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There are decades worth of epidemiological and clinical evidence suggesting that lifestyle factors contribute to the development of a significant portion of dementia cases, factors that include diet, activity level, smoking, alcohol consumption, and others.¹ Regarding diet, many studies have found evidence suggesting that adherence to a Mediterranean-style diet may prevent dementia and progression of cognitive decline, including two systematic reviews concluding that the diet is associated with prevention of cognitive impairment and dementia.^2,3 To the contrary, a recently published large prospective study found that midlife self-reported diet was not associated with subsequent reduced risk of developing dementia.⁴ Despite this finding, the conclusion of this study may not be as convincing as it seems on the surface.

Researchers conducted a longitudinal prospective cohort study of the inhabitants of the Swedish town of Malmo to see if their self-reported diet at baseline was associated with incident dementia in the following years. After enrolling more than 28,000 people (mean age=58, 61% women), researchers took baseline dietary information during the years 1991-1996 and then followed participants for an average of 20 years to determine the incidence of dementia. The nutrition evaluation at baseline was quite detailed, including a seven-day food diary, a detailed food frequency questionnaire, and a 45-60 minute in-person interview to evaluate dietary habits. The researchers scored participants based on their adherence to two dietary patterns: Swedish dietary guidelines designed to portray a healthy dietary pattern based on Swedish nutrition recommendations (adequate fiber, fruits, and vegetables; low added sugar and processed meats; high fish and shellfish) and a modified Mediterranean diet based on the one used in the PREDIMED study, focused on a high intake of vegetables, legumes, fruits, fish, and healthy fats and a low intake of dairy products, meat, and saturated fatty acids.⁴

The results found that individuals who adhered to conventional healthy dietary recommendations did not have a lower risk of developing dementia (hazard ratios compare groups with the best diet adherence scores to those with the worst):

• All-cause dementia (HR, 0.93; 95% CI, 0.81 – 1.08)
• Alzheimer’s disease (HR, 1.03; 95% CI, 0.85 – 1.23)
• Vascular dementia (HR, 0.93; 95% CI, 0.69 – 1.26)⁴

Adherence to the modified Mediterranean diet also did not appear to lower the risk of developing dementia:

• All-cause dementia (HR, 0.93; 95% CI, 0.75 – 1.15)
• Alzheimer’s disease (HR, 0.90; 95% CI, 0.68 – 1.19)
• Vascular dementia (HR, 1.00; 95% CI, 0.65 – 1.55)⁴

While the study has some methodological strengths, including its large sample size, thorough disease diagnosis data, and detailed dietary assessment, one serious limitation is the lack of subsequent assessment of dietary quality following a single baseline assessment. In essence, the study demonstrates that there is no association between diet at a single point in time and disease incidence decades later. There is no way to know if or how participants may have changed their diet in the intervening years. The authors attempt to explain this away by noting that they excluded anyone who had reported a recent change in diet prior to the study and also by noting that “dietary habits remain relatively stable during life.” This is unreferenced and it is unclear upon what they are basing that assertion. Indeed, some evidence suggests that this is decidedly not the case, even in Sweden.⁵ This is a limitation that undermines an otherwise thorough evaluation of diet.

Another potential weakness of the study is the region-specific adjustments made to the Mediterranean diet scoring to make it suitable in a Nordic population, most notably including all vegetable oils and not just olive oil as part of the diet. Given that olive oil is one of the main contributors to the known health impacts of a Mediterranean diet and that olive oil itself has been found to be protective against cognitive decline and dementia,^6,7 this factor alone may explain at least some of the difference between this study and others that have found an effect of Mediterranean-style diets on dementia.

One other point of interest is the age of the participants in the study. The authors point out that evaluating diet in midlife is important because individuals at that age are less likely to be in the prodromal phase of impending dementia. They point out that many studies of diet and dementia include elderly individuals (those over 65) who are more likely to already be in the very early stages of developing the disease, which could represent reverse causation, meaning that those who will go on to develop dementia may change their diet because of the incipient disease and not the other way around. However, while the 20-year follow-up window sounds long, because the study participants were in middle age at the outset, this may not be a long enough time window to see differences emerge. Since dementia incidence tends to increase with age, if the study had been extended another 5 or 10 years, the results may have reached statistical significance.

Finally, while the authors conclude simply that the Mediterranean diet and Swedish conventional healthy diet could not be confirmed to be associated with prevention of dementia, an accompanying editorial adds some insight that is aligned with the functional medicine approach in spirit: “Diet as a singular factor may not have a strong enough effect on cognition, but is more likely to be considered as one factor embedded with various others, the sum of which may influence the course of cognitive function (diet, regular exercise, vascular risk factor control, avoiding cigarette smoking, drinking alcohol in moderation, etc.). Thus, diet should rather be regarded as one part of a multidomain intervention with respect to cognitive performance.”⁸ Indeed, functional medicine recognizes that regardless of whether you are looking to prevent or to treat mild cognitive impairment, dementia, or Alzheimer’s disease, the most powerful approach is not a single pill nor even a single dietary intervention but a multifactorial approach that addresses all of the modifiable lifestyle factors, along with other relevant underlying physiological dysfunction.

References

1. Lee M, Whitsel E, Avery C, et al. Variation in population attributable fraction of dementia associated with potentially modifiable risk factors by race and ethnicity in the US. JAMA Netw Open. 2022;5(7):e2219672. doi:1001/jamanetworkopen.2022.19672
2. Petersson SD, Philippou E. Mediterranean diet, cognitive function, and dementia: a systematic review of the evidence. Adv Nutr. 2016;7(5):889-904. doi:3945/an.116.012138
3. García-Casares N, Gallego Fuentes P, Barbancho MÁ, López-Gigosos R, García-Rodríguez A, Gutiérrez-Bedmar M. Alzheimer’s disease, mild cognitive impairment and Mediterranean diet. A systematic review and dose-response meta-analysis. J Clin Med. 2021;10(20):4642. doi:3390/jcm10204642
4. Glans I, Sonestedt E, Nägga K, et al. Association between dietary habits in midlife with dementia incidence over a 20-year period. Neurology. Published online October 12, 2022. doi:1212/WNL.0000000000201336
5. Winkvist A, Klingberg S, Nilsson LM, et al. Longitudinal 10-year changes in dietary intake and associations with cardio-metabolic risk factors in the Northern Sweden Health and Disease Study. Nutr J. 2017;16(1):20. doi:1186/s12937-017-0241-x
6. Román GC, Jackson RE, Reis J, Román AN, Toledo JB, Toledo E. Extra-virgin olive oil for potential prevention of Alzheimer disease. Rev Neurol (Paris). 2019;175(10):705-723. doi:1016/j.neurol.2019.07.017
7. Guasch-Ferré M, Li Y, Willett WC, et al. Consumption of olive oil and risk of total and cause-specific mortality among U.S. adults. J Am Coll Cardiol. 2022;79(2):101-112. doi:1016/j.jacc.2021.10.041
8. Peters N, Nacmias B. Does diet matter? The implications of dietary habits for dementia. Neurology. Published online October 12, 2022. doi:10.1212/WNL.0000000000201420