Alzheimer’s disease (AD)—named after the German physician Alois Alzheimer, who first described its symptoms at the beginning of the last century—is a form of neurodegenerative dementia characterized by the progressive deterioration of an individual’s cognitive abilities.

Hallmark features of the early stages of the disease include the loss of short-term memory, language dysfunction (such as forgetting specific terms or making errors in speech or writing), an inability to recognize everyday objects or familiar people, and difficulty in performing tasks that require a degree of planning.

According to data collected in 2016, there are over 1,200,000 people in Italy living with Alzheimer’s disease—a figure destined to rise over time, given the ongoing increase in average life expectancy. In fact, the prevalence of Alzheimer’s disease has been shown to grow with age, rising from approximately 3% in individuals aged 65 to 74 to over 30% in those over 85. Although it has been established that the decline in cognitive function is associated with a reduction in brain volume—caused by significant and continuous neuronal death (hence the classification as a “neurodegenerative disease”)—the molecular details of the pathological process that triggers such degeneration of brain tissue remain not entirely clear.

What is known is that Alzheimer’s disease manifests clearly through two specific types of pathological alterations that impair the health of neuronal cells: the deposition of “β-amyloid plaques” and the formation of “neurofibrillary tangles.” β-amyloid plaques consist of accumulations of defective versions of the β-amyloid precursor protein; these create a physical obstruction that damages the connections between neurons. Neurofibrillary tangles, on the other hand, arise from structural alterations in specific protein filaments known as “microtubules.” These act as intracellular “highways” along which various molecules travel to reach different organelles or specific regions of the cytoplasmic membrane. In both cases, the stability of the neuronal network is compromised, and the resulting loss of connectivity between cells ultimately leads to neuronal death.

Alzheimer’s disease can be either familial or sporadic in origin. In familial cases, the onset is early (generally before the age of 65), and the development of the disease is linked to mutations in genes involved in regulating the processing of the β-amyloid protein. However, this genetic component is found in only about 5% of individuals with Alzheimer’s; in the vast majority—approximately 95%—of cases, the onset of the disease is attributable to a combination of environmental factors. The primary external variables that significantly increase the risk of developing Alzheimer’s include diet, a lack of adequate physical activity, and pre-existing metabolic dysfunctions. It is difficult, however, to isolate these three factors and consider their consequences independently, as they share both underlying causes and clinical manifestations, and they exert a mutual influence on one another.

Chronic inflammation, hyperglycemia (elevated fasting blood glucose levels), hyperinsulinemia (high levels of insulin in the blood), and hypertension are pathological conditions indicative of disruptions in the maintenance of metabolic homeostasis—such as insulin resistance, obesity, and type 2 diabetes mellitus. These conditions, in turn, serve as predisposing factors for other diseases, including cardiovascular complications and, notably, Alzheimer’s disease. In other words, insulin resistance—the inability of cells to respond physiologically to the hormone insulin—leads to defective glucose energy metabolism in the affected tissues. This triggers a series of interconnected, aberrant processes that ultimately amplify the initial pathological effects. One such process is persistent inflammation, which not only fuels insulin insensitivity but also drives the abnormal production of specific proteins that mediate inflammatory signaling—known as "cytokines"—as well as the accumulation of large quantities of free radicals, or reactive oxygen species (ROS). In the brain, a massive influx of pro-inflammatory cytokines, combined with oxidative stress caused by ROS, damages neurons. Consequently, these neurons lose their ability to efficiently clear defective β-amyloid proteins, regulate the formation of neuronal connections (synapses), and properly assemble microtubule filaments.

A sedentary lifestyle and a consistently unbalanced diet—particularly one rich in fatty foods and refined carbohydrates—impair proper metabolic function, thereby promoting the development of both obesity and insulin resistance. Given the link between insulin resistance and Alzheimer’s disease (AD), it is not surprising that a growing body of evidence highlights the beneficial effects of physical exercise and diet in helping to prevent and counteract the neurodegenerative symptoms of the disease. Both in individuals already diagnosed with AD and in those without an AD diagnosis who nonetheless exhibit signs of physical and cognitive "frailty," the implementation of a tailored program of physical activity and/or dietary intervention leads to a significant improvement in neuropsychiatric parameters.