Nutrition plays a crucial role in maintaining proper brain function as we age. Researchers have been increasingly studying the role of dietary and lifestyle factors, such as plant-based diets, in AD [25]. Brain health was found to be improved by diets such as the Mediterranean, Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), or Dietary Approaches to Stop Hypertension (DASH). Adhering to the Mediterranean, DASH, or MIND diet can decrease cognitive decline and AD risk [26,27,28]. What these diets have in common is that they limit sugar and saturated fat intake and recommend eating a high percentage of fruits, vegetables, whole grains, and nuts and consuming minimal amounts of red or processed meat. Several medical organizations have recommended a plant-based diet to optimize cognitive health and potentially prevent dementia [29,30,31]. To maintain cognitive health and prevent cognitive aging, consuming a plant-based diet can be a low-risk and beneficial lifestyle change.

However, plant-based and vegan diets are not synonymous. A vegan diet tends to be plant-based, but plant-based diets are not vegan by definition. In a plant-based diet, plants are the primary component, but animal products are also included in small amounts. A whole-food, plant-based diet is centered on whole, unrefined plant foods and minimizes highly refined foods, such as bleached flour, refined sugar, oil, and processed packaged foods [32]. A vegan diet entirely abstains from animal products and is a stricter version of vegetarianism. In addition to cutting out meat, vegans eliminate everything made or derived from an animal, including dairy, eggs, and honey. Additionally, vegans refrain from using animal products in other areas of their lives, including beauty products, footwear, and clothing [4].

The effects of a plant-based diet on brain health and cognition are well documented. A vegan diet seems effective for various outcomes, ranging from weight loss to cardiometabolic health [33] to reduced cancer incidence [34]. 

Vegetables, fruits, grains, legumes, nuts, and seeds constitute the bulk of a vegan diet. Several meta-analyses have found that the increased consumption of fruits and vegetables can reduce dementia risk and slow down cognitive decline in older adults [38,39,40]. Conversely, a low vegetable intake is associated with poorer cognition in AD dementia [41]. A high intake of fruits and vegetables could therefore act as secondary prevention in AD. Furthermore, the phytochemicals, vitamins, minerals, and fiber found in fruits and vegetables have well-established anti-inflammatory and antioxidant properties, which may protect the brain by reducing the pathological processes associated with aging and dementia [42] (Figure 1).

Inflammation plays an important role in the development of AD. Inflammatory cascades may contribute to AD pathogenesis when the amyloid beta (Aβ) levels are continuously high, mobilizing the innate immune system through microglia activation [43]. Patients with AD often present with high levels of inflammatory markers, and these markers are linked to cognitive decline as well [44,45].

Part of the protective mechanisms of a vegan diet could be attributed to its beneficial effect on the reduction of inflammatory markers (Figure 1), thus acting as secondary prevention in AD. It appears that meat-based dietary patterns are positively correlated with biomarkers of low-grade inflammation, while vegetable- and fruit-based diets are inversely correlated [46]. However, studies providing data on inflammatory biomarkers in vegans are sparse and inconsistent. In a cross-sectional study of 36 vegans and 36 omnivores, Menzel et al. found no significant differences in any of the seven investigated inflammatory biomarkers (high-sensitivity C-reactive protein (hsCRP), adiponectin, ICAM-1, IL-18, IL-1 RA, omentin-1, and resistin). The participants that adhered to the vegan diet for over 4.8 years were more likely to have lower hsCRP levels compared to those adhering to a vegan diet for less than 4.8 years [47], suggesting the length of the diet may be an essential factor in reducing systemic inflammation. Šebeková et al. also found that plasma CRP levels did not differ significantly between vegans and omnivores [48]. In contrast, Franco de Moreaes et al. detected lower values of inflammatory markers, CRP, and the TNF-α/IL-10 ratio in strict vegetarians (defined as consuming animal products less than once a month) compared to vegetarians and omnivores [49]. Suttlife et al. found reductions in the circulating CRP after a three-week lifestyle intervention that included a vegan diet [50]. Because the study included only overweight and obese participants, the decline in the CRP level between the baseline and follow-up could have been a result of various factors. The reduction in the body mass index was probably the most influential because overweight and obesity are associated with high levels of inflammation [51]. Researchers found that participants following a vegan diet prior to the intervention had the most favorable CRP profiles compared to vegetarians and omnivores [50], which may hint at the fact that a vegan diet may help to reduce inflammatory processes. Finally, a recent meta-analysis concluded that vegans have lower levels of CRP than omnivores [52].

Despite these data, the evidence regarding the effect of a vegan diet on inflammatory biomarkers is still limited. The majority of studies examining inflammatory biomarkers in vegans have small sample sizes and are cross-sectional, so causality cannot be determined. So far, only one vegan intervention study has been conducted, and because the participants were overweight, generalizing to other populations was not possible [50]. 

Other than genetic factors, hypertension [12,13,14], diabetes [15,16,17], obesity [18,19,20], and midlife elevated blood lipids [53,54,55,56] all increase the AD dementia risk. All these AD risk factors can be modified through a vegan diet; therefore, a vegan diet can also aid in the primary prevention of AD. As a whole, a vegan diet can indirectly improve cognition by maintaining a healthy body weight and by reducing cardiovascular risk factors, such as cholesterol [34], blood glucose [57], and blood pressure [58]. Furthermore, a vegan diet might be a valuable tool for preventing diabetes [59]. Vegan diets have a lower energy content, making the people adopting them more likely to have a healthier body mass index (BMI) and lower obesity rates than those following other diets [34,35]. Low BMIs, maintained on the vegan diet, likely contribute to improved lipid profiles, glycemic results, and insulin sensitivity.

A vegan diet influences nutrient intake in several ways, which may ultimately affect insulin sensitivity. A vegan diet increases the intake of protective nutrients, such as polyphenols [60]. Dietary polyphenols inhibit glucose absorption in the intestine, stimulate insulin secretion, and enhance insulin-dependent glucose uptake [61]. The glucose-lowering effect of a vegan diet may also be attributed to the higher fiber content. Soluble dietary fiber improves glycemic control by delaying gastric emptying and the consequent slower glucose absorption and uptake [59]. Additionally, both soluble and insoluble fiber consumption can result in improved glycemic control by increasing insulin sensitivity [62]. A low-fat vegan dietary intervention leads to lower intramyocellular and hepatocellular lipid storage and thus increased insulin sensitivity [63].

A growing body of research shows that the gut microbiome plays a crucial role in AD pathogenesis [64,65,66]. The gut microbiome of AD patients is compositionally different, and it has a decreased diversity compared with those of cognitively unimpaired people [67]. Interactions between the intestine and the brain are mediated by the nervous system or by chemical substances crossing the blood–brain barrier [68]. A dysbiotic gut microbiome may contribute to the progression and exacerbation of the disease, possibly by promoting immune activation, systemic inflammation, Aβ aggregation, and insulin resistance in the periphery and the brain [66]. 

The ability to target the gut microbiota and restore its composition through food-based therapy may provide new preventive and therapeutic options for AD. Diet is among the key factors affecting the gut microbiota ecosystem [69]. A vegan diet differs from an omnivorous diet in terms of its macronutrient composition. The protein, total fat, and saturated fat intake is lower, while the carbohydrate and fiber intake is higher on a vegan diet [35,70]. The macronutrient balance alters the composition of the gut microbiota and, in turn, affects the production of metabolites that may have a positive or negative effect on health. A vegan diet seems to promote a more diverse gut microbiome and a more even distribution of microbial species [71]. The diversity and stability of the vegan gut microbiota are primarily attributed to a higher intake of complex carbohydrates, fiber, and polyphenols [35,72]. However, researchers have reported mixed results about how exactly a vegan diet affects the microbiome and its diversity. A short-term, four-week vegan diet intervention in omnivorous participants that were randomized to a vegan or an omnivorous diet led to no remarkable changes in their gut microbiota [73]. No significant difference between the alpha diversity of the subjects on the vegan or omnivore diet was observed; there were, however, changes in the abundance of the genera Coprococcus, Roseburia, and Blautia after the trial, but most of them were only detectable in a few of the samples [73]. Coprococcus, which was enriched in a vegan diet and depleted in an omnivore diet [73], was previously reported to be depleted both in the gut microbiota of 3xTg-AD mice [74] and in the fecal microbiota of AD patients and positively correlated with Mini Mental State Exam (MMSE) scores [75]. Prochazkova et al. also found only modest differences in the microbiome composition associated with a long-term vegan vs. omnivore diet [76].

A recent systematic review of cross-sectional studies concluded that most studies report an increased abundance of Bacteroidetes on the phylum level and a higher abundance of Prevotella on the genus level in vegans compared to omnivores [77]. Prevotella is one of the fiber-utilizing bacterial species that ferments fiber into short-chain fatty acids (SCFAs). SCFAs are among the most abundant metabolites of the gut microbiota, and they play a crucial role in mediating gut–brain interactions. Their presence has been implicated in the occurrence and development of AD, and they play an important role in the disease process by regulating the synaptic plasticity, reducing the Aβ and tau pathology, and neuroinflammation [78]. In fecal samples, SCFAs decrease progressively from amnestic mild cognitive decline (MCI) to AD [79]. A vegan diet should in theory result in higher concentrations of SCFAs due to the increased intake of fiber, but the results of the studies are not unanimous. While Prochazkova et al. found a higher concentration of SCFAs in vegan fecal and serum metabolome [76], Trefflich et al., Wu et al., and Reiss et al. observed no significant differences in the fecal SCFA concentrations between vegans and omnivores [80,81,82]. While De Filippis et al. found that a vegan diet produced greater quantities of SCFAs, they also found a positive correlation between the SCFAs levels and adherence to a Mediterranean diet also in omnivores, irrespective of the diet type [83].

The vegan gut microbiota may also provide health benefits by reducing inflammation because it has been found to contain fewer pathobionts associated with low-grade inflammation [77]. Cattaneo et al. found that Aβ-positive AD patients have more pro-inflammatory bacteria in the gut than healthy controls and Aβ-negative patients. The inflammatory state, cognitive impairment, and Aβ presence in the brain were all positively related to the presence of pro-inflammatory microorganisms in the gut [84].

There is still some uncertainty about whether or not it leads to a more protective, healthier gut microbiota [77]. It seems that a vegan diet could be beneficial for the gut microbiota, although individual responses vary [73]. Despite the similarity between the gut microbiota of vegans and omnivores, their metabolomic profiles are quite different [76,81]. Veganism reduces the abundance of potentially harmful metabolites and increases the abundance of beneficial metabolites [76]. There is a need for further research to clarify the complicated mechanisms and interactions between the vegan diet, gut microbiota, and the subsequent effect of the diet on the pathophysiology and development of AD. Diet diversity is a critical driver of microbiota stability, and as such, it might be more essential to consume a variety of plant-based foods rather than to exclude animal products [85].

Trimethylamine N-Oxide (TMAO) is the product of a microbial metabolite that increases with red meat consumption and has been linked to neurological diseases [71,72,85]. It was shown that the accumulation of tau and Aβ in the brain may be enhanced by TMAO. TMAO is capable of controlling the folding and aggregation state of the Aβ and accelerating its random coil-to-β-sheet conformational change, which is essential for the formation of Aβ fibers, thus accelerating the amyloidogenic plaque formation [86]. Accordingly, in AD and MCI patients, elevated cerebrospinal fluid TMAO levels correlate positively with the biomarkers of AD pathology and neurodegeneration [87], suggesting that TMAO may contribute to AD pathology. A possible mechanism by which TMAO could contribute to the development of AD is through the exacerbation of neurodegenerative and neuroinflammatory processes. Additionally, TMAO has the potential to contribute to AD by stimulating insulin resistance and other metabolic disturbances associated with AD pathophysiology [88]. An increase in plasma TMAO has been shown to promote brain aging and cognitive impairment and to worsen AD by reducing the neurite density and increasing the synaptic damage in mice [89,90]. Conversely, reducing the TMAO levels in plasma has been shown to ameliorate cognitive decline in a mouse model of AD [91].

Vegan diets decrease the TMAO levels in plasma and urine, thus acting as a secondary prevention in AD, while diets high in animal protein have a negative effect [92]. In an interventional study investigating the impact of a vegan diet, the TMAO levels decreased after only eight weeks of consuming a vegan diet [93]. It has also been shown that following the consumption of L-carnitine, trimethylamine that is abundant in red meat, TMAO is produced in greater quantities by the intestinal microbiota of omnivores compared to vegetarians and vegans [94]. However, the plasma concentrations of TMAO between lacto-ovo-vegetarians and vegans do not seem to differ [95], suggesting that a vegetarian diet might be also powerful enough to lower TMAO levels.

Mental health could be an important factor to prevent AD insurgence. In the case of problems associated with mental health, it is possible that the risk of getting AD will increase. Factors such as chronic stress and depression can in fact increase the risk of developing AD [9,10,11]. In this regard, there is some light evidence that a vegan diet positively affects mental health and well-being, thus acting as primary prevention in AD.

Systemic reviews on the association between a vegan diet and depression reveal conflicting evidence, possibly due to the heterogeneity of the studies included. Thus, the pitfall of the existing studies is that the causal effect between depression and a vegan diet cannot be depicted [96].

Another meta-analysis found an association between a vegan diet and lower scores of anxiety [97]. The only intervention study with a raw vegan diet reported improvement in the overall QOL by 11.5% (p = 0.001), a decrease in anxiety by 18.6% (p = 0.009), and perceived stress by 16.4% (p < 0.001) after 12 weeks [98].

Possible mechanisms for the effects of a vegan diet in reducing depression and/or anxiety could be related to the action of quercetin, which is found only in plant foods [99]. Quercetin acts as an inhibitor of monoamine oxidase (MAO), an enzyme that breaks down the neurotransmitters regulating mood, such as serotonin, dopamine, and norepinephrine [100]. Thus, by acting as a sort of natural antidepressant, quercetin can increase the amount of serotonin, dopamine, and norepinephrine in the brain [101], an effect that can mitigate anxiety and depression. In addition to its antidepressant properties, it was shown that quercetin exerts a neuroprotective effect in AD animal models. Mice treated with quercetin show a significant improvement in cognitive performance [102]. As a neuroprotective agent, quercetin inhibits Aβ aggregation and tauopathy [103], reduces oxidative stress and inflammation [104], and stimulates neurogenesis and neuronal plasticity by increasing the BNDF/TrkB signaling [105].

Conversely, arachidonic acid, which is found mostly in animal food, increases inflammation in the body [106], which is subsequently associated with feelings of anxiety, stress, and depression.