November 30, 2018
Greater consumption of vegetables, fruit, and fruit juices in midlife may preserve cognitive function in later life, a large, longitudinal study suggests.
Leafy greens, berries, and orange juice conferred the greatest benefit. The research supports the potential protective effect of a diet higher in antioxidants and bioactive nutrients for preserving long-term cognition.
The findings "provide further evidence that dietary choices can be important to maintain brain health," principal investigator Changzheng Yuan, ScD, of the Department of Nutrition at the Harvard TH Chan School of Public Health in Boston, told Medscape Medical News.
The study was published online November 21, in Neurology.
Largest Study to Date
"The role of diet in age-related cognitive function is a subject of strong and growing research interest," Yuan said. Past studies on the association between diet and cognitive function have returned "inconsistent results," he added, possibly because of small sample sizes, limited dietary information, and shorter follow-up periods.
To provide robust answers, Yuan and colleagues studied 27,842 participants in the Health Professional's Follow-up Study (HPFS). The mean age of the cohort was 51 years at enrollment in 1986 and all participants were men.
"To our knowledge, this study is the largest evaluation of long-term intakes of vegetables, fruits, and fruit juice intake in relation to subjective cognitive function," Yuan said.
The investigators also chose subjective cognitive function (SCF) as their measure of cognition and memory changes, pointing out that more and more research validates that the self-reported questionnaire can detect early cognitive decline.
Participants in the current study are a subpopulation of the initial 51,529 dentists, optometrists, pharmacists, podiatrists, and veterinarians in the United States enrolled in HPFS. At baseline and every 2 years, the participants complete a detailed questionnaire with 130 questions about diet, lifestyle, and medical history. At the same time, they answer the six questions on the SCF:
- Do you have more trouble than usual remembering recent events?
- Do you have more trouble than usual remembering a short list of items, such as a shopping list?
- Do you have trouble remembering things from one second to the next?
- Do you have any difficulty in understanding things or following spoken instructions?
- Do you have more trouble than usual following a group conversation or a plot in a TV program due to your memory?
- Do you have trouble finding your way around familiar streets?
Each positive response received 1 point. Poor cognition was associated with a score of 3 to 6, moderate cognition with a score of 0.5 to 2.5 points, and good cognition with 0 points.
The researchers specifically assessed diet in 1986, 1990, 1994, 1998, and 2002 and SCF results in 2008 and 2012. They stopped updating dietary data in 2002 to evaluate the temporal relationship between diet and later cognition, and to minimize possible effects of altered cognitive function on diet.
Participants were an average age of 73 years in 2008 at the time of their first SCF measurement. Researchers found 55% had good cognitive function, 38% had moderate function, and 7% had poor function.
The researchers categorized frequency of consumption of each food from "never or less than once per month" to "six or more times per day."
Specific foods assessed included green leafy vegetables like spinach, kale, and lettuce; cruciferous vegetables such as broccoli, cauliflower, cabbage, sauerkraut, and Brussels sprouts; and carotenoid-rich food including tomatoes, tomato juice, tomato sauce, carrots, yams/sweet potatoes, squash, kale, and spinach.
The investigators also tracked intake of starchy and nonstarchy vegetables, citrus fruits, berry fruits, and other noncitrus fruits, as well as orange, grapefruit, and other juices.
The average total intake in the study was 3.5 servings/day for vegetables, 1.7 servings/day for fruit, and 0.8 servings/day for fruit juice. The researchers define one fruit serving as one cup of fruit or half a cup of fruit juice; a serving of vegetables was one cup of raw vegetables or two cups of leafy greens.
OJ and Tomato Sauce
"We observed that tomatoes, lettuce, Brussels sprouts, peppers, cantaloupe and strawberries were associated with significantly lower odds of moderate and poor SCF," the researchers note, "and especially strong associations were seen for tomato sauce and orange juice."
Orange juice accounted for most of the positive association between total juice intake and better SCF scores. Participants who reported drinking orange juice daily had substantially lower odds of poor SCF (0.53; range, 0.43 - 0.67; P trend < .001) compared with those who reported not drinking or drinking less than one serving per month.
The researchers also report 34% lower odds for poor SCF scores among people who ate a median 5.7 servings of vegetables per day (the top quintile) vs 1.7 servings (lowest quintile).
In a multivariate analysis, the odds ratio was 0.83 (95% confidence interval [CI], 0.76 - 0.92) for moderate SCF when investigators compared the top to bottom quintile of vegetable intake (P trend < .001). The odds ratio was 0.66 (95% CI, 0.55 - 0.80) for poor SCF (P trend < .001).
The investigators controlled for baseline age and profession, average BMI, physical activity, multivitamin use, smoking status in pack-years, diabetes, high blood pressure, elevated cholesterol, cardiovascular disease, cancer, and depression.
Factors that did not significantly alter results include marital status, working status, living arrangement, happiness, life satisfaction, and optimism.
In the primary analyses, total vegetables, total fruits, and total fruit juice were each significantly associated with lower odds of moderate and poor SCF after controlling for age.
These associations became stronger with further adjustment for other major nondietary factors and total energy intake, the researchers note.
However, associations with total fruit intake were weaker and marginally significant only for poor SCF after further adjusting for intakes of total vegetables, fruit juice, coffee, potatoes, legumes, refined grains, and dairy products.
The researchers also compared mean dietary intakes for 1986-1990 and 1998-2002 in a multivariable model to evaluate the independent association of remote and recent dietary intakes with SCF.
"Importantly, we observed that participants with higher consumption of vegetables and fruits 18 to 22 years earlier were less likely to develop cognitive problems, whether or not they kept eating larger amounts of vegetables and fruits about 6 years before their subjective cognitive assessment," Yuan said.
Clinical, Research Implications
In terms of a proposed mechanism, antioxidant nutrients and bioactive substances found naturally in certain fruits, vegetables, and juices could confer a benefit on later cognition. Vitamins A, B, C, and E, carotenoids, flavonoids, and polyphenols are examples.
These substances are hypothesized to reduce the brain oxidative stress, thereby preventing age-related neurologic dysfunction, the researchers note.
The investigators validated their results by finding a strong association between SCF findings and APOE*E4 genotype in a subgroup of 4,899 participants with such genetic information. The age-standardized prevalence of the homozygous APOE*E4 allele was 1.0% in the good SCF group, 1.4% in the moderate SCF group, and 4.6% in the poor SCF group (P trend < .001).
The protective role of regular consumption of fruit juice was mainly observed among the oldest men, Yuan said. In particular, orange juice, the major source of the carotenoid ß-cryptoxanthin, was the main contributor to this association.
"Future research is warranted to confirm this finding and to understand the possible mechanisms underlying this relationship," he said.
Yuan cautioned that fruit juice is usually high in calories from concentrated fruit sugars.
"It's generally best to consume no more than a small glass — four to six ounces — per day. Even better is choosing the whole piece of fruit instead, which contains the added benefit of fiber."
Strengths of the study include its prospective design, large sample size, careful control of various potential confounders, and more than 20 years of follow-up. Potential limitations include a lack of baseline cognitive assessment to derive cognitive decline over time.
"However, because all participants completed professional training, they can be assumed to have started with relatively high cognitive function in early adult life," the researchers note.
"Of note, our study participants were a large group of male health professionals followed from middle-adulthood," Yuan added. "Thus, the results may not apply to women and other groups of men."
Some of the same researchers, however, previously reported similar findings for total and specific vegetables in the Nurses' Health Study using a large sample and long-term repeated measures of diet and repeated objective telephone-administered cognitive tests ( Ann Neurol. 2005;57:713-720).
"We plan to replicate these analyses in another large prospective cohort study including women, the Nurses' Health Study," Yuan said.
"Eat Your Fruits and Vegetables"
"The paper by Yuan et al shows that intake of fruit and vegetables assessed up to five times at 4-year intervals was associated with a decreased risk of subjective cognitive complaints," Richard B. Lipton, MD, the Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine in the Bronx, New York, told Medscape Medical News when asked to comment on the findings.
"Importantly, midlife dietary patterns predicted the risk of subjective cognitive complaints 18 to 22 years later," added Lipton, who was not affiliated with the research.
This study supports previous results in women from the Nurses' Health Study, linking nutrition to cognitive outcomes, said Lipton, who is also director of the Division of Cognitive & Motor Aging at Albert Einstein and a fellow of the American Academy of Neurology.
Longitudinal studies demonstrate that subjective cognitive complaints in older adults are associated with an increased risk of Alzheimer's disease and other dementias, Lipton said.
"Based on this report and others, I plan to make a bigger effort to do what my mother told me and eat my fruits and vegetables."
An NIH grant and an anonymous gift to the Harvard TH Chan School of Public Health supported the study. Yuan and Lipton have disclosed no relevant financial relationships.