Decision Guide

HOW DO I KNOW IF ANTI-AMYLOID THERAPY IS RIGHT FOR ME?

DECIDING TO TAKE ANTI-AMYLOID-THERAPY The decision to take Anti-Amyloid Treatment is complex and involves weighing the potential benefits of the drug against its risks, costs, and the added burden of taking it. This is a highly individualized decision, given the risks and burdens are different across patients. This decision should be made together with a health care provider.

RISKS COSTS BURDENS

POTENTIAL BENEFITS

WHO IS IT FOR? Anti-Amyloid Therapy is for people with mild decline in memory and thinking who have confirmed elevated levels of amyloid in their brain.

COGNITIVE IMPAIRMENT IN THE MILD RANGE? EVIDENCE OF AMYLOID IN THE BRAIN? Treatment is unlikely to help those with moderate to severe cognitive decline. Additionally, it is not yet known if the drug helps individuals who have amyloid in their brain without any memory loss (we are studying this approach now in clinical trials).

WHAT ARE THE POTENTIAL BENEFITS? Anti-Amyloid Treatment slows the decline in cognition and function by about 30% over 18 months. This means those on the drug decline on average 5 to 6 months slower than those not treated (see figure).

HOW DOES IT WORK? Anti-Amyloid therapy is a “Monoclonal antibody” directed against amyloid, a key microscopic protein that builds up in the brain of patients with Alzheimer’s disease.

The drug is designed to “Stick” to amyloid and trigger the patient’s immune system to remove amyloid from the brain. The drug is given by infusion (through a vein) every two weeks for 18 months or more.

Anti-Amyloid Therapy drugs are not a cure.

We do not observe improvement, only a slowing of decline over time.

It is difficult to know who will respond favorably and who will not respond.

The evidence of a slower decline comes from averaging the results of hundreds of individuals.

ASSESSING THE RISKS The most significant concern is a 1% chance of serious side effects, such as stroke, seizures, or major brain swelling, which may require hospitalization.

Before starting treatment, we consider several factors to understand your risk:

SIDE EFFECT RATES BY APOE4 GENE SERIOUS SIDE EFFECTS

• • • • •

ARIA

LEQEMBI

KISUNLA

LEQEMBI

KISUNLA

NO E4 GENE

1%

1%

13%

25%

1 E4 GENE

1%

2%

19%

36%

2 E4 GENES

3%

3%

45%

55%

Baseline MRI: If your MRI shows “microhemorrhages,” your risk is higher. We do not recommend treatment if there are 5 or more.

ApoE Gene: Having one or two copies of the ApoE “E4” gene increases your risk (see table).

Cognitive Scores: Treatment is not effective for those in moderate or severe stages, so more impaired scores often mean treatment isn’t recommended.

Age: These treatments haven’t been tested in people over 90 (Leqembi hasn’t been tested in those over 85), so the benefits for older age groups are unclear.

Blood Thinners: Taking blood thinners may raise the risk of brain hemorrhage from 0.7% to 2.5%.

LESS FAVORABLE May indicate higher risk or less expected benefit

Low Score

E4/E4

E4

Microhemorrhages 85+ years

MORE FAVORABLE May indicate lower risk

COGNITIVE SCORE

High Score

APOE E4 STATUS MRI SCAN AGE

MONITORING FOR ARIA

WHAT IS ARIA?

We will perform regular MRIs (up to 5 times in the first year) to check for ARIA (“Amyloid-Related Imaging Abnormalities”), which usually occurs in the first 6 months. Rates vary by an individuals ApoE gene results and are highest in those with two copies of the E4 gene (see table above).

Scientists believe ARIA occurs when amyloid is present in blood vessels. In these individuals, removing amyloid can result in a “leaky”blood vessel.

ARIA occurs in about 21% of those taking Leqembi and 36% of those taking Kisunla, compared to 9-14% of those on a placebo.

Most people with ARIA have no symptoms, but it can increase the risk of serious side effects. If detected, we pause treatment, and it typically resolves in a few months, after which we can restart. About 3-6% of patients may have mild symptoms like headache, confusion, dizziness, or changes in vision or walking.

ARIA occurs in two forms: • ARIA-H: “Microhemorrhages” which are tiny areas of bleeding (and, rarely, larger areas of bleeding).

• ARIA-E: Edema (or swelling) occurs when fluid shifts out of blood vessels into the brain.

COMPARING ANTI-AMYLOID TREATMENTS Two anti-amyloid drugs are available, Leqembi and Kisunla. They work similarly but differ in their infusion schedules, safety, and monitoring requirements.

LEQEMBI

KISUNLA

INFUSION SCHEDULE

TWICE A MONTH

ONCE A MONTH

MAJOR BRAIN HEMORRHAGE RISK

0.7%

0.5%

ARIA RATES

21% OVERALL

36% OVERALL

MRI MONITORING (FIRST YEAR)

UP TO 4 TIMES AT 2, 3, 6, AND 12 MONTHS

UP TO 5 TIMES AT 1, 2, 3, 6, AND 12 MONTHS

INFUSION REACTIONS Approximately 1 in 4 people experience infusion reactions, usually during or shortly after the first treatments. Symptoms like fever, chills, headache, rash, nausea, stomach pain, and high blood pressure typically resolve within a day. These can be managed with medications like acetaminophen (Tylenol) and loratadine or diphenhydramine (Benadryl).

If symptoms are more intense, your doctor may recommend a short course of steroids.

BRAIN HEALTH CARE ACCELERATOR Ready to change the future? the online consent form by scanning the QR code or by 1. Open visiting kuadrc.org/BHCA the consent form to provide the research team access 2. Complete to your medical records and samples for the biorepository. to receive your care per usual — there’s no need for 3. Continue any additional visits or action on your part.

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