This summer, investigators published results from a highly-anticipated clinical trial on the efficacy of a dietary intervention in slowing or preventing cognitive decline. The “MIND” diet – or “Mediterranean–DASH Intervention for Neurodegenerative Delay” – was, as the name suggests, specifically developed as a diet optimized for decreasing risk of cognitive decline. But at the conclusion of Barnes et al.’s three-year trial, the diet’s performance in this regard was [spoiler] found to be underwhelming, to say the least. But the lackluster results hardly indicate that diet choices have no effect on cognitive health.
What is the MIND diet?
The MIND diet is based on a combination of the Mediterranean diet and the “Dietary Approaches to Stop Hypertension” diet – i.e., the DASH diet. Thus, the hybrid MIND diet prioritizes intake of whole grains, leafy greens, lean proteins such as fish and poultry, nuts and legumes, berries, and olive oil, and it recommends limiting intake of sweets, fried foods, and saturated fats.
Evidence from a few clinical trials have indicated that adherence to either the Mediterranean or DASH diets decreases risk of cognitive decline, but these studies have not typically been designed with cognitive endpoints in mind, leading to critical flaws that limit data interpretation. Additionally, a number of observational studies have shown that adherence to a MIND diet is associated with dementia risk reduction, but the supposed benefits of this “optimal” diet pattern had yet to be tested in a rigorous manner (i.e., using a longitudinal randomized trial specifically designed for the assessment of cognitive effects) – at least until Barnes et al.’s investigation.
About the Study
In Barnes et al.’s three-year trial, participants with suboptimal baseline diet patterns were randomized to either a MIND diet group (n=301) or a control diet group (n=303), with both diet assignments also involving mild calorie restriction (CR) designed to achieve a total weight loss of 3-5% between baseline and year 3. Apart from the CR, those assigned to the control diet group were asked to continue with their regular pre-trial diet pattern. Adherence to the respective diets was assessed through food questionnaires and, in a subgroup of participants, through testing of blood biomarkers related to diet components (specifically, these included the antioxidants lutein, zeaxanthin, and alpha and beta carotene).
The investigators used a standard battery of 12 cognitive tests to assess changes both in global cognition and in the specific cognitive domains of episodic memory, semantic memory, executive function, and perceptual speed. Following baseline assessments, cognition was tested again at months 6, 12, 24, and 36 of the intervention period. The researchers also conducted magnetic resonance imaging (MRI) tests on a subgroup of participants at baseline and at month 36 to assess any changes in volume of the whole brain or of the hippocampus, a key region for memory.
Both diet groups showed improvements in global cognitive scores from baseline to year 3 (an average increase of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group). However, as hinted in the introduction to this newsletter, the difference between groups was not statistically significant (P=0.23). The researchers likewise observed no significant differences between groups in any of the specific cognitive domains tested, nor did the groups diverge in other markers of neurological health, such as changes in whole-brain and hippocampal volumes.
Calorie Restriction is Key
Though controls maintained a suboptimal diet composition, they, like the MIND group, were also asked to adhere to mild calorie restriction, which led to comparable levels of weight loss between groups. Thus, the finding that both diet groups improved in cognition but did not differ significantly from each other indicates that the intervention they had in common (i.e., CR) likely matters more for cognitive health than the intervention that differed between groups (i.e., the specific diet pattern). Indeed, a closer look at the data reveals that change in cognition mirrored change in body weight: the bulk of the weight lost during the study occurred within the first year of the intervention, the period over which participants also saw the greatest improvements in cognitive scores.
The benefits of calorie restriction for cognition certainly are not unexpected. In this study, over half of all participants had hypertension at baseline, approximately 15% had pre-existing diabetes, and the average BMI for both groups fell within the obese range. As discussed in an “Ask Me Anything” episode on brain health, high blood pressure and poor metabolic health are two powerful risk factors for cognitive decline and neurodegenerative diseases, and both of these factors can be improved dramatically through weight loss – such as occurred as a result of CR in this trial.
Yet although Barnes et al.’s results provide compelling evidence for the benefits of CR and indicate that overall energy balance is likely the most important variable with respect to dietary effects on cognitive health, these findings absolutely should not be interpreted as proof that food choices are irrelevant. Indeed, this trial was not designed in such a way as to fully evaluate the potential of the MIND diet itself in improving cognitive trajectories relative to patterns more in line with the standard American diet.
Diet patterns can impact total calorie intake
The investigators’ choice to impose mild CR on both groups reflects one of the key differences between the MIND diet and the suboptimal diet of the control group: participants on the MIND diet were expected to lose weight simply as a result of the healthier diet pattern. Thus, the researchers introduced the additional intervention of CR to both groups in order to control for the expected weight loss in the MIND group. This approach better isolates the variable of diet composition, but it also masks a potential benefit of the MIND diet in reducing total calorie intake. In other words, it’s very likely that one of the key ways in which the MIND diet might promote cognitive health is by naturally resulting in calorie restriction. The imposition of CR thus makes the MIND diet trial a test of efficacy (the ability of an intervention to yield the desired result under ideal, strictly controlled conditions), but it prevents us from making conclusions about the diet’s effectiveness – the ability of an intervention to yield the desired result under “real world” conditions, such as when individuals are free to make their own choices regarding calorie consumption.
Are food choices irrelevant under isocaloric conditions?
Even if we ignore the potential for the MIND diet to reduce overall calorie intake, Barnes et al.’s data still leave ample room to doubt interpretations that this diet pattern offers no benefit under isocaloric conditions. Although differences in cognitive metrics between the MIND diet group and controls did not achieve statistical significance, overall trends consistently favored the MIND diet group for changes in global cognition, all neurological markers, and all sub-domains of cognition apart from semantic memory. The failure of these trends to reach significance might therefore suggest that a three-year trial of only 604 participants may not have been long enough or sufficiently powered to reveal a true difference in cognitive effects based on diet pattern.
In addition, although food questionnaires indicated that participants maintained high adherence to their respective diets throughout the trial, blood biomarker data instead suggest that adherence to the MIND diet likely declined substantially after the first year of the study. Thus, it’s possible that stricter adherence to the dietary intervention would have led to a greater divergence in cognitive scores between groups.
Finally, as with any clinical trial, we must be wary of examining results from a specific study design representing a specific population and extrapolating them to other contexts. This trial was designed to test the effect of the MIND diet versus any suboptimal diet on cognitive health specifically in the context of mild energy deficit in individuals with relatively poor baseline health (overweight or obesity was a requirement for inclusion, as was a family history of Alzheimer’s disease, and as noted above, many participants also suffered from relevant comorbidities). This study did not assess the effect of the MIND diet under eucaloric conditions (i.e., at a level of calorie intake designed to maintain baseline weight), nor did it test how the diet might impact cognition among individuals in good metabolic health at baseline. To truly determine the extent to which food choices affect cognitive health independently of overall calorie consumption, we would need a trial comparing eucaloric diets in relatively healthy individuals, as the effects and variability of weight loss due to CR – particularly in those with obesity and related metabolic disease – is otherwise likely to overshadow any effect of diet pattern.
The Bottom Line
The MIND diet trial is one of the few attempts to date at investigating the effect of whole diet patterns on cognition using a randomized controlled trial design. As I’ll discuss in greater depth in an upcoming newsletter, the task is fraught with challenges, and seldom have such studies – or for that matter, any studies related to nutrition – generated reliable answers to the questions they sought to address. Moreover, in such cases, a cursory summary of results can be misleading.
Data from the MIND diet trial have been interpreted by various popular press outlets as evidence that diet composition has no impact on cognitive health, but this conclusion betrays an egregiously superficial analysis. At the very least, this trial provides support for the cognitive benefits of calorie restriction and weight loss (albeit without a non-CR control group). Since numerous studies have linked food choices (which can vary in energy density, palatability, and nutrient composition) to overall energy intake, it’s very plausible that diet patterns can influence cognition via effects on total calorie consumption – an effect that this trial was not designed to evaluate. Further, a closer look at the Barnes et al.’s results suggest that the MIND diet may indeed be neuroprotective even under isocaloric conditions, despite the lack of statistical significance in these findings, though future studies will likely need to investigate this further under eucaloric conditions.
I applaud the effort made by Barnes and colleagues in exploring a vital subject with as robust a design as can reasonably be expected from a multi-year nutrition study, but unfortunately, their trial is the latest in a line of many that have fallen short of offering definitive conclusions. The jury may still be out on the impact of the MIND diet in preventing cognitive decline, but at least one thing is clear: whether in the context of cognitive health, cardiovascular health, metabolic health, or cancer prevention, the most important dietary principle is to maintain energy balance. If you find for yourself that adherence to a MIND diet is helpful in accomplishing that goal, you certainly don’t need to wait for validation from a randomized trial to put that strategy into effect.
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