, there is fair evidence that the presence of type 2
diabetes mellitus increases the risk of ACD and VaD.
4.3. Stroke
The presence of clinical strokes or of silent infarctions on
neuroimaging increases the risk of subsequent dementia.
The temporal relationship between stroke and onset of de-
mentia is a diagnostic criterion for VaD. Longitudinal stud-
ies have shown that stroke increases the subsequent risk of
ACD (RR, 2.4) [14] and AD (RR, 1.83) [15]. The presence
of silent brain infarctions visible on magnetic resonance
imaging scanning is associated with an increased risk of
 C. Patterson et al. / Alzheimer’s & Dementia 3 (2007) 341–347
Table1
Risk factors for dementia: RR (95% CI) [references]
ACD
Systolic hypertension 1.6 (1.1 to 2.2) [4]
DBP ⬍ 65 mm Hg 1.5 (1.0 to 2.1) [4]
PP ⬎ 84 mm Hg 1.3 (0.9 to 1.7) [9]
PP ⬍ 70 mm Hg 1.4 (1.0 to 1.9) [9]
SBP decline ⱖ 15 mm Hg 3.1 (1.5 to 6.3) [8]
SBP ⬍ 140 mm Hg 1.9 (1.2 to 3.2) [5]
Diabetes mellitus, type 2 1.26 (0.9 to 1.76) [10]
2.38 (0.92 to 6.12) [13]
2.83 (1.4 to 5.71) [11]
Stroke 2.4 (1.6 to 3.7) [14]
Silent infarcts on neuroimaging 2.17 (1.04 to 4.54) [18]
HR, 2.26 (1.09 to 4.70) [16]
Serum cholesterol 1 3.1 (1.5 to 6.3) [19]
Serum homocysteine 1 2.08 (1.31 to 3.30) [20]
Serum thyroid-stimulating hormone 2
Sex hormones: higher total estrogen 1.45 (1.08 to 1.94) [22]
level (women)
Sex hormones: higher free testosterone 0.74 (0.57 to 0.96) [23]
index (men)
Depression 1.87 (1.09 to 3.20) [26]
Men: OR, 3.5 (1.9 to 6.5)
Women: OR, 1.2 (0.7 to 2.0) [24]
High fat intake 2.4 (1.1 to 5.4) [27]
Fish consumption ⬎ once/week 0.4 (0.2 to 0.9) [27]
0.73 (0.52 to 1.03) [28]
Vitamin E: lowest tertile serum level 2.54 (1.06 to 6.10) [29]
Moderate wine consumption, 250 to OR, 0.19 (.05 to 0.66) [30]
500 mL/day 0.56 (0.36 to 0.92) [28]
Activity: highest level, physical 0.58 (0.41 to 0.83) [33]
0.63 (0.40 to 0.98) [32]
Activity: highest level, mental, daily 0.59 (0.37 to 0.96) [34]
Smoking
Occupation Manual work: 1.6 (1.0 to 2.5) [49]
Exposure to toxins (pesticides,
fertilizers, fumigants), defoliants
Head injury With LOC: 1.14 (0.84 to 1.56) [37]
Moderate: HR, 2.39 (1.24 to 4.58) [38]
Severe: HR, 4.48 (2.09 to 9.63) [38]
Education ⬎ 15 vs ⬍ 12 0.64 (0.4 to 1.0) [48]
Statin drugs 1.19 (0.82 to 1.75) [41]
HR, 1.19 (0.53 to 2.34) [40]
All lipid-lowering drugs
NSAIDs 0.51 (0.37 to 0.70) [44]
Benzodiazepines Ever used: OR, 1.7 (1.2 to 2.4)
Former use: OR, 2.3 (1.2 to 4.5) [45]
Vaccination
Abbreviation: LOC, loss of consciousness; NSAIDs, nonsteroidal anti-inflammatory drugs.
343
AD VAD
RR, 1.5 (1.0 to 2.3) [4]; 2.05 (1.2 to 3.53) [25],
OR, 2.3 (1.0 to 5.5) [7] women only
1.7 (1.1 to 2.4) [4]
1.4 (1.0 to 2.0) [9]
1.7 (1.2 to 2.3) [9]
3.1 (1.3 to 7.0) [8]
2.2 (1.2 to 3.8) [5]
1.3 (0.83 to 2.03) [10] 2.03 (1.15 to 3.57) [10]
1.3 (0.9 to 2.1) [12] HR, 2.6 (1.2 to 6.1) [12]
1.83 (1.14 to 2.95) [15] Required for diagnosis
2.1 (1.0 to 4.4) [7]
3.1 (1.2 to 8.5) [19]
2.11 (1.19 to 3.76) [20]
3.5 (1.1 to 11.5) [21]
1.30 (0.88 to 1.99) [22]
Men: OR, 4.2 (2.1 to 8.8) OR, 2.41 (1.22 to 4.52) [25]
Women: OR, 1.0 (0.5 to 1.9) [24]
0.3 (0.1 to 0.9) [27] Shellfish: OR, 0.45
(.22 to .88) [25]
2.10 (0.81 to 5.54) [29]
0.53 (0.3 to 0.95) [28]
0.5 (0.28 to 0.90) [32] OR, 0.46 (0.25 to 0.82),
0.55 (0.34 to 0.88) [33] women [25]
0.69 (0.5 to 0.96) [31]
1.10 (0.94 to 1.29) [37]
1.99 (1.33 to 2.98) [3]
Manual work: 1.4 (0.9 to 2.1) [49]
4.35 (1.05 to 17.90) [36] OR, 2.05 (1.03 to 3.85) [25]
With LOC: 1.02 (0.68 to 1.15) [37]
Moderate: HR, 2.32 (1.04 to 5.1) [38]
Severe: HR, 4.51 (1.77 to 11.47) [38]
0.48 (0.27 to 0.84) [48]
0.82 (0.46 to 1.46) [41]
HR, 1.19 (0.35 to 2.96) [40]
OR, 0.26 (0.08 to 0.88) [39], age less
than 80 y
0.42 (0.26 to 0.66) [42]
Any vaccination: 0.40
(0.17 to 0.96) [36]
Influenza: 0.75 (0.54 to 1.04)
Poliomyelitis: 0.6 (.37 to .99)
Diphtheria or tetanus: 0.41
(.27 to .62) [47]
344 C. Patterson et al. / Alzheimer’s & Dementia 3 (2007) 341–347
ACD (HR, 2.26) [16]. From a prospective study of stroke
patients in hospital in Lille, France, in which prestroke
cognitive function was assessed with the IQCODE [17],
the presence of silent infarctions increased the risk of sub-
sequent ACD (RR, 2.7) [18]. Thus, there is compelling
evidence that the presence of strokes increases the risk of
both ACD and VaD.
4.4. Serum cholesterol
Midlife elevation in serum cholesterol has been associ-
ated with increased risk of subsequent AD (OR, 2.1) [7] and
(OR, 3.1) [19]. The risk of ACD was also elevated (RR, 3.1)
with higher levels of cholesterol [19]. There appears to be
good evidence that elevated serum cholesterol is associated
with an increased risk of ACD and AD.
4.5. Hyperhomocysteinemia
A single prospective study has established an association
between serum homocysteine levels in excess of 15 ␮mol/L
and ACD (RR, 2.08) and AD (RR, 2.11; 95% confidence
interval [CI], 1.19 to 3.76) [20].
4.6. Hyperthyroidism
A single study showed an association between a de-
pressed level of serum thyroid-stimulating hormone and
subsequent development of AD [21].
4.7. Sex hormone levels
In women, levels of total estrogen are associated with a
higher risk of ACD (RR, 1.45) [22], whereas in men, higher
levels of free testosterone index are associated with lower
risk of AD (RR, 0.74) [23].
4.8. Depression
The presence of depressive symptoms was associated
with subsequent development of dementia only in men in
the PAQUID Study. For men, the OR of developing ACD
was 3.5, and the RR for AD was 4.3. In women there was
no statistically significant association [24]. For VaD, data
from the CSHA indicated that the presence of depression
increased the risk of VaD (OR, 2.41) [25]. A systematic
evidence review concluded that depression is associated
with an RR of 1.87 for ACD [26].
4.9. Lifestyle factors
4.9.1. Diet
A high intake of total fat (⬎ 85.5 g/day) increases the RR
for ACD by 2.4 compared with a fat intake of ⬍ 75.5 g/day
[27], but in this longitudinal population study from the
Netherlands, increased amounts of saturated fat and choles-
terol were not established as definite risk factors. The con-
sumption of fish greater than 18.5 g/day compared with less
than 3.0 g/day lowered the risk of both ACD (RR, 0.4) and
AD (RR, 0.3). Other studies have also suggested the benefit
of eating fish regularly. In the PAQUID longitudinal study,
weekly consumption of fish was associated with an RR of
0.73 for ACD, although this was of marginal significance
[28]. Regular consumption of shellfish was also associated
with a reduced risk of VaD in the CSHA, with an OR of
0.45 [25]. There appears to be consistent epidemiologic
evidence that regular consumption of fish and seafood is
associated with reduced risk of dementia. A single study
reported an association between the lowest tertile of serum
vitamin E levels and elevated risk of both ACD and AD, but
statistical significance was not reached [29].
4.9.2. Wine
The PAQUID study in France established that the con-
sumption of moderate amounts of red wine (250 to 500
mL/day) was associated with a RR of 0.56 for ACD and a
RR of 0.53 for AD [28]. In the same study population,
moderate consumption, compared with other degrees of
usage, was associated with a lower risk of ACD (RR, 0.19)
[30]. Furthermore, in the CSHA population, consumption of
wine at least weekly was associated with a reduced risk of
AD (OR, 0.49), although this lost statistical significance
when decedents were included in the analysis [31].
4.9.3. Activity
There is evidence that regular physical activity is asso-
ciated with a reduced risk of dementia. In the CSHA, reg-
ular physical activity was associated with an OR of 0.69 for
AD [31], and when this was quantified, those with the
highest level of physical activity had a reduced risk of ACD
(OR, 0.63) and of AD (OR, 0.5) [32]. In the Cardiovascular
Health Study from the USA, when those expending the
highest quartile of energy expenditure were compared with
the lowest, the RR was 0.58 for ACD and 0.55 for AD [33].
Regular exercise was also associated with RR of VaD in the
CSHA; in women only, OR for VaD was 0.46 [25].
Daily mental activities were associated with a RR of 0.59
for ACD in the Kungsholmen Study [34]. In the Washington
Heights District of New York, a longitudinal study found an
association between high leisure activities and decreased
incidence of ACD, with a RR of 0.62 [35]. It is thus
plausible that maintaining a high level of mental activity
might be associated with reduced subsequent incidence of
ACD.
4.9.4. Smoking
A systematic review [3] compared the association of
smoking with dementia in case-controlled and prospective
cohort studies. Although there appeared to be a protective
effect in the case-controlled studies, the prospective cohort
studies established an increased risk for AD (RR, 1.99) in
studies that described the number of smokers at baseline [3].
This should settle, once and for all, the positive association
between smoking and AD.
 C. Patterson et al. / Alzheimer’s & Dementia 3 (2007) 341–347
4.9.5. Exposure to toxins
Evidence from CSHA established an association be-
tween exposure to pesticides or fertilizers and VaD (OR,
2.05) [25]. Exposure to defoliants and fumigants was asso-
ciated with an increased risk of AD (RR, 4.35) in a longi-
tudinal study from Manitoba, Canada [36].
4.9.6. Head trauma
Four population-based samples comprised the EURODEM
Study. In this study head trauma with unconsciousness was
associated with an increased RR of both ACD (1.14) and AD
(1.02); however, neither of these reached statistical signifi-
cance [37]. In the CSHA, prior head injury with or without
loss of consciousness did not show any increased risk of AD
(OR, 0.87; 95% CI, 0.56 to 1.36) [31]. However, in a
long-term study of U.S. servicemen who had been injured
during World War II, moderate head injury was associated
with an HR of 2.39 for ACD and 2.32 for AD [38]. For
severe injury the HR for ACD was 4.48 and 4.51 for AD. A
conclusive association between head injury and subsequent
dementia remains to be established.
4.10. Drug exposure
4.10.1. Lipid-lowering agents
Although a nested case-control study within the CSHA
suggested that in individuals younger than 80 years of age,
use of all types of lipid-lowering agents reduced the risk of
AD, with an OR of 0.26 at 5 years [39], other studies have
not confirmed this finding. In the Cache County Study, the
use of statin-type drugs was associated with a nonsignificant
increased HR of 1.19 for both ACD (95% CI, 0.53 to 2.34)
and AD (95% CI, 0.53 to 2.96) at 3 years [40]. There were
similar findings in an American community-based study in
which use of statin agents was associated with a nonsignif-
icant increased HR of 1.19 (95% CI, 0.83 to 1.75) for ACD
but a nonsignificant reduced HR of 0.82 (95% CI, 0.46 to
1.46) for AD [41].
4.10.2. Nonsteroidal anti-inflammatory drugs
Individual studies such as the Cache County popula-
tion have concluded that exposure to nonsteroidal anti-
inflammatory drugs (NSAIDs) is associated with reduced
risk of AD (RR, 0.42) [42]. A systematic review of six
longitudinal studies in 2003 concluded that there was a
nonsignificant reduction in RR of 0.84 (95% CI, 0.54
to1.05) for AD [43]. However, a more recent and compre-
hensive systematic review of 25 studies, both cohort and
case-controlled, concluded that NSAID exposure was asso-
ciated with a significantly reduced risk of both prevalent
(RR, 0.51) and incident (RR, 0.79) cases of ACD [44].
4.10.3. Benzodiazepines
In a French population-based study, exposure to benzo-
diazepine drugs at any time was associated with an in-
creased risk of ACD (OR, 1.7), and for former use the OR
was 2.3 [45]. However, a systematic review of six prospec-
345
tive studies concluded that increased risk of cognitive de-
cline was reported in three, decreased in two, and un-
changed in one [46].
4.10.4. Vaccinations
Prior inoculations against poliomyelitis, diphtheria, or
tetanus and influenza are all associated with a lower risk of
AD [47]. In addition, inoculations of any kind appear to
reduce AD risk [36].
4.11. Education
Longer periods of education have been associated with
reduced risk of AD, and this relationship has been con-
firmed. When compared with those receiving less than 12
years of education, people engaged in more than 15 years of
education had a reduced risk of both ACD (RR, 0.64) and
AD (RR, 0.48) [48].
4.12. Occupation
Data from the Kungsholmen project in Sweden sug-
gested that manual labor increased the risk of both ACD
(RR, 1.6) and AD (RR, 1.4), although the latter just missed
statistical significance [49]. Other studies have not con-
firmed this relationship.
5. Conclusion
This systematic review has explored the current state of
evidence concerning risk factors for ACD, AD, and VaD,
which are presented in Table 1. Although for many of these
risk factors the evidence remains inconclusive or contradic-
tory, for others an emerging picture of consensus is appear-
ing. It should be noted that with rare exceptions, there are no
data on the effects of multiple risk factors in the same
individual. One exception is a Finnish study in which the
combined risk of systolic hypertension (OR, 2.3) and hy-
percholesterolemia (OR, 2.1) increases the OR for AD to
3.5 [7]. Research priorities should focus on remediable risk
factors that have the highest chance of being corrected.
These include such risk factors as hypertension, hypercho-
lesterolemia, inadequate physical and mental activity, and
dietary factors. Attempts to limit the noxious effects of
smoking and head injury are justifiable for their own sake
and might also have benefits in the cognitive domain.
Author Disclosures
Angeles Garcia has received support from Janssen-Ortho
(Consultant, Advisor), Pfizer (Consultant, Advisor), Novartis
(Consultant, Advisor), and Lundbeck (Consultant, Advisor).
Chris MacKnight has received support from Alzheimer
Society of Nova Scotia (Board Member), Janssen-Ortho
(Speaker, Trial Investigator), Pfizer Canada (Speaker, Trial
Investigator), Novartis (Speaker, Trial Investigator), Lund-
beck Canada (Speaker, Trial Investigator), Voyager Phar-
346 C. Patterson et al. / Alzheimer’s & Dementia 3 (2007) 341–347
maceuticals (Trial Investigator), Myriad (Trial Investiga-
tor), and Neurochem (Trial Investigator).
Acknowledgments
During preparation of this article, Christopher Patterson
received financial support from the Institute of Advanced
Studies, University of Bologna, Bologna, Italy.
Chris MacKnight is supported from a CIHR New Inves-
tigator Award.
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Appendix. Search strategies
1966 to December 2005
RF & Dementia or AD AND
((Relative [title/abstract] AND risk* [title/abstract]) OR
(relative risk [Text Word]) OR risks [Text word] OR Cohort
studies [MeSH: no exp] OR (cohort [Title/Abstract] AND
stud* [Title/Abstract]) Limits – Abstracts, Review, Human
1966 to December 2005
((“risk factors” [MeSH Terms] OR risk factors {Text
Word]) AND (“dementia” [MeSH Terms] OR dementia
[Text Word]) OR (((“alzheimer disease” [TIAB] NOT Med-
line [SB]) OR “alzheimer disease” [MeSH Terms] OR alz-
heimer [Text Word]) AND s [All Fields] AND (“disease”
[MeSH Terms] OR disease [Text Word])) NOT (“therapy”
[Subheading] OR (“therapeutics” [TIAB] NOT Medline
[SB]) OR “Therapeutics” [MeSH Terms] OR therapy [Text
Word])) AND systematic [sb] AND ((“humans” [TIAB]
NOT Medline [SB]) or “humans” [MeSH Terms] OR Hu-
man [Text Word])
1996 to 2006
(Prevention of Alzheimer*) AND systematic [sb] OR
(prevention of dementia) AND systematic [sb] OR (“risk
factors AND (dementia OR alzheimer*)) AND systematic
[sb] All fields, publication date from 1996 to 2006, core
clinical journals OR (”risk factors AND (dementia OR Alz-
heimer*)) AND systematic [sb]