Alzheimer's disease (AD) accounts for 60-70% of all neurodegenerative disorders globally, underscoring its significant impact on public health. AD primarily affects the brain's neural structures, neuroplasticity, and metabolism, leading to progressive nerve cell death in the affected brain regions. Consequently, loss of neuronal connections and cognitive, emotional, and behavioural alterations are prevalent in advanced AD stages. While effective therapies remain largely elusive, current approaches predominantly target symptom management. However, emerging evidence indicates that nutritional interventions and modulation of certain hormonal pathways may offer innovative, efficacious strategies.

Numerous studies suggest a compelling correlation between AD, glucose metabolism, and diabetes. Impaired glucose metabolism, characteristic of type 2 diabetes, is identified as a considerable risk factor in nearly 80% of AD cases. Reduced glucose uptake and metabolism, often observed in AD patients' brains, contribute to neuronal dysfunction and death, a phenomenon coined "brain insulin resistance". This resistance is believed to expedite the accumulation of beta-amyloid plaques and hyperphosphorylated tau, two AD hallmarks. Furthermore, insulin dysregulation, intrinsic to diabetes, appears to hinder synaptic plasticity, learning, and memory processes, thereby linking diabetes and cognitive decline. Consequently, AD, often referred to as "Type 3 Diabetes", suggests a metabolic disorder resulting from neurons' failure to respond to insulin and insulin-like growth factors, ultimately leading to cognitive decline and dementia.

As AD progresses into moderate and severe stages, cognitive and functional decline becomes more prominent. Symptoms such as agitation, hallucinations, delusions, and wandering increase in the advanced stages of AD, with malnutrition becoming a significant risk due to various factors. Nutritional interventions, lifestyle alterations, and comprehensive approaches promise to improve patient health and potentially delay AD progression. Nutritional strategies play a crucial role in mitigating disease symptoms like increased inflammation, altered metabolism, and impoverished commensal microbiota, otherwise known as dysbiosis. Several nutritional regimens have been evaluated for AD management, with the Mediterranean diet, rich in diverse foods with broad nutritional values, appearing as the most successful preventive approach.

During Alzheimer's disease advancement, nutritional needs rise in response to physiological changes accompanying disease progression. Patients may require a high-calorie diet to combat unintentional weight loss, while adequate hydration becomes crucial to prevent common afflictions like constipation and urinary tract infections. Increased intake of antioxidants, omega-3 fatty acids, and B vitamins could prove beneficial due to their potential neuroprotective effects. However, nutritional interventions should be tailored to consider the individual's overall health status, concurrent conditions, and tolerability. The goal is to maintain optimal nutritional status to support physical health, alleviate disease-related symptoms, and enhance the quality of life.

With AD often referred to as "Type 3 Diabetes", nutritional interventions and glucose metabolism modulation by a newer group of medicines are being explored in AD management. Incretin hormones, traditionally recognized for their role in glucose homeostasis, have recently gained attention for their neuroprotective effects. Preliminary studies suggest that GLP-1 and GIP agonists may delay neurodegeneration in AD by reducing inflammation, improving cognition and memory, and promoting neuron survival through their glucose-modulating effect. Therefore, GLP-1 agonists and GIP pathways are being evaluated in the management and possible treatment of AD.

Potential strategies to improve AD patients' nutritional habits abound. Extensive evidence supports the benefits of consuming plant-based whole foods, such as vegetables, fruits, nuts, and cereals, in alleviating AD symptoms and fine-tuning the patients' energy needs. Therefore, the research topic will focus on nutritional constituents that can potentially alleviate symptoms at different disease stages, taking into account the specific needs for certain nutritional compounds that may play a role in preventing and treating specific AD symptoms.

The aim of this research topic is to gather original research studies, meta-analyses, mini-reviews, and case reports focused on developing nutritional strategies focusing on, but not limited to, the following areas:

• Improvement of the well-being of AD patients, concentrating on individual approaches, personalized diets, and symptom management.
• Nutritional habits influencing AD etiology.
• The role of mental health stressors such as depression, anxiety, agitation, sleep difficulties, behavioral changes, and medication use.
• Research reports on foods that can modulate the energy metabolism related to "Type 3 Diabetes" and their impact on potential behavioural improvements.
• The role of diet in modulating the gut-brain axis, which is emerging as a critical aspect of AD pathogenesis and potential novel therapeutic approaches.

Contributions should address at least one of the AD symptoms that can be alleviated by protective foods.

In summary, this research topic aims to consolidate existing knowledge, introduce new insights, and propose future research directions in the realm of nutritional and hormonal interventions applicable to AD. The objective is to stimulate a comprehensive, multidisciplinary dialogue aimed at developing more effective strategies to address the growing burden of AD.

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Frontiers in Nutrition

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