TREATMENTS

There is currently no cure for AD. The goals of treatment for AD are to improve cognition, mood, and behavior and to sustain quality of life; to maximize the ability to perform daily activities; and to establish a safe and, if permitting, social environment for the patient.1,2

Current recommendations to maintain mental health begin with nonpharmacological approaches. Following a healthy diet—primarily composed of fish, vegetables, legumes, fruit, cereals, unsaturated fatty acids (eg, olive oil), and limited meat and dairy products—has been protective in observational studies.1 Similarly, pursuing exercise and social activities can stimulate brain activity, while establishing regular sleep patterns and managing stress can reduce brain damage risks.1 In addition, controlling for vascular risk factors (eg, hypertension, smoking) can protect from further brain injury.

Pharmacological treatment with FDA-approved medications should be considered when appropriate with the goal of improving and/or stabilizing symptoms.The most effective pharmacological approach derived so far targets abnormal signaling by neurotransmitters.The neurotransmitter acetylcholine has a particularly important role in memory, and deficiency of acetylcholine in the brain has been postulated as responsible for the cognitive impairment seen in AD.Acetylcholinesterase inhibitors— drugs that reversibly bind to and inactivate the enzyme that breaks down acetylcholine—have modest but significant effects in improving and/or stabilizing the symptoms of memory loss and confusion in mild-to-moderate AD.2 A different class of medications, called glutamate or NMDA (N-methyl-D-aspartate) receptor antagonists, block abnormal glutamate transmission by inhibiting NMDA receptor-operated cation channels.2 Combination therapy with acetylcholinesterase inhibitors and an NMDA receptor antagonist has been recommended for severe AD.2 Unfortunately, these agents are poorly tolerated by many patients, and the current recommendations are to switch agents or discontinue therapy upon loss of effectiveness or at patient preference.1,2 The most common side effects are nausea, vomiting, diarrhea, muscle cramps, urinary incontinence, syncope, anorexia, and fatigue.2

Finally, clinicians should offer patients the possibility to enroll in ongoing clinical trials.3

There are new approaches in clinical development that aim to target crucial pathological processes and to alter the course of AD progression. These strategies are being developed with an increased understanding of AD biomarkers and the ability to identify early stages of the disease. They include (among others):

-β-secretase (BACE1) inhibitors
-γ-secretase inhibitors
-anti-amyloid antibodies
-anti-tau agents
-anti-inflammatory compounds
-receptor for advanced glycation end products (RAGE) inhibitors

For an advanced look at the mechanism of action of these investigational agents, please see the 3D animations available here 3D animations.

Drug name
Class
Approved for
FDA Approval

Donepezil
acetylcholinesterase inhibitor
All stages of AD
1996
Rivastigmine
acetylcholinesterase inhibitor
All stages
2000
Galantamine
acetylcholinesterase inhibitor
Mild to moderate AD
2001
Memantine
NMDA receptor antagonist
Moderate to severe AD
2003
donepezil and memantine combination treatment
acetylcholinesterase inhibitor and NMDA receptor antagonist
Moderate to severe AD
2014

References

  1. Cummings JL, Isaacson RS, Schmitt FA, Velting DM. A practical algorithm for managing Alzheimer’s disease: what, when, and why? Ann Clin Transl Neurol.2015;2:307-323.
  2. Winslow BT, Onysko MK, Stob CM, Hazlewood KA. Treatment of Alzheimer disease. Am Fam Physician. 2011;83:1403-1412.
  3. California Workgroup on Guidelines for Alzheimer’s Disease Management. Guidelines for Alzheimer’s Disease Management. Sacramento, CA. Report available at www.cdph.ca.gov/programs/alzheimers/Documents/professional_GuidelineFullReport.pdf

Epidemiology

Challenges

Diagnosis

Biomarkers

Treatments

Additional Reading