US Pharm. 2023;48(6):22-24.
Alzheimer’s disease (AD) is a progressive disorder that damages and destroys nerve cells in the brain. Over time, the disease leads to a gradual loss of cognitive functions, including the ability to remember, reason, use language, and recognize familiar places. It can also cause a range of behavioral changes.
AD is the most common cause of memory loss and other cognitive abilities that are serious enough to interfere with daily life. This disease accounts for 60% to 80% of dementia cases.1
AD is not a necessary part of the natural aging process, but its greatest known risk factor is increasing age. The majority of people with AD are aged 65 years and older. AD is considered to be early-onset AD if it affects a person aged younger than 65 years. Early-onset is also referred to as younger-onset Alzheimer’s.1
This disease is progressive, wherein dementia symptoms gradually worsen over a number of years. In its early stages, memory loss is mild, but with late-stage AD, individuals lose the ability to carry on conversations and respond to their environment. It has been reported that a person with AD lives 4 to 8 years after diagnosis but can live as long as 20 years, depending on other factors.2
AD has no cure, but recently two FDA-approved monoclonal antibody treatments—aducanumab and lecanemab—demonstrated that removing beta-amyloids, one of the known main causes of AD, from the brain reduces cognitive and functional decline in people living with early AD. Other treatments can slow the worsening of dementia symptoms and improve quality of life for those with AD and their caregivers. Today, a global effort is underway to find better ways to treat the disease, delay its onset, and prevent it from developing.3
This disease is named for its discoverer, Alois Alzheimer. In 1906, Dr. Alzheimer found unusual changes in the brain tissue of one of his patients who had died of a mental illness. This patient had memory loss, language problems, and unpredictable behavior. After she died, he found many abnormal clumps made of a toxic protein (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) in her brain. Plaques and tangles in the brain are two of the main features of AD. The third is the loss of connections between nerve cells (neurons) in the brain.4
AD accounts for almost three-quarters of cases of dementia, with the remainder accounted for by vascular dementia (VaD), mixed AD and VaD, dementia with Lewy bodies, and frontotemporal dementia.5
AD is the most common form of dementia (aging loss of memory) and is a progressive brain disease that slowly steals the minds of its victims, destroying memory and thinking skills, and, eventually, the ability to carry out the simplest tasks. There are two types of patients with AD: those with type 1 AD (early-onset, before age 65 years) and those with type 2 AD (late-onset, after age 65 years). In most people with AD, symptoms first appear after age 65 years.5
Signs and Symptoms
The first sign of AD is memory problems. In comparison, some people have more memory problems than others of their age. This is called amnestic mild cognitive impairment (MCI). The symptoms are not as severe as those in people with AD, but those with MCI are likely to develop the disease.6
There are other changes that also signal the very early stages of AD. These include problems with the sense of smell and cognitive issues. These findings may offer tools that could help detect AD early, follow the course of the disease, and monitor response to treatments. AD progresses from mild to severe forms. By the final stage, plaques and tangles spread throughout the brain, and the brain tissue shrinks significantly. People with severe AD cannot communicate and are completely dependent on others for their care. Toward the end, patients with AD may rest in bed most of the time as the body starts to shut down.6
The neuropathologic process consists of neuronal loss and atrophy with an inflammatory response to the deposition of amyloid plaques and the abnormal clustering of protein fragments and neurofibrillary tangles. This damaging process spreads to a nearby structure, called the hippocampus, which is essential in forming memories.6,7
Several factors that cause AD have been identified, and they include environmental, genetic, and lifestyle factors. Because people differ in their genetic makeup and lifestyle, the importance of these factors in preventing or delaying AD differs from person to person. The plaques can now be visualized by imaging the brains of living individuals, and findings from these studies will help clinicians understand the underlying causes of AD. Also, individuals with AD have increased presence of monocytes/macrophages in the cerebral vessel walls. The main protein component of amyloid in AD is the 39-42 amino acid (beta-amyloid peptide).6,7
One of the puzzles of AD is why it largely strikes older adults. Research on how the brain changes normally with age is shedding light on this question. For example, scientists are learning how age-related changes in the brain may harm neurons and contribute to AD damage. These age-related changes include shrinking of certain parts of the brain, inflammation, and the production of very damaging and unstable molecules called free radicals due to oxidative stress and cell respiration.6,7
Accumulating data from the clinical research support that the core AD cerebrospinal fluid (CSF) biomarkers amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) reflect key elements of AD pathophysiology.8
One of the most controversial theories concerns the metal aluminum, which became a suspect when researchers found traces of this metal in the brains of patients with AD. Many studies since then have either not been able to confirm this finding or had questionable results. Aluminum turns up in higher amounts than normal in some, but not all, autopsy studies of patients with AD. Aluminum and lead are found in small amounts in numerous household products and in many foods. As a result, there have been fears that aluminum consumed in the diet or absorbed from other sources could be a factor in AD.9
Naturally occurring metals such as zinc, copper, and iron are present in our bodies and are essential to keep our brains working properly. Too much zinc and certain toxins in food are also believed to cause neurologic damage and are linked with early dementia.9
It has been reported that a minority of people develop AD in their 30s, 40s, and 50s (type 1). Many of these people have a mutation, or permanent change, in one of three genes that they inherited from a parent. We know that these gene mutations cause AD in these early-onset familial cases. Not all early-onset cases are caused by such mutations.6
Most people with AD have late-onset AD, which usually develops after age 65 years (type 2). Many studies have linked a gene called APOE to late-onset AD. This gene has several forms, and one of them, APOE e4, increases a person’s risk of getting the disease. About 40% of all people who develop late-onset AD carry this gene. However, carrying the APOE e4 form of the gene does not necessarily mean that a person will develop AD, and people carrying no APOE e4 forms can also develop the disease. There are reports by experts in the field that additional genes may influence the development of late-onset AD in some way.6
Early AD diagnosis by CT and MRI is beneficial for several reasons. Getting an early diagnosis and starting treatment in the early stages of the disease can help preserve function for months to years, even though the underlying disease process cannot be changed. Having an early diagnosis also helps families plan for the future, make living arrangements, take care of financial and legal matters, and develop support networks. In addition, an early diagnosis can provide greater opportunities for people to get involved in clinical trials.
Research into AD has developed to the point that scientists can look beyond treating symptoms to address the underlying disease process. In ongoing clinical trials, scientists are looking at many possible interventions, such as cardiovascular and diabetes treatments, antioxidants, immunization therapy, cognitive training, and physical activity.10
The past 20 years have seen an enormous expansion in research on fluid biomarkers for AD. The core AD CSF biomarkers T-tau, P-tau, and Aβ42 (and the Aβ42/40 ratio) have been evaluated in hundreds of clinical neurochemical studies with extraordinarily consistent results, showing high diagnostic accuracy not only for AD dementia but, importantly, also for prodromal AD.8
AD is a complex disease, and no single drug is likely to prevent or cure it. That is why current treatments focus on several different aspects, including helping people maintain mental function and managing behavioral symptoms to slow, delay, or prevent the disease.11
Four medications with cholinergic activity are approved by the FDA to treat AD. Donepezil (Aricept), rivastigmine (Exelon), and Aβ42/40 galantamine (Razadyne) are used to treat mild-to-moderate AD (donepezil can be used for severe AD as well). These drugs act to stop the breakdown of acetylcholine by delaying formation of the enzyme acetylcholinesterase. This appears to result in increased concentrations of acetylcholine available for synaptic transmission in the central nervous system to improve cognitive deficits.5,6,11
The fourth drug, memantine (Namenda), is an N-methyl-D-aspartate receptor antagonist used to treat moderate-to-severe AD. This drug works by regulating neurotransmitters and may help maintain thinking, memory, and speaking skills, plus assist with certain behavioral problems. However, these drugs do not change the underlying disease process and may help only for a few months to a few years. They also have their own side effects and drug interactions.5,6,11
Antipsychotic drugs help with agitation and outbursts. These medicines are often reserved for advanced AD symptoms with psychotic features, such as delusions, hallucinations, and paranoia.5
The FDA recently approved aducanumab (Aduhelm) for people with mild symptoms of AD, such as individuals who are still independent in basic daily functioning. Aducanumab reduces brain amyloid plaque (protein deposits), a main feature of AD. Plaque reduction, however, has not been a reliable marker for cognitive function in past trials. Not everyone with plaques has or will get AD, and other plaque-reducing medications have not shown meaningful patient benefit.3
The FDA recently granted accelerated approval to another new AD treatment called lecanemab (Leqembi), which has been shown to moderately slow cognitive and functional decline in the early stages of the disease. Lecanemab works by removing a sticky protein from the brain that is believed to cause AD to advance. The drug is delivered by an IV infusion (100 mg/mL) every 2 weeks.3 The FDA’s accelerated pathway allows for earlier approval of drugs that treat serious conditions for which other treatments are not available or may no longer be effective.
1. Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006;368:387-403.
2. Alzheimer’s Association. Alzheimer’s and dementia. www.alz.org/alzheimer_s_dementia. Accessed March 1, 2023.
3. Marsool MDM, Prajjwal P, Reddy YB, et al. Newer modalities in the management of Alzheimer’s dementia along with the role of aducanumab and lecanemab in the treatment of its refractory cases. Dis Mon. 2023;69(5):101547.
4. Alzheimer’s Association. 2009 Alzheimer’s disease facts and figures. Alzheimers Dement. 2009;5(3):234-274.
5. Briggs R, Kennelly SP, O’Neill D. Drug treatments in Alzheimer’s disease. Clin Med (Lond). 2016;16(3):247-253.
6. Saljoughian M. Curcumin: a promising antiamyloidogenic agent. US Pharm. 2011;36(8):HS-27-HS-32.
7. Buschert V, Bokde AL, Hampel H. Cognitive intervention in Alzheimer disease: physical exercise. 2011. www.medscape.org/viewarticle/726725_4. Accessed March 1, 2023.
8. Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673-684.
9. Cleveland Clinic Foundation. Environmental factors in Alzheimer’s disease. www.nbrc.ac.in/faculty/ranjit/Giri-JNChem-Curcumin.pdf.pdf. Accessed March 1, 2023.
10. Masters CL, Bateman R, Blennow K, et al. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056.
11. Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer’s disease. Am J Med. 2007;120(5):388-397.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
To comment on this article, contact firstname.lastname@example.org.