Chair, Stephen P. Salloway, MD, MS, Tammie L.S. Benzinger, MD, PhD, and Catherine Mummery, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/MOC/AAPA/APA activity titled “Case by Case: Actioning Patient-Centered Strategies for Risk Assessment, Diagnosis, and Management of Amyloid-Related Imaging Abnormalities (ARIA).” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA/APA information, and to apply for credit, please visit us at https://bit.ly/3UaOse6. CME/MOC/AAPA/APA credit will be available until August 16, 2024.

1. Integrating Anti-Aβ Monoclonal Antibodies Into
Patient-Centered Management of Early AD1-5
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
Participant Feature
Age
Clinical diagnosis
Cognitive status
Amyloid status
Body mass index
Genetic testing
Magnetic resonance imaging
Cardiovascular history
Medical history
Psychiatric history
Concomitant medications
Care partner
Informed consent
Important considerations
50-90 years; younger or older patients meeting all other criteria for treatment may be considered
candidates for therapy
MCI due to AD or mild AD dementia
Mild decline of cognition with no or limited impairment of activities of daily living established by objective
cognitive testing (eg, MMSE 22-30)
Amyloid-positive PET (visual read) or CSF findings consistent with AD
BMI >17 and <35; physician judgement used for patients at the extremes of BMI
APOE genotype determined
Baseline MRI obtained
Stable cardiovascular conditions required
Stable medical conditions required
Stable psychiatrically
Patients can be on standard of care with cholinesterase inhibitors and memantine
Have a care partner or family member(s) who can ensure that the patient has the
support needed to be treated with anti-Aβ monoclonal antibodies
Patient and care partner must understand the nature and requirements of therapy
(eg, bimonthly or monthly infusions) and the expected outcome of therapy
(removal of amyloid and slowing of decline of clinical features)
Anti-amyloid therapies should be prescribed only after appropriate and qualified team members
(eg, neurologist, pharmacy, infusion nurse, radiologist) are in place to monitor safety,
tolerability and effectiveness of the therapy
Inclusion Criteria
Appropriate Use of Anti-Aβ Monoclonal Antibodies in Clinical Practice

2. Integrating Anti-Aβ Monoclonal Antibodies Into
Patient-Centered Management of Early AD1-5
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
Participant Feature
Cognitive impairment
etiologies
Baseline MRI
findings
Additional CNS
injuries/findings
Autoimmune
disease/treatments
Bleeding disorders
Anticoagulants
Other
medical/psychiatric
conditions
Any medical, neurologic, or psychiatric condition that may be contributing to the cognitive impairment or any
non-AD MCI or dementia
• >4 microhemorrhages (defined as ≤10 mm at the greatest diameter)
• A single macrohemorrhage (defined as >10 mm at the greatest diameter)
• An area of superficial siderosis
• Evidence of vasogenic edema
• >2 lacunar infarcts or stroke involving a major vascular territory
• Severe subcortical hyperintensities consistent with a Fazekas score of 3
• Evidence of ABRA
• Evidence of CAA-ri
• Any other major intracranial pathology that may cause cognitive impairment
• MRI evidence of a non-AD dementia
Recent history (within 12 mo) of stroke or TIA or any history of seizures
Any history of immunologic disease (eg, lupus erythematosus, rheumatoid arthritis, Crohn’s disease) or systemic treatment
with immunosuppressants, immunoglobulins, or monoclonal antibodies or their derivatives
Patients with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or INR >1.5 for
participants who are not on anticoagulants)
Patients on anticoagulants (coumadin, dabigatran, edoxaban, rivaroxaban, apixaban, betrixaban, or heparin) should not
receive anti-Aβ monoclonal antibodies; tPA should not be administered to individuals on treatment with anti-Aβ
monoclonal antibody
• Mental illness (eg, psychosis) that interferes with comprehension of the requirements, potential benefit, and potential
harms of treatment and are considered by the physician to render the patient unable to comply with management
requirements
• Major depression that will interfere with comprehension of the requirements, potential benefit, and potential harms of
treatment; patients for whom disclosure of a positive biomarker may trigger suicidal ideation. Patients with less severe
depression or whose depression resolves may be treatment candidates
• Unstable medical conditions that may affect or be affected by treatment
Exclusion Criteria
Appropriate Use of Anti-Aβ Monoclonal Antibodies in Clinical Practice (Cont’d)

3. Integrating Anti-Aβ Monoclonal Antibodies Into
Patient-Centered Management of Early AD1-5
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
1. Cummings J et al. J Prev Alzheimers Dis. 2023;10:362-377. 2. Cummings J et al. J Prev Alzheimers Dis. 2022;2:221-230. 3. van Dyck CH et al. N Engl J Med. 2023;388:9-21. 4. Aduhelm (aducanumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/
label/2023/761178s007lbl.pdf. 5. Leqembi (lecanemab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269s001lbl.pdf.
1. Clinician skilled in the assessment of cognition to identify individuals with MCI or mild dementia due to Alzheimer’s disease
2. MRI available for baseline assessment of cerebrovascular pathology and for monitoring of ARIA
3. Radiologists, neurologists, or other clinicians expert in the identification and interpretation of cerebrovascular lesions and ARIA
4. Amyloid PET or lumbar puncture capability to determine the amyloid status of treatment candidates
5. Radiologists, nuclear medicine specialists, neurologists, or other specialists skilled in the interpretation of amyloid imaging or neurologists,
radiologists, or other clinicians skilled in the conduct of lumbar puncture
6. APOE genotyping resources
7. Genetic expertise to counsel patients on the implications of APOE genotyping
8. Expertise in communicating with patients and care partners regarding anticipated benefits, potential harm, and requirements for
administration and monitoring while on anti-Aβ monoclonal antibodies
9. Infusion settings that can be made available to patients receiving therapy
10. Knowledgeable staff at infusion sites capable of recognizing and managing infusion reactions
11. Communication channels established between experts interpreting MRIs and clinicians treating patients with anti-Aβ
monoclonal antibodies
12. Communication channels established between clinicians treating patients with anti-Aβ monoclonal antibodies and the patient and
care partner
13. Availability of hospital resources including intensive care unit
14. Expertise in the management of seizures and status epilepticus patients with severe or serious ARIA
15. Protocol with standard operating procedures for management of serious and severe ARIA
Resources Needed by a Clinician or Medical Center for the Safe and Effective Use of Anti-Aβ
Monoclonal Antibodies in Clinical Practice

4. Detecting, Monitoring, and Treating Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
ARIA Type
ARIA-E
ARIA-H
microhemorrhage
ARIA-H superficial
siderosis
FLAIR hyperintensity
confined to sulcus and/or
cortex/subcortical white
matter in one location <5 cm
Mild Moderate
Radiographic Severity
Severe
≤4 new incident
microhemorrhages
One focal area
of superficial siderosis
FLAIR hyperintensity 5-10 cm,
or more than one site
of involvement, each
measuring <10 cm
5-9 new incident
microhemorrhages
Two focal areas
of superficial siderosis
FLAIR hyperintensity measures
>10 cm, often with significant
subcortical white matter
and/or sulcal involvement;
≥1 separate sites of
involvement might be noted
≥10 new incident
microhemorrhages
>2 focal areas
of superficial siderosis
Classifying ARIA by Radiographic Severity1,2

5. Detecting, Monitoring, and Treating Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
3T scanner (recommended)
1.5T scanner (minimal)
High field strength scanners have greater sensitivity but limited availability. The use of 1.5T
scanner is endorsed as a minimum standard
Slice thickness: ≤5 mm Thinner slices increase resolution, but decrease signal-to-noise ratio
TE: ≥20 ms Longer TE increases sensitivity to detection
2D T2* GRE or SWI
(for ARIA-H)
To identify superficial siderosis and microhemorrhages (ARIA-H), T2* GRE and SWI are MRI
sequences used to improve the detection and visualization of microhemorrhages
T2-FLAIR (for ARIA-E) To monitor brain edema or sulcal effusion (ARIA-E)
Diffusion-weighted imaging Recommended for differential diagnosis
MRI Acquisition Protocols to Detect and Monitor ARIA3-5

6. Detecting, Monitoring, and Treating Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
Anti-Aβ antibodies require MRI assessment and monitoring before and during treatment
• At baseline (up to one year prior to treatment initiation)
• At recommended intervals (particularly during titration)
• In response to symptoms suggesting possible ARIA
• Important to obtain consistent serial imaging by using a standardized imaging protocol with the same field strength for every
MRI assessment
• After 12 months of treatment, decision about whether to continue to obtain safety MRIs should be guided by patient symptoms and
prior MRI findings
Recommended MRI Monitoring Schedules
Aducanumab and lecanemab Aducanumab only Lecanemab only
MRI within
1 year prior
to initiation
MRI if any
symptoms
suggestive of
ARIA occur
MRI
prior to
5th dose
MRI
prior to
7th dose
MRI
prior to
9th dose
MRI
prior to
12th dose
MRI
prior to
14th dose
T1 T2 T3 T4 T5 T6 T7 T8 T9 T12 T13 T14
Recommended MRI Monitoring Strategy to Detect ARIA in Patients Receiving Anti-Aβ Antibodies1-4,6-9

7. Detecting, Monitoring, and Treating Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
Headache
Confusion and
dizziness
Neuropsychiatric
symptoms
Nausea
Gait
disturbance
Visual
disturbance/
blurred vision
Seizure
Less frequent Uncommon
Symptom Severity
Mild
Discomfort noted;
no disruption of
daily activity
Moderate
Discomfort sufficient
to reduce or affect
normal daily activity
Severe
Incapacitating,
with inability to perform
normal daily activity
Symptoms Consistent With ARIA That Should Trigger Out-of-Sequence MRI6-8

8. Detecting, Monitoring, and Treating Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
Baseline MRI has no exclusion factors
MRI routine or conducted because of symptoms suggestive of ARIA
ARIA-E or ARIA-H detected
Symptomatic Asymptomatic
Radiographically mild ARIA-E
or mild ARIA-H
Continue treatment with
anti-Aβ antibody; monthly MRI
Continue treatment;
discontinue monthly MRI if ARIA-E
resolves or ARIA-H stabilizes
Resume treatment with anti-Aβ antibody
Suspend treatment; clinical assessment;
repeat MRI monthly
Radiographically
moderate/severe ARIA-E
or moderate/severe ARIA-H
MRI shows resolution of ARIA-E or
stabilization of ARIA-H; symptoms
resolve; patient wishes to continue
Stop anti-Aβ antibody therapy for any of the following
• Any macrohemorrhage
• >1 area of superficial siderosis
• >10 microhemorrhages since treatment initiation
• >2 episodes of ARIA
• Severe symptoms of ARIA
• Patient requires treatment with an anticoagulant
Severity of Changes Observed on MRI
Radiographic ARIA-E: Mild
Radiographic ARIA-E: Moderate
Radiographic ARIA-E: Severe
Radiographic ARIA-H: Mild
Radiographic ARIA-H: Moderate
Radiographic ARIA-H: Severe
Symptom Description
No Symptoms Mild Symptoms Moderate Symptoms Severe Symptoms
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Suspend dosing
Suspend dosing Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Discontinue dosing Discontinue dosing
Continue dosing
Continue dosing
ARIA Management Algorithm6-8

9. Detecting, Monitoring, and Treating Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
1. Aduhelm (aducanumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761178s007lbl.pdf. 2. Leqembi (lecanemab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269s000lbl.pdf. 3. Cogswell
PM et al. AJNR Am J Neuroradiol. 2022;43:E19-E35. 4. Sperling RA et al. Alzheimers Dement. 2011;7:367-385. 5. Barakos J et al. J Prev Alzheimers Dis. 2022;9:211-220. 6. Cummings J et al. J Prev Alzheimers Dis. 2023;10:362-377. 7. Cummings J et al. J Prev Alzheimers Dis. 2022;2:221-230.
8. Cummings J et al. J Prev Alzheimers Dis. 2021;4:398-410. 9. van Dyck CH et al. N Engl J Med. 2023;388:9-21.
• Referral of patient to emergency department for thorough assessment of suspected/known ARIA
• Brain MRI without contrast enhancement if not already obtained (FLAIR, T2* GRE or SWI, and DWI sequences)
• MRI review by a reader proficient in detection of ARIA (preferably with access to past MRIs for comparison) and rapid
communication between MRI reader and clinicians responsible for patient’s treatment and AD care
• Discontinuation of anti-amyloid therapy
• Consultation by a neurologist
• Admittance to hospital ward for close neurologic monitoring and tiered level of monitoring and management
• Admit or transfer to a stroke care unit or neurological intensive care unit if warranted
• When warranted, protocols for
– Early initiation of treatment with IV methylprednisolone 1 g/d for 5 d
– Conducting electroencephalography to detect epileptiform activity
– Treatment with anticonvulsants for seizure management or prophylaxis if electroencephalography suggests they
are indicated
– Consideration of additional immunosuppressive treatment if not responding to methylprednisolone after
5 d of treatment
– Plan transition to oral steroid treatment and taper as outpatient
• Support and communicate with patient and family members/care partners throughout the event with informed
patient-centered decision-making
Triage Strategy for Severe Symptomatic Cases of ARIA7

10. Selected Images of Amyloid-Related Imaging
Abnormalities (ARIA) and Its Mimics
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
Parenchymal Edema
New T2-FLAIR hyperintense signal with mild local
mass effect and sulcal effacement measuring <5 cm
(mild ARIA-E)
New multifocal, patchy T2-FLAIR hyperintense
signal, each region measuring <5 cm (moderate
ARIA-E); multiple ARIA-E yields a classification of
moderate, as long as each region is <10 cm
Extensive T2-FLAIR hyperintense signal throughout the
right frontal and parietal lobes measuring >10 cm
(severe ARIA-E); associated mass effect and sulcal
effacement throughout much of the right hemisphere
Baseline Baseline Baseline
Post-treatment Post-treatment Post-treatment
Mild Moderate Severe
New sulcal T2-FLAIR hyperintense signal measuring
<5 cm in transverse dimensions (mild ARIA-E)
New T2-FLAIR sulcal effusion involving the right
posterior temporal and parietal lobes measuring
5-10 cm (moderate ARIA-E)
Extensive T2-FLAIR sulcal effusion involving the
bilateral temporal and occipital lobes measuring
≥10 cm in extent (severe ARIA-E)
Baseline Post-treatment
Mild
Sulcal Effusion
Baseline Post-treatment
Moderate
Baseline Post-treatment
Severe
ARIA-E Examples (Detected With T2-FLAIR Sequence)1

11. Selected Images of Amyloid-Related Imaging
Abnormalities (ARIA) and Its Mimics
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
Microhemorrhage
Postdosing, ≥10 new microhemorrhages
(severe ARIA-H)
Baseline Post-treatment
Severe
Postdosing, 5 treatment-emergent
microhemorrhages (moderate ARIA-H)
Baseline Post-treatment
Moderate
Postdosing, few (<5) new peripheral left frontal
microhemorrhages (mild ARIA-H)
Baseline Post-treatment
Mild
Superficial Siderosis
Postdosing, new right temporal superficial siderosis, which involves
contiguous sulci when viewed over multiple slices (mild ARIA-H,
siderosis); this patient also had two treatment-emergent
microhemorrhages (mild ARIA-H, microhemorrhage)
Two regions of treatment-emergent superficial siderosis in the
right greater-than-left frontal lobes (moderate ARIA-H)
Baseline Post-treatment
Mild
Baseline Post-treatment
Moderate
ARIA-H Examples (Detected With T2-GRE or SWI Sequence)1

12. Selected Images of Amyloid-Related Imaging
Abnormalities (ARIA) and Its Mimics
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
Infarct (Early Subacute)
FLAIR+ (hyperintensity)
• In addition to FLAIR and GRE/SWI sequences, a trace DWI
sequence should be included as routine protocol in ARIA
monitoring examinations to help with the differential
diagnosis of new signal abnormalities
• For example, the DWI sequence plays an important role in
helping to differentiate ARIA-E from potential cytotoxic
edema caused by an incidental infarct
• In classic cases of ARIA, the diffusion restriction will be
absent, because intense diffusion restriction associated
with an infarct is not a characteristic of ARIA
• The DWI sequence helped to identify the underlying
etiology of this patient’s radiographic findings
• Diffusion restriction was identified, which indicated that it
was not ARIA
• However, the diffusion restriction was located in the sulci,
which is not a typical pattern seen with acute or subacute
infarcts
• This patient was diagnosed with bacterial meningitis
following confirmatory lab testing
Infection (Bacterial Meningitis)
FLAIR+ (vasogenic edema
and sulcal effusions)
GRE/SWI+ (microhemorrhages
and superficial siderosis)
DWI+ (with restricted
diffusion in the sulci)
DWI+ (with restricted diffusion)
GRE/SWI+ (microhemorrhage)
ARIA Mimics2

13. Selected Images of Amyloid-Related Imaging
Abnormalities (ARIA) and Its Mimics
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QVT40
1. Cogswell PM et al. Am J Neuroradiol. 2022;43:E19-E35. 2. Images courtesy of Tammie L.S. Benzinger, MD, PhD.
ARIA Mimics2
Brain Metastasis
FLAIR+ (hyperintensity)
• New signal abnormalities detected in ARIA monitoring
examinations may require T1-weighted gadolinium-enhanced
imaging to differentiate between ARIA and brain metastases
• Contrast-enhanced imaging should be considered based on
the patient’s medical history and/or any clinical findings that
may suggest the possibility of a metastatic etiology
• ARIA and PRES are usually indistinguishable based on MRI (eg, both
will typically have FLAIR hyperintensities and no restricted
diffusion)
• Therefore, the clinical context is critical to differentiate between
ARIA and PRES
• This patient presented to the emergency department with
confusion, headache, and very high blood pressure (which is a
classic presentation for PRES)
• They were treated for their hypertension, which resolved their
clinical symptoms and their edema
Posterior Reversible Encephalopathy Syndrome (PRES)
FLAIR+ (hyperintensities) GRE/SWI negative DWI negative
(no diffusion restriction)
T1 postcontrast + enhancement
GRE/SWI+ (microhemorrhage)
T1 postcontrast