Alzheimer’s Disease (AD) is a progressive neurodegenerative disease, which can be prevented in many cases, but not cured1. As many as 416 million people worldwide have AD. About 32, 69, and 315 million, respectively, have AD dementia, prodromal AD, and preclinical AD2. About 22% of people over 50 years of age are affected. There are seven clinical stages of AD: Most people have no objective or subjective symptoms of cognitive or functional decline. They have none of the changes in behavior and mood that occur in later stages. So, mentally healthy people are in stage 1 and are considered normal. At stage 2, subjective memory loss occurs, followed by mild cognitive impairment at stage 3. At stage 3, people have subtle mental deficits that may only be noticed by people who see them frequently or live with them. Moreover, people at stage 3 may ask the same question over and over because they don’t remember asking the question. They may also experience anxiety and difficulty concentrating.
At stage 4, a person has moderate cognitive decline and AD can be diagnosed with some accuracy (although false negatives do occur). Some people can remain free of symptoms of AD but be diagnosed with it after death and their brain is observed during an autopsy. The most common functioning deficit in these persons is a decreased ability to do some of the complex activities involved in everyday life. Also, they may not be able to remember major recent events, such as birthdays, holidays, or even the current month or year. Their dominant mood at this stage is frequently what psychiatrists call a flattening of affect and withdrawal. In other words, at this stage often seems less emotionally responsive than previously. By stage 5, people have moderately severe cognitive decline. In stage 5, deficits become so bad that catastrophe-free, independent living is no longer possible. Some basic activities of daily life become difficult or impossible. They need someone to help provide adequate care. For people who are not properly supervised, predatory strangers may become a problem. Very common reactions for persons at stage 5 who are not given adequate support are anger and suspiciousness.
By stage 6, one has severe cognitive decline and moderately severe dementia. One’s ability to perform basic activities of daily life becomes compromised. There are five successive substages. People initially in stage 6a, lose the ability to choose their clothing without assistance and begin to require assistance in putting on their clothing properly. The total duration of the stage of moderately severe Alzheimer’s disease (stages 6a through 6e) is approximately 2.5 years in otherwise healthy persons. At stage 6b, one loses the ability to bathe oneself. In stages 6c through 6e one loses the ability to manage the mechanics of using a toilet and may become incontinent. Also, cognitive deficits are generally so severe that one has little or no knowledge about major aspects of their current life circumstances, such as one’s current address or the weather conditions of the day. In this stage, the AD person’s cognitive deficits are generally of such magnitude that the person with AD may, at times, confuse their wife with their mother or otherwise misidentify or be uncertain of the identity of close family members. At the end of this sixth stage, the ability to speak begins to break down.
Emotional changes generally become most overt and disturbing in this sixth stage of AD. People at this stage can no longer channel their energies into productive activities. Consequently, persons may begin to fidget, to pace, move objects around, or manifest other forms of purposeless or inappropriate activities. Because of their fear, frustration, and shame regarding their circumstances, these persons frequently develop verbal outbursts and also threatening, even violent behavior. Because these AD patients can no longer survive independently, they commonly develop a fear of being left alone. By stage 7, one has very severe cognitive decline and severe dementia. Speech can become limited to just a few words that are barely intelligible. Once intelligible speech is lost, the ability to ambulate independently (without assistance), is invariably lost. For those patients who remain alive, stage 7c lasts about one year, after which they lose the ability not only to ambulate independently but also to sit up independently. In the end, the brain can no longer send appropriate signals to the heart and it stops beating.
There are many things that people can do to prevent AD. This includes consuming a healthy diet (with little or no meat and plenty of dietary fiber), staying physically active and having meaningful relationships. On the other hand, an unhealthy diet, obesity, a lack of physical activity and untreated depression are major risk factors for AD. Smoldering inflammation can be caused by these things, as well as by a leaky gut produced by an unhealthy microbiome (collection of bacteria). In addition, as our cells age, they can produce improperly folded proteins, senescent cells and cellular debris that should be removed. There are some compounds called senolytics that can remove these things and prevent the damage that they can cause. This includes folic acid (also known as folate and vitamin B9), quercetin, resveratrol, fisetin, kaempferol, apigenin, EGCG, piperlongumine and curcumin. These are present in a variety of fruits and vegetables, as well as turmeric. Unfortunately, millions of people are not able to avoid AD and dementia that it can cause. However, it is possible to have all the neurodegeneration that occurs in AD and not exhibit any of the symptoms while alive. This was revealed in a study done with retired Catholic nuns, who agreed to undergo tests and evaluations while alive and then an autopsy when dead3. At least one nun was diagnosed with AD only after dying. She exhibited none of the symptoms while alive. She was well-known for being a happy, wonderful person who was loved by many.
The United States Food and Drug Administration (FDA) has approved two prescription drugs for people who have either mild cognitive impairment or are in the early stages of AD4-5. They are humanized monoclonal antibodies called lecanemab (Leqembi®) and aducanumab (Aduhelm®). They are not a cure and may not be appropriate for people who are susceptible to stroke, encephalitis or edema. It is given as an intravenous (IV) infusion once every two weeks. Infusion centers have been preparing for a potential surge of new patients.
These monoclonal antibodies bind to defective proteins called β-amyloid that form plaques. The pathogenesis of AD involves the deposition of β-amyloid plaques and the formation of neurotoxic oligomers of the amyloid-β (Aβ) peptide6. This causes neurofibrillary tangles that are made up of the hyperphosphorylated microtubule-associated protein called Tau (p-Tau), as well as neuroinflammation, neuronal and synaptic loss, and dementia. The β-amyloid plaques begin to deposit in the brain a decade or more before the onset of cognitive decline. This means that medicine that lowers or removes Aβ, would be best used presymptomatically, preferably a decade or more before the propagation of AD pathologies. However, there is a risk of very harmful adverse side effects7-8. These include edema, stroke and encephalitis. Many AD patients have risk factors such as obesity, lack of physical activity and advanced age. So, it may or may not be advisable to give such patients this new medicine.
It has also been suggested that the high cost of these drugs may cause the governments of the USA and other countries to increase the amount that people might have to pay in Medicare premiums or similar programs in other countries. This is somewhat reductionist. Certainly, the relatively high cost of these drugs will put some pressure on health insurance costs. However, these drugs may lower the costs of insurance as they keep people in the early stages of AD and their caregivers healthier, more productive and able to contribute to the economy. Moreover, taking care of AD patients is quite expensive – especially in the later stages of AD. If these drugs can keep these patients from having to be in a hospital or assisted living, the costs of insurance will go down.
Most importantly, these drugs can prevent extensive human suffering in both the patient and the caregivers. One of the loneliest experiences in life is taking care of a loved one who is slowly suffering and dying. So, I choose not to eat meat. Instead, I eat many fruits and vegetables as well as other sources of dietary fiber, stay active, practice mindfulness, pray, and maintain loving relationships with fantastic people.
1 Gustafsson, A. et al. Global estimates on the number of persons across the Alzheimer's disease continuum. Alzheimer’s & Dementia, Volume 19, p. 658-670, 2022.
2 Alzheimer’s Disease International. World Health Organization, 2023.
3 Snowden D. Aging with Grace: What the Nun Study Teaches Us About Leading Longer, Healthier and More Meaningful Lives, Bantam Books, New York, 2001.
4 U.S. Food & Drug Administration. Aducanumab (marketed as Aduhelm) Information. 8 July, 2021.
5 U.S. Food & Drug Administration. FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. 6 July, 2023.
6 Karran, E. & De Strooper, B. The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics. Nature Reviews Drug Discovery, Volume 21, p. 306-318, 2023.
7 Iwatsubo, T. Clinical implications of Lecanemab: challenges, questions and solutions. Journal of the Prevention of Alzheimer’s Disease, Volume 3, p. 353-355, 2023.
8 Perry, G. Russian roulette with Alzheimer’s Disease patients: do the cognitive benefits of lecanemab outweigh the risk of edema, stroke and encephalitis? Journal of Alzheimer’s Disease, Volume 92, p. 799-801, 2023.