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

Management goals for Alzheimer’s Disease include strategizing to optimize dementia outcomes, focusing on lessening symptoms and maintaining quality of life through maximizing function, cognition, behavior and safety.19 A multidisciplinary approach and collaborative care model focuses on long-term, systematic approaches for management of chronic conditions like AD, possibly utilizing cost-efficient strategies to improve health outcomes and shared decision-making for individualized treatment.20 This team can help facilitate adaptation to cognitive and behavioral changes with disease progression as well as refer for participation in dementia-related clinical trials.19,21 Nonmedical issues related to long-term care planning for changing needs over the course of AD can also be discussed, such as establishing a healthcare power of attorney, creating a living will, determining end-of-life care preferences and reviewing finances.19
Click here to view and download a cognitive impairment care planning toolkit provided by the Alzheimer’s Association®.

References

  1. Press, D & Buss, SS. Treatment of Alzheimer Disease. UpToDate. https://www.uptodate.com/contents/treatment-of-alzheimer-disease
  2. 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
  3. Kumar A, Sidhu J, Goyal A, et al. Alzheimer Disease. StatPearls. 2022. https://www.ncbi.nlm.nih.gov/books/NBK499922/
  4. Alzheimer’s Association®. Alternative treatments. https://www.alz.org/alzheimers-dementia/treatments/alternative-treatments
  5. National Institute on Aging (NIA). How is Alzheimer’s Disease Treated. https://www.nia.nih.gov/health/how-alzheimers-disease-treated
  6. Abeysinghe AADT, Deshapriya RDUS, Udawatte C. Alzheimer’s disease; a review of the pathophysiological basis and therapeutic interventions. Life Sci. 2020;256:117996.
  7. Alzheimer’s Association®. Treatments and research. https://www.alz.org/help-support/i-have-alz/treatments-research
  8. Aducanumab (Aduhelm®) Prescribing Information. October 2022. https://www.biogencdn.com/us/aduhelm-pi.pdf
  9. Lecanemab (Leqembi®) Prescribing Information. January 2023. https://www.leqembi.com/-/media/Files/Leqembi/Prescribing-Information.pdf?hash=3d7bf1a2-5db2-4990-8388-81086f415676
  10. Tampi RR, Forester BP, Agronin M. Aducanumab: evidence from clinical trial data and controversies. Drugs Context. 2021;10:2021-7-3.
  11. 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.
  12. Ten Kate M, Ingala S, Schwarz AJ, et al. Secondary prevention of Alzheimer’s dementia: neuroimaging contributions. Alzheimers Res Ther. 2018:10:112.
  13. 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
  14. Mintun MA, Lo AC, Evans CD, et al. Donanemab in Early Alzheimer’s Disease. N Engl J Med. 2021;384:1691-1704.
  15. 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.
  16. 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
  17. 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.
  18. 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
  19. Alzheimer’s Association®. Management. https://www.alz.org/professionals/health-systems-medical-professionals/management
  20. Galvin JE, Valois L, Zweig Y. Collaborative transdisciplinary team approach for dementia care. Neurodegener Dis Manag. 2014;4:455-469.
  21. Alzheimer’s Association®. Clinical trials recruiting. https://www.alz.org/professionals/health-systems-medical-professionals/clinical_trials_recruiting

All URLs accessed January 27, 2023.

Scientific Council

Liana G. Apostolova, MD, MSc, FAAN

Indiana University Distinguished Professor
Barbara and Peer Baekgaard Professor in Alzheimer's Disease Research
Professor in Neurology, Radiology, Medical and Molecular Genetics
Indiana University School of Medicine
Department of Neurology
Indianapolis, IN

Alireza Atri, MD, PhD

Director, Banner Sun Health Research Institute
Banner Health
Sun City, AZ
Lecturer on Neurology, Center for Brain/Mind Medicine
Brigham and Women’s Hospital and Harvard Medical School
Boston, MA

Ariel F. Cole, MD, FAAFP

Program Director, AdventHealth Geriatric Fellowship
Winter Park, FL

Brad Dickerson, MD

Director, Frontotemporal Disorders Unit
Massachusetts General Hospital
Professor of Neurology, Harvard Medical School
Boston, MA

Richard M. Dupee, MD, MACP, AGSF

Clinical Professor of Medicine
Tufts University School of Medicine
Clinical professor, Department of Public Health and Community Medicine, Tufts University
Chief, Geriatrics Service, Tufts Medical Center
Senior Physician, Pratt Diagnostic Center
Dean ex officio, Office of International Affairs, Tufts University School of Medicine
Boston, MA

James E. Galvin, MD, MPH

Professor of Neurology
University of Miami Miller School of Medicine
Miami, FL

David S. Geldmacher, MD

Professor and Director
Division of Memory Disorders and Behavioral Neurology
Department of Neurology
Heersink School of Medicine
University of Alabama at Birmingham
Birmingham, AL

George T. Grossberg MD

Professor and Director, Division of Geriatric Psychiatry
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, MO

Scott A. Kaiser, MD

Director of Geriatric Cognitive Health
Pacific Neuroscience Institute
Santa Monica, CA

Diana R. Kerwin, MD, CPI

President, Kerwin Medical Center
Chief, Geriatric Medicine, Texas Health Presbyterian Hospital
Dallas, TX

Scott McGinnis, MD

Assistant Professor of Neurology, Harvard Medical School
Center for Alzheimer Research and Treatment
Brigham and Women's Hospital
Frontotemporal Disorders Unit
Massachusetts General Hospital
Boston, MA

Giulio M. Pasinetti, MD, PhD

The Saunders Family Chair and Professor of Neurology
Director of the Center for Molecular Integrative Neuroresilience,
Professor of Psychiatry and Neuroscience
Professor of Geriatrics and Adult Development
Department of Neurology and Friedman Brain Institute
Icahn School of Medicine at Mount Sinai
New York, NY

Marwan N. Sabbagh, MD, FAAN, CCRI

Professor of Neurology
Alzheimer’s and Memory Disorders Division
Associate Program Director for Research-Neurology Residency
Barrow Neurological Institute
Research Professor, University of Arizona College of Medicine-Phoenix
Clinical Professor of Neurology, Creighton University
Phoenix, AZ

Paul E. Schulz, MD

Rick McCord Professor in Neurology
Umphrey Family Professor of Neurodegenerative Diseases
Director, Neurocognitive Disorders Center
Director, Neurocognitive Disorders Fellowship
McGovern Medical School at UTHealth Houston
Houston, TX

Geoffrey C. Wall, PharmD, FCCP, BCPS

John R. Ellis Distinguished Chair of Pharmacy Practice
Professor of Clinical Sciences
Director, Drake Drug Information Center
Drake University College of Pharmacy and Health Sciences
Internal Medicine Clinical Pharmacist
Iowa Methodist Medical Center
Des Moines, IA

David A. Wolk, MD, FAAN

Professor of Neurology
Director, Penn Alzheimer’s Disease Research Center
University of Pennsylvania
Philadelphia, PA