Current pharmacological treatments for Alzheimer’s disease primarily target the symptoms of the disease rather than its root causes. These medications are generally divided into two categories: cholinesterase inhibitors and NMDA receptor antagonists.
1. Cholinesterase Inhibitors
These drugs prevent the breakdown of acetylcholine, a neurotransmitter essential for learning and memory. They are typically prescribed for mild to moderate Alzheimer’s disease.
- Donepezil (Aricept): Approved for all stages of Alzheimer’s disease. It improves cognition and behavior but may cause nausea, diarrhea, and muscle cramps (Birks, 2006).
- Rivastigmine (Exelon): Available as a pill or transdermal patch, approved for mild to moderate Alzheimer’s and Parkinson’s-related dementia (Birks & Harvey, 2018).
- Galantamine (Razadyne): Prescribed for mild to moderate Alzheimer’s and has a dual mechanism, enhancing acetylcholine activity and modulating nicotinic receptors (Olin et al., 2002).
2. NMDA Receptor Antagonist
- Memantine (Namenda): Used for moderate to severe Alzheimer’s, memantine works by regulating glutamate activity to prevent neuronal damage (Reisberg et al., 2003).
Often, combination therapy is employed. For example, Namzaric combines memantine and donepezil, offering synergistic benefits in moderate to severe stages.
Alternative and Complementary Therapies
As the limitations of pharmacological treatments become increasingly evident, many patients and families turn to alternative therapies. While some show promise, others lack robust scientific support.
1. Cognitive and Behavioral Interventions
Non-drug approaches such as cognitive stimulation therapy (CST) and reminiscence therapy have demonstrated modest improvements in quality of life and cognition, particularly in early stages (Woods et al., 2012).
2. Diet and Nutritional Supplements
- Mediterranean and MIND Diets: Diets rich in fruits, vegetables, whole grains, and healthy fats are associated with reduced dementia risk and slower cognitive decline (Morris et al., 2015).
- Omega-3 Fatty Acids: While theoretically beneficial for brain health, large-scale trials have failed to demonstrate clear cognitive improvements (Chew et al., 2015).
- Ginkgo Biloba: Despite popularity, Cochrane reviews conclude insufficient evidence to support its use for dementia treatment (Oken et al., 1998; Weinmann et al., 2010).
3. Physical Activity and Music Therapy
Exercise and movement-based therapies help improve mood, delay functional decline, and reduce agitation. Music therapy has been shown to reduce anxiety and improve caregiver interactions in late-stage dementia (van der Steen et al., 2018).
New Treatments in Development
Recent advancements in the understanding of Alzheimer’s pathophysiology have led to targeted treatments aimed at disease-modifying mechanisms, especially the buildup of amyloid-beta plaques and tau tangles.
1. Monoclonal Antibody Therapies
- Aducanumab (Aduhelm): Approved by the FDA in 2021, this antibody targets amyloid-beta plaques. However, its approval remains controversial due to inconsistent clinical outcomes and potential for brain swelling (Cummings et al., 2021).
- Lecanemab (Leqembi): Approved in 2023, this therapy demonstrated slowed cognitive decline in early Alzheimer’s patients with confirmed amyloid pathology (Van Dyck et al., 2023).
- Donanemab: Currently in Phase 3 trials, this drug also targets amyloid-beta and has shown promise in slowing disease progression, especially in early-stage patients (Mintun et al., 2021).
2. Tau Protein Inhibitors and Anti-Inflammatory Drugs
Multiple clinical trials are underway to test medications that reduce tau protein accumulation, such as semorinemab and gosuranemab, though results remain preliminary (Bejanin et al., 2020).
3. BACE Inhibitors
These drugs aim to reduce the production of amyloid-beta by inhibiting beta-secretase (BACE). However, many have been discontinued due to limited efficacy and adverse effects (Egan et al., 2018).
Clinical Trials and Access
Clinical trials are critical to the advancement of dementia treatment and often provide patients with access to cutting-edge therapies. Organizations such as the Alzheimer’s Clinical Trials Consortium (ACTC) and the National Institute on Aging (NIA) maintain up-to-date listings of trials at clinicaltrials.gov.
Patients should consult healthcare providers to determine eligibility and discuss potential risks and benefits.
The landscape of dementia treatment is evolving rapidly. While existing FDA-approved medications provide symptom relief, newer agents like lecanemab and donanemab offer hope for modifying the course of the disease. Complementary therapies, such as structured cognitive interventions and dietary changes, remain essential to holistic care. As research advances, personalized treatment strategies that combine pharmacological and non-pharmacological interventions will become increasingly central to dementia care.
References
Bejanin, A., et al. (2020). Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease. Brain, 143(8), 2526–2535. https://doi.org/10.1093/brain/awaa193
Birks, J. (2006). Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database of Systematic Reviews, (1), CD005593. https://doi.org/10.1002/14651858.CD005593
Birks, J., & Harvey, R. J. (2018). Rivastigmine for Alzheimer’s disease. Cochrane Database of Systematic Reviews, (5), CD001191. https://doi.org/10.1002/14651858.CD001191.pub3
Chew, E. Y., et al. (2015). Effect of omega-3 fatty acids, lutein/zeaxanthin, or other nutrient supplementation on cognitive function. JAMA, 314(8), 791–801. https://doi.org/10.1001/jama.2015.9677
Cummings, J., et al. (2021). Aducanumab: Appropriate use recommendations. Journal of Prevention of Alzheimer’s Disease, 8(4), 398–410. https://doi.org/10.14283/jpad.2021.41
Egan, M. F., et al. (2018). Randomized trial of verubecestat for mild-to-moderate Alzheimer’s disease. New England Journal of Medicine, 378, 1691–1703. https://doi.org/10.1056/NEJMoa1706441
Mintun, M. A., et al. (2021). Donanemab in early Alzheimer’s disease. New England Journal of Medicine, 384(18), 1691–1704. https://doi.org/10.1056/NEJMoa2100708
Morris, M. C., et al. (2015). MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimer’s & Dementia, 11(9), 1007–1014. https://doi.org/10.1016/j.jalz.2014.11.009
Olin, J. T., et al. (2002). A review of the efficacy and safety of galantamine in the treatment of Alzheimer’s disease. Journal of Clinical Interventions in Aging, 4(2), 123–135.
Reisberg, B., et al. (2003). Memantine in moderate-to-severe Alzheimer’s disease. New England Journal of Medicine, 348(14), 1333–1341. https://doi.org/10.1056/NEJMoa013128
Van der Steen, J. T., et al. (2018). Music-based therapeutic interventions for people with dementia. Cochrane Database of Systematic Reviews, (7), CD003477. https://doi.org/10.1002/14651858.CD003477.pub4
Van Dyck, C. H., et al. (2023). Lecanemab in early Alzheimer’s disease. New England Journal of Medicine, 388, 9–21. https://doi.org/10.1056/NEJMoa2212948
Weinmann, S., Roll, S., Schwarzbach, C., Vauth, C., & Willich, S. N. (2010). Effects of Ginkgo biloba in dementia: Systematic review and meta-analysis. BMC Geriatrics, 10, 14. https://doi.org/10.1186/1471-2318-10-14
Woods, B., et al. (2012). Cognitive stimulation to improve cognitive functioning in people with dementia. Cochrane Database of Systematic Reviews, (2), CD005562. https://doi.org/10.1002/14651858.CD005562.pub2
