Treatment

There is no cure for Alzheimer disease. However, there are several therapeutic agents that can be used to slow disease progression or to alleviate symptoms. In roughly 50 percent of patients, the progression of amnestic MCI can be delayed for about one year by drugs called acetylcholinesterase inhibitors (or anticholinesterases). These drugs, which include galantamine, donepezil, and rivastigmine, work by slowing the breakdown of acetylcholine. Common side effects of acetylcholinesterase inhibitors include nausea, vomiting, and diarrhea. Symptoms of Alzheimer disease can be reduced in some patients by the drug memantine, which decreases abnormal brain activity by blocking the binding of glutamate (an excitatory neurotransmitter) to certain receptors in the brain. While this drug can improve cognition and enable patients to become more engaged in daily activities, it may cause certain patients to become unusually agitated or delusional. Other treatments aim to control the depression, behavioral problems, and insomnia that often accompany the disease.

There are also a number of experimental drugs for Alzheimer disease in early- and late-stage clinical trials. One drug that has demonstrated some success is methylthioninium chloride (Rember), more commonly known as methylene blue (an organic dye), targets the tau protein of neurofibrillary tangles. In clinical trials, methylthioninium chloride either stopped or significantly slowed the progression of cognitive decline in patients with Alzheimer disease. It is the first drug capable of dissolving tau protein fibres and preventing the formation of neurofibrillary tangles.

Another example of an experimental therapy is the monoclonal antibody lecanemab, which has the ability to clear away as well as block the formation of amyloid deposits. In clinical trials lecanemab was found to slow disease progression in human patients with early-stage Alzheimer disease; the drug was approved in 2023 by the U.S. Food and Drug Administration for the treatment of early-stage Alzheimer disease. In animal studies, a derivative of the naturally occurring flavonoid fisetin, found particularly in onions, cucumbers, and fruits such as strawberries and apples, demonstrated potential for reversing memory loss in individuals symptomatic for Alzheimer disease.

Early detection

Improved detection and treatments for Alzheimer disease are areas of concentrated scientific investigation. Progress in early detection has been of special significance, underlying important changes in diagnostic guidelines for Alzheimer disease. The first guidelines, implemented in 1984, restricted clinical diagnosis to the final stage of dementia, generally with diagnosis confirmed on autopsy. However, in 2011, as a result of improvements in diagnostic methods and in scientists’ understanding of the pathophysiology of Alzheimer disease, new guidelines that accommodated diagnosis at three different stages of the disease (preclinical, MCI, and dementia) were developed, allowing for more rapid incorporation of new or experimental diagnostic technologies and for earlier disease detection.

Early detection of Alzheimer disease is based largely on advances in diagnostic imaging, on the discovery of biomarkers (physiological changes specific to and indicative of a disease), and on the development of methods sensitive enough to measure those biomarkers. Several detection methods being developed for Alzheimer disease include blood tests to measure increased expression of a protein present in certain white blood cells and positron emission tomography to detect increased levels of an enzyme in cerebrospinal fluid.

A test designed to analyze spinal fluid for certain biomarker signatures indicative of Alzheimer disease has shown promise in early detection of the disease. Fluid for the test is collected via lumbar puncture (spinal tap). The sensitivity of the test is such that it can identify persons who are affected by mild cognitive impairment and hence are at the greatest risk of later developing the disease, thereby providing time for intervention strategies to delay its onset.

Lifestyle factors and prevention

A number of lifestyle factors that benefit cardiovascular health are associated with decreased risk of dementia and Alzheimer disease. Examples of such factors include regular physical exercise, a healthy diet, and low stress. In contrast, in persons genetically predisposed to Alzheimer disease, diets high in fat and sugar are suspected to negatively affect the brain by facilitating the development of neuritic plaques.

Dietary substances such as vitamin B, caffeine, and alcohol also have been implicated in reducing the risk of Alzheimer disease. For example, a clinical trial involving a small number of subjects found that vitamin B₁₂ can slow the rate of brain atrophy in some persons with MCI. This effect is attributed to the ability of vitamin B₁₂ to control blood levels of an amino acid known as homocysteine. Unusually high levels of homocysteine have been associated with an increased risk for Alzheimer disease. In studies of Alzheimer mice, intake of caffeine at concentrations equivalent to five cups of coffee in humans resulted in decreased levels of amyloid-beta proteins in the brain and blood. The effects of caffeine were strongest in mice displaying MCI. The substance also was found to improve memory significantly in these animals. In persons aged 75 and older who have normal cognitive function, the consumption of moderate amounts of alcohol, defined as being between 8 and 14 drinks per week (one drink equals 0.5 ounce of 100 percent alcohol), has been shown to reduce the risk of dementia by nearly 40 percent. However, in persons in the transitional stage to Alzheimer disease, who have symptoms of MCI, alcohol consumption is linked to accelerated progression toward dementia.

Another factor associated with a decreased risk for Alzheimer disease is rheumatoid arthritis, a chronic inflammatory disease of the connective tissues of the body. A protein known as GM-CSF (granulocyte-macrophage colony-stimulating factor), which is present in arthritis patients, is thought to stimulate the production of immune cells that destroy the amyloid-beta proteins. In studies of mice affected by cognitive impairment mimicking Alzheimer disease in humans, treatment with GM-CSF reduced the burden of amyloid plaques in the brain and was associated with improved performance on memory and learning tests. A form of GM-CSF known as sargramostim, which is used in the treatment of patients with acute myelogenous leukemia, has been investigated as a form of treatment for persons with Alzheimer disease.

Alzheimer disease risk may be linked to periodontitis, a form of gum disease. Research has shown that persons with chronic periodontitis have a significantly higher risk of developing Alzheimer disease compared with persons without gum disease. Scientists have also found Porphyromonas gingivalis, a bacterium associated with gum disease, in the brains of patients with Alzheimer disease. P. gingivalis secretes a protein known as gingipain, which is toxic to neurons and is associated with increased amyloid beta production in the brain. Whether periodontitis and the entry of P. gingivalis into the brain causes or is a consequence of Alzheimer disease remains unclear, however.