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Critique the article

Critique the article.

Alzheimer’s & Dementia 11 (2015) 1015-1022

MIND diet slows cognitive decline with aging

Martha Clare Morrisa,*, Christy C. Tangneyb, Yamin Wanga, Frank M. Sacksc, Lisa L. Barnesd,e,f,
David A. Bennette,f, Neelum T. Aggarwale,f

aDepartment of Internal Medicine at Rush University Medical Center, Chicago, IL, USA
bDepartment of Clinical Nutrition at Rush University Medical Center, Chicago, IL, USA

cDepartment of Nutrition, Harvard School of Public Health, Harvard University, Boston, MA, USA
dDepartment of Behavioral Sciences at Rush University Medical Center, Chicago, IL, USA

eDepartment of Neurological Sciences at Rush University Medical Center, Chicago, IL, USA
fRush Alzheimer’s Disease Center at Rush University Medical Center, Chicago, IL, USA

Abstract Introduction: The Mediterranean and dash diets have been shown to slow cognitive decline; how-

The authors have n

*Corresponding a

2861.

E-mail address: m

http://dx.doi.org/10.10

1552-5260/� 2015 Th

ever, neither diet is specific to the nutrition literature on dementia prevention.
Methods: We devised the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet
intervention for neurodegenerative delay (MIND) diet score that specifically captures dietary compo-
nents shown to be neuroprotective and related it to change in cognition over an average 4.7 years
among 960 participants of the Memory and Aging Project.
Results: In adjusted mixed models, the MIND score was positively associated with slower decline in
global cognitive score (b5 0.0092; P, .0001) and with each of five cognitive domains. The differ-
ence in decline rates for being in the top tertile of MIND diet scores versus the lowest was equivalent
to being 7.5 years younger in age.
Discussion: The study findings suggest that theMIND diet substantially slows cognitive declinewith
age. Replication of these findings in a dietary intervention trial would be required to verify its rele-
vance to brain health.
� 2015 Th

e Alzheimer’s Association. Published by Elsevier Inc. All r

ights reserved.

Keywords: Cognition; Cognitive decline; Nutrition; Diet; Epidemiologic study; Aging

1. Introduction

Dementia is now the sixth leading cause of death in the
United States [1] and the prevention of cognitive decline,
the hallmark feature of dementia, is a public health priority.
It is estimated that delaying disease onset by just 5 years will
reduce the cost and prevalence by half [2]. Diet interventions
have the potential to be effective preventive strategies. Two
randomized trials of the cultural-based Mediterranean diet
[3] and of the blood pressure lowering DASH diet (Dietary
Approach to Systolic Hypertension) [4] observed protective

o relevant disclosures of potential conflicts of interest.

uthor. Tel.: 11-312-942-3223; Fax: 11-312-942-

artha_c_morris@rush.edu

16/j.jalz.2015.04.011

e Alzheimer’s Association. Published by Elsevier Inc. All r

effects on cognitive decline [5,6]. We devised a new diet that
is tailored to protection of the brain, called the
Mediterranean-DASH diet intervention for neurodegenera-
tive delay (MIND). The diet is styled after theMediterranean
and DASH diets but with modifications based on the most
compelling findings in the diet-dementia field. For example,
a number of prospective studies [7–10] observed slower
decline in cognitive abilities with high consumption of
vegetables, and in the two US studies, the greatest
protection was from green leafy vegetables [7,8].
Furthermore, all these studies found no association of
overall fruit consumption with cognitive decline. However,
animal models [11] and one large prospective cohort study
[12] indicate that at least one particular type of fruit—
berries—may protect the brain against cognitive loss.

ights reserved.

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mailto:martha_c_morris@rush.edu

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http://dx.doi.org/10.1016/j.jalz.2015.04.011

M.C. Morris et al. / Alzheimer’s & Dementia 11 (2015) 1015-10221016

Thus, among the unique components of the MIND diet score
are that it specifies consumption of green leafy

vegetables

and berries but does not score other types of fruit. In this
study, we related the MIND diet score to cognitive decline
in the Memory and Aging Project (MAP) and compared
the estimated effects to those of the Mediterranean and
DASH diets; dietary patterns that we previously reported
were protective against cognitive decline among the MAP
study participants [13].

2. Methods

2.1. Study population

The analytic sample is drawn from the RushMAP, a study
of residents of.40 retirement communities and senior pub-
lic housing units in the Chicago area. Details of the MAP
study were published previously [14]. Briefly, the ongoing
open cohort study began in 1997 and includes annual clinical
neurologic examinations. At enrollment, participants are
free of known dementia [15,16] and agree to annual
clinical evaluation and organ donation after death. We
excluded persons with dementia based on accepted clinical
criteria as previously described [15,16]. Participants
meeting criteria for mild cognitive impairment [17]
(n 5 220) were not excluded except in secondary analyses.
From February 2004 to 2013, the MAP study participants
were invited to complete food frequency questionnaires
(FFQs) at the time of their annual clinical evaluations. Dur-
ing that period, a total of 1545 older persons had enrolled in
the MAP study, 90 died and 149 withdrew before the diet
study began, leaving 1306 participants eligible for these an-
alyses. Of these, 1068 completed the dietary questionnaires
of which 960 survived and had at least two cognitive assess-
ments for the analyses of change. The analytic sample was
95% white and 98.5% non-Hispanic. The Institutional Re-
view Board of Rush University Medical Center approved
the study, and all participants gavewritten informed consent.

2.2. Cognitive assessments

Each participant underwent annual structured clinical
evaluations including cognitive testing. Technicians, trained
and certified according to standardized neuropsychological
testing methods, administered 21 tests, 19 of which summa-
rized cognition in five cognitive domains (episodic memory,
working memory, semantic memory, visuospatial ability,
and perceptual speed) as described previously [18]. Com-
posite scores were computed for each cognitive domain
and for a global measure of all 19 tests. Raw scores for
each test were standardized using the mean and standard de-
viation from the baseline population scores, and the stan-
dardized scores averaged. The number of annual cognitive
assessments analyzed for participants ranged from 2 to 10
with 52% of sample participants having five or more cogni-
tive assessments.

2.3. Diet assessment

FFQs were collected at each annual clinical evaluation.
For these prospective analyses of the estimated dietary ef-
fects on cognitive change, we used the first obtained FFQ
to relate dietary scores to cognitive change from that point
forward. Longitudinal analyses of change in MIND diet
score using all available FFQs in a linear mixed model indi-
cated a very small but statistically significant decrease in
MIND score of20.026 (P 5 .02) compared to the intercept
MIND diet score of 7.37.

Diet scores were computed from responses to a modified
Harvard semiquantitative FFQ that was validated for use in
older Chicago community residents [19]. The FFQ ascer-
tains usual frequency of intake over the previous 12 months
of 144 food items. For some food items, natural portion sizes
(e.g., one banana) were used to determine serving sizes and
calorie and nutrient levels. Serving sizes for other food items
were based on sex-specific mean portion sizes reported by
the oldest men and women of national surveys.

2.4. MIND diet score

The MIND diet score was developed in three stages: (1)
determination of dietary components of the Mediterranean
and DASH diets including the foods and nutrients shown to
be important to incident dementia and cognitive decline
through detailed reviews of the literature [20–22], (2)
selection of FFQ items that were relevant to each MIND diet
component, and (3) determination of daily servings to be
assigned to component scores guided by published studies
on diet and dementia. Among the MIND diet components
are 10 brain healthy food groups (green leafy vegetables,
other vegetables, nuts, berries, beans, whole grains, seafood,
poultry, olive oil, and wine) and five unhealthy food groups
(red meats, butter and stick margarine, cheese, pastries and
sweets, and fried/fast food). Olive oil consumption was
scored 1 if identified by the participant as the primary oil
usually used at home and 0 otherwise. For all other diet
score components, we summed the frequency of
consumption of each food item portion associated with that
component and then assigned a concordance score of 0, 0.5,
or 1 (Table 1). The total MIND diet score was computed by
summing over all 15 of the component scores.

2.5. DASH and Mediterranean diet scores

We used the DASH diet scoring of the Exercise and Nutri-
tion Interventions for Cardiovascular Health (ENCORE)
trial [23] in which 10 dietary components were each scored
0, 0.5, or 1 and summed for a total score ranging from
0 (lowest) to 10 (highest) diet concordance. The Mediterra-
nean diet score was that described by Panagiotakos et al. [3]
that includes 11 dietary components each scored 0–5 that are
summed for a total score ranging from 0 to 55 (highest die-
tary concordance). We used serving quantities specific to the
traditional Greek Mediterranean diet [3] to score

Table 1

MIND diet component servings and scoring

Diet component 0 0.5 1

Green leafy*

vegetables

�2 servings/wk .2 to ,6/wk �6 servings/wk

Other vegetablesy ,5 serving/wk 5 to ,7 wk �1 serving/d
Berriesz ,1 serving/wk 1/wk �2 servings/wk
Nuts ,1/mo 1/mo to ,5/wk �5 servings/wk
Olive oil Not primary oil Primary oil used

Butter, margarine .2 T/d 1–2/d ,1 T/d
Cheese 7 1 servings/wk 1–6/wk ,1 serving/wk
Whole grains ,1 serving/d 1–2/d �3 servings/d
Fish (not fried)k Rarely 1–3/mo �1 meals/wk
Beansx ,1 meal/wk 1–3/wk .3 meals/wk
Poultry (not

fried){
,1 meal/wk 1/wk �2 meals/wk

Red meat and

products#
7 1 meals/wk 4–6/wk ,4 meals/wk

Fast fried foods** 4 1 times/wk 1–3/wk ,1 time/wk
Pastries and

sweetsyy
7 1 servings/wk 5–6/wk ,5 servings/wk

Wine .1 glass/d or
never

1/mo–6/wk 1 glass/d

Total score 15

Abbreviation: MIND, Mediterranean-DASH diet intervention for neuro-

degenerative delay.

*Kale, collards, greens; spinach; lettuce/tossed salad.
yGreen/red peppers, squash, cooked carrots, raw carrots, broccoli, celery,

potatoes, peas or lima beans, tomatoes, tomato sauce, string beans, beets,

corn, zucchini/summer squash/eggplant, coleslaw, potato salad.
zStrawberries.
xBeans, lentils, soybeans.
kTuna sandwich, fresh fish as main dish; not fried fish cakes, sticks, or

sandwiches.
{Chicken or turkey sandwich, chicken or turkey as main dish, and never

eat fried at home or away from home.
#Cheeseburger, hamburger, beef tacos/burritos, hot dogs/sausages, roast

beef or ham sandwich, salami, bologna, or other deli meat sandwich, beef

(steak, roast) or lamb as main dish, pork or ham as main dish, meatballs

or meatloaf.

**How often do you eat fried food away from home (like French fries,

chicken nuggets)?
yyBiscuit/roll, poptarts, cake, snack cakes/twinkies, Danish/sweet rolls/

pastry, donuts, cookies, brownies, pie, candy bars, other candy, ice cream,

pudding, and milkshakes/frappes.

M.C. Morris et al. / Alzheimer’s & Dementia 11 (2015) 1015-1022 1017

concordance in contrast to the use of sex-specific within pop-
ulation median servings used by other studies so that the
scoring metric aligned with the actual Mediterranean diet.

2.6. Covariates

Total energy intake was computed based on responses of
frequency of consumption of the FFQ food items. Nondiet-
ary variables were obtained from structured interview ques-
tions and measurements at the participants’ annual clinical
evaluations. Age (in years) was computed from self-
reported birth date and date of the first cognitive assessment
in this analysis. Education was based on self-reported years
of regular schooling. Apolipoprotein E genotyping was per-
formed using high throughput sequencing as previously
described [24]. Smoking history was categorized as never,

past, and current smoker. All other covariates were based
on data collected at the time of each cognitive assessment
and were modeled as time-varying covariates to represent
updated information from participants’ previous evalua-
tions. Avariable for frequency of participation in cognitively
stimulating activities was computed as the average fre-
quency rating, based on a 5-point scale, of different activities
(e.g., reading, playing games, writing letters, visiting the li-
brary) [25]. Hours per week of physical activity was
computed based on the sum of self-reported minutes spent
over the previous two weeks on five activities (walking for
exercise, yard work, calisthenics, biking, and water exercise)
[26]. Number of depressive symptoms was assessed by a
modified 10-item version of the Center for Epidemiological
Studies-Depression scale [27] that has been related to inci-
dent dementia. Body mass index (BMI, weight in kg/height
in m2) was computed from measured weight and height and
modeled as two indicator variables, BMI�20 and BMI�30.
Hypertension history was determined by self-reported med-
ical diagnosis, measured blood pressure (average of 2 mea-
surements �160 mm Hg systolic or �90 mm Hg diastolic),
or current use of hypertensive medications. Myocardial
infarction history was based on self-reported medical diag-
nosis or interviewer recorded use of cardiac glycosides
(e.g., lanoxin, digitoxin). Diabetes history was determined
by self-reported medical diagnosis or current use of medica-
tions. Medication use was based on interviewer inspection.
Clinical diagnosis of stroke was based on clinician review
of self-reported history, neurologic examination, and cogni-
tive testing history [28].

2.7. Statistical methods

We used separate linear mixed models with random ef-
fects in SAS to examine the relations of the MIND diet score
to change in the global cognitive score and in each cognitive
domain score. The basic-adjusted model included terms for
age, sex, education, apolipoprotein E (APOE) ε4, smoking
history, physical activity, participation in cognitive activ-
ities, total energy intake, MIND diet score, a variable for
time, and multiplicative terms between time and each model
covariate, the latter providing the covariate effect on cogni-
tive decline. For all analyses, we investigated both linear
(MIND diet score modeled as a continuous term) and
nonlinear associations (MIND diet score modeled in tertiles)
with the cognitive scores. Because the study results were
identical for the two sets of models, we report the effect es-
timates for the continuous linear term in tables and text and
the tertile estimates in Fig. 1. Nonstatic covariates (e.g.,
cognitive and physical activities, BMI, depressive symptoms
and cardiovascular conditions) were modeled as time-
varying except when they were analyzed as potential effect
modifiers in which case only the baseline measure for that
covariate was modeled. Tests for statistical interaction by
potential effect modifiers were computed in the basic-
adjusted model by modeling two-way and three-way

Fig. 1. Rates of change in global cognitive score over 10 years forMAP par-

ticipants with MIND diet scores in the highest tertile of scores (- – -; median,

9.5; range, 8.5–12.5), the second tertile of scores (.; median, 7.5; range,
7.0–8.0), and the lowest tertile of scores (—; median, 6; range, 2.5–6.5).

The rates of change were based on the mixed model with MIND diet score

modeled as two indicator variables for tertile 2 and tertile 3 (tertile 1, the

referent) and adjusted for age, sex, education, smoking, physical activity,

participation in cognitively stimulating activities, and total energy intake.

For tertile 3: b5 0.0366, standard error5 0.0101, and P5 .003 and for ter-
tile 2: b 5 0.0243, standard error 5 0.0099, and P 5 .01. Abbreviations:
MAP, Memory and Aging Project; MIND, Mediterranean-DASH diet inter-

vention for neurodegenerative delay.

Table 2

Baseline characteristics* of analyzed MAP participants according to tertile

of MIND diet score

Characteristic n

MIND diet score tertile

Tertile 1 Tertile 2 Tertile 3

M.C. Morris et al. / Alzheimer’s & Dementia 11 (2015) 1015-10221018

multiplicative terms betweenMIND diet score, time, and the
effect modifier, with the three-way multiplicative term test
for interaction set at P � .05. We compared the relative ef-
fects of the MIND, Mediterranean and DASH diet scores
on cognitive decline by computing standardized b coeffi-
cients (b to four decimal places/standard error) for each
diet score based on the parameter estimates of the basic
model. We then performed formal statistical tests using
Meng et al.’s [29] revision of Hotelling’s [30] procedure
for comparing two nonindependent correlation coefficients,
in this case, the correlations between the diet scores and
cognitive change from the basic model. To provide an esti-
mate of the equivalent age difference in years to the differ-
ence in decline rates for tertiles 3 and 1 of the MIND diet
score, we computed the ratio of the beta coefficients [b
(time ! age)/b (time ! tertile 3 MIND score) in the
basic-adjusted model.

Age, mean y 960 81.9 81.7 80.5

Male, percent 960 28 26 23

APOE ε4, percent 823 22 26 21

Education, mean y 960 14.3 15.1 15.6

Cognitive activities, mean 959 3.1 3.2 3.4

Total energy intake, mean kcal 960 1665 1788 1794

Smoking, percent never 960 40 38 42

Physical activity, mean h/wk 958 2.5 3.4 4.3

Depressive symptoms, mean

number

959 1.4 0.9 0.9

BMI, mean 927 27.5 27.1 26.7

Hypertension, percent 954 79 76 72

Diabetes, percent 960 24 20 17

Heart disease history, percent 959 18 12 18

Clinical stroke history, percent 870 11 7 9

Abbreviations: MAP, Memory and Aging Project; MIND,

Mediterranean-DASH diet intervention for neurodegenerative delay;

APOE, apolipoprotein E; BMI, body mass index.

*Characteristics were standardized by age in 5-year categories.

3. Results

The analytic sample aged, on average, 81.4 years (67.2),
was primarily female (75%), had a mean educational level of
14.9 years (62.9), and was demographically comparable
with the entire MAP cohort of 1545 participants (mean
age, 80.1 years; 73% female; mean education, 14.4 years).
Computed MIND scores from food frequency data on
MAP study participants averaged 7.4 (range, 2.5–12.5).
MIND diet scores were positively correlated with both the
Mediterranean (r 5 0.62) and the DASH (r 5 0.50) diet
scores. MAP participants with the highest MIND diet scores
tended to have a more favorable risk profile for preserving
cognitive abilities including higher education, greater partic-
ipation in cognitive and physical activities, and lower prev-
alence of cardiovascular conditions (Table 2).

The overall rate of change in cognitive score was a
decline of 0.08 standardized score units per year. In mixed
models adjusted for age, sex, education, total energy intake
APOE ε4, smoking history, physical activity, and participa-
tion in cognitive activities, the MIND diet score was posi-
tively and statistically significantly associated with slower
rate of cognitive decline (Table 3). Compared to the decline
rate of participants in the lowest tertile of scores, the rate for
participants in the highest tertile was substantially slower
(Fig. 1). The difference in rates was the equivalent of being
7.5 years younger. The MIND diet score was statistically
significantly associated with each cognitive domain, partic-
ularly for episodic memory, semantic memory, and percep-
tual speed (Table 3).

TheMediterranean and DASH diets have demonstrated ef-
fects on the reduction of cardiovascular conditions and risk
factors [31–34], which raises the possibility that the
association of the MIND diet with cognitive decline may be
because of its effects on cardiovascular disease. To
investigate potential mediation by these factors, we
reanalyzed the basic model for the global cognitive score
and each cognitive domain score with the inclusion of terms
for hypertension, stroke, myocardial infarction, and diabetes;
however, the effect estimates did not change (Table 3).

Depression and weight have complex relations with de-
mentia; they are known both as risk factors (depression
and obesity) and as outcomes of the disease (depressive
symptoms and weight loss). Both factors are also affected
by diet quality. Therefore, we examined in the basic model
what impact additional control for these variables might
have on the observed association between the MIND diet
score and cognitive decline but these adjustments also did
not change the results for any of the cognitive measures

M.C. Morris et al. / Alzheimer’s & Dementia 11 (2015) 1015-1022 1019

(e.g., for global cognitive function b 5 0.0092, standard
error 5 0.0022, P , .0001).

We also investigated potential modifications in the esti-
mated effect of the MIND diet score on cognitive decline
by age, sex, APOE ε4, education, physical activity, low
weight (BMI �20), obese (BMI �30), and each of the
cardiovascular-related conditions (hypertension, myocardial
infarction, stroke, and diabetes). However, there was no sta-
tistical evidence that the diet effect on the global or individ-
ual domain cognitive scores differed by level or presence of
any of these risk factors (data not shown).

To examine whether the observed MIND diet—cognitive
decline relation—may be due to dementia effects on dietary
behaviors or to reporting accuracy, we reanalyzed the data
after eliminating 220 participants who had mild cognitive
impairment at the baseline; the resulting decline rate for
higher MIND diet score (b 5 0.0104, P , .00001) was
even more protective, by 9.5%, compared with that of the
entire sample (b 5 0.0095).

We also investigated the potential effects of dietary
changes over time on the observed associations of baseline
MIND diet score with cognitive change. We reanalyzed
the data after excluding 144 participants whose MIND diet
scores either improved (top 10%) or decreased (bottom
10%) over the study period. The protective estimates of ef-
fect of the MIND diet score on change in global cognitive
score increased considerably (b 5 0.0120, P , .00001) in
the basic-adjusted model. The estimated effects of the
MIND diet on the individual cognitive domains also
increased by 30%–78% with the exception of visuospatial
ability, which had little change (b 5 0.0072, P 5 .02).

In a previous study of the MAP participants [35], we
observed protective relations of both the MedDiet and
DASH diet scores to cognitive decline. A comparison of these
diet components and scores is provided in Supplementary
Table 1.We analyzed the data for these twodiet scores in sepa-
rate basic-adjusted models of the global cognitive scores and
compared the standardized regression coefficients for all three
diet scores. The MIND diet score was more predictive of
cognitive decline than either of the other diet scores; the stan-
dardized b coefficients of the estimated diet effects were 4.39
forMIND, 2.46 for theMedDiet, and 2.60 forDASH.The cor-
relation between the MIND score with cognitive change was
statistically significantly higher compared with that for either
the MedDiet (P5 .02) or the DASH (P5 .03) scores.

4. Discussion

In this community-based study of older persons, we
investigated the relation of diet to change in cognitive func-
tion using an �a priori-defined diet composition score
(MIND) based on the foods and nutrients shown to be pro-
tective for dementia. HigherMIND diet scorewas associated
with slower decline in cognitive abilities. The rate reduction
for persons in the highest tertile of diet scores compared with
the lowest tertile was the equivalent of being 7.5 years

younger. Strong associations of the MIND diet were
observed with the global cognitive measure as well as with
each of the five cognitive domains. The strength of the esti-
mated effect was virtually unchanged after statistical control
for many of the important confounders, including physical
activity and education as well as with the exclusion of indi-
viduals with the lowest baseline cognitive scores.

The MIND diet was based on the dietary components of
the Mediterranean and DASH diets, including emphasis on
natural plant-based foods and limited intake of animal and
high saturated fat foods. However, the MIND diet uniquely
specifies consumption of berries and green leafy vegetables
and does not specify high fruit consumption (both DASH
and Mediterranean), high dairy (DASH), high potato con-
sumption, or .1 fish meal per week (Mediterranean). The
MIND modifications highlight the foods and nutrients
shown through the scientific literature to be associated
with dementia prevention [21,22,36]. A number of
prospective cohort studies found that higher consumption
of vegetables was associated with slower cognitive decline
[7–10] with the strongest relations observed for green
leafy vegetables [7,8]. Green leafy vegetables are sources
of folate, vitamin E, carotenoids, and flavonoids, nutrients
that have been related to lower risk of dementia and
cognitive decline. There is a vast literature demonstrating
neuroprotection of the brain by vitamin E, rich sources of
which are vegetable oils, nuts, and whole grains [21]. Die-
tary intakes of berries were demonstrated to improve mem-
ory and learning in animal models [11] and to slow cognitive
decline in the Nurses’ Health Study [12]. However, the pro-
spective epidemiologic studies of cognitive decline or de-
mentia do not observe protective benefit from the
consumption of fruits in general [7–10]. These dietary
components have been demonstrated to protect the brain
through their antioxidant and anti-inflammatory properties
(vitamin E) [37,38] and inhibition of b-amyloid deposition
(vitamin E, folate, flavonoids, and carotenoids) [38–42]
and neurotoxic death (vitamin E and flavonoids) [43].
Studies of fish consumption observed lower risk of dementia
with just one fish meal a week with no additional benefit
evident for higher servings per week [44–46]. Thus, the
highest possible score for this component of the MIND
diet score is attributed to one or more servings per week.
Mediterranean diet interventions supplemented with either
nuts or extra-virgin olive oil were effective in maintaining
higher cognitive scores compared with a low-fat diet in a
substudy of PREDIMED [6], a randomized trial designed
to test diet effects on cardiovascular outcomes among Span-
iards at high cardiovascular risk. The MIND diet compo-
nents directed to limiting intake of unhealthy foods for the
brain target foods that contribute to saturated and trans fat in-
takes; these include red meat and meat products, butter and
stick margarine, whole fat cheese, pastries and sweets, and
fried/fast foods. Fat composition that is higher in saturated
and trans fats and lower in polyunsaturated and monounsat-
urated fats lead to blood-brain barrier dysfunction and

Table 3

Estimated effects (b)* of theMIND diet score on the rate of change in global cognitive score and change in five cognitive domains amongMAP participants over

an average 4.7 years of follow-up in adjusted* mixed models

Estimated effects Global cognition

Episodick

memory

Semantic{

memory

Perceptual#

organization

Perceptual**

speed

Workingyy

memory

Age-adjusted

ny 960 949 945 932 934 957
b 0.0090 0.0079 0.0069 0.0057 0.0088 0.0049

Standard error 0.0023 0.0027 0.0026 0.0025 0.0024 0.0024

P value .0001 .003 .007 .02 .0002 .04

Basicz

ny 818 808 804 793 794 816
b 0.0095 0.0080 0.0105 0.0077 0.0084 0.0050

Standard error 0.0023 0.0028 0.0027 0.0025 0.0024 0.0024

P value ,.0001 .004 .0001 .002 .0003 .04
Basic 1 cardiovascular conditionsx

ny 860 850 846 835 836 858
b 0.0106 0.0090 0.0113 0.0077 0.0097 0.0060

Standard error 0.0023 0.0028 0.0027 0.0025 0.0023 0.0024

P value ,.0001 .001 ,.0001 .002 ,.0001 .01

Abbreviations: MIND, Mediterranean-DASH diet intervention for neurodegenerative delay; MAP, Memory and Aging Project.

*b 5 beta coefficient from the model for the interaction term between MIND diet score and time.
yn 5 total number of participants with complete data for model.
zBasic model includes age at the first cognitive assessment, Mind diet score, sex, education, participation in cognitive activities, APOE ε4 (any ε4 allele),

smoking history (current, past, and never), physical activity hours per week, total energy intake, time and interaction terms between time and each model co-

variate.
xBasic model plus history of stroke, myocardial infarction, diabetes, hypertension, and interaction terms between each covariate and time.
kComposite score of the following seven instruments: Immediate memory test and delayedmemory test from Story A Logical Memory subset of theWechsler

memory scale-revised; immediate word recall and delayed word recall of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list

recall; CERAD word list recognition; and immediate memory test and delayed memory test of the East Boston Story.
{Composite score of the following three instruments: Verbal fluency from CERAD; 15-item version of the Boston naming test; and 15-item reading test.
#Composite score of the 15-item version of judgment of line orientation and the 16-item version of standard progressive matrice.

**Composite score of the following four measures: Oral version of the symbol digit modalities test; number comparison; and two indices from a modified

version of the Stroop neuropsychological screening test.
yyComposite score of the following three instruments: digit span subtests-forward of the Wechsler memory scale-revised; digit span subtests-backward of the

Wechsler memory scale-revised; and digit ordering.

M.C. Morris et al. / Alzheimer’s & Dementia 11 (2015) 1015-10221020

increased Ab aggregation [22]. Fish are a rich source of
long-chain n-3 fatty acids which have been shown to reduce
Ab formation and oxidative damage and to increase synaptic
proteins and dendritic spine density [47,48].

The study findings are supported by a number of strengths
including the prospective study design with up to 10 years of
follow-up, annual assessment of cognitive function using a
battery of standardized tests, comprehensive assessment of
diet using a validated questionnaire, and statistical control
of the important confounding factors. Another important
strength is that the MIND diet score was devised based on
expansive reviews of studies relating diet to brain function
[20–22,36]. None of the studies included in these reviews
were conducted in the MAP study cohort. The fact that the
food components were selected independently of the best
statistical prediction of the outcome in the MAP study
population lends validity to the MIND diet as a preventive
measure for cognitive decline with aging.

A limitation of the study is that the dietary questionnaire
had few questions to measure some of the dietary compo-
nents and limited information on frequency of consumption.
For example, a single item each provided information on con-
sumption of nuts, berries (strawberries), beans, and olive oil.

However, this imprecision in the measurement of the MIND
scorewould tend to underestimate the diet effect on cognitive
decline. Another limitation is the self-report of diet which
some studies suggest can lead to biased reporting in over-
weight [49] and cognitively impaired [50] adults. Concern
that biased diet reporting could explain the findings is miti-
gated by the fact that statistical control for factors such as
obesity, education, age, and physical activity had no impact
on the estimated MIND diet effect and the association re-
mained strong in analyses that omitted the participants with
mild cognitive impairment and whose diet scores changed
over the study period. Furthermore, we observed no modifi-
cation in the effect by level of these potential confounders.

The primary limitation of the study is that it is observa-
tional and thus the findings cannot be interpreted as a
cause-and-effect relation. Replication of the findings in
other cohort studies is important for confirmation of the as-
sociation; however, a diet intervention trial is required to
establish a causal relation between diet and prevention of
cognitive decline. Furthermore, the findings were based on
an old, largely non-Hispanic white study population and
cannot be generalized to younger populations or different
racial/ethnic groups.

M.C. Morris et al. / Alzheimer’s & Dementia 11 (2015) 1015-1022 1021

The MIND diet is a refinement of the extensively studied
cardiovascular diets, the Mediterranean and DASH diets,
with modifications based on the scientific literature relevant
to nutrition and the brain. This literature is underdeveloped
and, therefore, modifications to the MIND diet score would
be expected as new scientific advances are made.

Acknowledgment

The study was funded by grants (R01AG031553 and
R01AG17917) from the National Institute on Aging.

Supplementary data

Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.jalz.2015.04.011.

RESEARCH IN CONTEXT

1. Systematic review: We performed extensive reviews
of the literature on nutrition and neurodegenerative
diseases and cognitive decline to devise a brain
healthy diet called MIND. The reviews included an-
imal models, prospective epidemiologic studies, and
randomized trials of nutrients, individual foods, and
whole diets.

2. Interpretation: The MIND diet builds on previously
tested diets, particularly the Mediterranean and
DASH diets, for prevention of dementia outcomes
by incorporating specific foods and intake levels
that reflect the current state of knowledge in the field.

3. Future directions: In the present study, theMIND diet
was strongly associated with slower cognitive
decline and had greater estimated effects than either
the Mediterranean diet or the DASH diet. Future
studies should evaluate and confirm the preventive
relation of the MIND diet to cognitive change in
other populations. As the field develops, the MIND
dietary components should be modified to reflect
new knowledge on nutrition and the brain.

References

[1] 2013 Alzheimer’s Disease Facts and Figures. Volume 9, Issue 2. 2013.

Alzheimer’s Association, Chicago.

[2] Changing the trajectory of Alzheimer’s disease: How a treatment by

2025 saves lives and dollars. Chicago: Alzheimer’s Association; 2015.

[3] Panagiotakos DB, Pitsavos C, Arvaniti F, Stefanadis C. Adherence to

the Mediterranean food pattern predicts the prevalence of hyperten-

sion, hypercholesterolemia, diabetes and obesity, among healthy

adults; the accuracy of the MedDiet score. Prev Med 2007;44:335–40.

[4] Sacks FM, Appel LJ, Moore TJ, Obarzanek E, Vollmer WM,

Svetkey LP, et al. A dietary approach to prevent hypertension: A re-

view of the dietary approaches to stop hypertension (DASH) study.

Clin Cardiol 1999;22:III6–10.

[5] Smith PJ, Blumenthal JA, Babyak MA, Craighead L, Welsh-

Bohmer KA, Browndyke JN, et al. Effects of the dietary approaches

to stop hypertension diet, exercise, and caloric restriction on neurocog-

nition in overweight adults with high blood pressure. Hypertension

2010;55:1331–1338.

[6] Martinez-Lapiscina EH, Clavero P, Toledo E, Estruc R, Salas-

Salvado J, San JB, et al. Mediterranean diet improves cognition: the

PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psy-

chiatry 2013;84:1318–1325.

[7] Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Associ-

ations of vegetable and fruit consumption with age-related cognitive

change. Neurology 2006;67:1370–1376.

[8] Kang JH, Ascherio A, Grodstein F. Fruit and vegetable consump-

tion and cognitive decline in aging women. Ann Neurol 2005;

57:713–720.

[9] Nooyens AC, Bueno-de-Mesquita HB, van Boxtel MP, van

Gelder BM, Verhagen H, Verschuren WM. Fruit and vegetable intake

and cognitive decline in middle-aged men and women: The Doetin-

chem cohort study. Br J Nutr 2011;106:752–761.

[10] Chen X, Huang Y, Cheng HG. Lower intake of vegetables and legumes

associated with cognitive decline among illiterate elderly Chinese: A

3-year cohort study. J Nutr Health Aging 2012;16:549–552.

[11] Willis LM, Shukitt-Hale B, Joseph JA. Recent advances in berry sup-

plementation and age-related cognitive decline. Curr Opin Clin Nutr

Metab Care 2009;12:91–94.

[12] Devore EE, Kang JH, Breteler MM, Grodstein F. Dietary intakes of

berries and flavonoids in relation to cognitive decline. Ann Neurol

2012;72:135–143.

[13] Tangney CC, Li H, Wang Y, Barnes LL, Schneider JA, Bennett DA,

et al. Relation of DASH- and Mediterranean-like dietary patterns on

cognitive decline in older persons. Neurology 2014;83:1410–1416.

[14] Bennett DA, Schneider JA, Buchman AS, Barnes LL, Boyle PA,

Wilson RS. Overview and findings from the rush memory and aging

project. Curr Alzheimer Res 2012;9:646–663.

[15] McKhann G, Drachman D, Folstein M, Katzman R, Price D,

Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the

NINCDS-ADRDAWork Group under the auspices of Department of

Health and Human Services Task Force on Alzheimer’s Disease.

Neurology 1984;34:939–944.

[16] Bennett DA, Schneider JA, Aggarwal NT, Arvanitakis Z, Shah RC,

Kelly RF, et al. Decision rules guiding the clinical diagnosis of Alz-

heimer’s disease in two community-based cohort studies compared

to standard practice in a clinic-based cohort study. Neuroepidemiology

2006;27:169–176.

[17] Bennett DA, Wilson RS, Schneider JA, Evans DA, Beckett LA,

Aggarwal NT, et al. Natural history of mild cognitive impairment in

older persons. Neurology 2002;59:198–205.

[18] Wilson RS, Arnold SE, Tang Y, Bennett DA. Odor identification and

decline in different cognitive domains in old age. Neuroepidemiology

2006;26:61–67.

[19] Morris MC, Tangney CC, Bienias JL, Evans DA, Wilson RS. Validity

and reproducibility of a food frequency questionnaire by cognition in

an older biracial sample. Am J Epidemiol 2003;158:1213–1217.

[20] Barnes JL, Tian M, Edens NK, Morris MC. Consideration of nutrient

levels in studies of cognitive decline: A review. Nutr Rev 2014;

72:707–719.

[21] Morris MC. Nutritional determinants of cognitive aging and dementia.

Proc Nutr Soc 2012;71:1–13.

[22] Morris MC, Tangney CC. Dietary fat composition and dementia risk.

Neurobiol Aging 2014;35 Suppl 2:S59–64.

[23] Epstein DE, Sherwood A, Smith PJ, Craighead L, Caccia C, Lin PH,

et al. Determinants and consequences of adherence to the dietary ap-

proaches to stop hypertension diet in African-American and white

http://dx.doi.org/10.1016/j.jalz.2015.04.011

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref1

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref2

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref3

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref4

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref5

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref6

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref7

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref8

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref9

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref10

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref11

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref12

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref13

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref14

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref15

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref16

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref17

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref18

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref19

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref20

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref21

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref22

M.C. Morris et al. / Alzheimer’s & Dementia 11 (2015) 1015-10221022

adults with high blood pressure: Results from the ENCORE trial. J

Acad Nutr Diet 2012;112:1763–73.

[24] Buchman AS, Boyle PA, Wilson RS, Beck TL, Kelly JF, Bennett DA.

Apolipoprotein E e4 allele is associated with more rapid motor decline

in older persons. Alzheimer Dis Assoc Disord 2009;23:63–9.

[25] Wilson RS, Barnes LL, Krueger KR, Hoganson G, Bienias JL,

Bennett DA. Early and late life cognitive activity and cognitive sys-

tems in old age. J Int Neuropsychol Soc 2005;11:400–7.

[26] BuchmanAS, Boyle PA,Wilson RS, Bienias JL, Bennett DA. Physical

activity and motor decline in older persons. Muscle Nerve 2007;

35:354–62.

[27] Kohout FJ, Berkman LF, Evans DA, Cornoni-Huntley J. Two shorter

forms of the CES-D depression symptoms index. J Aging Health

1993;5:179–93.

[28] Bennett DA. Secular trends in stroke incidence and survival, and the

occurrence of dementia. Stroke 2006;37:1144–5.

[29] Meng XL, Rosenthal R, Rubin DB. Comparison of correlated correla-

tion coefficients. Psychol Bull 1992;111:172–5.

[30] Hotelling H. The selection of variates for use in prediction, with some

comments in the general problem of nuisance parameters. Ann Math

Stat 1940;11:271–83.

[31] Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP,

Sacks FM, et al. A clinical trial of the effects of dietary patterns on

blood pressure. DASH Collaborative Research Group. N Engl J Med

1997;336:1117–24.

[32] Salas-Salvado J, Bullo M, Babio N, Martinez-Gonzalez MA, Ibarrola-

Jurado N, Basora J, et al. Reduction in the incidence of type 2 diabetes

with the Mediterranean diet: Results of the PREDIMED-Reus nutri-

tion intervention randomized trial. Diabetes Care 2011;34:14–9.

[33] Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, et al.

Primary prevention of cardiovascular disease with a Mediterranean

diet. N Engl J Med 2013;368:1279–90.

[34] Toledo E, Hu FB, Estruch R, Buil-Cosiales P, Corella D, Salas-

Salvado J, et al. Effect of the Mediterranean diet on blood pressure

in the PREDIMED trial: Results from a randomized controlled trial.

BMC Med 2013;11:207.

[35] Tangney CC, Li H, Barnes LL, Schneider JA, Bennett DA, Morris MC.

Accordance to dietary approaches to stop hypertension (DASH) is asso-

ciatedwith slower cognitive decline. AlzheimersDement 2013;9:605–6.

[36] Gillette GS, bellan Van KG, Andrieu S, Salas-Salvado J, Berr C,

Bonnefoy M, et al. IANA task force on nutrition and cognitive decline

with aging. J Nutr Health Aging 2007;11:132–52.

[37] Yamada K, Tanaka T, Han D, Senzaki K, Kameyama T, Nabeshima T.

Protective effects of idebenone and alpha-tocopherol on beta-amyloid-

(1-42)-induced learning and memory deficits in rats: Implication of

oxidative stress in beta-amyloid-induced neurotoxicity in vivo. Eur J

Neurosci 1999;11:83–90.

[38] Jiang Q, Ames BN, Jiang Q, Lykkesfeldt J, Shigenaga MK,

Shigeno ET, et al. Gamma-tocopherol, but not alpha-tocopherol, de-

creases proinflammatory eicosanoids and inflammation damage in

rats. FASEB J 2003;17:816–22.

[39] Chan A, Shea TB. Folate deprivation increases presenilin expression,

gamma-secretase activity, and Abeta levels in murine brain: Potentia-

tion by ApoE deficiency and alleviation by dietary S-adenosyl methi-

onine. J Neurochem 2007;102:753–60.

[40] Nishida Y, Ito S, Ohtsuki S, Yamamoto N, Takahashi T, Iwata N, et al.

Depletion of vitamin E increases amyloid beta accumulation by

decreasing its clearances from brain and blood in a mouse model of

Alzheimer disease. J Biol Chem 2009;284:33400–8.

[41] Katayama S, Ogawa H, Nakamura S. Apricot carotenoids possess

potent anti-amyloidogenic activity in vitro. J Agric Food Chem

2011;59:12691–6.

[42] Obulesu M, DowlathabadMR, Bramhachari PV. Carotenoids and Alz-

heimer’s disease: An insight into therapeutic role of retinoids in animal

models. Neurochem Int 2011;59:535–41.

[43] Jalsrai A, Numakawa T, Ooshima Y, Adachi N, Kunugi H. Phos-

phatase-mediated intracellular signaling contributes to neuroprotec-

tion by flavonoids of Iris tenuifolia. Am J Chin Med 2014;

42:119–30.

[44] Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Fish con-

sumption and cognitive decline with age in a large community study.

Arch Neurol 2005;62:1849–53.

[45] Larrieu S, Letenneur L, Helmer C, Dartigues JF, Barberger-Gateau P.

Nutritional factors and risk of incident dementia in the PAQUID lon-

gitudinal cohort. J Nutr Health Aging 2004;8:150–4.

[46] Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ,

Au R, et al. Plasma phosphatidylcholine docosahexaenoic acid con-

tent and risk of dementia and Alzheimer disease: The Framingham

Heart Study. Arch Neurol 2006;63:1545–50.

[47] Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, et al. A diet

enriched with the omega-3 fatty acid docosahexaenoic acid reduces

amyloid burden in an aged Alzheimer mouse model. J Neurosci

2005;25:3032–40.

[48] Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, et al. Doco-

sahexaenoic acid protects from dendritic pathology in an Alzheimer’s

disease mouse model. Neuron 2004;43:633–45.

[49] Neuhouser ML, Tinker L, Shaw PA, Schoeller D, Bingham SA,

Horn LV, et al. Use of recovery biomarkers to calibrate nutrient con-

sumption self-reports in the Women’s Health Initiative. Am J Epide-

miol 2008;167:1247–59.

[50] Bowman GL, Shannon J, Ho E, Traber MG, Frei B, Oken BS, et al.

Reliability and validity of food frequency questionnaire and nutrient

biomarkers in elders with and without mild cognitive impairment. Alz-

heimer Dis Assoc Disord 2011;25:49–57.

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref22

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref23

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref24

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref25

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref26

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref27

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref28

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref29

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref30

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref31

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref32

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref33

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref34

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref35

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref36

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref37

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref38

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref39

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref40

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref41

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref42

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref43

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref44

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref45

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref46

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref47

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref48

http://refhub.elsevier.com/S1552-5260(15)00194-6/sref49

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