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- Cocoa (Theobroma cacao)
- Cognitive Function
- Blood Pressure
- Insulin Resistance
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Date:
02-28-2013 | HC# 111224-467
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Re: Cocoa Flavanol Consumption Demonstrates Cognitive Improvements in First Long-term Study in Older Adults with Mild Cognitive Impairment
Desideri G,
Kwik-Uribe C, Grassi D, et al. Benefits in cognitive function, blood pressure and insulin resistance through cocoa flavanol consumption in elderly subjects
with mild cognitive impairment: The Cocoa, Cognition, and Aging (CoCoA) study. Hypertension. 2012;60(3):794-801.
Cocoa (Theobroma cacao) has been associated
with cognitive benefits. Mild cognitive impairment (MCI) can lead to dementia,
but at this earlier stage can be impacted positively by dietary intervention. Flavanols, such as those found in cocoa, have been shown to reverse age-related
cognitive decline by increasing the number and strength of connections between
neurons, reducing neuronal loss attributed to neurodegenerative processes, and interacting with the cellular and molecular architecture of the brain
responsible for memory. In addition, there is strong evidence of a link between cognitive health and cardiovascular health and insulin function, both of which
can also be favorably impacted by flavanols. This double-blind, randomized, parallel-arm study is the first to examine the effects of a beverage containing
cocoa flavanols on the cognitive performance of patients with MCI. Effects on blood pressure, glucose metabolism, and oxidative stress were also studied
because of their probable effect on cognitive function.
Patients (n=90; aged
65-82 years) who had been referred for MCI and were diagnosed according to the
revised Petersen criteria were recruited from the University of L'Aquila Geriatric Division (L'Aquila, Italy). After a 1-week run-in period, patients
were randomly assigned to receive a dairy-based cocoa drink containing cocoa
flavanols (Cocoapro® processed powder; Mars, Inc.; McLean, Virginia)
at either a high-flavanol (HF; ~990 mg of flavanols per serving), intermediate-flavanol
(IF; ~520 mg of flavanols per serving), or low-flavanol level (LF; ~45 mg of
flavanols per serving) for 8 weeks. The 3 drinks were matched for taste,
appearance, and caloric, macronutrient, caffeine, and theobromine content. The LF
drink was made with a highly processed, alkalized cocoa powder.
The primary outcome
measure was a change in cognitive function after 8 weeks of treatment.
Secondary outcome measures were changes in blood pressure, metabolic
parameters, and plasma markers of lipid peroxidation. Cognitive function was
assessed at baseline and 8 weeks using a combination of 4 well-validated
standardized tests – the Mini-Mental State Examination (MMSE), Trail Making
Test (TMT)-A, TMT-B, and a verbal fluency test.
The study population
did not consist of any individuals who were obese, smokers, or taking statins.
There was no difference in anthropometric parameters or dietary flavanol intake
between the 3 groups. Two patients withdrew from the IF group for personal
reasons, and 1 patient withdrew from the LF group due to gastrointestinal
discomfort; however, they were followed up for the duration of the study and were
included in the intention-to-treat analysis. Compliance was greater than 99%
for all groups at both 4 and 8 weeks, and patients complied with the
restriction on consuming other flavanol-rich foods and beverages during the
study period.
Baseline cognitive
performance was similar between groups, showing that randomization was
adequate. The MMSE did not change for any of the treatment groups compared to
their baselines (P<0.13).
The time to complete
the TMT-A declined significantly for both the HF (-14.3 ± 4.2 seconds; P<0.0001)
and IF (-8.8 ± 3.4 seconds; P<0.0001) groups, but not for the LF group (+1.1
± 13.0 seconds; P<0.65). Similar results were seen for the TMT-B, with
significant reductions among the HF (-29.2 ± 8.0 seconds; P<0.0001) and IF
groups (-22.8 ± 5.1 seconds; P<0.0001), but not in the LF intervention (+3.8
± 16.3 seconds; P<0.21). For the TMT-A and TMT-B, both the HF and IF groups
were significantly better than the LF group (P<0.05).
Verbal fluency test
scores also significantly improved in both the HF (+8.0 ± 5.3 words per 60
seconds) and IF (+5.1 ± 3.1 words per 60 seconds) (P<0.0001 for both) groups,
but not in the LF group (+1.2 ± 2.7 words per 60 seconds). The HF group scores
were statistically significantly higher than the LF group scores (P<0.05).
Given these changes,
the composite cognitive z score
significantly changed during the study period (P<0.0001), with significant
improvement in both the HF (+0.693 ± 0.223; P<0.0001) and IF (+0.404 ± 0.141;
P<0.0001) groups, but no change in the LF group (-0.072 ± 0.383; P<0.31).
The composite cognitive z score was
significantly better in the HF group compared to that of the LF group
(P<0.05).
There were no
differences in blood pressure or other metabolic parameters between the groups
at baseline. Blood pressure decreased significantly in both the HF (systolic: -10.0
± 3.1 mmHg, P<0.0001; diastolic: -4.8 ± 1.8 mmHg, P<0.0001) and IF
(systolic: -8.2 ± 3.5 mmHg, P<0.0001; diastolic: -3.4 ± 2.0 mmHg,
P<0.0001) groups, but not in the LF group (systolic: -1.4 ± 5.4 mmHg,
P=0.16; diastolic: -0.9 ± 3.4 mmHg, P=0.14). The HF and IF scores for both
systolic and diastolic blood pressure were statistically significantly higher
than the LF scores (P<0.05).
Plasma glucose levels
decreased significantly in the HF (-0.6 ± 0.3 mmol/L; P<0.0001) and IF (-0.5
± 0.1 mmol/L; P<0.0001) groups, but not in the LF group (-0.1 ± 0.5 mmol/L;
P=0.19). The glucose levels for the HF and IF groups were statistically
significantly higher than the LF levels (P<0.05). The homeostatic model
assessment of insulin resistance (HOMA-IR) also improved significantly in the
HF (-1.6 ± 1.0; P<0.0001) and IF (-0.9 ± 0.2; P<0.0001) groups, but not
in the LF group (-0.1 ± 0.5; P=0.29). There was a significant correlation between
changes of plasma glucose and HOMA-IR during treatment compared to baseline
levels (r=-0.325, P=0.0018 and r=-0.421 and P<0.0001, respectively). No
significant differences were found in plasma insulin levels for any group.
No significant
differences were found in total cholesterol, low-density lipoprotein cholesterol,
high-density lipoprotein cholesterol, or triglycerides for any group. Plasma
total 8-iso-prostaglandin F2α (8-iso-PGF2α) levels
significantly decreased in the HF (-99.8 ± 60.3 pg/L; P<0.0001) and IF
(-65.2 ± 87.2 pg/L; P=0.0003) groups, but not in the LF group (-3.6 ± 51.4
pg/L; P=0.71). The HF and IF scores for plasma total 8-iso-PGF2α
levels were statistically significantly higher than the LF scores (P<0.05).
Changes of HOMA-IR
were found to be the main determinants of changes in cognitive function,
explaining ~40% of the composite cognitive z
score variability through the study period (r2=0.4013, β=-0.2910;
P<0.0001). Changes in systolic blood pressure levels and plasma isoprostane
concentrations explained ~2% and ~7% of the cognitive improvement throughout
the study period, respectively.
This paper describes the first, well-controlled dietary intervention study of this size and duration
using multiple doses of cocoa flavanols to show cognitive benefits in older
adults with MCI, in particular for processing speed, executive function,
language, and working memory. The lack of effect on the MMSE may reflect its
low sensitivity to detect small changes at the upper levels of function.
Though the use of 2
different doses did show a dose-dependence, the study did not determine
effective dose levels. It also did not elucidate the mechanisms by which
cognitive improvements occurred; however, results do suggest a possible
influential role of insulin resistance in modulating cognitive function.
Cardiovascular parameters (blood pressure), oxidative stress (isoprostane), and
increased blood perfusion in the brain may also contribute to the improvements
seen.
While the results of
the intervention were quite remarkable, their clinical significance must be considered
carefully, given the testing of only some aspects of complex cognitive
functions, the short 2-month duration, the use of a healthy population, and the
inability to distinguish whether cognitive improvements were due to cocoa
flavanols, or rather, their effects on the cardiovascular system which in turn
affected cognition.
Nonetheless, the authors
conclude by saying, "The results of the current study provide encouraging
evidence that the regular inclusion of flavanol-containing foods may be an
effective dietary approach for improving some aspects of cognitive dysfunction
in adults with MCI."
—Risa Schulman, PhD
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