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Dietary Patterns, Cognitive Decline, and Dementia: A Systematic Review

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Dietary Patterns, Cognitive Decline, and Dementia: A Systematic Review

Abstract and Figures

Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline. © 2015 American Society for Nutrition.
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REVIEW
Dietary Patterns, Cognitive Decline, and Dementia:
A Systematic Review
1,2
Ondine van de Rest,
3
* Agnes AM Berendsen,
3
Annemien Haveman-Nies, and Lisette CPGM de Groot
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
ABSTRACT
Nutrition is an important modiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional
effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects,
such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the
complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been
investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of
the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation
to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline,
dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy
dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score)
and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline
and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to
reach more targeted and detailed guidelines to prevent or postpone cognitive decline. Adv Nutr 2015;6:154168.
Keywords: Mediterranean diet, healthy diet, dietary pattern, cognitive decline, dementia
Introduction
It has been estimated that, worldwide, 44 million people
lived with dementia in 2013. With the aging of the popula-
tion and with an estimated 7.7 million new cases per year
this number doubles every 20 y and will reach 135 million
patients with dementia by 2050 (1). The impact of dementia
worldwide and the public health importance has been de-
scribed by the WHO and Alzheimers Disease International
(2). These organizations propose to make dementia a global
health priority, which underlines the importance of finding
strategies to prevent dementia. Because there is currently
still no effective treatment to modify the course of dementia,
prevention is an urgent priority, both to reduce incidence
and to slow down progression. Important risk factors need
to be further identified and, in particular, the factors that
can be modified, such as lifestyle factors. In this systematic
review we focus on the risk factor nutrition, for which
promising indications exist that it can contribute in reducing
the risk of developing dementia. Over the past years the atten-
tion has shifted from the role of single nutrients or foods to
the role of dietary patterns, such as the promising association
of the Mediterranean diet with cognitive decline and demen-
tia. A dietary pattern approach better reflects the complexity
of the diet and our daily eating behavior (36). Multiple re-
views and meta-analyses have been written in the past years
that summarize the evidence of a substantial number of stud-
ies investigating the influence of a Mediterranean diet on cog-
nitive decline and dementia (713). In addition to the
Mediterranean diet, there are several other knowledge-based
(a priori) dietary patterns, such as the Healthy Diet Indicator
(HDI)
4
and the Healthy Eating Index (HEI)2005, and em-
pirically (a posteriori) derived dietary patterns (e.g., by using
factor analysis or principal components analysis) that could
be associated with cognitive decline and dementia. So far,
there has only been one review summarizing the literature
on different dietary patterns and cognitive aging until 2011
1
The authors reported no funding received for this study.
2
Author disclosures: O van de Rest, AAM Berendsen, A Haveman-Nies, and LCPGM de Groot,
no conflicts of interest.
3
These authors contributed equally to this work.
* To whom correspondence should be addressed. E-mail: ondine.vanderest@wur.nl.
4
Abbreviations used: AD, Alzheimer disease; DASH, Dietary Approaches to Stop
Hypertension; HDI, Healthy Diet Indicator; HEI, Healthy Eating Index; MCI, mild cognitive
impairment; MeSH, medical subject heading; MMSE, Mini-Mental State Examination.
154 ã2015 American Society for Nutrition. Adv. Nutr. 6: 154–168, 2015; doi:10.3945/an.114.007617.
(14). Therefore, the reviews describing studies on the Medi-
terranean diet and cognitive decline can be updated with sev-
eral new studies that have been published since that review.
The aim of this systematic review is to summarize and eval-
uate available evidence from studies investigating dietary pat-
terns, both a priori and a posteriori, in relation to cognitive
decline and dementia in older adults and elderly persons. Al-
though underlying biological mechanisms will be touched on
briey, this review is not intended to provide an extended de-
scription of mechanisms underlying the association between
dietary patterns and cognitive performance. Instead, our spe-
cic goals are as follows: 1) to summarize studies on the Med-
iterranean diet, 2) to summarize studies of other dietary
patterns, and 3) to critically evaluate and summarize all evi-
dence emerging from these studies on associations between di-
etary patterns and cognitive performance and/or dementia.
Methods
Search strategy. The role of a healthy diet (Mediterranean diet, dietary pat-
terns) in the development of cognitive decline and dementia has been the
subject of several recent systematic reviews that were the starting point of
the current review. Medline databases and the Cochrane database were
searched up to May 2014 for additional, recently published studies. The
search strategies used text words and relevant indexing [medical subject
heading (MeSH) terms] to capture studies investigating the association be-
tween healthy diet (Mediterranean diet, dietary patterns) with cognitive de-
cline and dementia. When no systematic reviews were found, narrative
reviews were used and both checked and updated by using a combination
of MeSH and text-based terms: Diet, Mediterranean(MeSH terms) or
Mediterranean dietor (Mediterraneanand Diet)orDietary pattern
and memory(MeSH terms) or memory(all fields) or cognition
(MeSH terms) or cognition(all fields) or cognitive (all fields) or alzheimer
disease(MeSH terms) or alzheimer(all fields) and disease(all fields) or
alzheimer disease(all fields) or alzheimer(all fields) or dementia
(MeSH terms) or dementia(all fields) and humans(MeSH terms). We
included only studies performed in older adults and elderly persons and
for which full articles were published.
Study selection process. Our search strategy resulted in 65 studies, reviews,
and meta-analyses on diet and cognition and an additional search via refer-
ence lists of reviews and meta-analyses resulted in 33 more studies. This re-
sulted in a total of 98 studies, of which 36 were selected based on full
abstracts and texts. In total, we found 26 studies on the Mediterranean
diet and cognitive function or dementia and 15 on other dietary patterns
in relation to cognitive function (Figure 1). Five studies performed analyses
on both the Mediterranean diet and other patterns (1519). Study selection,
data extraction, and quality assessment were performed independently by 2
reviewers (OVDR and AAMB).
Results
Specication and potential underlying mechanisms
In Table 1, characteristics of frequently reported a priori
(2025) and a posteriori (3, 7, 2628) dietary patterns are
shown. The majority of a priori dietary patterns consist of
adequacy components, such as fruits, vegetables, cereals,
fatty fish, and dairy, and limitation components, such as to-
tal fat, SFAs, cholesterol, and sodium. In an a posteriori
data-driven approach, data are reduced into dietary patterns
either based on differences in intakes between subjects or on
intercorrelations between dietary items (29). Usually this re-
sults in dietary patterns consisting of combinations of high
or low loadings of similar components as defined by the a
priori methods. It has been proposed that these components
in combination could affect several biological mechanisms,
which may explain how certain healthy dietary patterns
can exert their effects on cognitive health and decline. Pre-
vailing mechanisms that are believed to play a role in the
pathogenesis of age-related diseases, including cognitive im-
pairment and Alzheimer disease (AD), are oxidative stress,
inflammation, and vascular risk factors, which are mecha-
nisms that are ideal targets for nutritional intervention
with dietary patterns such as the Mediterranean diet that
are abundant in antioxidants and MUFAs and have a bal-
anced ratio of essential n6 and n3 FAs. Based on the mul-
tiple plausible biological mechanisms, there is a strong
theoretical basis that the intake and status of these nutrients
may affect the known mechanisms for neurodegeneration.
Mediterranean diet
The role of the Mediterranean diet on cognitive decline and
dementia risk was only recently systematically reviewed by
Lourida et al. (8). This review included literature published
until January 2012. In addition, Alzheimers Disease Inter-
national published a report on the available evidence on
this subject in the beginning of 2014 (30). However, because
this area of research is developing rapidly, the results of these
2 reviews can already be updated by adding at least 10 new
studies on the Mediterranean diet and cognition and de-
mentia. We found a total of 6 cross-sectional studies, 15 pro-
spective studies, and 1 intervention trial. The characteristics
of these studies are summarized in Table 2.
Observational evidence. Four of the 6 cross-sectional stud-
ies showed an inverse association of the Mediterranean diet
FIGURE 1 Flow chart of selection process resulting in 36
studies included in the review, 5 of which performed analyses
on both the Mediterranean diet and other dietary patterns.
Dietary patterns and cognitive decline 155
with cognitive functioning (16, 19, 31) or AD (31, 32) in
American, Puerto Rican, and Australian older adults and el-
derly persons. One cross-sectional study in Greek elderly in-
dividuals observed a protective association with a 1-unit
increase in Mediterranean diet score in men (OR: 0.88;
95% CI: 0.80, 0.98) but, in contrast, a suggestion of an in-
creased risk of cognitive impairment in women (OR: 1.11;
95% CI: 1.00, 1.22) (33). A study in Hong Kong did not
TABLE 1 Characterization of most investigated a prioriand a posterioridefined dietary patterns in relation to neurodegeneration
1
Dietary pattern (ref) Characterization
A priori (hypothesis driven approach)
MeDi (25) Based on traditional eating habits in Crete, south Italy, and other Mediterranean countries
·High in fruits, vegetables, cereals, and legumes
·Low in saturated fats; olive oil main fat source
·Moderate in fish
·Low to moderate in dairy products
·Low in red meat and meat products
·Moderate in alcohol (wine)
HDI (21) Based on WHO recommendations for the prevention of chronic diseases
·SFAs: #10en%
·PUFAs: 37en%
·Protein: 1015en%
·Complex carbohydrates: 5070en%
·Dietary fiber: 2740 g/d
·Fruits and vegetables: .400 g/d
·Pulses, nuts, and seeds: .30 g/d
·Oligo-/mono- and disaccharides: #10en%
·Cholesterol: #300 mg/d
HEI (23) Based on the food patterns found in MyPyramid and is a sum of 10 individual components
·Adequacy of total whole fruits, vegetables, dark-green and orange vegetables and legumes, total
grains, whole grains, milk, meat and beans, oil
·Low intakes of saturated fat, sodium, and calories from solid fats, alcoholic beverages, and added
sugars
RFS (22) Based on the Dietary Guidelines for Americans and calculated as the sum of 23 items that are
consumed at least once a week
1) Apples or pears; 2) oranges; 3) cantaloupe; 4) orange or grapefruit juice; 5) grapefruit; 6) other fruit
juices; 7) dried beans; 8) tomatoes; 9) broccoli; 10) spinach; 11) mustard, turnip, or collard greens;
12) carrots or mixed vegetables with carrots; 13) green salad; 14) sweet potatoes, yams; 15) other
potatoes; 16) baked or stewed chicken or turkey; 17) baked or broiled fish; 18) dark breads, such as
whole wheat, rye, or pumpernickel; 19) cornbread, tortillas, and grits; 20) high-fiber cereals, such
as bran, granola, or shredded wheat; 21) cooked cereals; 22) 2%-fat milk and beverages with 2%-
fat milk; 23) 1%-fat or skim milk
DASH trial (24) Based on intakes of nutrients hypothesized to alter blood pressure
·Rich in fruits and vegetables
·Rich in low-fat dairy food
·Reduced amounts of saturated fat, total fat, and cholesterol
French National Nutrition
and Health Program (PNNS-GS) (20)
Based on French National Nutrition and Health Program recommendations to improve the health
status of the general population
·Fruits and vegetables at least 5 servings/d
·Bread, cereals, potatoes, and legumes at each meal
·Choose whole-grain food and whole-grain bread more often
·Milk and dairy products 3 servings/d
·Meat and poultry, seafood, eggs 12 servings/d
·Seafood at least twice per week
·Limit consumption of added fats
·Favor fats of vegetable origin
·Drink water as desired
·Limit sweetened beverages
·Limit salt consumption
·At least 30 min of brisk walking or equivalent per day of physical activity
A posteriori (exploratory approach)
Cluster analysis (3, 7, 27) Classication technique, which aggregates subjects with similar dened variables such as dietary
pattern and the energy contribution of each food group
PCA (7, 15) Common approach of factor analysis to dene dietary patterns, aggregates highly correlated food
items to identify underlying dietary patterns
RRR (7, 26, 28) Mix of an exploratory and hypothesis-driven approach, involves the elements of an a priori ap-
proach to derive dietary patterns
1
DASH, Dietary Approaches to Stop Hypertension; en%, percentage of energy intake; HDI, Healthy Diet Indicator; HEI, Healthy Eating Index; MeDi, Mediterranean diet; PCA,
principal component analysis; PNNS-GS, Program National Nutrition Santé guideline score; ref, reference; RFS, Recommended Food Score; RRR, reduced rank regression.
156 van de Rest et al.
TABLE 2 Characteristics of included studies on Mediterranean diet, cognitive decline, and dementia
1
Author, year (ref), country,
study name
Population (sample
size, mean age) Follow-up, y
Exposure/ intervention
measure Outcome measure Effect measure
Cross-sectional studies
Samieri et al., 2013 (16), USA,
NHS
n= 10,670 FFQ, A-MeDi score Cognitive decline (TICS), mental
health (SF-36)
No signicant association be-
tween the A-MeDi and mental
health or cognitive impairment
(OR
Q5vsQ1
: 1.12; 95% CI: 1.01,
1.20; P-trend ,0.001; and OR:
0.97; 95% CI: 0.95, 1.00; P-trend
= 0.020, respectively)
59 y
Chan et al., 2013 (15), Hong
Kong
n= 3670 FFQ, MeDi score Cognitive function (CSI-D) No signicant association be-
tween the MeDi and cognitive
function in either men or
women (OR
T3vsT1
: 0.89; 95% CI:
0.56, 1.41; P-trend = 0.882; and
OR: 1.02; 95% CI: 0.75, 1.41;
P-trend = 0.952, respectively).
71.8 y
Ye et al., 2013 (19), Puerto Rico,
BPRHS
n= 1269 FFQ, MeDi score Cognitive function and cognitive
impairment (MMSE)
A signicant association between
a higher MeDi score, higher
MMSE scores (P-trend = 0.012)
and a lower risk of cognitive
impairment (OR: 0.80; 95% CI:
0.80, 0.94; P,0.001)
57.3 y
Katsiardanis et al., 2013 (33),
Greece, Velestino Study
n= 557 157-item FFQ, MeDi score Cognitive impairment (MMSE) Signicant lower risk of cognitive
impairment in men per 1-unit
increase in adherence to the
MeDi (OR: 0.88; 95% CI: 0.80,
0.98; P= 0.02) but a higher risk
in women (OR: 1.11; 95% CI:
1.00, 1.22; P= 0.04)
.65 y
Gardener et al., 2012 (31),
Australia, AIBL study
n= 970 74-item CCV FFQ, MeDi
score
MCI (MMSE), AD (DSM-IV, NINCDS-
ADRDA)
Each unit increase in MeDi score
was signicantly associated
with a reduced risk of MCI or
AD (OR: 0.87; 95% CI: 0.75, 1.00;
P,0.05, and OR: 0.81; 95% CI:
0.71, 0.92; P,0.01,
respectively)
.60 y
Scarmeas et al., 2006 (32), USA,
WHICAP
n= 1984 Nested case control 61-item FFQ, MeDi score Prevalent AD (NINCDS-ADRDA) Better adherence to the MeDi was
signicantly associated with
lower risk of AD (OR: 0.76; 95%
CI: 0.67, 0.87; P,0.01; OR
T3vsT1
:
0.32; 95% CI: 0.17, 0.59; P-trend
,0.001)
76.3 y
(Continued)
Dietary patterns and cognitive decline 157
TABLE 2 (Continued )
Author, year (ref), country,
study name
Population (sample
size, mean age) Follow-up, y
Exposure/ intervention
measure Outcome measure Effect measure
Longitudinal studies
Wengreen et al., 2013, (18), USA,
CCMS
n= 3831 11 142-item FFQ, MeDi score Cognitive impairment (3MS) Better adherence to MeDiet was
signicantly associated with
higher 3MS scores
(MeDiet
Q5vsQ1
: 0.94 60.29;
P-trend = 0.0022)
74.1 y
Tsivgoulis et al., 2013 (37), USA,
REGARDS study
n= 17,478 4 FFQ, MeDi score Incident cognitive impairment
(SIS)
Higher adherence to MeDiet was
signicantly associated with a
lower likelihood of ICI (OR: 0.87;
95% CI: 0.76, 1.00), especially in
nondiabetic participants (OR:
0.81; 95% CI: 0.70, 0.94; P=
0.0066), but not in diabetic
participants (OR: 1.27; 95% CI:
0.95, 1.71; P= 0.1063)
64.6 y
Samieri et al., 2013 (35), USA,
NHS
n= 16,058 6 116-item FFQ, A-MeDi
score
Cognitive status and cognitive
decline (TICS), verbal memory,
global cognition
Highest adherence to MeDi was
signicantly associated with
cognitive status at older ages
[adjusted mean differences in z
scores Q5vsQ1 (95% CI): 0.06
(0.01, 0.11), P-trend = 0.004 for
TICS; 0.05 (0.01, 0.08), P-trend =
0.002 for global score; and 0.06
(0.03, 0.10), P-trend ,0.001 for
verbal memory score], but not
with cognitive decline [0.004
(20.011, 0.019), P-trend 0.31;
20.001 (20.010, 0.007), P-trend
= 0.84; 20.001 (20.011, 0.010),
P-trend = 0.70]
74.3 y
Samieri et al., 2013 (39), USA,
Womens Health Study
n= 6174 2 131-item FFQ, A-MeDi
score
Cognitive decline (TICS), global
cognition, verbal memory
No signicant associations be-
tween higher A-MeDi scores
and mean differences in aver-
aged measures of global cog-
nition and verbal memory
(Q5vsQ1: 0.02; 95% CI: 20.03,
0.06; P-trend = 0.63; and 0.03;
95% CI: 20.02, 0.07. P-trend =
0.44, respectively), nor over
time (Pfor quintile medians 3
time interaction = 0.26 for
global score and 0.40 for score
and cognitive decline)
72 y
(Continued)
158 van de Rest et al.
TABLE 2 (Continued )
Author, year (ref), country,
study name
Population (sample
size, mean age) Follow-up, y
Exposure/ intervention
measure Outcome measure Effect measure
Kesse-Guyot et al., 2013 (41),
France, SU.VI.MAX
n= 3083 13 Repeated 24-h records,
MeDi score, and MSDPS
Cognitive function; episodic and
lexical-semantic memory, men-
tal exibility
No signicant association be-
tween higher adherence to
MeDi and MSDPS and cognitive
scores, except for a lower pho-
nemic uency (21.00; 95% CI:
21.85, 20.15; P= 0.048) with
decreasing MSDPS and lower
backward digit with decreasing
MDS (20.64; 95% CI: 21.60,
0.32; P= 0.03)
65.4 y
Vercambre et al., 2012 (40), USA,
WACS
n= 2504 5.4 116-item FFQ, MeDi score Cognitive decline (TICS), verbal
memory, category uency
score
No signicant association be-
tween higher adherence to
MeDi and adjusted mean dif-
ferences in annual rates of
cognitive decline [T3vsT1 (95%
CI): 0.00 (20.02, 0.01), P= 0.88,
for global cognition; 20.03
(20.11, 0.05), P= 0.53, for TICS;
0.00 (20.02, 0.02), P=0.97, for
verbal memory; and 20.03
(20.14, 0.08), P=0.64 for cate-
gory fluency]
72.3 y
Cherbuin and Anstey, 2012 (42),
Australia, PATH
n= 1528 4 215-item FFQ, MeDi score MCI, cognitive decline, any MCD
(ICC, CDR)
No signicant association be-
tween the MeDiet and transi-
tion from normal aging to MCI,
CDR 0.5, and any MCD [OR (95%
CI): 1.41 (0.95, 2.10); 1.18 (0.88,
1.57); and 1.20 (0.98, 1.47),
respectively]
62.5 y
Tangney et al., 2011 (17), USA,
CHAP
n= 3790 7.6 139-item FFQ, MeDi score Global cognitive function (MMSE,
EBMT, SDMT)
Higher MeDi scores were signi-
cantly associated with better
global cognitive scores at
baseline (b= 0.0070; SEE =
0.0022, P=0.0013) and with
slower rates of decline over
time (b= 0.0014; SEE = 0.0004,
P=0.0004)
75.4 y
Roberts et al., 2010 (38), USA,
MCSA
n= 1233 2.2 128-item FFQ, MeDi score MCI (CDR) A high MeDi score was not statis-
tically associated with risk of
incident MCI or dementia
(HR
T3vsT1
: 0.75; 95% CI: 0.46, 1.21;
P=0.24)
79.6 y
(Continued)
Dietary patterns and cognitive decline 159
TABLE 2 (Continued )
Author, year (ref), country,
study name
Population (sample
size, mean age) Follow-up, y
Exposure/ intervention
measure Outcome measure Effect measure
Gu et al., 2010 (45), USA,
WHICAP
n= 1219 3.8 61-item SFFQ, MeDi score AD (NINCDS-ADRDA) Better adherence to MeDi was
borderline signicantly associ-
ated with lower risk for AD in
fully adjusted model (HR: 0.87;
95% CI: 0.78, 0.97; P=0.01; and
HR
T3vsT1
: 0.68; 95% CI: 0.42, 1.08;
P-trend = 0.06)
76.7 y
Scarmeas et al., 2009 (36), USA,
WHICAP
n= 1393 4.5 FFQ, MeDi score MCI (DSM-III-R), AD (NINCDS-
ADRDA)
Better adherence to MeDi was
signicantly associated with a
lower risk of MCI (HR: 0.85; 95%
CI: 0.72, 1.00; P-trend = 0.05;
HR
T3vsT1
: 0.72; 95% CI: 0.52, 1.00;
P= 0.05) and a lower risk of
developing AD after MCI (HR:
0.71; 95% CI: 0.53, 0.95; P-trend
= 0.02; HR
T3vsT1
: 0.52; 95% CI:
0.30, 0.91; P=0.02)
76.9 y
Scarmeas et al., 2009 (46), USA,
WHICAP
n= 1880 5.4 61-item FFQ, MeDi score AD (NINCDS-ADRDA) Better MeDi adherence was sig-
nicantly associated with lower
AD risk (HR
T3vsT1
: 0.60; 95% CI:
0.42, 0.97; P-trend = 0.008)
77.2 y
Feart et al., 2009 (34), France, 3C
study
n= 1410 FFQ and 24-HR, MeDi
score
Cognitive performance, dementia
risk, and AD risk (MMSE,
DSM-III-R)
A 1-point increase in the MeDi
was signicantly associated
with fewer MMSE errors (b=
20.006, P= 0.04) and was bor-
derline significant across cate-
gories of MeDi (b
T3vsT1
=20.02,
P=0.06); there was no signifi-
cant association with dementia
risk and AD risk (HR: 1.06; 95%
CI: 0.92, 1.21; P= 0.43; HR
T3vsT1
:
1.12; 95% CI: 0.60, 2.10; P=0.72;
HR: 1.00; 95% CI: 0.85, 1.19; P=
0.96; and HR
T3vsT1
: 0.86; 95% CI:
0.39, 1.88; P=0.71, respectively)
75.9 y
Psaltopoulou et al., 2008 (43),
Greece, EPIC
n= 732 8 150-food FFQ, MeDi score Cognitive decline, MMSE No signicant association per 1-
unit increase in MeDi and MSSE
(b= 0.05; 95% CI: 20.09, 0.19; P
=0.485)
.60 y
(Continued)
160 van de Rest et al.
TABLE 2 (Continued )
Author, year (ref), country,
study name
Population (sample
size, mean age) Follow-up, y
Exposure/ intervention
measure Outcome measure Effect measure
Scarmeas et al., 2006 (44), USA,
WHICAP
n= 2258 4 61-item SFFQ, MeDi score AD (NINCDS-ADRDA) Better adherence to MeDi was
associated with lower risk of AD
(HR: 0.91; 95% CI: 0.83, 0.98; P=
0.015; HR
T3vsT1
: 0.60; 95% CI:
0.42, 0.87; P-trend = 0.007)
77.2 y
Randomized controlled trials
Martinez-Lapiscina et al. 2013
(47, 48), Spain, PREDIMED-
Navarra
n= 522 (47) 6.5 137-item FFQ; MedDiet
intervention
Cognitive performance (MMSE,
CDT)
Participants in the MeDi + olive oil
and the MeDi + nuts group
showed better cognitive per-
formance compared with the
control group for MMSE and
CDT [adjusted differences (95%
CI): 0.62 (0.18, 1.05, P=0.005,
and 0.57 (0.11, 1.03), P=0.015
for MMSE; 0.51 (0.20, 0.82), P=
0.001, and 0.33 (0.003, 0.67), P=
0.048 for CDT]
74.6 y 3 arms:
n= 268 (48) MeDi + olive oil Cognitive performance, MCI MeDi with olive oil was related to
better cognitive performance
(for 5 of 16 tests) and lower MCI
(OR: 0.34; 95% CI: 0.12, 0.97)
compared with control group
74.1 y MeDi + nuts MeDi with nuts was not related to
better cognitive performance
or MCI (OR: 0.56; 95% CI: 0.22,
1.43)
Low-fat diet
1
AD, Alzheimer disease; AIBL, Australian Imaging, Biomarkers, and Lifestyle Study of Ageing cohort; A-MeDi, alternate Mediterranean diet; BPRHS, Boston Puerto Rican Health Study; CCMS, Cache County Memory Study; CDR, Clinical Dementia
Rating; CDT, Clock Drawing Test; CHAP, Chicago Health and Aging Project; CSI-D, Community Screening Instrument for Dementia; DSM, Diagnostic and Statistical Manual of Mental Disorders; EBMT, East Boston Memory Test; EPIC, European
Prospective Investigation into Cancer and Nutrition; ICC, International Consensus Criteria; MCD, mild cognitive disorder; MCI, mild cognitive impairment; MCSA, Mayo Clinic Study of Aging; MeDi, Mediterranean diet; MMSE, Mini-Mental State
Examination; MSDPS, Mediterranean Style Dietary Pattern Score; NHS, NursesHealth Study; NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association;
PATH, Personality and Total Health Through Life Project; PREDIMED, PREvencion con DIeta MEDiterranea; Q, quintile; ref, reference; REGARDS, Reasons for Geographic and Racial Differences in Stroke; SDMT, Symbol Digit Modalities Test; SF-36,
Medical Outcomes Short-Form 36 Health Survey; SIS, Six-item Screener; SU.VI.MAX, Supplementation en VItamines et Mineraux Anti-oXydants; T, tertile; TICS, Telephone Interview for Cognitive Status; WACS, Womens Antioxidant Cardiovascular
Study; WHICAP, Washington Heights-Inwood Columbia Aging Project; 3C, Three-City; 3MS, Modified Mini-Mental State Examination; 24-HR, 24-h dietary recall.
Dietary patterns and cognitive decline 161
nd associations in either men or women [ORs (95% CIs) for
tertile 3 vs. tertile 1: 0.89 (0.56, 1.41) vs. 1.02 (0.75, 1.41)]
(15).
Of the 12 prospective studies on adherence to the Medi-
terranean diet and better cognitive performance, 6 observed
a benecial association after 3 to 7.6 y of follow-up (17, 18,
3437). Of these studies, 5 were performed in the United
States (17, 18, 3537) and 1 in France (34). All 5 studies per-
formed in the United States showed marginal, but signifi-
cant, associations. The French study showed that a 1-point
increase in the Mediterranean diet was associated with fewer
errors on the Mini-Mental State Examination (MMSE) but
was only marginally significant across categories of the Med-
iterranean diet (b
T3vsT1
:20.02, P= 0.06). In the other 6
studies, of which 3 were performed in the United States
(3840) and the others in France (41), Australia (42), and
Greece (43), the association was beneficial but not signifi-
cant after 23 y of follow-up (3843).
With respect to dementia and AD, 4 of 6 studies showed a
reduced risk of AD with better adherence to the Mediterra-
nean diet after 35.4 y of follow-up in US populations [HR:
0.91; 95% CI: 0.83, 0.98 (44); HR: 0.87; 95% CI: 0.78, 0.97
(45); HR: 0.60; 95% CI: 0.42, 0.97 (46)] and a lower risk of
developing AD after mild cognitive impairment (MCI; HR:
0.71; 95% CI: 0.53, 0.95) (36). Two studies, performed in a
France (34) and in a US population (38), did not find
associations.
Trial evidence. The only trial until now that investigated the
effect of a Mediterranean-type diet either rich in olive oil or
rich in nuts was performed in 522 participants with a high
cardiovascular risk prole. After 6.5 y of intervention, par-
ticipants in both types of the Mediterranean diet had a
higher cognitive performance than did the control group
[adjusted differences for MMSE (95% CI): +0.62 (+0.18,
+1.05), P= 0.005; and +0.57 (+0.11, +1.03), P=0.015]
(47). In a smaller subgroup (n= 285) of this same trial,
only the Mediterranean diet with olive oil showed better re-
sults for 5 of 16 specific cognitive tests and MCI (OR: 0.34;
95% CI: 0.12, 0.97) (48).
Meta-analyses. An updated systematic review and meta-
analysis from 2010 pooled data of prospective cohort studies
on adherence to the Mediterranean diet and risk of AD, Par-
kinson disease, cognitive decline, dementia, and MCI
showed an inverse association between a 2-point increase
of adherence to the Mediterranean diet and neurodegenera-
tive diseases (RR: 0.87; 95% CI: 0.81, 0.94; I
2
= 0%; P= 0.73)
(Table 3) (12).
Another meta-analysis (9) pooled data of 2 case-control
studies, 5 longitudinal studies, and 5 cross-sectional studies
on moderate and high adherence to the Mediterranean diet
and risk of cognitive impairment, which resulted in inverse
associations [RRs (95% CIs): 0.79 (0.67, 0.94), I
2
= 28.3%,
and 0.60 (0.43, 0.83), I
2
= 76.4%; P=0.000].
A more recent systematic review and meta-analysis by
Singh et al. (11) analyzed data of prospective cohort studies
with at least 1 y of follow-up on the Mediterranean diet and
cognitive outcomes (MCI or AD). On the basis of 2 longitu-
dinal studies performed in the United States, there was an
association with high adherence to the Mediterranean diet
(HR
T3vsT1
: 0.73; 95% CI: 0.56, 0.96; I
2
= 0%), but there
TABLE 3 Characteristics of included reviews and meta-analyses on Mediterranean diet, cognitive decline, and dementia
1
Author,
year (ref) Studies included
Update
until Exposure Outcomes measure Effect
Singh et al.,
2014 (11)
Five prospective cohort
studies with at least
1 y follow-up
November
2012
MeDi score From normal to MCI, from
normal to AD, cognitive
impairment
Better adherence to MeDi was associated
with a lower risk of MCI (HR
T3vsT1
: 0.73;
95% CI: 0.56, 0.96; I
2
= 0%; HR
T2vsT1
; 0.82;
95% CI: 0.64, 1.05; I
2
= 0%; HR: 0.98; 95%
CI: 0.84, 1.08; I
2
= 33%), AD (HR: 0.92;
95% CI: 0.85, 0.99; HR
T2vsT1
: 0.87; 95% CI:
0.66, 1.14; HR
T3vsT1
: 0.64; 95% CI: 0.46,
0.89), and cognitive impairment (HR:
0.92; 95% CI: 0.88; 0.97; HR
T2vsT1
: 0.80;
95% CI: 0.67, 0.95; HR
T3vsT1
: 0.67; 95% CI:
0.55, 0.81; I
2
= 0%)
Psaltopoulou
et al., 2013 (9)
9 studies; case-control,
longitudinal,
cross-sectional
31 October
2012
MeDi score Cognitive impairment,
depression
Both a moderate and a high adherence to
MeDi were associated with a reduced
risk of cognitive impairment and de-
pression (RR: 0.79; 95% CI: 0.67, 0.94; I
2
=
28.3%; P=0.193, vs. RR: 0.60; 95% CI:
0.43, 0.83; I
2
= 76.4%; P=0.000; and RR
0.77; 95% CI: 0.62, 0.95; I
2
= 54.4%, vs. RR:
0.68; 95% CI: 0.54, 0.86; I
2
= 53.4%, re-
spectively). No effect measure modifi-
cation by sex was observed
Sofi et al.,
2010 (12)
Five prospective
cohort studies
June 2010 MeDi score Neurodegenerative diseases
(cognitive decline, risk of
dementia, MCI, AD,
Parkinson disease)
Per 2-point increase of adherence to the
MeDi score, the risk of incidence of
neurodegenerative diseases decreased
(RR: 0.87; 95% CI: 0.81, 0.94)
1
MCI, mild cognitive impairment; MeDi, Mediterranean diet; ref, reference.
162 van de Rest et al.
was no association with moderate adherence compared with
poor adherence [HR
T2vsT2
: 0.82; 95% CI: 0.64, 1.05; I
2
=
0%], nor per 1-unit increase in the Mediterranean diet score
(HR: 0.95; 95% CI: 0.84, 1.08; I
2
= 33%). Pooled analyses of
2 other longitudinal studies showed an inverse association
between adherence to the Mediterranean diet (both contin-
uous and categorical) and risk of AD among cognitively nor-
mal individuals [HR (95% CI): 0.92 (0.85, 0.99), I
2
= 0%;
and HR
T3vsT1
: 0.64 (0.46, 0.89), I
2
= 0%]. When combining
all of the data, this resulted in an inverse association between
a better adherence to the Mediterranean diet and cognitive
impairment: HR (95% CI): 0.92 (0.88, 0.97), I
2
= 0%;
HR
T2vsT1
: 0.80 (0.67, 0.95), I
2
= 0%; HR
T3vsT1
: 0.67 (0.55,
0.81), I
2
= 0%.
Other dietary patterns
Fewer studies have been performed on dietary patterns
other than the Mediterranean diet. So far, there has been
only 1 review summarizing the literature of studies on dif-
ferent dietary patterns and cognitive aging until 2011 and
this review included a total of 13 studies (14). We found a
total of 16 studies of which there were 8 cross-sectional stud-
ies, 7 prospective studies, and 1 trial investigating a priori
derived dietary patterns and a posterioriderived dietary
patterns in relation to cognitive decline (Table 4).
Observational evidence. Of the 6 cross-sectional studies, 4
used a priori knowledge to study dietary patterns. Better ad-
herence to the HDI was associated with a lower prevalence of
cognitive decit [OR: 0.85; 95% CI 0.77, 0.93 (49)] and a re-
duced risk of cognitive impairment (OR: 0.75; 95% CI: 0.58,
0.97) in an Italian cohort but not in a Dutch cohort (OR:
0.81; 95% CI: 0.63, 1.04) (50). Higher adherence to the
HEI-2005 was associated with a lower risk of cognitive im-
pairment in a Puerto Rican population (OR: 0.86; 95% CI:
0.74, 0.99) (19), but this was not found for higher adherence
to the 2010 alternative HEI in a US population (OR for
quintile 5 vs. quintile 1: 0.99; 95% CI: 0.97, 1.01) (16).
Two studies used an empirical approach such as principal
components analysis (15) or cluster analysis (51). One study
observed fewer errors on the MMSE with a better adherence
to a healthy dietary pattern in both men and women [b
(95% CI): 20.11 (20.22, 20.0004) and 20.13 (20.22,
20.04), respectively] (51). The other study found a benefi-
cial association only in Chinese women with a higher veg-
etables-fruitsand snacks-drinks-milk productspattern
score and cognitive function but not in men (15).
Of the 8 prospective studies, 5 used a prioridefined di-
etary scores (17, 18, 5254) and 3 studies used data-driven
approaches (26, 55, 56). Results from studies using a priori
diet scores showed mixed results, with higher cognitive
function scores for the Dietary Approaches to Stop Hyper-
tension (DASH) diet [Modified MMSE (3MS) score for
DASH quintile 5 vs. quintile 1: 0.97 60.29] (18) and less
cognitive decline for the Recommended Food Score after
11 y of follow-up (3MS score for Recommended Food Score
quartile 4 vs. quartile 1: 1.79) (53), whereas there was no
association between the HEI-2005 (b= 0.00002, P=
0.214) (17) and the Canadian Healthy Eating Index (b=
0.00008, P= 0.852) (52) and cognitive decline after 7.6
and 3 y of follow-up, respectively. A better adherence to
the French guidelines [Program National Nutrition Santé
guideline score (PNNS-GS)] was associated with better cog-
nitive function as measured by many specific cognitive func-
tion tests (54). The other 3 of the 7 studies used data-driven
approaches showing consistent beneficial associations be-
tween dietary patterns and risk of dementia (56), cognitive
function (55), and AD (26, 56). Two studies used reduced
rank regression, for which 1 study observed a typical Japanese
pattern and the other study reported on a healthypattern.
After 15 y of follow-up, the Japanese pattern was associated
with a reduced risk of dementia (HR: 0.66; 95% CI: 0.46.
0.95), AD (HR: 0.65; 95% CI: 0.40, 1.06), and vascular de-
mentia (HR: 0.45; 95% CI: 0.22, 0.91) (56). The healthy pat-
tern was strongly associated with a lower risk of AD
(HR
T3vsT1
: 0.62; 95% CI: 0.43, 0.89) after 3.9 y of follow-
up (26). The other study used factor analysis and reported
higher cognitive function scores for the healthy pattern
than for a traditionalpattern (50.1 60.7 vs. 48.9 60.7,
P-trend = 0.001) after 13 y of follow-up (55).
Trial evidence. The single trial that was performed ob-
served better scores on 1 of 9 cognitive function tests (psy-
chomotor speed; Cohensd= 0.440, P=0.036) after a 4-mo
intervention with the DASH diet compared with a usual-diet
control group in 124 overweight adults with high blood
pressure (57).
Discussion
We reviewed the current evidence from observational stud-
ies and intervention trials investigating healthy dietary pat-
terns in relation to cognitive decline and dementia.
Overall, the results of all types of dietary pattern approaches
suggest that better adherence to a healthy dietary pattern is
associated with less cognitive decline and/or a lower risk of
dementia. However, most studies were observational and ev-
idence from intervention trials is limited to 2 trials, one of
which investigated the effect of the Mediterranean diet
(47, 48) and one the effect of the DASH diet (57). There
were several different methodologic factors between the
studies. This heterogeneity hinders comparison between
studies; therefore, the most important points are discussed
below.
Both a priori and a posteriori approaches to dene die-
tary patterns (3, 7, 58) were used in studies included in
this review and each method has its strengths and limita-
tions. A limitation of a priori indexes is that they are based
on current scientic knowledge on what a healthy diet com-
prises. Evolutions in knowledge should be considered each
time the index is applied, which also changes the index
over time (59). In addition, few cues about how to weight
food groups or guidelines have been proposed. A limitation
of both a priori and a posteriori approaches is that complex
correlations of food matrixes are not taken into account,
Dietary patterns and cognitive decline 163
TABLE 4 Characteristics of included studies on dietary patterns other than the Mediterranean diet, cognitive decline, and dementia
1
Author, year (ref),
country, study name
Population (sample
size, mean age) Follow-up Exposure/ intervention measure Outcome measure Effect
Cross-sectional studies
Ye et al., 2013 (19),
Puerto Rico, BPRHS
n= 1269 FFQ, HEI-2005 Cognitive function and cognitive
impairment (MMSE)
A higher HEI-2005 score was signicantly associated
with a higher MMSE score (P-trend = 0.011) and
lower risk of cognitive impairment (OR
10points
: 0.86;
95% CI: 0.74, 0.99; P=0.033)
57.3 y
Chan et al., 2013 (15),
Hong Kong
n= 1926 FFQ, factor analysis, 3 patterns: vegeta-
bles-fruits,”“snacks-drinks-milk pro-
ducts,”“meat-fish
Cognitive function (CSI-D) A higher vegetables-fruitsand snacks-drinks-milk
productspattern score was significantly associ-
ated with a reduced risk of cognitive impairment in
women (OR
Q4vsQ1
: 0.73; 95% CI: 0.54, 1.00; P-trend =
0.018; and OR
Q4vsQ1
: 0.65; 95% CI: 0.47, 0.90; P-trend
= 0.003, respectively) but not in men
71.8 y
Samieri et al., 2013
(16), USA, NHS
n= 10,670 FFQ, AHEI-2010 Cognitive decline (TICS), mental
health (SF-36)
The AHEI-2010 was signicantly associated with
greater likelihood of no major limitations in mental
health (OR
Q5vsQ1
: 1.31; 95% CI: 1.05, 1.22; P-trend ,
0.001) and marginally associated with no cognitive
impairment (OR
Q5vsQ1
: 0.99; 95% CI: 0.97, 1.01; P-
trend = 0.09)
59 y
Samieri et al., 2008
(51), France, 3C
n= 1724 FFQ, cluster analysis, 5 patterns: small
eaters,”“biscuits and snacking,
healthy,”“charcuterie, meat, and alco-
hol,”“pasta eaters
Cognitive function (MMSE) Better adherence to the healthydietary pattern was
significantly associated with fewer errors on the
MMSE (b=20.11; 95% CI: 20.22, 20.004, in men;
and b=20.13; 95% CI: 20.22, 20.04, in women)
76.0 y
Corrêa Leite et al.,
2001 (49), Pavia, Italy
n= 1651 180-item FFQ, HDI Cognitive decit (NPT) Better adherence to the HDI was associated with a
lower prevalence of cognitive decit (OR: 0.85; 95%
CI: 0.77, 0.93)
76.6 y
Huijbregts et al., 1998
(50), Seven Countries
Study
n= 1049 Cross-check dietary history, HDI Cognitive impairment (MMSE) Better adherence to the HDI had a protective effect
on cognitive impairment, although not consistent
over all cohorts (Zutphen OR: 0.81; 95% CI: 0.63,
1.04; Italian OR: 0.75; 95% CI: 0.58, 0.97)
76.1 y
Longitudinal studies
Wengreen et al., 2013
(18), USA, CCMS
n= 3831 11 y 142-item FFQ, DASH score Cognitive impairment, 3MS Better adherence to DASH diet was signicantly as-
sociated with higher 3MS scores (DASH
Q5vsQ1
: 0.97
60.29 points; P-trend = 0.0001)
74.1 y
Kesse-Guyot et al.,
2011 (54), France, SU.
VI.MAX
n= 2135 12 y Repeated 24-HR, PNNS-GS scores Verbal memory, executive
functioning
Better adherence to nutritional recommendations
was signicantly associated with the verbal mem-
ory factor (b= 0.41; 95% CI: 0.17, 0.64), whereas no
association was shown with the executive func-
tioning factor
65.5 y
Ozawa et al., 2013
(56), Japan, Hisayama
Study
n= 1006 15 y 70-item FFQ, RRR, 7 patterns; only
Japanesepresented
Dementia risk, AD, vascular de-
mentia (HDS, HDSR, MMSE)
Better adherence to the Japanesepattern was as-
sociated with a reduced risk of dementia (all-cause
dementia HR: 0.66; 95% CI: 0.46, 0.95; AD HR: 0.65;
95% CI: 0.40, 1.06; and VaD HR: 0.45; 95% CI: 0.22,
0.91)
68.5 y
(Continued)
164 van de Rest et al.
TABLE 4 (Continued )
Author, year (ref),
country, study name
Population (sample
size, mean age) Follow-up Exposure/ intervention measure Outcome measure Effect
Kesse-Guyot et al.,
2012 (55), France, SU.
VI.MAX
n= 3054 13 y Repeated 24-HR, factor analysis, 2 pat-
terns: healthy,”“traditional
Global cognitive function, verbal
memory, executive functioning
Signicantly higher cognitive function scores were
found with better adherence to the healthypat-
tern vs. traditionalpattern (adjusted means 6
SDs: 50.1 60.7 vs. 48.9 60.7, P-trend = 0.001 for
global cognitive function; 49.7 60.4 vs. 48.7 60.4,
P-trend 0.01 for verbal memory)
65.4 y
Shatenstein et al.,
2012 (52), Canada,
NuAge
n= 1488 3 y 78-item FFQ, C-HEI Cognitive decline (3MS) There was no signicant association between global
diet quality (total C-HEI/100) and cognitive decline
after 3-y follow-up (b= 0.00008, P=0.852)
74.2 y
Tangney et al., 2011
(17), USA, CHAP
n= 3790 7.6 y 139-item FFQ, HEI-2005 Cognitive function (MMSE) HEI-2005 was neither associated with better global
cognitive score at baseline nor with changes in
global cognitive score at follow-up (b=20.0011
60.001, P=0.236, and b= 0.00002 60.0002, P=
0.214, respectively)
75.4 y
Gu et al., 2010 (26),
USA, WHICAP
n= 2148 3.9 y FFQ, RRR, 7 patterns: DP1DP7 AD (DSM) Better adherence to the healthypattern was sig-
nificantly associated with a lower AD risk (HR
T3vsT1
:
0.62; 95% CI: 0.43, 0.89)
77.2 y
Wengreen et al., 2009
(53), USA, Cache
County
n= 3634 11 y 142-item FFQ, RFS vs. non-RFS Cognitive decline, 3MS Better adherence to RFS at baseline was associated
with less decline in 3MS scores after 11 y of follow-
up (RFS
T3vsT1
: 1.79 points, P=0.0013)
74.7 y
Randomized controlled
trials
Smith et al., 2010 (57),
USA, ENCORE
n= 124 4 mo DASH diet 3-arms: Cognitive functioning DASH diet alone resulted in better psychomotor
speed (Cohensd= 0.440; P=0.036) compared
with control group in subjects with high blood
pressure
52.3y DASH alone
DASH weight Management
Usual care
1
AD, Alzheimer disease; AHEI-2010, Alternative Healthy Eating Index2010; BPRHS, Boston Puerto Rican Health Study; CCMS, Cache County Memory Study; CHAP, Chicago Health and Aging Project; C-HEI, Canadian Healthy Eating Index; CSI-D,
Community Screening Instrument for Dementia; DASH, Dietary Approaches to Stop Hypertension; DSM, Diagnostic and Statistical Manual of Mental Disorders; ENCORE, Exercise and Nutrition Interventions for Cardiovascular Health Study; HDI,
Healthy Diet Indicator; HDS, Hasegawa Dementia Scale; HDSR, Hasegawa Dementia ScaleRevised; HEI, Healthy Eating Index, MMSE, Mini-Mental State Examination; NHS, NursesHealth Study; NPT, neuropsychological test; NuAge, Longitudinal
Study on Nutrition and Successful Aging; PNNS-GS, Program National Nutrition Santé guideline score; Q, quartile/quintile; ref, reference; RFS, Recommended Food Score; RRR, reduced rank regression; SF-36, Medical Outcomes Short-Form 36
Health Survey; SU.VI.MAX, Supplementation en VItamines et Mineraux Anti-oXydants; T, tertile; TICS, Telephone Interview for Cognitive Status; VaD, vascular dementia; WHICAP, Washington Heights-Inwood Columbia Aging Project; 3C, Three-
City; 3MS, Modified Mini-Mental State Examination; 24-HR, 24-h dietary recall.
Dietary patterns and cognitive decline 165
neither are all components specically related to cognitive
outcomes. Indexes described in this review are mainly based
on improving overall health status (2023, 25) or blood
pressure (60) rather than improving cognitive health specif-
ically. A limitation of a posteriori methods is the limited
comparability and reproducibility in other study samples,
because dietary patterns are based on food behavior in spe-
cific study samples (61). Another limitation of a posteriori
methods is that good skills in multidimensional statistical
methods are required to select the best components of which
the choice is subjective (62).
Another subjective choice, which could be confusing, is
the naming of the dietary patterns. Therefore, for studies
performed in different populations, the food consumption
characterizing the pattern should be described clearly. Pop-
ulations studied were almost all Western populations,
mostly from the United States and the Mediterranean coun-
tries in Europe, and a few studies were performed in Aus-
tralia, China, or Japan. According to Solfrizzi and Panza
(63), the components of the Mediterranean diet in Western
countries could be different from the traditional Mediterra-
nean diet, in particular for the high intakes of olive oil and
regular consumption of wine with meals. In general, a
healthy dietary pattern comprises a diet high in fruits, vege-
tables, other plant-derived products, and sh and lower in-
takes of meat, saturated fats, and added rened sugar. We
found no clear differences in associations between healthy
dietary patterns and cognitive decline and dementia across
countries. In addition, Singh et al. (11) did not nd any het-
erogeneity in their analysis; however, this could be due to the
fact that they included 3 US studies and 1 French study.
Dietary intake can be assessed with different methods,
such as food records, 24-h recalls, or FFQs, of which the lat-
ter have been mostly used in the studies included in the
current review. Different intake methods not only limit
comparisons between studies but also affect the number of
variables to be used for dietary pattern analyses. This could
affect both the number of derived dietary patterns as well as
the dietary patterns itself (62). It has been shown in studies
using principal components analyses that this could lead to
attenuated disease odds (62, 64).
The outcome measures that were included in our review
ranged from cognitive performance in cross-sectional stud-
ies to cognitive decline and risk of AD or dementia in longi-
tudinal studies. There are many differences in the way
cognitive outcomes were measured and reported. This
makes comparison between studies more difcult and limits
comparison of studies in a meta-analysis, which would pro-
vide a more quantitative understanding of the relation
between dietary patterns and cognitive impairment. The
length of follow-up time of longitudinal studies ranged
from 2 to 15 y. To capture changes in cognitive functioning,
several years of follow-up are needed, but how long exactly is
sufcient and what the best period to start follow-up are not
clear. It is currently suggested to already start at middle age.
Some of the inconsistency in ndings may be explained
by the general considerations that should be taken into
account when interpreting results of observational studies,
such as residual confounding, possible overadjustment,
and the fact that different covariates were included across
the studies. Another important issue with observational
studies is that they do not allow causal inference. This can
be overcome with well-designed intervention studies. How-
ever, the only trial on the effect of the Mediterranean diet
and cognitive decline did not measure cognition at baseline
but only at follow-up, which limits the possibility to establish
a cause-effect relationship.
Another point to take into account when interpreting re-
sults could be effect modication by sex as suggested by
ndings from Chan et al. (15), who found that higher in-
takes of vegetables-fruitsand snacks-drinks-milkpat-
terns were associated with reduced risk of cognitive
impairment in women, but no association was observed in
men. In contrast, a Greek study reported an increased risk
of cognitive impairment with better adherence to the Med-
iterranean diet in women, but a reduced risk in men (33).
Because eating behavior may differ between men and
women it should be taken into account that dietary patterns
could have been derived for men and women separately. Un-
fortunately, none of the included studies examined dietary
patterns by sex. These possible sex-specific differences merit
further investigation and clarification.
Conclusions and Recommendations
The results suggest that better adherence to a Mediterranean
diet is associated with less cognitive decline, dementia, or
AD as shown by 4 of 6 cross-sectional studies, 6 of 12 lon-
gitudinal studies, 1 trial, and 3 meta-analyses. Other healthy
dietary patterns, derived both a priori (e.g., HDI, HEI, and
PNNS-GS) and a posteriori (e.g., factor analysis, cluster
analysis, and reduced rank regression), were shown to be as-
sociated with reduced cognitive decline and/or a reduced
risk of dementia as shown by all 7 cross-sectional studies
and 5 of 7 longitudinal studies.
Investigating whole-diet approaches instead of individual
nutrients is an attractive strategy, because combined effects
may yield larger results since effects of individual nutrients
may be small. Furthermore, a whole-diet approach is more
comparable to dietary intake in daily life. A dietary index
specically aimed at improving cognitive performance
would be desirable. To further advance this eld of research,
more intervention trials of sufcient sample size investigat-
ing what type of dietary pattern is favorable with respect to
prevention of cognitive decline are recommended. In this re-
spect, ndings of the ongoing NU-AGE dietary intervention
study, in which the effect of a 1-y healthful diet on cognitive
performance is investigated, are to be awaited (65). Further-
more, more observational studies starting in middle-aged
adults and with a sufcient duration of at least 1015 y of
follow-up are warranted. Those studies should, if possible,
take into account the methodologic issues as pointed out
above and should aim for more homogeneity in, for exam-
ple, cognitive outcomes and composition of dietary patterns
to facilitate comparison between studies. In addition, the
166 van de Rest et al.
suggestion of differences in associations between men and
women needs further investigation. If effects of certain die-
tary approaches are proven, it will be a challenging task to
change peoples dietary habits, but it is important to take
up the challenge now in order to provide (pre-) dementia
patients some perspective of treatment or delay of the dis-
ease process and to reach clear recommendations in the fu-
ture for a cost-effective, safe, and sustainable solution. This
is of special importance because there are currently no cur-
ative treatments for this disease.
Acknowledgments
All authors read and approved the nal manuscript.
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... It is characterised by high consumption of fruit, vegetables, unrefined cereals and olive oil, high-to-moderate intake of fish, low-to-moderate intake of dairy products (mainly cheese and yogurt), low intake of meat and poultry and moderate intake of red wine, usually with meals [5]. Adherence to the Mediterranean diet has been associated with better global cognition in older adults [6], slower cognitive decline [7][8][9], lower risk of dementia and Alzheimer's disease [9] and lower mortality [10]. However, methodological differences between studies such as differences in how the diet is operationalised and evaluated have resulted in inconsistent results, and other studies have not found such effects [3,11,12]. ...
... It is characterised by high consumption of fruit, vegetables, unrefined cereals and olive oil, high-to-moderate intake of fish, low-to-moderate intake of dairy products (mainly cheese and yogurt), low intake of meat and poultry and moderate intake of red wine, usually with meals [5]. Adherence to the Mediterranean diet has been associated with better global cognition in older adults [6], slower cognitive decline [7][8][9], lower risk of dementia and Alzheimer's disease [9] and lower mortality [10]. However, methodological differences between studies such as differences in how the diet is operationalised and evaluated have resulted in inconsistent results, and other studies have not found such effects [3,11,12]. ...
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The proportion of European elderly is expected to increase to 30% in 2060. Combining dietary components may modulate many processes involved in ageing. So, it is likely that a healthful diet approach might have greater favourable impact on age-related decline than individual dietary components. This paper describes the design of a healthful diet intervention on inflammageing and its consequences in the elderly. The NU-AGE study is a parallel randomized one year trial in 1,250 apparently healthy, independently living European participants aged 65 to 80 years. Participants are randomised into either the diet group or control group. Participants in the diet group received dietary advice aimed at meeting the nutritional requirements of the ageing population. Special attention was paid to nutrients that may be inadequate or limiting in diets of elderly, such as vitamin D, vitamin B12, and calcium. C-reactive protein is measured as primary outcome. The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly. Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline.