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In this large prospective study of UK adults, higher adherence to a WFPB diet (reflected by high hPDI) was associated with 61% lower dementia risk among those with CMDs (Central Illustration). In contrast, people with CMDs consuming an unhealthy plant-based diet had 3.24-fold increased risk of dementia. The beneficial association between additional healthy lifestyle behaviors and lower CMD-associated dementia risk was most prominent among those not adhering to a WFPB diet. These findings expand on the growing literature pointing to the importance of consuming a diet rich in whole plant foods and low in processed and animal-based foods for reducing dementia risk. To our knowledge, our study is among the first to investigate dementia risk in relation to plant-based diet quality among those with CMDs, an especially vulnerable group.

Central Illustration Interplay of Cardiometabolic Diseases, Plant-Based Diet Quality, and Lifestyle With Dementia

Prevalent CMDs including heart disease, type 2 diabetes, and stroke were associated with increased dementia risk among older UK Biobank participants. The risk of dementia among those with CMDs was reduced with high hPDI and increased with high uPDI. Dementia risk for those with CMDs and low hPDI was attenuated in the presence of other healthy lifestyle behaviors (high physical activity, nonsmoking, and nonheavy alcohol drinking). Image attributions: Male body with organs. Reactome, release 88, https://reactome.org/content/detail/R-ICO-013956. Heart-front, pancreas, and brain-2 by Servier https://smart.servier.com/is licensed under CC-BY 3.0 Unported https://creativecommons.org/licenses/by/3.0/. CMD = cardiometabolic disease; hPDI = healthful plant-based diet index; hPDI = healthful plant-based diet index; Q = quintile; uPDI = unhealthful plant-based diet index.

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Plant-based diet quality and dementia risk in CMDs

Two prospective studies examining associations between the PDIs and dementia risk have reported results somewhat similar to ours. Higher hPDI and lower uPDI scores, although not overall PDI scores, were associated with reduced incidence of dementia in 180,532 middle-aged and older UK Biobank participants.²⁰ Unlike our study, this prior UK Biobank investigation did not consider the interplay between CMDs and plant-based diet quality in the context of dementia, and also did not examine other healthy lifestyle behaviors.²⁰ In a sample of 9,543 adults aged ≥55 years from the Rotterdam Study, higher hPDI scores were associated with lower dementia risk only among men and APOE4 carriers.²¹ The consistent lack of association between overall PDI scores and dementia risk in our study and the 2 prior reports^20,21 is revealing, implying that general plant-based diet consumption may not be enough to mitigate dementia risk. Rather, the quality of plant-based diet—one that consists primarily of whole plant foods and minimizes less healthy, more processed plant foods—seems essential. This is further supported by reports of elevated dementia risk in relation to higher consumption of ultraprocessed foods (eg, sugary beverages and packaged, ready-to-eat foods)¹³ and some animal-based foods, especially processed and red meat.^11,12

It is also worth noting that associations of hPDI and uPDI with dementia risk were strongest among adults <65 years of age and at shorter follow-up times. While the age difference could partly reflect greater statistical power in the younger group (n = 53,109 vs n = 18,539), the observed risk variation by age and follow-up time is consistent with prior studies.^36-38 Attenuation of effect estimates with age and longer follow-up may be explained by regression dilution bias^36,38 due to dietary changes and accumulating risk factors with age. Previous studies of plant-based diet quality and dementia risk involved long follow-up periods (median of 10 years²⁰ and mean of 14.5 years²¹), which may have similarly led to underestimation of dementia risk. This underscores the importance of incorporating repeated dietary assessments in future diet-dementia investigations to obtain more accurate risk estimates.^36,38

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Higher hPDI and lower uPDI scores have previously been associated with significantly lower risk of CMDs, although their association with CMD-related dementia risk has not been reported.^27,39,40 Our group previously found that an anti-inflammatory diet, measured by the nutrient-based Dietary Inflammatory Index, was associated with lower dementia risk among older adults with CMDs.⁴¹ A WFPB diet is theoretically one of the most anti-inflammatory diets^14,42,43 and can be more readily translated into accessible dietary recommendations than the Dietary Inflammatory Index due its emphasis on whole foods rather than micronutrients and macronutrients. In the current study, dementia risk among older adults with CMDs was substantially attenuated for those with high hPDI or low uPDI, and this risk increased considerably with lower hPDI and higher uPDI scores. These trends underscore the possibility for dementia prevention through a WFPB diet among those with poor cardiometabolic health. Interestingly, among CMD-free individuals, higher uPDI but not lower hPDI scores were associated with increased dementia risk. The stronger associations of both hPDI and uPDI scores with dementia among those with CMDs could allude to cardiometabolic health as a major intermediary factor linking plant-based diet quality with dementia development. This possibility is further supported by the partial mediation of hPDI and dementia risk by hemoglobin A1c, although future investigations involving repeated measurements are needed for verification.

A number of mechanisms may underpin the association between plant-based diet quality and CMD-associated dementia risk. Consumption of saturated fat (present in animal products, tropical oils, and many ultraprocessed foods) and cholesterol (found exclusively in animal products) has been shown to increase the burden of Alzheimer disease pathology in animal models of the disease.^44,45 Many animal-based and processed foods promote oxidative stress and systemic inflammation—key drivers of CMD and Alzheimer disease pathogenesis—due to harmful compounds such as advanced glycation end-products⁴⁶ and initiation of trimethylamine N-oxide production in the gut.^47,48 While fish is anti-inflammatory and tends to be associated with lower dementia risk,⁴⁹ it is also a primary source of exposure to toxic industrial pollutants^50,51 implicated in the pathology of cardiovascular disease and dementia, including heavy metals, microplastics and nanoplastics, and perfluoroalkyl and polyfluoroalkyl substances.^52-56 Aside from limiting exposure to these harmful substances, a WFPB diet is rich in dietary fiber, antioxidants, and anti-inflammatory nutrients that support a myriad of cardiometabolic functions closely tied to cognitive health, including endothelial function, glycemic control, insulin sensitivity, weight management, blood lipids, and blood pressure.^57-59

Role of other lifestyle behaviors

Additional lifestyle behaviors aside from diet may also be important for dementia risk modification.² Several prior investigations have detected lower dementia risk among people with cardiovascular disease, type 2 diabetes, or ≥2 CMDs adhering to a combination of healthy lifestyle factors.^60-62 These include former/never smoking, moderate to vigorous physical activity, moderate alcohol intake, adequate sleep, minimal sedentary time, frequent social contact, and BMI <30 kg/m² in combination with a healthy diet (high intake of fruits, vegetables, high-fiber bread, whole grains, and fish; low intake of refined grains and meat).^60-62 We found that healthy lifestyle behaviors (high physical activity, nonsmoking, and avoidance of heavy alcohol drinking) were associated with lower dementia risk among those with CMDs and a diet high in animal-based and processed foods. Interestingly, for those with CMDs consuming a WFPB diet, additional healthy lifestyle behaviors were only related to a nonsignificant reduction of dementia risk. This could suggest that a WFPB diet has a greater ability to modify CMD-associated dementia risk than other lifestyle factors. However, for those with CMDs who are not adhering to this diet, engaging in other healthy lifestyle behaviors may then play a larger role in dementia risk modification.

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