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Treating and Managing Alzheimer’s
While there is no cure for Alzheimer’s disease (AD), non-pharmacologic and pharmacologic therapy and treatments are available.1,2 AD is a neurodegenerative condition that typically gets worse over time, and treatments are generally most effective in the early or middle stage of the disease process.3
Non-pharmacologic interventions do not change the underlying disease course, however, are often implemented to help maintain or improve cognitive function as well as reduce behavioral symptoms.2 Such intervention can include cognitive stimulation, music-based therapy, psychological treatment (ie, cognitive behavioral therapy), physical therapy/exercise, and a healthy diet.2,3 Safety, effectiveness and purity of alternative therapies/supplements is largely unknown, although trials evaluating the effectiveness of some “medical foods”, such as medium-chain triglycerides, are being conducted.4
Mainstays for pharmacologic therapy focus on either temporarily managing Alzheimer’s Disease symptoms or treating the underlying cause of disease.5 Symptomatic treatment consists of cholinesterase inhibitors and memantine, an N-Methyl D-aspartate (NMDA) antagonist, affecting intra-brain neurotransmitters.2,3 Alternatively, while disease modifying treatment is not a cure, it aims to slow cognitive and functional impairment by reducing amyloid-beta plaques.2,7
Pharmacologic Therapy and Treatment for Cognitive Symptoms
People with AD have diminished cholinergic function due to decreased acetylcholine synthesis.1 Cholinesterase inhibitors, like donepezil, rivastigmine, and galantamine, can increase cholinergic transmission leading to an improvement in AD symptoms.1
People with all stages of AD may benefit from a trial of cholinesterase inhibitors as they may show a small benefit in cognition, neuropsychiatric symptoms, and activities of daily living (ADLs).1 However, results may be variable, as studies suggest that no observable benefit is seen in up to 30%-50% of people with AD.1 On the other end of the spectrum, up to 20% of people may see above-average improvement in symptoms.1 Side effects of cholinesterase inhibitors include nausea, vomiting, diarrhea, sleep disturbances, bradycardia, cardiac conduction defects, and syncope.3 Additionally, avoidance of tricyclic antidepressants for treatment of anxiety, depression and psychosis is key due to their anticholinergic activity.3
Memantine is another therapeutic option for AD that can be given as monotherapy or in combination with cholinesterase inhibitors.3 This agent acts by blocking pathologic stimulation of NMDA receptors by neurotransmitter glutamate and slowing intracellular calcium accumulation.1,2,3 This distinct mechanism of action is considered neuroprotective against glutamate and may restore physiologic neuronal function.1,2 Studies also suggest memantine may give patients a small improvement in cognition, dementia, and quality of life.1 Common side effects of memantine include dizziness, body aches, headache, and constipation.3
Alzheimer's Disease Modifying Treatments
The United States Food and Drug Administration (FDA) has approved aducanumab (2021) and lecanemab (2023) through an accelerated approval pathway.8,9 Aducanumab is a recombinant monoclonal antibody targeting amyloid-beta (EMERGE and ENGAGE trials) approved for people with mild cognitive impairment (MCI) and the mild dementia stage of AD, but is recommended to limit use to those with documented amyloid pathology on amyloid positron emission tomography (PET) scans.1,2,7,10 Aducanumab is associated with an increased risk of amyloid-related imaging abnormities (ARIA) which can be an indicator of brain swelling; post-approval trials are required to verify clinical benefit.1, 2 Lecanemab is another monoclonal antibody targeting β-amyloid protofibrils (CLARITY-AD), with approved indications of use in those with MCI and the mild dementia stage of AD, following confirmed presence of amyloid-beta pathology.5,11 ARIA events have also been associated with lecanemab; post approval trials are required to verify clinical benefit.5
Another emerging treatment option for Alzheimer’s Disease is donanemab, also a monoclonal antibody targeting the N-terminal pyroglutamate epitope, a modified form of amyloid-beta present only in established plaques.13,14 Clinical trials suggest that this new medication not only reduces amyloid plaques as measured by 18 F-florbetapir uptake on PET, but also lowers levels of plasma tau biomarkers (TRAILBLAZER-ALZ trial).13,14 Donanemab has also been shown to have less cognitive and functional decline over placebo.14 ARIA has also been observed with use of donanemab in the clinical trial setting.14
Another theraputic in the research pipeline includes gantenerumab, a monoclonal antibody targeting amyloid-beta.11,15 Gantenerumab binds aggregated amyloid beta plaques by phagocytosis, and also showed a robust decrease in amyloid plaques after 2 years of treatment.15
Embracing a Team Approach in AD
Click here to view and download a cognitive impairment care planning toolkit provided by the Alzheimer’s Association®.
- Press, D & Buss, SS. Treatment of Alzheimer Disease. UpToDate. https://www.uptodate.com/contents/treatment-of-alzheimer-disease
- Alzheimer’s Association®. 2022 Alzheimer’s disease facts and figures: special report. More than normal aging: understanding mild cognitive impairment. Alzheimer’s Dement. 2022;18. https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf
- Kumar A, Sidhu J, Goyal A, et al. Alzheimer Disease. StatPearls. 2022. https://www.ncbi.nlm.nih.gov/books/NBK499922/
- Alzheimer’s Association®. Alternative treatments. https://www.alz.org/alzheimers-dementia/treatments/alternative-treatments
- National Institute on Aging (NIA). How is Alzheimer’s Disease Treated. https://www.nia.nih.gov/health/how-alzheimers-disease-treated
- Abeysinghe AADT, Deshapriya RDUS, Udawatte C. Alzheimer’s disease; a review of the pathophysiological basis and therapeutic interventions. Life Sci. 2020;256:117996.
- Alzheimer’s Association®. Treatments and research. https://www.alz.org/help-support/i-have-alz/treatments-research
- Aducanumab (Aduhelm®) Prescribing Information. October 2022. https://www.biogencdn.com/us/aduhelm-pi.pdf
- Lecanemab (Leqembi®) Prescribing Information. January 2023. https://www.leqembi.com/-/media/Files/Leqembi/Prescribing-Information.pdf?hash=3d7bf1a2-5db2-4990-8388-81086f415676
- Tampi RR, Forester BP, Agronin M. Aducanumab: evidence from clinical trial data and controversies. Drugs Context. 2021;10:2021-7-3.
- Swanson CJ, Zhang Y, Dhadda S, et al. A randomized, double-blind,
phase 2b proof-of-concept clinical trial in early Alzheimer’s disease
with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13:80.
- Ten Kate M, Ingala S, Schwarz AJ, et al. Secondary prevention of Alzheimer’s dementia: neuroimaging contributions. Alzheimers Res Ther. 2018:10:112.
- Lily Press Release. Lilly releases donanemab data that demonstrated relationship between reduction of amyloid plaque and slowing of cognitive decline. https://lilly.mediaroom.com/2021-07-29-Lilly-releases-donanemab-data-that-demonstrated-relationship-between-reduction-of-amyloid-plaque-and-slowing-of-cognitive-decline
- Mintun MA, Lo AC, Evans CD, et al. Donanemab in Early Alzheimer’s Disease. N Engl J Med. 2021;384:1691-1704.
- Klein G, Delmar P, Voyle N, et al. Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: a PET substudy interim analysis. Alzheimers Res Ther. 2019;11:101.
- Ellison JM. Understanding the healthcare team in Alzheimer’s disease. 8/11/2021. https://www.brightfocus.org/alzheimers/article/understanding-health-care-team-alzheimers-disease
- Jurkowski CL. A Multidisciplinary Approach to Alzheimer’s Disease: Who Should Be Members of the Team? Am J Med. 1998;104(suppl 1);13S-16S.
- UCSF Department of Radiology & Biomedical Imaging. Radiology’s Role in Determining the Impact of Amyloid PET Imaging on Real-World Alzheimer’s Disease and Dementia Care. 6/19/2019. https://radiology.ucsf.edu/blog/radiologys-role-determining-impact-amyloid-pet-imaging-real-world-alzheimers-disease-and
- Alzheimer’s Association®. Management. https://www.alz.org/professionals/health-systems-medical-professionals/management
- Galvin JE, Valois L, Zweig Y. Collaborative transdisciplinary team approach for dementia care. Neurodegener Dis Manag. 2014;4:455-469.
- Alzheimer’s Association®. Clinical trials recruiting. https://www.alz.org/professionals/health-systems-medical-professionals/clinical_trials_recruiting
All URLs accessed January 27, 2023.