Cholinesterase Inhibitors, Memantine (Namenda®), and Combination Therapy

A pharmacist-reviewed guide for mild, moderate, and progressing Alzheimer’s disease

What Are Cholinesterase Inhibitors?

Cholinesterase inhibitors are prescription medications commonly used in the early and middle stages of Alzheimer’s disease. While they do not cure Alzheimer’s, they may help slow cognitive decline and support daily functioning for some individuals.

FDA-approved options include:

• Donepezil (Aricept®)

• Rivastigmine (Exelon®) – oral capsule or transdermal patch

• Galantamine (Razadyne®)

These medications are most effective when started earlier in the disease course, though donepezil may be continued into later stages for select patients.

How These Medications Work

Alzheimer’s disease reduces levels of acetylcholine, a chemical messenger essential for memory, attention, and learning.

Cholinesterase inhibitors slow the breakdown of acetylcholine, helping brain cells communicate more effectively for a longer period of time. This may temporarily preserve cognitive function and daily abilities, though it does not stop disease progression.

What Benefits Can Patients and Caregivers Expect?

Research shows modest but meaningful benefits for some individuals:

• Small improvements in memory and thinking (often 2–3 points on standardized tests)

• Improved ability to perform daily activities

• Slower decline compared to no treatment

Timeline:

Benefits are usually evaluated after 8–12 weeks, with the strongest effects seen during the first 6–18 months.

Responses vary widely — benefit is individual, not guaranteed.

How Benefits Differ by Stage of Alzheimer’s Disease

Early (Mild) Alzheimer’s Disease

• Highest likelihood of noticeable benefit

• May support memory, focus, and problem-solving

• Often helps preserve independence longer

Best stage to combine medication with lifestyle-based brain support

Middle (Moderate) Alzheimer’s Disease

• Benefits shift toward maintaining daily function rather than improving memory

• May help with language, routine tasks, and behavioral symptoms

• Caregiver involvement and safety monitoring become increasingly important

Side Effects and Safety Considerations (Cholinesterase Inhibitors)

Common:

• Nausea, diarrhea, reduced appetite

• Weight loss

• Muscle cramps

• Sleep disturbances or vivid dreams

Less common but important:

• Slow heart rate

• Dizziness or fainting

• Increased fall risk in frail older adults

• Starting low, increasing slowly, and taking medication with food can reduce side effects.

Memantine (Namenda®): What It Is and When It’s Used

Memantine (Namenda®) is a different type of Alzheimer’s medication, approved for moderate to severe Alzheimer’s disease.

Unlike cholinesterase inhibitors, memantine works on the glutamate system, which is involved in learning and memory but can become overactive in Alzheimer’s disease.

Memantine helps by:

• Reducing excess glutamate activity

• Protecting brain cells from overstimulation

• Supporting daily function and behavior rather than memory improvement

What Patients and Caregivers May Notice

• Stabilization of daily functioning

• Possible improvement in agitation or confusion

• Easier caregiving routines in some individuals

Memantine is not typically used alone in early Alzheimer’s, but becomes more relevant as symptoms progress.

Combination Therapy: Using Both Together

Many individuals with moderate Alzheimer’s disease are treated with a combination of a cholinesterase inhibitor and memantine.

There is also a single combination capsule, Namzaric®, which contains donepezil (Aricept®) + memantine extended-release (Namenda XR®).

Why Combine Them?

• They work on different brain pathways

• Effects may be additive rather than overlapping

• Combination therapy may better support daily function and slow decline compared to either medication alone

What to Expect from Combination Therapy

• Benefits are still modest and gradual

• Focus is often on maintaining function and quality of life

• Side effects must be monitored carefully, especially dizziness and falls

Combination therapy is not appropriate for everyone and should be reassessed regularly.

Practical Guidance for Patients and Caregivers

• Track changes in memory, daily function, behavior, appetite, sleep, and falls

• Monitor blood pressure, heart rate, and dizziness

• Avoid stopping medications abruptly without guidance

• Reassess benefit every 6–12 months with a clinician

• Align medication decisions with goals of care as disease progresses

Medications tend to work best when combined with:

• Physical activity

• Good sleep habits

• Cognitive and social engagement

• Cardiovascular risk management

Key Takeaway

Alzheimer’s medications — including cholinesterase inhibitors and memantine — do not cure the disease. However, when used thoughtfully, they may slow decline, support daily function, and improve quality of life for some individuals.

The right approach depends on stage of disease, tolerance, caregiver support, and personal goals.

Talk to a ReCODE 2.0 Certified Pharmacist About Your Options

Frequently Asked Questions

Explore Related Alzheimer’s Resources

Alzheimer’s Treatment Overview – how medications and lifestyle strategies fit together

SCI vs MCI vs Dementia Explained – understanding early cognitive changes

Lifestyle Strategies for Brain Health – evidence-based non-drug support

Positive Caregiving for Cognitive Decline – tools for caregivers