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Cognitive Effects of Intentional Weight Loss in Elderly Obese Individuals With Mild Cognitive Impairment


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Context: Obesity in midlife is a risk factor for dementia, but it is unknown if caloric restriction-induced weight loss could prevent cognitive decline and therefore dementia in elderly patients with cognitive impairment. Objective: To evaluate the cognitive effect of intentional weight loss in obese elderly patients with mild cognitive impairment (MCI), considering the influence of age, apolipoprotein E genotype (APOE), physical activity, biochemical markers and diet. Design: Single-center, prospective controlled trial. Setting: Academic medical center Participants: Eighty obese patients with MCI, aged 60 or older (68.1±4.9 years, body mass index (BMI) 35.5±4.4kg/m(2), 83.7% women, 26.3% APOE4 carriers). Intervention: Random allocation to conventional medical care alone (n=40) or together with nutritional counselling (n=40) in group meetings aiming to promote weight loss through caloric restriction for 12 months. Outcome: Measurements: Clinical data, body composition, neuropsychological tests (main outcome), serum biomarkers, APOE genotype, physical performance, dietary recalls. Results: Seventy-five patients completed the follow-up. BMI, on average, decreased 1.7 ±1.8kg/m(2) (p=0.021), and most of the cognitive tests improved, without difference between the groups. In analysis with linear generalized models, the BMI decrease was associated with improvements in verbal memory, verbal fluency, executive function and global cognition, after adjustment for education, gender, physical activity and baseline tests: this association was strongest in younger seniors (for memory and fluency) and in APOE4 carriers (for executive function). Changes in HOMA-IR, C-reactive protein, leptin and intake of energy, carbohydrates and fats were associated with improvement in cognitive tests. Conclusions: Intentional weight loss through diet was associated with cognitive improvement in patients with MCI.
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Cognitive effects of intentional weight loss in elderly
obese individuals with mild cognitive impairment
Nidia Celeste Horie
, Valeria T Serrao
, Sharon Sanz Simon
Maria Rita Polo Gascon
, Alessandra Xavier dos Santos
Maria Aquimara Zambone
, Marta Merenciana del Bigio de Freitas
Edecio Cunha-Neto
, Emerson Leonildo Marques
, Alfredo Halpern
Maria Edna de Melo
, Marcio C Mancini
, Cintia Cercato
1- Obesity and Metabolic Syndrome Group- Sao Paulo University, School of Medicine; 2- Psychology
Division- Hospital das Clínicas, Sao Paulo University; 3- Institute of Psychiatry - Sao Paulo University,
School of Medicine; 4- Nutrition Division- Clinical Hospital - Sao Paulo University, School of Medicine; 5-
Discipline of Geriatrics - Sao Paulo University, School of Medicine; 6- Division of Clinical Immunology and
Allergy- Sao Paulo University, School of Medicine
Context: Obesity in midlife is a risk factor for dementia, but it is unknown if caloric restriction-
induced weight loss could prevent cognitive decline and therefore dementia in elderly patients
with cognitive impairment.
Objective: To evaluate the cognitive effect of intentional weight loss in obese elderly patients with
mild cognitive impairment (MCI), considering the influence of age, apolipoprotein E genotype
(APOE), physical activity, biochemical markers and diet.
Design: Single-center, prospective controlled trial.
Setting: Academic medical center
Participants: Eighty obese patients with MCI, aged 60 or older (68.14.9 years, body mass index
(BMI) 35.54.4kg/m
, 83.7% women, 26.3% APOE4 carriers).
Intervention: Random allocation to conventional medical care alone (n40) or together with
nutritional counselling (n40) in group meetings aiming to promote weight loss through caloric
restriction for 12 months.
Outcome: Measurements: Clinical data, body composition, neuropsychological tests (main out-
come), serum biomarkers, APOE genotype, physical performance, dietary recalls.
Results: Seventy-five patients completed the follow-up. BMI, on average, decreased 1.7 1.8kg/m
(p0.021), and most of the cognitive tests improved, without difference between the groups. In
analysis with linear generalized models, the BMI decrease was associated with improvements in
verbal memory, verbal fluency, executive function and global cognition, after adjustment for
education, gender, physical activity and baseline tests: this association was strongest in younger
seniors (for memory and fluency) and in APOE4 carriers (for executive function). Changes in HOMA-
IR, C-reactive protein, leptin and intake of energy, carbohydrates and fats were associated with
improvement in cognitive tests.
Conclusions: Intentional weight loss through diet was associated with cognitive improvement in
patients with MCI.
ISSN Print 0021-972X ISSN Online 1945-7197
Printed in USA
Copyright © 2015 by the Endocrine Society
Received May 17, 2015. Accepted December 11, 2015.
doi: 10.1210/jc.2015-2315 J Clin Endocrinol Metab 1
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Dementia is a syndrome characterized mainly by dete-
rioration in cognitive function and is one of the ma-
jor causes of disability and dependency among older peo-
ple. Nearly50 milion people worldwide have dementia,
and it is caused by a variety of conditions that affect the
brain, of which the most common is Alzheimer’s Disease
(1). Studies of secondary prevention have been performed
with subjects with mild cognitive impairment (MCI), who
have increased risk of dementia, but few strategies, such as
physical activity, have been shown to reduce cognitive
decline in prospective studies (2).
According to several epidemiological studies, obesity in
midlife increases the risk of dementia later in life (3, 4), and
insulin resistance, dyslipidemia, hypertension, low grade
inflammation and leptin resistance are associated with
both obesity and cognitive decline. Caloric restriction is
one of the mainstays of obesity treatment, and its neuro-
protective effect has largely been demonstrated in both
animal models (5) and also in cognitively normal humans
(6, 7). In patients with cognitive impairment, however, its
effects have not yet been tested. Research on the effects of
a hypocaloric diet in the elderly faces major obstacles:
late-life obesity has been associated with decreased de-
mentia risk (8), and many studies show that weight loss is
associated with increased mortality and disability, espe-
cially in subjects over 70 years of age (9). These risks,
however, seem to be more important in underweight or
normal-weight subjects than in obese (10) ones.
We hypothesized that intentional weight loss via caloric
restriction in elderly obese subjects with MCI could slow
the cognitive decline. We also evaluated the influence of
other risk factors for dementia, such as age, presence of the
apolipoprotein E allele
4 (APOE4 carriers or APOE4
noncarriers), metabolic and inflammatory parameters,
and diet. Considering the risks of lean mass and strength
loss following weight loss, the safety of the intervention
was verified by measuring changes in lean mass and phys-
ical functioning.
Materials and Methods
This study was approved by the ethics committee of the institu-
tion and was conducted in adherence with the Helsinki Decla-
ration; the trial is registered with NCT
01 286 389. Informed consent was obtained from all partici-
pants for being included in the study. A complete description of
the inclusion and exclusion criteria, participants selection, mea-
surements, and statistical analysis is in the Supplementary
Trial design
This was a prospective, 1:1, randomized study to assess the
cognitive effects of weight loss via caloric restriction in obese
subjects with MCI according to the European Consortium on
Alzheimer’s Disease (11), comparing groups who received con-
ventional care with or without nutritional counseling for 12
months (Figure 1). It was performed from June 2011 to May
2013 at the outpatient clinic of the of Hospital das Clinicas, São
Paulo University.
All patients were advised to engage in physical activity ac-
cording “The global recommendations on physical activity for
health” from the World Health Organization (12), briefly, they
should do at least 150 minutes of moderate-intensity aerobic
physical activity or walking throughout the week, or if limited
due to health conditions, they should be as physically active as
their abilities and conditions allow. All patients received con-
ventional medical care which was provided through consultation
with a geriatrician approximately every two months an which
focused on control of comorbidities. Half of the patients received
additionally nutritional counseling in groups conducted by nu-
tritionists (26 to 28 one-hour meetings held over the course of 12
months) that aimed to promote healthy eating habits and weight
loss through caloric restriction. The group meetings included
advice on eating a diet rich in fiber, fruits, vegetables, and whole
grains, and included at least 1g/kg of weight of protein per day,
with a recommended calorie deficit of approximately 500 kcal
per day (or to a minimum of 1200 kcal/d), and the meetings also
included lectures on food composition, meal preparation, eating
habits and self-monitoring techniques.
Participants and measurements
Eighty subjects with MCI (13), body mass index (BMI) 30
kg/m2, age 60 years, without conditions that interfere with
weight loss or cognition (eg, major depression [evaluated by the
module “Major Depressive Episode” of “Mini International
Neuropsychiatric Interview” (14)], hypothyroidism, heart fail-
ure, cancer, alcoholism, infectious diseases and auto-immune
activity; use of antiobesity drugs, benzodiazepines, neuroleptics
or estrogen replacement therapy in the past 2 months) were
Socio-demographic, anthropometric and clinical data were
recorded. Biochemical analysis included glucose, insulin, gly-
cated hemoglobin (HbA1c), HOMA-IR (homeostasis model as-
sessment-estimated insulin resistance), lipid profile, leptin, adi-
ponectin, interleukin 6 (IL6), tumor necrosis factor (TNF) alpha
), C-reactive protein (CRP) and apolipoprotein E (APOE)
genotype. As we had a small number of patients for some geno-
types, the patients were classified as APOE4 carriers (homozy-
gote or heterozygote for APOE4) or noncarriers. Physical per-
formance was measured with the Short Physical Performance
Battery (15) (SPPB). Food intake was estimated through 24-hour
diet recall collected by trained nutritionists. The calculations for
the energy and macronutrient intake were performed using the
Avanutri 4.0 software (16). As a reference table for nutritional
composition of foods was adopted the Brazilian Table of Food
Composition (TACO) (17) and when food was not listed in the
table, was used as a reference table of the United States Depart-
ment of Agriculture - USDA (18). We recorded the level of phys-
ical activity using the IPAQ (ie, the International Physical Ac-
tivity questionnaire [IPAQ] short version (19)) and classified the
patients as active or sedentary (active 150 minutes physical
activity/wk). All these measures, except genotyping, were re-
peated after 12 months.
The neuropsychological battery included measures of pre-
2Cognition and weight loss in obese elderly J Clin Endocrinol Metab
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morbid Intelligence Quotient (IQ estimated by Vocabulary and
Matrix reasoning (20) tests), verbal memory (Rey Auditory Ver-
bal Learning Test- RAVLT (21); RAVLT-A7delayed recall;
RAVLTA1A5total learning; RAVLT A6recall; RAVLT
recognition), attention [Digit Span forward (DF) and backwards
(DB) (22), Trail Making Test part A (TMA)], working memory
[DB, Trail Making Test part B (TMB)], psychomotor processing
speed (TMA, TMB (23)), executive function (Modified Wiscon-
sin Card Sorting Test – 48 cards version- MWCST (24),TMB
and verbal fluency), language [phonemic verbal fluency (25)
(measured with words starting with FAS) and semantic verbal
fluency (measured with number of animals)] and cognitive com-
plaints (Informant Questionnaire on Cognitive Decline in the
Elderly - IQCODE (26)). Two tests of global cognition were used
at the screening, Montreal Cognitive Assessment (MoCA) (27,
28) and CAMCog (29) (cognitive session of CAMDEX). All of
these tests except MoCA and IQ were repeated after 12 months.
The statistical analyses were performed using the Statistical
Package for Social Science software version 20.0 (SPSS, Chicago,
Figure 1. Study flow chart from recruitment until 12-month follow-up.
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IL). A p-value 0.05 was considered significant and all tests
were two-sided. Bivariate analysis was performed with two-sam-
ple t-tests or Mann-Whitney test for continuous variables and
test or Fisher’s test for categorical variables. The Generalized
Estimating Equation was used in the longitudinal analysis. The
independent variable group shows the main effect of intervention
group, the time variable shows the effect of time between pretest
and follow-up, while the interaction term group x time can be
interpreted as the effect of the intervention (Table 1, Supplemen-
tary material). As both groups lost similar amounts of weight
after the intervention period (mean delta BMI intensive group
–2.1 (-4.8; 0.7) kg/m
, conventional group –1.3 (-4.1; 1.4)
,P.428, Table 1, Supplementary material), we decided
to a posteriori pool the longitudinal analysis between groups,
and to test for the effects of change of BMI as a continuous
To evaluate the relationship between BMI change and vari-
ation in cognitive domains, considering the effect of covariates,
the regression with the generalized linear model with normal
distribution and identity link function was used. Cognitive tests
were grouped according to the following domains on the basis of
a generally accepted description: global cognition (CAMCOG
and IQCODE), verbal memory (RAVLTA1A5, A6, A7, rec-
ognition), executive ability (TMA, TMB, MWCST, digits back-
wards), language/fluency (phonemic verbal fluency and semantic
verbal fluency) and attention (digits forward and backwards).
With scores from 2 time points, principal-components analysis
with varimax rotation and Kaiser normalization was performed
on these domain-specific test groups to generate single compo-
nents for each domain. Standardized regression factor scores
were then generated from these components by Bartlett´s
method. The difference () between the cognitive tests results at
12 month follow up, subtracted from the baseline score, was
considered the dependent variable. The variables BMI, gender,
APOE4, physical activity at 12 months, age, education and base-
line test score were all considered predictors of change in cog-
nitive status. Age and APOE4 genotype (carrier) are two impor-
tant risk factors for dementia, and had been described as
influence for weight loss; therefore, the interaction between
weight loss and cognitive change was also verified. The result was
presented with tests of the main effects for age, APOE4 and
BMI and the interaction between a risk factor and BMI, with
values of
(indicating the linear fit), SE (standard error), and
Partial linear correlation analysis between changes in cogni-
tive tests and clinical and laboratory variables was performed
(the adjustments are described at the Supplementary material).
Table 1. Baseline characteristics by intervention group
Groups conventional intensive p
Characteristics mean (SD) mean (SD)
n (%) n (%)
Age (years) 68.3 (5.3) 67.9 (4.5) 0.688
Gender (female) 34 (85%) 33 (82.5%) 0762
Education (years) 8.3 (4.3) 9.4 (4.8) 0.277
IQ (intelligence quotient) 97,6 (11) 98 (10.6) 0.845
MoCA (0 to 30) 19.1 (3.5) 19.2 (3.1) 0.920
IADL (9 to 27) 25.8 (2.1) 25.6 (1.6) 0.156
BMI class 0.280
BMI 35 (kg/m
) 23 (57.5%) 24 (60%)
BMI 35–39,9 (kg/m
) 13 (32.5%) 8 (20%)
BMI 40 (kg/m
) 4 (10%) 8 (20%)
Charlson comorbidity index 1.3 (1.1) 1.5 (1.4) 0.538
Hypertension (%) 34 (85%) 28 (70%) 0.108
Diabetes (%) 18 (45%) 15 (37,5%) 0.496
(%) 14 (35%) 16 (40%) 0.644
Metabolic syndrome (%) 35 (87,5%) 32 (80%) 0.546
Previous smoking
(%) 11 (27.5%) 16 (40%) 0.237
Physical function
Physically active (%) 23 (57.5%) 27 (67.5%) 0.356
SPPB (0–12) 10.5 (1.8) 10.5 (1.5) 0.694
Balance (04) 3.8 (0.6) 3.8 (0.7) 0.748
4 meters walk (sec) 4.7 (1.0) 4.8 (0.9) 0.644
Sit/get up (sec) 12.3 (5.0) 11.4 (2.7) 0.298
Genotype 0.834
4 n (%) 0 1 (2.5%)
4 n (%) 7 (17.5%) 7 (17.5%)
4 n (%) 3 (7.5%) 3 (7.5%)
3 n (%) 27 (67.5%) 26 (65%)
3 n (%) 3 (7.5%) 3 (7.5%)
APOE4 carriers (%) 10 (25%) 11 (27.5%)
MCI type 0.993
amnestic multiple domain 18 (45%) 19 (47.5%)
amnestic single domain 8 (20%) 7 (17.5%)
nonamnestic mult.domain 2 (5%) 2 (5%)
nonamnestic single domain 12 (30%) 12 (30%)
nnumber; SD standart deviation; MoCA Montreal Cognitive Assessment; IADL: instrumental activities of daily life, IPAQ: international
physical activity questionnaire, SPPB: short physical performance battery, BMI: body mass índex; MCI: mild cognitive impairment; a: pre-diabetes:
fasting glucose between 100 and 125 mg/dL or impaired glucose tolerance; b: just one patient was current smoker.
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Baseline characteristics of the study participants can be
found in Table 1. There were 80 patients, mean age 68.1
4.9 years, without premorbid IQ deficit, BMI between 30
and 49.5 kg/m
. The estimated energy intake was
1517 515 kcal/d (17.3 kcal/kg weight). The average diet
composition was 50.2% carbohydrate, 29.1% lipid, and
20.7% protein. Twenty one patients (26.3%) were
APOE4 carriers. There were no significant differences be-
tween the groups at baseline for age, gender, education,
comorbidities, genotype, measurements or laboratory
Five women did not complete the follow-up: four
dropped out and one died of pneumonia (Figure 1).
BMI decreased by an average of 1.7 1.8 kg/m
.021), without significant change of lean mass, and 35
(43.8%) patients had weight loss greater than 5% of initial
body weight. The proportion of physically active patients
did not change (initial 62.5%, final 70.7%, P.282). The
SPPB, gait speed and time to sit/get up improved signifi-
cantly. There was improvement on most of the cognitive
tests (Table 2, supplementary material, Table 2).
The generalized estimating equation was used for com-
parisons between groups in the longitudinal analysis. The
complete results for body composition, biochemical
markers, physical function, and diet can be found in the
Supplementary Material – Table 1, and for cognitive tests
in the Supplementary Material- Table 2. There was no
significant time-group interaction for most of the tests af-
ter 12 months, except for time to walk 4 m [conventional
group: –0.2 seconds (CI95%: – 0.7; 0.3), intensive group:
0.9 seconds (CI95%:-1.4;-0.4), P.012].
Generalized linear models were used to analyze the re-
lationship between BMI change and cognitive change (Ta-
ble 3, Figure 2). Improvements in global cognition, verbal
memory, language and executive function were correlated
with a decrease in BMI. For verbal memory and language,
there was interaction between BMI change and age, mean-
ing that the effect of weight loss was more beneficial to
younger patients. For executive function, age had an in-
dependent effect (the older the patient, the worse the per-
formance), and there was interaction between APOE4 sta-
tus and BMI change: among APOE4 carriers, a decrease in
BMI was more beneficial. The change in attention did not
Table 2. Cognitive evaluation at baseline and variation after 12 months
Baseline Change
mean CI 95% mean CI 95% p
Global cognition
CAMCog (0
85.2 83.7, 86.8 2.7 1.7; 3.7 0.0001
IQCODE (1–5) 3.49 3.4, 3.56 0.28 0.38;
RAVLT-A7(0–15) 6.6 6.0, 7.2 1.2 0.7, 1.8 0.0001
38.5 36.8, 40.2 2.6 0.9; 4.3 0.002
Digits forward
6.7 6.4, 7.1 0.2 0.6, 0.2 0.357
Digits backward
4.2 3.8, 4.5 0.1 0.2, 0.5 0.371
fluency FAS
29.1 27.2, 30.9 0.9 0.4; 2.3 0.165
Semantic fluency 14.3 13.4, 15.2 1.5 0.5; 2.4 0.002
2.9 2.6, 3.3 0.5 0.1; 0.9 0.017
TMA (sec) 65.1 59.3, 71.5 4.3 9.8; 1.1 0.119
TMB (sec) 185.1 163.4, 209.8 3.8 23.4; 15.9 0.709
CI95 95% confidence interval; difference between time (initial vs. final) tested by Generalized Estimation Equation. IQCODE: Informant
Questionnaire on Cognitive Decline in Elderly; CAMcog: cognitive session of the Cambridge Examination for Mental Disorders of the Elderly;
RAVLT-A7: Rey auditory verbal learning test - delayed recall; RAVLTSA1A5: Rey auditory verbal learning test - total learning; TMA: trail making test
part A; TMB: trail making test part B
doi: 10.1210/jc.2015-2315 5
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correlate with BMI, age or APOE4 status (data not
shown). At figure 2, the correlation between BMI and
cognitive change (standardized scores) was illustrated,
and for didactical purposes the patients were separated in
2 age groups and 2 genotype groups.
A correlation analysis between changes in cognitive test
scores and clinical variables was performed (Table 4; Sup-
plementary material- Table 3 and 4). Leptin increase was
associated to attention improvement (DF). Reductions in
HOMA-IR correlated with improvements in global cog-
nition (CAMCog) and phonemic fluency. Decreased CRP
correlated with an increase in delayed memory. The de-
crease in caloric intake correlated with improvement in
verbal memory and executive function (TMB). The de-
crease in carbohydrate intake was associated with im-
provement in verbal memory, executive function (TMB)
and subjective complaints (IQCODE). Decreases in fat
intake were associated with improvements in verbal mem-
ory and TMB.
Table 3. Adjusted model for change in cognitive domains related to variation in BMI (body mass index), age,
APOE4 genotype (carrier or not) and interaction between BMI change and age (for language) or between BMI
change and APOE4 genotype (for executive function)
domains global cognition Verbal memory Language/ Fluency Executive
BMI 0.12 0.05 4.96 0.026 1.81 0.82 4.87 0.027 2.32 0.82 8.04 0.005 0.18 0.08 4.75 0.029
age (years) 0.00 0.02 0.00 .956 0.01 0.03 0.06 .811 0.01 0.02 0.09 .765 0.04 0.02 4.11 0.043
APOE40.13 0.21 0.39 .533 0.18 0.19 0.87 .352 0.01 0.19 0.00 .951 0.48 0.29 2.69 .101
BMI* age 0.02 0.01 4.03 0.045 0.03 0.01 8.17 0.004
BMI*E4⫹ ⫺0.20 0.10 3.88 0.049
Legend: BMI: body mass index. APOE4: Carrier of apolipoprotein E4 genotype. SE.standard error.
: Wald
-Square. a: Model adjusted for
age, the presence of APOE4, baseline testing, education (years), gender and level of physical activity; Global cognition: CAMcog (cognitive session
of CAMDEX) and IQCODE; Verbal memory: composite score of RAVLT SA1A5: Rey auditory verbal learning test - total learning; A6: recall, A7:
delayed recall, recognition; Executive: composite score of TMA: trail making test part A; TMB: trail making test part B, Wisconsin classification
cards and digits backwards; Language/ Fluency: composite score corresponding to phonemic and phonetic fluency. BMI*E4: parameter of
interaction between
BMI and APOE4 genotype; BMI* age: parameter of interaction between
BMI and age in years.
Figure 2. Adjusted scatter plot showing the relation between BMI (kg/m
) change and cognitive change after 12 months intervention, by group
(aged below or above 70 years or APOE4 carrier or noncarrier): Legend: BMI: BMI. APOE4: Carrier of apolipoprotein E4 genotype. Global
cognition: CAMcog (cognitive session of CAMDEX) and IQCODE; Verbal memory: composite score of RAVLT A1A5: Rey auditory verbal
learning test - total learning; A6: recall, A7: delayed recall, recognition; Executive: composite score of TMA: trail making test part A; TMB: trail
making test part B, WI classification cards and digits backwards; Language/Fluency: composite score corresponding to phonemic and phonetic
fluency. All the tests were adjusted to gender, education, baseline test and physical activity.
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As far as we know, this is the first clinical trial that inves-
tigated the effects of intentional weight loss via caloric
restriction in patients with MCI. Cognitive tests have
proven to be good predictors of the conversion of MCI to
dementia and are suitable to evaluate treatment response
(30); for this study we evaluated multiple cognitive do-
mains. Delayed recall is considered one of the main tests
for predicting the progression of cognitive impairment
(31). Worsened performances on the TMB have already
been associated with obesity (32), metabolic syndrome
and type 2 Diabetes (33), and it is considered useful for
predicting dementia (34). One previous study has demon-
strated its improvement associated with intentional
weight loss in patients without cognitive impairment (35).
In our study, for tests of verbal memory, language, exec-
utive function and global cognition, improved scores were
correlated with a decrease in BMI. Even considering that
it is a secondary analysis, it is interesting that it endorses
the main study´s hypothesis. For younger patients, the ef-
fect was more pronounced particularly to memory and
language. The concept of a better therapeutic window for
cognitive protection was already discussed at the context
of hormone therapy (HT) (36): apparently, starting some
hormone combinations nearby menopause is beneficial,
but starting many years after menopause increases demen-
tia risk. Other therapies, like monoclonal antibodies
against B amyloid (37), also had shown mixed results, and
one of the possible influences was considered the treat-
ment window: maybe after the amyloid plaques are wide
spread, treatments that target the amyloid are no longer
enough to prevent the development of dementia. It is pos-
sible that older patients, having a more advanced neuro-
pathology, were less responsive to metabolic changes and
then less responsive to our intervention.
Among APOE4 carriers, a decrease in BMI was asso-
ciated with executive improvements, showing greater ben-
efits in patients with greater dementia risk. The effect of
APOE polymorphism on treatment response has been
demonstrated in other studies; APOE4 carriers with de-
mentia appear to have a worse response to treatment than
noncarriers (38); yet in patients with MCI or mild demen-
tia, this effect varies: cognitive improvement with rosigli-
tazone was demonstrated only among APOE4 noncarriers
(39), and carriers showed better response with bapineu-
zumabe (40) and donepezil (41). A former study (42) re-
ported that APOE4 carriers who consumed a high-fat diet
had a greater risk of developing AD compared with non-
carriers, effect probably linked with the function of APOE
at the lipoprotein transport. In our study, APOE4 carriers
showed a slight better cognitive response to caloric re-
striction; although this pattern did not repeated in all cog-
nitive areas, this finding deserves attention in future
The value of plasma leptin for predicting cognitive
change is uncertain, since a prior longitudinal study with
a community-based sample found that higher leptin levels
were associated with lower dementia risk (43), however a
study of elderly obese individuals found that higher leptin
levels were associated with brain atrophy (44). The use of
leptin in animal models has been associated with memory
improvement (45). In our group, an increase in leptin was
associated with greater improvement in attention (DF),
and in executive function (phonemic fluency) there was
the same trend. Analysis of the correlation between met-
abolic variables and changes in cognitive performance re-
vealed associations between a decrease in insulin resis-
tance and an improvement in cognition, and a decrease in
CRP and improvement in memory. Insulin resistance is
associated with increased risk of cognitive decline and the
Table 4. Partial linear correlation between change in cognitive tests and change in leptin, HOMA-IR, C-reactive
protein and diet, adjusted to age, gender, baseline test, education, presence of apolipoprotein
4 allele and
physical activity level
leptin HOMAIR CRP kcal carbo-hydrate lipid
CAMCog 0.085 -0.393** 0.002 0.154 0.110 0.113
SA1A5 0.074 0.212 0.049 -0.346** -0.253*-0.318**
A7 0.151 -0.238#-0.299*-0.303*-0.336** -0.312**
0.383** 0.143 0.212#0.167 0.137 0.166
0.227#-0.273*0.038 0.184 0.027 -0.218#
0.176 0.090 0.047 0.267*0.290*0.241*
0.004 0.039 0.056 0.216#0.315** 0.139
#P0,1; * P0,05; **P0,01. &: greater the score, worst de performance, for the other tests, greater the score, better the performance;
CAMcog: cognitive session of CAMDEX; RAVLT SA1A5: Rey auditory verbal learning test - total learning; RAVLT-A7: Rey auditory verbal learning
test - delayed recall; TMB: trail making test part B; IQCODE: Informant Questionnaire on Cognitive Decline in Elderly. Leptin and dietary
parameters: adjusted also to initial body mass índex.
doi: 10.1210/jc.2015-2315 7
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correlation between improvement in memory and a de-
crease in insulin resistance and CRP (6) has already been
In a previous study, we found that weight loss after
bariatric surgery for severely obese women (mean age
40.5, mean BMI 51.1 kg/m
) was associated with a reverse
in hypermetabolism in the posterior cingulate gyrus and
an improvement in executive function (7). A previous
study with healthy subjects (6) (mean age 60.5) also dem-
onstrated an improvement in memory after a caloric re-
striction of only 11.6%. The decrease in reported caloric
intake of the patients in our study was only 8.7% (-132
kcal/d, P.061); even so, improvements in memory and
executive function were correlated with decreased con-
sumption of energy, carbohydrates, and fat.
Of note, most tests involving memory and executive
function showed improvements. As the interval between
baseline and final evaluation was long (ie, 12 months), it
is unlikely that this improvement is attributable only to a
learning effect, especially considering that patients with
cognitive deficit suffer less effect learning (46) and cogni-
tive change showed a dose-response relationship with the
variation in BMI. As variation in some tests were related
to clinical and metabolic variables, it is possible that the
clinical management of comorbidities contributed to this
improvement. Even though loss of muscle mass, strength,
and functional capacity are potential risks associated with
of weight loss in the elderly (47), our results actually dem-
onstrated a functional improvement and stability of lean
The weight loss difference between the groups was
lower than expected, limiting the analyses by the initial
study design. Thus, the initial goal, which depended on
comparing cognition variations in groups with different
degrees of weight loss, was not fully achieved. It is possible
that the long period of intervention and the mobility dif-
ficulties of the elderly decreased adherence to group meet-
ings, and the nutritional counseling was a mild interven-
tion. As the process of recruiting volunteers included
information on the risks of obesity, it is also possible that
this may have increased motivation to lose weight in both
groups. We therefore considered it most useful to make an
exploratory analysis considering the decrease of BMI as a
continuous variable and to observe its influence on cog-
nitive tests. Also, due to the exploratory nature of the
analyses and the relatively small sample, it was not pos-
sible to carry a multiple comparisons correction.
Our group was predominantly women, so the results
may not be generalizable. The number of patients might
have been too small for a detailed analysis by genotype.
Intentional weight loss through caloric restriction in obese
subjects with MCI was safe and correlated with improve-
ments in memory, executive function, global cognition
and language, and this association was strongest in
younger seniors and in APOE4 carriers. Changes in met-
abolic markers and diet were also associated with im-
provement in cognitive tests.
This work was supported by FAPESP (Fundação de Amparo à
Pesquisa do Estado de São Paulo) (2011/06194 –6) and Hospital
das Clinicas - Universidade de São Paulo.
Address all correspondence and requests for reprints to:
Dr.Nidia Celeste Horie Ph.D. Fac-
uldade de Medicina da Universidade de São Paulo - Endocrinol-
ogy R Dr Ené as de Carvalho Aguiar, 155 8andar, Endocrino-
logia Sao Paulo SP BRAZIL 05403–000 55– 011–99640 6475.
Corresponding author and person to whom reprint requests
should be adressed: Nidia Celeste Horie,, Rua Dr Enéas de Carvalho Aguiar,
155, 8o. Andar, bloco 3 (Endocrinologia), CEP: 05403–000,
São Paulo – SP - Brasil
Disclosure Summary: The authors have nothing to disclose.
Clinical Trial Registration Number: NCT01286389.
This work was supported by This research was supported by
FAPESP (Fundação de Amparo à Pesquisa do Estado de São
Paulo) (2011/06194 6) and Hospital das Clinicas - Universi-
dade de São Paulo. The funding agency was not involved in any
aspects of the planning or execution of this study.
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Supplementary resource (1)

... Another interesting approach may be lifestyle intervention. Both physical activity and nutritional intervention have been associated to cognitive health in the elderly, as well as cardiometabolic risk profile [160][161][162][163]. For example, consumption of prebiotics has beneficial effects on cognition in obese-insulin resistant subjects, leading to improved hippocampal plasticity, brain mitochondrial function and decreased microglial activation [164,165]. ...
Epidemiologic studies have documented an association between diabetes and increased risk of cognitive decline in the elderly. Based on animal model studies, several mechanisms have been proposed to explain such an association, including central insulin signaling, neurodegeneration, brain amyloidosis, and neuroinflammation. Nevertheless, the exact mechanisms in humans remain poorly defined. It is reasonable, however, that many pathways may be involved in these patients leading to cognitive impairment. A major aim of clinicians is identifying early onset of neurologic signs and symptoms in elderly diabetics to improve quality of life of those with cognitive impairment and reduce costs associated with long-term complications. Several biomarkers have been proposed to identify diabetics at higher risk of developing dementia and diagnose early stage dementia. Although biomarkers of brain amyloidosis, neurodegeneration and synaptic plasticity are commonly used to diagnose dementia, especially Alzheimer disease, their role in diabetes remains unclear. The aim of this review is to explore the molecular mechanisms linking diabetes with cognitive decline and present the most important findings on the clinical use of biomarkers for diagnosing and predicting early cognitive decline in diabetics.
... Ketone substrates also improve the structural and functional synaptic plasticity and lead to the activation of the signaling pathway that reinforces neural bioenergy and resistance to oxidative stress (30,31). The benefits of cognition can be translated into improvements in verbal and recognition memory, verbal fluency, executive function, and global cognition (21,32,33). Nevertheless, further research is needed to clarify the mechanisms by which KD improves cognition and behavior function of patients with developmental delay and ASD. ...
Full-text available
Objective Tuberous sclerosis complex (TSC) is a rare disease with a high risk of epilepsy and cognitive impairment in children. Ketogenic diet (KD) therapy has been consistently reported to be beneficial to TSC patients. In this study, we aimed to investigate the efficacy and safety of KD in the treatment of drug-resistant epilepsy and cognitive impairment in children with TSC. Methods In this multicenter study, 53 children (33 males and 20 females) with drug-resistant epilepsy or cognitive impairment caused by TSC were retrospectively recruited from 10 hospitals from January 1, 2010, to December 31, 2020. Intention-to-treat analysis was used to evaluate seizure reduction and cognition improvement as outcomes after KD therapy. Results Of the 53 TSC patients included, 51 failed to be seizure-free with an average of 5.0 (range, 4–6) different anti-seizure medications (ASMs), before KD therapy. Although the other two patients achieved seizure freedom before KD, they still showed psychomotor development delay and electroencephalogram (EEG) abnormalities. At 1, 3, 6, and 12 months after the KD therapy, 51 (100%), 46 (90.2%), 35 (68.6%), and 16 patients (31.4%) remained on the diet therapy, respectively. At these time points, there were 26 (51.0%), 24 (47.1%), 22 (43.1%) and 13 patients (25.5%) having ≥50% reductions in seizure, including 11 (21.6%), 12 (23.5%), 9 (17.6%) and 3 patients (5.9%) achieving seizure freedom. In addition, of 51 patients with psychomotor retardation, 36 (36 of 51, 70.6%) showed cognitive and behavioral improvements. During the KD therapy, no serious side effects occurred in any patient. The most common side effects were gastrointestinal disturbance (20 of 53, 37.7%) and hyperlipidemia (6 of 53, 11.3%). The side effects were gradually relieved after adjustment of the ketogenic ratio and symptomatic treatment. Conclusion KD is an effective and safe treatment for TSC-related drug-resistant epilepsy and cognitive impairment in children. KD can reduce seizure frequency and may potentially improve cognition and behavior.
... Our study did not find an association between normal or impaired baseline cognitive functioning and weight loss success. This finding is in agreement with another study, where patients with mild cognitive impairment can respond correctly to weight loss programs, regardless of baseline cognitive functioning [47]. ...
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There is a relationship between obesity and cognitive functioning. Our aim was to assess weight loss influence on global cognition and executive functioning (EF) in adults with obesity under a multidisciplinary weight loss program. In this six-month longitudinal study, we assessed 81 adults (age < 50 years) with body mass index (BMI) ≥ 30. EF and global cognitive performance were evaluated with the Montreal Cognitive Assessment (MoCA), Neuropsychological Battery of Executive Functions (BANFE-2) and Trail Making Test-Part B (TMT-B). Median age was 40.0 years (IQR: 31.5–47, 61% women), and the median BMI was 41.4 (IQR: 36.7–45.9). At a six-month follow-up, the mean weight loss was 2.67% (29.6% of patients achieved ≥5% weight loss). There was an improvement in EF evaluated with BANFE (p = 0.0024) and global cognition with MoCA (p = 0.0024). Women experienced more remarkable change, especially in EF. Weight loss did not correlate with cognitive performance, except for TMT-B (r-0.258, p = 0.026). In the regression analysis, only years of education predicted the MoCA score. This study showed that patients improved cognitive performance during the follow-up; nevertheless, the magnitude of weight loss did not correlate with cognitive improvement. Future studies are warranted to demonstrate if patients achieving ≥5% weight loss can improve cognition, secondary to weight loss.
... Given the proven association between obesity, insulin resistance, and the development of cognitive impairment and some forms of dementia, strategies aimed at reducing weight excess may also lead to beneficial results in terms of reducing the burden of neurological manifestations. Indeed, several studies have shown that weight loss via caloric restriction leads to improvement in verbal and working memory, language, executive functions, and global cognition [10,81]. ...
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We are facing an obesity epidemic, and obesity itself and its close companion, type 2 diabetes, are independent risk factors for neurodegeneration. While most medical treatments fail to induce a clinically meaningful improvement in neurodegenerative disorders, lifestyle interventions have emerged in the spotlight. A recently rediscovered approach is intermittent fasting (IF), which, compared to the classic caloric restriction regimens, limits only the time of eating, rather than the number of calories allowed per day. There is already a large amount of evidence from preclinical and clinical studies showing the beneficial effects of IF. In this review, we specifically focus on the effects of IF on brain metabolism. Key molecular players modified during IF and involved in its beneficial central effects (ketone bodies, BDNF, GABA, GH/IGF-1, FGF2, sirtuin-3, mTOR, and gut microbiota) are identified and discussed. Studies suggest that IF induces several molecular and cellular adaptations in neurons, which, overall, enhance cellular stress resistance, synaptic plasticity, and neurogenesis. Still, the absence of guidelines regarding the application of IF to patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge on the different IF protocols and long-term effects of IF on brain metabolism before it can be widely prescribed.
... Subsequently, this research team further evaluated the associations between each component of energy balance on cognition and found that CR improved cognitive performance along with resting metabolic rate proportionally, independent of changes in energy intake and body mass in non-obese adults (Grigolon et al., 2020). In obese elderly patients with MCI, those who adhered to CR for 12 months demonstrated better improvements in executive function, verbal memory, and global cognition (Horie et al., 2016). Long-term CR without malnutrition in humans results in positive effects on verbal memory (Witte et al., 2009), spatial processing, and visuospatial working memory (Solianik et al., 2018). ...
Alzheimer's disease (AD) is one of the fastest growing cognitive decline-related neurological diseases. To date, effective curative strategies have remained elusive. A growing body of evidence indicates that dietary patterns have significant effects on cognitive function and the risk of developing AD. Previous studies on the association between diet and AD risk have mainly focused on individual food components and specific nutrients, and the mechanisms responsible for the beneficial effects of dietary patterns on AD are not well understood. This article provides a comprehensive overview of the effects of dietary patterns, including the Mediterranean diet (MedDiet), dietary approaches to stop hypertension (DASH) diet, Mediterranean-DASH diet intervention for neurological delay (MIND), ketogenic diet, caloric restriction, intermittent fasting, methionine restriction, and low-protein and high-carbohydrate diet, on cognitive impairment and summarizes the underlying mechanisms by which dietary patterns attenuate cognitive impairment, especially highlighting the modulation of dietary patterns on cognitive impairment through gut microbiota. Furthermore, considering the variability in individual metabolic responses to dietary intake, we put forward a framework to develop personalized dietary patterns for people with cognitive disorders or AD based on individual gut microbiome compositions.
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Obesity and sarcopenic obesity (SO) are characterized by excess body fat with or without low muscle mass affecting bio‐psycho‐social health, functioning, and subsequently quality of life in older adults. We mapped outcomes addressed in randomized controlled trials (RCTs) on lifestyle interventions in community‐dwelling older people with (sarcopenic) obesity. Systematic searches in Medline, Embase, Cochrane Central, CINAHL, PsycInfo, Web of Science were conducted. Two reviewers independently performed screening and extracted data on outcomes, outcome domains, assessment methods, units, and measurement time. A bubble chart and heat maps were generated to visually display results. Fifty‐four RCTs (7 in SO) reporting 464 outcomes in the outcome domains: physical function (n = 42), body composition/anthropometry (n = 120), biomarkers (n = 190), physiological (n = 30), psychological (n = 47), quality of life (n = 14), pain (n = 4), sleep (n = 2), medications (n = 3), and risk of adverse health events (n = 5) were included. Heterogeneity in terms of outcome definition, assessment methods, measurement units, and measurement times was found. Psychological and quality of life domains were investigated in a minority of studies. There is almost no information beyond 52 weeks. This evidence map is the first step of a harmonization process to improve comparability of RCTs in older people with (sarcopenic) obesity and facilitate the derivation of evidence‐based clinical decisions.
Sex and gender differences are seen in cognitive disturbances in a variety of neurological and psychiatry diseases. Men are more likely to have cognitive symptoms in schizophrenia whereas women are more likely to have more severe cognitive symptoms with major depressive disorder and Alzheimer’s disease. Thus, it is important to understand sex and gender differences in underlying cognitive abilities with and without disease. Sex differences are noted in performance across various cognitive domains – with males typically outperforming females in spatial tasks and females typically outperforming males in verbal tasks. Furthermore, there are striking sex differences in brain networks that are activated during cognitive tasks and in learning strategies. Although rarely studied, there are also sex differences in the trajectory of cognitive aging. It is important to pay attention to these sex differences as they inform researchers of potential differences in resilience to age-related cognitive decline and underlying mechanisms for both healthy and pathological cognitive aging, depending on sex. We review literature on the progressive neurodegenerative disorder, Alzheimer’s disease, as an example of pathological cognitive aging in which human females show greater lifetime risk, neuropathology, and cognitive impairment, compared to human males. Not surprisingly, the relationships between sex and cognition, cognitive aging, and Alzheimer’s disease are nuanced and multifaceted. As such, this chapter will end with a discussion of lifestyle factors, like education and diet, as modifiable factors that can alter cognitive aging by sex. Understanding how cognition changes across age and contributing factors, like sex differences, will be essential to improving care for older adults.
Aging is often associated with cognitive decline and recurrent cellular and molecular impairments. While life-long caloric restriction (CR) may delay age-related cognitive deterioration as well as the onset of neurological disease, recent studies suggest that late-onset, short-term intermittent fasting (IF), may show comparable beneficial effects as those of life-long CR to improve brain health. We used a new optogenetic aging model to study the effects of late-onset (>18 months), short-term (4-6 weeks) IF on age-related changes in GABAergic synaptic transmission, intracellular calcium (Ca2+) buffering and cognitive status. We utilized male mice from a bacterial artificial chromosome (BAC) transgenic mouse line with stable expression of the channelrhodopsin-2 (ChR2) variant H134R [VGAT-ChR2(H134R)-EYFP] in a reduced synaptic preparation that allows for specific optogenetic light stimulation on GABAergic synaptic terminals across aging. We performed quantal analysis using the method of failures in this model and show that short-term IF reverses the age-related decrease in quantal content of GABAergic synapses. Likewise, short-term IF also reversed age-related changes in Ca2+ buffering and spontaneous GABAergic synaptic transmission in basal forebrain (BF) neurons of aged mice. Our findings suggest that late-onset short-term IF can reverse age-related physiological impairments in mouse BF neurons but that 4 weeks IF is not sufficient to reverse age-related cognitive decline.SIGNIFICANT STATEMENTHere we demonstrate plasticity of the aging brain and reversal of well-defined hallmarks of brain aging using short-term intermittent fasting initiated later in life. Few therapeutics are currently available to treat age-related neurological dysfunction although synaptic dysfunction occurs during aging and neurological disease is a topic of intense research. Using a new reduced synaptic preparation and optogenetic stimulation we are able to study age-related synaptic mechanisms in greater detail. Several neurophysiological parameters including quantal content were altered during aging and were reversed with short-term intermittent fasting. These methods can be used to identify potential therapies to reverse physiological dysfunction during aging.
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Age-associated diseases are rising to pandemic proportions, exposing the need for efficient and low-cost methods to tackle these maladies at symptomatic, behavioral, metabolic, and physiological levels. While nutrition and health are closely intertwined, our limited understanding of how diet precisely influences disease often precludes the medical use of specific dietary interventions. Caloric restriction (CR) has approached clinical application as a powerful, yet simple, dietary modulation that extends both life- and healthspan in model organisms and ameliorates various diseases. However, due to psychological and social-behavioral limitations, CR may be challenging to implement into real life. Thus, CR-mimicking interventions have been developed, including intermittent fasting, time-restricted eating, and macronutrient modulation. Nonetheless, possible side effects of CR and alternatives thereof must be carefully considered. We summarize key concepts and differences in these dietary interventions in humans, discuss their molecular effects, and shed light on advantages and disadvantages.
Objective To determine whether body mass index (BMI) and leptin were longitudinally associated over 10 years with neuropsychological performance (NP) among middle-aged women with HIV (WWH) versus without HIV. Methods Women’s Interagency HIV Study (WIHS) participants (301 WWH, 113 women without HIV from Brooklyn, New York City and Chicago had baseline and 10-year BMI (kg/m2) and fasting plasma leptin levels using commercial ELISA (ng/mL); and demographically-adjusted NP T-scores (attention/working memory, executive function (EF), processing speed, memory, learning, verbal fluency, motor function, global) at 10-year follow-up. Multivariable linear regression analyses, stratified by HIV-serostatus, examined associations between BMI, leptin, and NP. Results Over 10 years, women (baseline age 39.8+/-9.2 years, 73% Black, 73% WWH) transitioned from average overweight (29.1+/-7.9 kg/m 2) to obese (30.5+/-7.9 kg/m 2) BMI. Leptin increased 11.4+/-26.4 ng/mL (p<0.0001). Higher baseline BMI and leptin predicted poorer 10-year EF among all women (BMI B=-6.97, 95%CI(-11.5, -2.45) p=0.003; leptin B=-1.90, 95%CI(-3.03, -0.76), p=0.001); higher baseline BMI predicted better memory performance (B=6.35, 95%CI(1.96, 10.7), p=0.005). Greater 10-year leptin increase predicted poorer EF (p=0.004), speed (p=0.029), verbal (p=0.021) and global (p=0.005) performance among all women, and WWH. Greater 10-year BMI increase predicted slower processing speed (p=0.043) among all women; and among WWH, poorer EF (p=0.012) and global (p=0.035) performance. Conclusions In middle-aged WIHS participants, 10-year increases in BMI and leptin were associated with poorer performance across multiple NP domains among all and WWH. Trajectories of adiposity measures over time may provide insight into the role of adipose tissue in brain health with aging.
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Objetivos: O MINI é uma entrevista diagnóstica padronizada breve (15-30 minutos), compatível com os critérios do DSM-III-R/IV e da CID-10, que é destinada à utilização na prática clínica e na pesquisa em atenção primária e em psiquiatria, e pode ser utilizada por clínicos após um treinamento rápido (de 1 a 3 horas). A versão Plus do MINI, mais detalhada, gera diagnósticos positivos dos principais transtornos psicóticos e do humor do DSM-IV. Este artigo apresenta os resultados de quatro estudos de validação do instrumento, realizados na Europa e nos EUA. Métodos: Os estudos 1 (França) e 2 (EUA) testaram a confiabilidade -entre avaliadores e teste-reteste -da versão DSM-III-R do MINI (n=84, sendo 42 pacientes psiquiátricos de cada centro) e sua validade com relação ao CIDI (n=346, sendo 296 pacientes psiquiátricos e 50 controles) e ao SCID-P (n=370, sendo 308 pacientes psiquiátricos e 62 controles), respectivamente. O estudo 3 testou a validade de diagnósticos gerados por clínicos gerais usando o MINI (DSM-IV) com relação aos diagnósticos clínicos habituais de psiquiatras, em 409 pacientes de centros de atenção primária de quatro países (França, Espanha, Itália e Reino Unido). O estudo 4 testou a confiabilidade entre avaliadores (n=20 pacientes psiquiátricos) e a validade dos módulos Transtornos Psicóticos, Depressão e Mania do MINI Plus - DSM IV (n=104 pacientes psiquiátricos) com relação a dois critérios de referência: diagnósticos do CIDI e diagnósticos clínicos de psiquiatras. Análises quantitativas (índices de concordância e de validade) e qualitativas (razões de discordância) foram realizadas. Resultados: Os índices de confiabilidade do MINI (estudos 1 e 2) e do MINI Plus (estudo 4) foram globalmente satisfatórios. Comparados a vários critérios de referência (CIDI, SCID-P, opinião de peritos), em diferentes contextos (unidades psiquiátricas e centros de atenção primária), o MINI e o MINI Plus mostraram qualidades psicométricas similares às de outras entrevistas diagnósticas padronizadas mais complexas, permitindo uma redução de 50% ou mais no tempo da avaliação. Análises qualitativas identificaram dificuldades e erros diagnósticos ligados aos casos, métodos de avaliação e critérios de diagnósticos estudados. Modificações foram introduzidas para corrigir os problemas identificados e otimizar as propriedades psicométricas do MINI e do MINI Plus. Conclusões: O MINI e sua versão Plus são adaptados ao contexto clínico e à avaliação de pacientes mais graves, e representam uma alternativa econômica para a seleção de pacientes, segundo critérios internacionais, em estudos clínicos e epidemiológicos. O MINI já está disponível em aproximadamente 30 idiomas, incluindo a versão brasileira. As perspectivas atuais de adaptação e aplicação transcultural do instrumento são discutidas.
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Context: The mechanisms by which obesity alters the cerebral function and the effect of weight loss on the brain have not been completely clarified. Objective: The objective of the study was to assess the effect of bariatric surgery on the cognitive function and cerebral metabolism. Design: Seventeen obese women were studied prior to and 24 weeks after bariatric surgery using neuropsychological tests and positron emission tomography. Setting: The study was conducted in a reference center for the treatment of obesity of a Brazilian public university. Participants: Thirty-three women paired by age and level of education made up two groups: 17 severely obese patients and 16 lean patients. They did not have diabetes mellitus or a family history of dementia. Main outcome measures: Comparison of performance in neuropsychological tests and cerebral metabolism of the obese women before and after bariatric surgery was measured. The results found at the two moments were compared with those of the women of normal weight. Results: Women with a mean age of 40.5 years and mean body mass index of 50.1 kg/m(2) when compared with women with mean body mass index of 22.3 kg/m(2) showed increased cerebral metabolism, especially in the posterior cingulate gyrus (P < .004). No difference was found between the groups for the neuropsychological tests. After 24 weeks the cerebral metabolism of the obese women was lower, similar to the lean women, and there was an improvement of executive function, accompanying changes of metabolic and inflammatory parameters. Conclusions: Obese women may have increased cerebral metabolism when compared with women of normal weight, and this appears to reverse after weight loss induced by bariatric surgery, accompanied by improved executive function.
Este estudo e parte de um esforco internacional para validar um questionario internacional de atividade fisica (IPAQ) proposto pela Organizacao Mundial de Saude (1998), e que pretende servir como um instrumento mundial para determinar o nivel de atividade fisica em nivel populacional. O objetivo deste estudo foi determinar a validade do IPAQ em uma amostra de adultos brasileiros. A amostra foi consti­tuida por257 homens e mulheres que responderam o IPAQ (versao da ultima semana, formas curta e longa) no inicio do estudo e apos 7 dias. Para validar o instrumento parte da amostra (n:.28) usou o sensor de movimento Computer Science & Aplications (CSA). A reprodutibilidade do questionario foi determinada depois de 7 dias e a correlacao de Spearman foi significante e alta (rho=0,69 - 0,71:p 7 ultimos dias apresentam resultados similares. Concluimos que as formas de IPAQ foram aceitaveis e apresentaram resultados similares a outros instru­mentos para medir nivel de atividade fisica, no entanto pela primeira vez o estudo de validacao diversos paises e culturas foram envolvidos na validacao do instrumento.
Obesity causes serious medical complications and impairs quality of life. Moreover, in older persons, obesity can exacerbate the age-related decline in physical function and lead to frailty. However, appropriate treatment for obesity in older persons is controversial because of the reduction in relative health risks associated with increasing body mass index and the concern that weight loss could have potential harmful effects in the older population. This joint position statement from the American Society for Nutrition and the NAASO, The Obesity Society reviews the clinical issues related to obesity in older persons and provides health professionals with appropriate weight-management guidelines for obese older patients. The current data show that weight-loss therapy improves physical function, quality of life, and the medical complications associated with obesity in older persons. Therefore, weight-loss therapy that minimizes muscle and bone losses is recommended for older persons who are obese and who have functional impairments or medical complications that can benefit from weight loss.
WHO developed the Global Recommendations on Physical Activity for Health with the overall aim of providing national and regional level policy makers with guidance on the dose-response relationship between the frequency, duration, intensity, type and total amount of physical activity needed for the prevention of NCDs. The recommendations set out in this document address three age groups: 5-17 years old; 18-64 years old; and 65 years old and above. The section below includes the recommendations for each age group. For further information click below and download the complete document or click on the individual age groups for specific recommendations.
Cognitive decline is a common and feared aspect of aging. Mild cognitive impairment (MCI) is defined as the symptomatic predementia stage on the continuum of cognitive decline, characterized by objective impairment in cognition that is not severe enough to require help with usual activities of daily living. To present evidence on the diagnosis, treatment, and prognosis of MCI and to provide physicians with an evidence-based framework for caring for older patients with MCI and their caregivers. We searched PubMed for English-language articles in peer-reviewed journals and the Cochrane Library database from inception through July 2014. Relevant references from retrieved articles were also evaluated. The prevalence of MCI in adults aged 65 years and older is 10% to 20%; risk increases with age and men appear to be at higher risk than women. In older patients with MCI, clinicians should consider depression, polypharmacy, and uncontrolled cardiovascular risk factors, all of which may increase risk for cognitive impairment and other negative outcomes. Currently, no medications have proven effective for MCI; treatments and interventions should be aimed at reducing cardiovascular risk factors and prevention of stroke. Aerobic exercise, mental activity, and social engagement may help decrease risk of further cognitive decline. Although patients with MCI are at greater risk for developing dementia compared with the general population, there is currently substantial variation in risk estimates (from <5% to 20% annual conversion rates), depending on the population studied. Current research targets improving early detection and treatment of MCI, particularly in patients at high risk for progression to dementia. Cognitive decline and MCI have important implications for patients and their families and will require that primary care clinicians be skilled in identifying and managing this common disorder as the number of older adults increases in coming decades. Current evidence supports aerobic exercise, mental activity, and cardiovascular risk factor control in patients with MCI.