Early Identification of Alzheimer Disease Is Key

Pharmacy Times Health Systems Edition, January 2022 , Volume 11, Issue 01

Tau protein, plaque, and brain waves maybe the solutions to treating the progressive condition.

Alzheimer disease (AD) is the most common type of dementia and affects an estimated 6 million individuals in the United States.1,2

Characterized by symptoms of behavioral and cognitive impairment, it is not just a disease of older adults. Up to 200,000 individuals younger than 65 years have early-onset AD.2 AD is the fifth-leading cause of death in those 65 years or older and has an estimated annual cost of $355 billion.2,3

Most approved medications for the treatment of AD are symptomatic therapies that work on the acetylcholine or glutamate neurotransmitters. The standard medical treatment for AD includes cholinesterase inhibitors and a partial N-methyl-D-aspartate (NMDA) antagonist that aid the symptoms of learning and memory.4 Most recently, Biogen’s aducanumab (Aduhelm) received FDA approval for patients with AD with mild cognitive impairment or mild dementia, although it has been the subject of controversy. There are no treatments that delay, prevent, or stop disease progression.

AD is a progressive neurodegenerative disorder, and the risk of developing AD doubles every 5 years after an individual turns 65 years old.1,2 It is characterized by a continuous decline in completion of familiar tasks, memory loss, and thinking.1-3 Risk factors include aging, brain trauma, diabetes, family history, high blood pressure, and smoking.2,3

Most experts acknowledge that development of AD occurs through several mechanisms in the brain. Neuropathological changes include the appearance of extracellular amyloid plaques, neuritic plaques associated with neural injury, and neurofibrillary degeneration exemplified by neurofibrillary tangles. The pathogenesis also involves tau protein, which aids in microtubule assembly. The formation of neurofibrillary tangles involving tau protein lead to neuronal injury and the progressive loss of neurons results in cognitive impairment.5

Treatment

The standard of care continues to focus on the symptoms of AD. For treatment of mild to moderate AD, first-line cholinesterase inhibitors give small improvements in cognition, daily activities, and neuropsychiatric symptoms. For moderate to severe disease, the NMDA receptor antagonist memantine is recommended in combination with a cholinesterase inhibitor.4,6

Aducanumab, a recombinant monoclonal antibody directed against amyloid-β, obtained approval in June 2021 to a mixed response from neurologists and investigators. Although aducanumab demonstrated the ability to reduce brain amyloid-β levels in research trials, other clinical end point benefits have been inconsistent and small. With controversial results and a steep price, clinical practice has been varied to date and will likely evolve over time.7

Aducanumab is indicated for mild AD and is administered intravenously every 4 weeks. A recent brain MRI study is required priot to initiating treatment, and additional MRIs are required during dose escalation.8 Adverse effects include amyloid-β–related imaging abnormalities, confusion, diarrhea, falls, headaches, and hypersensitivity.9 No clear guidance has been given regarding treatment duration. Other treatments studied for their antioxidant effects in AD are vitamin E and the monoamine oxidase inhibitor selegiline. Vitamin E at a dose of 2000 IU per day has shown modest but inconclusive benefits for delaying progression in patients with mild to moderate AD. However, some studies suggest additional AD risk in patients with cardiovascular disease.10,11 Selegiline does not have strong long-term evidence of benefit in clinical research and is significantly more costly.11

On the Horizon

The AD pipeline continues to be robust, with 126 agents in development and 28 of those in phase 3 trials. Most of these drugs target the underlying biology of the disease.12 For example, donanemab, lecanemab, and solanezumab are monoclonal antibodies that target amyloid-β plaque and are in phase 2 and 3 trials. The remaining targets focus on enhancing cognitive abilities and reducing neuropsychiatric symptoms. New biomarker technologies are also transforming the epidemiologic study of AD. Future research will target the tau protein and brain waves and will include an antibody and vaccine.13

Lifestyle Factors

A healthy lifestyle that includes exercise, mentally stimulating pursuits, a nutritious diet, quality sleep, and social engagement has shown to benefit individuals as they age and may also help reduce cognitive decline in AD.14 The CDC recommends that individuals 65 years or older get 30 minutes of moderate-intensity activity 5 days a week to improve their overall health.1,15

Not only does good nutrition help with chronic disease risk factors such as cardiovascular disease and diabetes, it also may protect the brain through anti-inflammatory and antioxidant processes. So far there is no hard evidence that avoiding or eating certain foods lowers AD risk, but there are clues that show that eating fish and green, leafy vegetables, as well as following a low-salt and low-sugar diet, may lower the risk of developing dementia.

Although investigators are still debating whether dementia leads to poor sleep or poor sleep exacerbates dementia, they agree that there is a link.

In 2018, the National Institutes of Health reported that sleep deficits might increase the amyloid-β proteins in the brain linked to AD.16

The results of another study that followed individuals 25 years and older showed a 30% increased dementia risk in 50-, 60-, and 70-year-old participants who slept 6 or less hours a night.17

Lifelong learning and social interaction also show evidence of slowing cognitive decline. However, most of these trials need longer term follow-up.18

What Can Pharmacists Do?

Pharmacists should stay up-to-date on the research. Early identification is a priority. Screening patients and identifying AD earlier can have a lasting impact. Finally, there are lifestyle factors that may reduce the risk of developing AD. Pharmacists should promote healthy choices, such as cognitive engagement, diet, and exercise.

Joanna Lewis, PharmD, MBA, is the 340B compliance coordinator at Baptist Health in Jacksonville, Florida.

REFERENCES

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  2. 2021 Alzheimer’s Disease facts and figures. Alzheimer’s Association. Accessed December 20, 2021. https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf
  3. Brookmeyer R, Abdalla N, Kawas CH, Corrada MM. Forecasting the prevalence of preclinical and clinical Alzheimer’s disease in the United States. Alzheimers Dement. 2018;14(2):121-129. doi:10.1016/j.jalz.2017.10.009
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  9. Aduhelm. Prescribing information. Biogen; 2021. https://www.biogencdn.com/us/aduhelm-pi.pdf
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  13. Bakrania P, Hall G, Bouter Y, et al. Discovery of a novel pseudo β-hairpin structure of N-truncated amyloid-β for use as a vaccine against Alzheimer’s disease. Mol Psychiatry. Published online November 15, 2021. doi:10.1038/s41380-021-01385-7
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  16. National Institutes of Health. Sleep deprivation increases Alzheimer’s protein. April 24, 2018. Accessed Nov 26, 2021. https://www.nih.gov/news-events/nih-research-matters/sleep-deprivation-increases-alzheimers-protein
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