Alzheimer’s Disease (AD) is a neurodegenerative disorder that affects memory, behavior, and cognition and is the leading cause of dementia.1 The underlying etiology involves the accumulation of beta-amyloid (Ab) and tau proteins, which contribute to brain atrophy and progressive cognitive decline. As of 2024, approximately 6.9 million Americans older than 65 years and 57 million adults worldwide were affected by AD.2,3 No cure exists for this disease, and current pharmacologic therapies target symptomatic relief only.3 This review examines the relationship between diet and dementia, with a focus on the role of a Mediterranean diet (MedDi) in potentially preventing or delaying cognitive decline in AD.
Pathophysiology of Alzheimer’s Disease
Several alterations in brain structure and function underlie the neuropathology of AD. The accumulation of Ab and tau proteins, neuronal loss, and atrophy are central features.4 Ab protein fragments aggregate extracellularly as plaques, and misfolded tau accumulates within neurons as neurofibrillary tangles. Ab plaques interfere with neuronal synaptic function, and tau tangles hinder internal cellular processes essential for neuron survival.2,4,5 These mechanisms result in neurodegeneration, synaptic loss, and chronic inflammation. Accelerated brain atrophy, beyond typical age-related volume decline, is a hallmark of AD, with additional contributions from oxidative stress and the disruption of gut microbiota composition.6,7
Risk Factors
AD is associated with both non-modifiable and modifiable risk factors. The most significant non-modifiable risk factor is advanced age, with prevalence doubling every 5 years after age 65.2,8 Other non-modifiable factors include family history, sex, and genetics.9 Key genetic influences include mutations in amyloid precursor protein, Presenilin-1 and -2, and apolipoprotein E.4,5 Although these factors are important, an estimated one-third of AD cases are attributable to modifiable risk factors, emphasizing an opportunity for prevention.3,9 Modifiable risks include type 2 diabetes (T2DM), atherosclerosis, cigarette smoking, obesity, hypertension, depression, decreased cerebral perfusion, lack of physical activity, and diet.3,4,9,10
Changes Occur Years Before Diagnosis
Neurodegenerative changes in AD typically begin up to 20 years before symptom onset, in the preclinical stage. Symptoms reflect the brain regions affected, especially those involved with memory, language, and executive function,11 and are classified as mild, moderate, or severe. Amnestic mild cognitive impairment (MCI), a precursor to AD, involves subtle cognitive changes but preserved functional independence; one-third of cases progress to mild AD within 5 years.2
Mild AD is characterized by mild memory loss, impaired judgment, mood changes, depression, diminished executive function, and difficulty managing finances.2,4 Individuals may require assistance with certain tasks, but largely function independently.2 In moderate AD, patients experience confusion; difficulty recognizing familiar faces; and trouble with reading, writing, speaking, and completing multi-step tasks.2,4 Severe AD, the final stage, manifests with motor dysfunction, speech and swallowing difficulties, profound memory loss, and reliance on full-time care. Physical complications, such as infections, are common.2
Significance of Prevention
Despite more than a century of research, no cure for AD has been identified.3,9,12 Pharmacologic regimens involving memantine, rivastigmine, galantamine, and donepezil provide only symptomatic benefit and minor improvements in quality of life.2,9,12 Newer infusion medications, such as lecanemab and donanemab, may delay progression but do not stop or reverse the disease and may cause significant risks like brain swelling and bleeding. These limitations highlight the importance of lifestyle modifications to prevent the onset and progression of AD.3,8,9
Burden of Alzheimer’s Disease
With increasing life expectancy and age as a primary risk factor, AD represents a growing worldwide burden.3 The Global Burden of Disease classification system ranks AD as the sixth most burdensome condition by disability-adjusted life years (DALYs).2 In 2000, there were an estimated 4.5 million adults diagnosed with AD in the United States; by 2050, this is expected to reach 13.2 million. Approximately 43% of patients with AD require around-the-clock care in nursing homes, placing a significant financial strain on patients, families, and infrastructure.8 The United States is projected to spend more than $600 billion on AD care by 2050.12
The rising prevalence also increases the demand for care partners, including both professionals and family members, to assist with daily activities such as managing medications, finances, transportation, and personal hygiene. Serving as a care partner for someone with AD can be mentally and physically demanding. According to the Alzheimer’s Association, 59% of caregivers report high levels of emotional stress, and 38% report high levels of physical stress.2 Care partners describe greater emotional, physical, and financial hardship caring for individuals with AD compared with other illnesses.2 As care needs increase in the coming years, the implementation of preventative strategies is vital for managing the effects of AD on health care systems and families.
Dietary Components and Mechanisms
Western Diet
The Western diet (WD) is associated with obesity, hypercholesterolemia, cardiovascular (CV) disease, hypertension, and T2DM—all of which are modifiable risk factors for the development and progression of AD.4,9,10,13 It is characterized by high intake of ultra-processed foods and drinks; refined carbohydrates, such as added sugars, white bread, and other processed grain products; unhealthy fats, including saturated fats and refined oils; and excess sodium and red meat.2,10,13 It lacks nuts, legumes, whole grains, fruits, and vegetables, which are sources of essential nutrients, including vitamins, fiber, and antioxidants.3,14
This diet over-emphasizes pro-inflammatory foods that have been linked to pathologic brain changes.2,10,13 For example, consuming significant amounts of high-fructose corn syrup, glucose, and sodium contributes to neuronal loss, brain atrophy, hypertension, and neurodegeneration.3,14 Excessive consumption of red meat increases risk for insulin resistance, atherosclerosis, obesity, systemic inflammation, and the development of T2DM; studies show that this may be among the most important contributors to AD pathology.14 Higher dairy and saturated fatty acid intake is also associated with cognitive decline.6,15 Processing also eliminates healthy fats, antioxidants, and nutrients that provide neuroprotection and reduce the risk for AD progression.3
Mediterranean Diet
The MedDi is extensively studied for cognitive function.3,6 Originating from the region surrounding the Mediterranean Sea, it emphasizes whole, minimally processed produce and healthy fats, abundant fresh fruits and vegetables, legumes, beans, nuts, seeds, whole grains, and extra-virgin olive oil.3,15,16 It also incorporates moderate intake of fatty, non-fried fish, lean white meat, low-fat dairy, potatoes, and eggs.6,16 MedDi foods are rich in omega-3 fatty acids, polyphenols, antioxidants, vitamins C and E, folate, and numerous minerals that are neuroprotective. This diet restricts sugar, fried foods, red or processed meats, refined oils, and high-fat dairy—all of which are linked to modifiable risks for AD.3,6
Growing evidence indicates that the nutrients in the MedDi provide neuroprotection by mitigating AD pathology and modifiable risk factors.7,9,17 Fruits and vegetables contain antioxidants, such as vitamin C, hydroxycinnamic acids, flavonoids, carotenoids, and anthocyanins, which reduce oxidative stress and inflammation. Cold-water ocean fish provide high levels of omega-3 fatty acids and vitamin D, which are anti-inflammatory and neuroprotective.12,14 Vitamin D has also been linked to a reduction in Ab production and improved protein clearance.14 Extra-virgin olive oil lowers LDL-cholesterol, reduces inflammation by inhibiting cyclooxygenase, contains antioxidants and polyphenols, and prevents Ab aggregation.6,12,14 It has been found to reduce the risk for diabetic diseases and protect the CV system through these mechanisms. Legumes supply folate, which reduces levels of homocysteine, a marker for increased AD risk. Overall, the MedDi reduces inflammation, oxidative stress, and risk for T2DM and CV disease via a nutrient-rich style of eating that protects brain health.3,7
MedDi Effects on AD Progression
Substantial evidence supports the role of the MedDi in reducing risk for the development and progression of AD.4,12,14,17 Systematic reviews show a strong association between adherence to the MedDi and reduced cognitive impairment and AD progression.17 Other studies show that the MedDi lowers risk for AD subsequent to MCI6,12,16 and reduces rates of obesity, CV disease, insulin resistance, strokes, and consequently, AD.4,12 Greater adherence has been correlated with improved episodic memory, enhanced global cognition, and defense against AD for up to 3.5 years.6,18 A recent investigation predicted that early implementation of the MedDi could reduce cases of AD by 9 million within the next 4 decades.9
These benefits may relate to specific nutrients as well as overall calorie reduction, and the mechanism warrants further study. Some studies have not demonstrated neuroprotective effects with the MedDi.7 Possible explanations for these findings include inconsistency in levels of specific nutrients consumed by subjects, self-reported data, confounding lifestyle factors, such as exercise and smoking, and irregularities in the scoring systems used to assess cognitive improvement.7,17,18
Conclusion
The lack of pharmacologic interventions to stop or reverse AD progression underscores the need to explore other prevention and treatment approaches.3,5,12 The MedDi has emerged as a promising non-pharmacologic strategy to decrease the risk for cognitive decline in AD.18 Its emphasis on whole, unprocessed foods rich in omega-3 fatty acids, antioxidants, and other neuroprotective nutrients offers a viable option for promoting brain health and delaying the onset of AD.14,16 The MedDi is associated with reduced inflammation and oxidative stress and lower rates of known modifiable risk factors for AD, such as T2DM and CV disease.9,12,14 Although further research is warranted to elucidate the precise mechanisms and validate long-term efficacy in diverse populations,18 the incorporation of MedDi principles into public health and patient care may help reduce the burden of AD and improve quality of life for patients and caregivers.3
Dining and Cooking