Keeping PACE™ in Alzheimer’s Disease: Precision Strategies to Achieve Early Diagnosis and Safely Integrate Disease-Modifying Treatment
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About This Presentation
Co-Chairs, Stephen Salloway, MD, MS, and Sharon J. Sha, MD, MS, discuss Alzheimer’s disease in this CME/MOC/NCPD/AAPA activity titled “Keeping PACE™ in Alzheimer’s Disease: Precision Strategies to Achieve Early Diagnosis and Safely Integrate Disease-Modifying Treatment.” For the full prese...
Slide Content
Keeping PACE™ in Alzheimer’s Disease
Precision Strategies to Achieve Early Diagnosis and
Safely Integrate Disease-Modifying Treatment
Stephen Salloway, MD, MS 11 Sharon J. Sha, MD, MS
Professor, Psychiatry and Human Behavior Clinical Professor
Professor of Neurology, Alpert Medical School of Chief, Memory Disorders Division
Brown University Associate Vice Chair, Clinical Research
Associate Director of the Brown Center for .. Neurology and Neurological Sciences
Alzheimer’s Research Stanford Center for Memory Disorders
Providence, Rhode Island Palo Alto, California
Go online to access full CME/MOC/NCPD/AAPA information, including faculty disclosures.
Copyright © 2000-2024, PeerView
Precision Strategies to Achieve Early Diagnosis and
Safely Integrate Disease-Modifying Treatment
Stephen Salloway, MD, MS 11 Sharon J. Sha, MD, MS
Professor, Psychiatry and Human Behavior Clinical Professor
Professor of Neurology, Alpert Medical School of Chief, Memory Disorders Division
Brown University Associate Vice Chair, Clinical Research
Associate Director of the Brown Center for .. Neurology and Neurological Sciences
Alzheimer’s Research Stanford Center for Memory Disorders
Providence, Rhode Island Palo Alto, California
Go online to access full CME/MOC/NCPD/AAPA information, including faculty disclosures.
Copyright © 2000-2024, PeerView
Disclosures
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Co-Chair & Presenter
Stephen Salloway, MD, MS
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of
Brown University
Associate Director of the Brown Center for
Alzheimer's Research
Providence, Rhode Island
Stephen Salloway, MD, MS, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Acumen Pharmaceutics,
Inc.; Biogen; Eisai Inc.; F. Hoffmann-La Roche Ltd;
Genentech, Inc.; Lilly; Novo Nordisk; and Prothena
Grant/Research Support from Biogen; Eisai Inc.; F.
Hoffmann-La Roche Ltd; Genentech, Inc.; and Lilly.
PeerView.com/JNE827
Co-Chair & Presenter
Sharon J. Sha, MD, MS
Clinical Professor
Chief, Memory Disorders Division
Associate Vice Chair, Clinical Research
Neurology and Neurological Sciences
Stanford Center for Memory Disorders
Palo Alto, California
Sharon J. Sha, MD, MS, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Cognition Therapeutics and
Eisai Inc.
Grant/Research Support from ARIBIO; Biogen; Cognition
Therapeutics; Eisai Inc.; and Lilly
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Co-Chair & Presenter
Stephen Salloway, MD, MS
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of
Brown University
Associate Director of the Brown Center for
Alzheimer's Research
Providence, Rhode Island
Stephen Salloway, MD, MS, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Acumen Pharmaceutics,
Inc.; Biogen; Eisai Inc.; F. Hoffmann-La Roche Ltd;
Genentech, Inc.; Lilly; Novo Nordisk; and Prothena
Grant/Research Support from Biogen; Eisai Inc.; F.
Hoffmann-La Roche Ltd; Genentech, Inc.; and Lilly.
PeerView.com/JNE827
Co-Chair & Presenter
Sharon J. Sha, MD, MS
Clinical Professor
Chief, Memory Disorders Division
Associate Vice Chair, Clinical Research
Neurology and Neurological Sciences
Stanford Center for Memory Disorders
Palo Alto, California
Sharon J. Sha, MD, MS, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Cognition Therapeutics and
Eisai Inc.
Grant/Research Support from ARIBIO; Biogen; Cognition
Therapeutics; Eisai Inc.; and Lilly
Introduction
Stephen Salloway, MD, MS
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of Brown University
Associate Director of the Brown Center for Alzheimer’s Research
Providence, Rhode Island
Copyright © 200
Stephen Salloway, MD, MS
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of Brown University
Associate Director of the Brown Center for Alzheimer’s Research
Providence, Rhode Island
Copyright © 200
Our Goals for Today
Enhance your understanding of the relationships between specific AD
biomarkers, the underlying neuropathological changes that define AD, and the
clinical manifestations and severity of cognitive and functional decline
Increase your ability to employ validated biomarkers to make an accurate
neuropathological diagnosis of AD in patients who present with symptoms of
cognitive impairment
Augment your capacity to select appropriate patients for treatment with ATTs
Improve your ability to educate patients regarding the risks, benefits, goals,
expectations, and delivery/monitoring aspects of treatment with ATTs based on
the principles of shared decision-making
Equip you with the skills needed to monitor and manage patients being
treated with ATTs, to optimize the safety and efficacy of these treatments
Copyright © 2000-2024, PeerView
Enhance your understanding of the relationships between specific AD
biomarkers, the underlying neuropathological changes that define AD, and the
clinical manifestations and severity of cognitive and functional decline
Increase your ability to employ validated biomarkers to make an accurate
neuropathological diagnosis of AD in patients who present with symptoms of
cognitive impairment
Augment your capacity to select appropriate patients for treatment with ATTs
Improve your ability to educate patients regarding the risks, benefits, goals,
expectations, and delivery/monitoring aspects of treatment with ATTs based on
the principles of shared decision-making
Equip you with the skills needed to monitor and manage patients being
treated with ATTs, to optimize the safety and efficacy of these treatments
Copyright © 2000-2024, PeerView
Alzheimer’s Disease: A Growing Epidemic!+
Currently there are more than 55 million people worldwide living with dementia
+ Number is set to grow to 139 million by 2050 because of the aging population
across the globe
AD is the most common cause of dementia and thought to account for 60%-80*
of global dementia cases
+ Total estimated annual worldwide cost of dementia is currently over US$1.3 trillion;
this is set to increase to more than US$2.8 trillion by 2030
1 ps: sno invnews-cooniact sheetadetitdementi. 2, ps:lapps who ri ktrarhanda/10668/34470 /9789240039245-209. pl ñ
3: https ww al-org/media/Documentsaizhoimers-act-ard figures pat. 4. Rajan KB et al Alzheimers Dement. 2021;17: 1966-1975, PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Currently there are more than 55 million people worldwide living with dementia
+ Number is set to grow to 139 million by 2050 because of the aging population
across the globe
AD is the most common cause of dementia and thought to account for 60%-80*
of global dementia cases
+ Total estimated annual worldwide cost of dementia is currently over US$1.3 trillion;
this is set to increase to more than US$2.8 trillion by 2030
1 ps: sno invnews-cooniact sheetadetitdementi. 2, ps:lapps who ri ktrarhanda/10668/34470 /9789240039245-209. pl ñ
3: https ww al-org/media/Documentsaizhoimers-act-ard figures pat. 4. Rajan KB et al Alzheimers Dement. 2021;17: 1966-1975, PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Healthcare/Practice Gaps in the Management of AD
ing thera
Des; significant advances in diagnostic testing and disease-modi
for AD, many healthcare/practice gaps persist, including
Underdiagnosis of early-stage AD!3
Underutilization of validated diagnostic biomarker testing*
1. Podhoma Jet al. Adv Mar 20207 889-685. 2. Marasoo R. Am J Manag Gare 2020;25(8 Suppl) S167-S176. 3. Rasmussen J, Langeman H. Dogonar
tigulogeal euremuseu Dis 20108 '29-190 4 Judge Oot al ni J Alzheimer Di. 2010 20194042562 5, Au-Osa Hal Ho! oc Care Communi
202200 09265-49276, 8 Low LF tl, Demat 2019,182056-2903. 7 Kunnaman Mela. Alhwine's man: Trans Ras Cn itr. 2017.9314322.8. Yang Mt
Ta modpaqecdsy conlpinon/socondopeiens 102608 9 Duck! SMD et Arg Nour Pequot 2022:005 Sup 131523. 10, Greonber BD ota
‘honors Damen. andi Ras Cn nos 2023 12820 1. Palma. Nat, 2022:510.15:0. 12 pe ereopharma coaching euros paint
bieakogemb-taunenpeture-saheimers-druprps-nostchalonges. 13. Baras Je al. Am J Neuroradiol. 2013:34 1958-1965. 14, Keter N et al J Alzheima's Ds A
2017/57 557-573 PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, Peerview
ing thera
Des; significant advances in diagnostic testing and disease-modi
for AD, many healthcare/practice gaps persist, including
Underdiagnosis of early-stage AD!3
Underutilization of validated diagnostic biomarker testing*
1. Podhoma Jet al. Adv Mar 20207 889-685. 2. Marasoo R. Am J Manag Gare 2020;25(8 Suppl) S167-S176. 3. Rasmussen J, Langeman H. Dogonar
tigulogeal euremuseu Dis 20108 '29-190 4 Judge Oot al ni J Alzheimer Di. 2010 20194042562 5, Au-Osa Hal Ho! oc Care Communi
202200 09265-49276, 8 Low LF tl, Demat 2019,182056-2903. 7 Kunnaman Mela. Alhwine's man: Trans Ras Cn itr. 2017.9314322.8. Yang Mt
Ta modpaqecdsy conlpinon/socondopeiens 102608 9 Duck! SMD et Arg Nour Pequot 2022:005 Sup 131523. 10, Greonber BD ota
‘honors Damen. andi Ras Cn nos 2023 12820 1. Palma. Nat, 2022:510.15:0. 12 pe ereopharma coaching euros paint
bieakogemb-taunenpeture-saheimers-druprps-nostchalonges. 13. Baras Je al. Am J Neuroradiol. 2013:34 1958-1965. 14, Keter N et al J Alzheima's Ds A
2017/57 557-573 PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, Peerview
A Multidisciplinary, Team-Based Approach Is Required
to Improve Care for Patients With Early AD
Memory clinics must shift to a medicalized practice model that ©
offers biological diagnostic testing and disease-modifying
therapies
+ CSF testing, PET scans, infusion centers for new treatments,
MRI safety monitoring
+ Multidisciplinary team may include neurologists, geriatric
psychiatrists, geriatricians, neuroradiologists, nuclear
medicine specialists, infusion therapists, neuropsychologists,
and geneticists
PeerView.com
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to Improve Care for Patients With Early AD
Memory clinics must shift to a medicalized practice model that ©
offers biological diagnostic testing and disease-modifying
therapies
+ CSF testing, PET scans, infusion centers for new treatments,
MRI safety monitoring
+ Multidisciplinary team may include neurologists, geriatric
psychiatrists, geriatricians, neuroradiologists, nuclear
medicine specialists, infusion therapists, neuropsychologists,
and geneticists
PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Implications for the Healthcare Team
A broad range of multidisciplinary providers need to be educated
about biomarker tests and DMTs
For example
+ PCPs and APPs should proactively inquire about memory loss
and take subjective memory complaints seriously; should also
conduct basic testing (eg, MMSE, PHQ-9, blood tests) and
structural imaging prior to referral
+ Nuclear medicine physicians need to learn amyloid and tau PET
+ Neuroradiologists need to learn how to monitor for ARIA
+ Emergency physicians need to know how ARIA may present in
the ED
PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
A broad range of multidisciplinary providers need to be educated
about biomarker tests and DMTs
For example
+ PCPs and APPs should proactively inquire about memory loss
and take subjective memory complaints seriously; should also
conduct basic testing (eg, MMSE, PHQ-9, blood tests) and
structural imaging prior to referral
+ Nuclear medicine physicians need to learn amyloid and tau PET
+ Neuroradiologists need to learn how to monitor for ARIA
+ Emergency physicians need to know how ARIA may present in
the ED
PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Increasing the Number of Clinicians Who Can Provide AD Care
Through a Training of Trainers Approach’
+ Current activity was inspired by the CDC’s Training of Trainers model
— Master Trainers coach new trainers with less experience to build a pool of
competent instructors who can then teach the material to other people
+ Aim to provide practical guidance to AD specialists on early diagnosis and treatment of
AD consistent with most recent evidence and best practice guidelines
— Hope this will motivate participants to train peers and colleagues, and serve as
mentors/champions in their local practice settings
+ A Virtual Training Center (www.PACE-ALZ.com) has also been developed to facilitate
training of additional clinicians and improve practice behaviors
- Contains other current educational activities on AD, podcasts, slide sets, and
point-of-care Practice Aid tools
1. ps wa cdo govineathyschoos/professional_ developmentidocuments17_279600_TrainersModol-FactSheot v3. S08Final pot PeerView.com
Copyright © 2001
Through a Training of Trainers Approach’
+ Current activity was inspired by the CDC’s Training of Trainers model
— Master Trainers coach new trainers with less experience to build a pool of
competent instructors who can then teach the material to other people
+ Aim to provide practical guidance to AD specialists on early diagnosis and treatment of
AD consistent with most recent evidence and best practice guidelines
— Hope this will motivate participants to train peers and colleagues, and serve as
mentors/champions in their local practice settings
+ A Virtual Training Center (www.PACE-ALZ.com) has also been developed to facilitate
training of additional clinicians and improve practice behaviors
- Contains other current educational activities on AD, podcasts, slide sets, and
point-of-care Practice Aid tools
1. ps wa cdo govineathyschoos/professional_ developmentidocuments17_279600_TrainersModol-FactSheot v3. S08Final pot PeerView.com
Copyright © 2001
Visit the Virtual Training Center (PACE-ALZ.com) for
Downloadable Resources to Share With Your Colleagues
PACE-ALZ.com pendium of
tools that has be urated to pro] te training
Slide Library
PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Downloadable Resources to Share With Your Colleagues
PACE-ALZ.com pendium of
tools that has be urated to pro] te training
Slide Library
PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Keeping PACE™ in the Diagnosis of
Alzheimer’s Disease
Biomarker Testing in the Era of
Amyloid-Targeting Therapies
Sharon J. Sha, MD, MS
Clinical Professor
Chief, Memory Disorders Division
Associate Vice Chair, Clinical Research
Neurology and Neurological Sciences
Stanford Center for Memory Disorders
Palo Alto, California
Copyright
Alzheimer’s Disease
Biomarker Testing in the Era of
Amyloid-Targeting Therapies
Sharon J. Sha, MD, MS
Clinical Professor
Chief, Memory Disorders Division
Associate Vice Chair, Clinical Research
Neurology and Neurological Sciences
Stanford Center for Memory Disorders
Palo Alto, California
Copyright
Patient Case: Charlotte
66-year-old woman
Initial Presentation to Primary Care
+ 66-year-old Black woman with 16 years of education
+ Reported memory complaints for past 6 months and new difficulties with multitasking
Medical and Family History
+ Hypertension, T2DM, arthritis; controlled on medication
Lab work (CBC, glucose, HbA1o, TSH, B12, hepatic and renal function, lipids) all normal
Current medications: lisinopril, metformin, aspirin
+ Family history positive for dementia (mother had dementia when she died of breast cancer at 80 y; father died of stroke at 79 y)
Cognitive, Functional, and Mood Assessments Structural MRI
PCP administered MOCA; score = 22/30 Charlotte’s MRI findings included
+ PHQ-9 indicated mild symptoms of depression and anxiety + Mild-moderate bilateral parietal atrophy, minimal bilateral
+ FAQ: 3/30 (difficulty with taxes but still does them on her own) frontal atrophy, mild bilateral hippocampal atrophy
+ Mid-moderate small vessel ischemic disease
+ Evidence of 1 lacunar infarct (<1.0 em)
PCP referred patient to memory clinic for further interpretation and assessment
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66-year-old woman
Initial Presentation to Primary Care
+ 66-year-old Black woman with 16 years of education
+ Reported memory complaints for past 6 months and new difficulties with multitasking
Medical and Family History
+ Hypertension, T2DM, arthritis; controlled on medication
Lab work (CBC, glucose, HbA1o, TSH, B12, hepatic and renal function, lipids) all normal
Current medications: lisinopril, metformin, aspirin
+ Family history positive for dementia (mother had dementia when she died of breast cancer at 80 y; father died of stroke at 79 y)
Cognitive, Functional, and Mood Assessments Structural MRI
PCP administered MOCA; score = 22/30 Charlotte’s MRI findings included
+ PHQ-9 indicated mild symptoms of depression and anxiety + Mild-moderate bilateral parietal atrophy, minimal bilateral
+ FAQ: 3/30 (difficulty with taxes but still does them on her own) frontal atrophy, mild bilateral hippocampal atrophy
+ Mid-moderate small vessel ischemic disease
+ Evidence of 1 lacunar infarct (<1.0 em)
PCP referred patient to memory clinic for further interpretation and assessment
PeerView.com
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Clinical Stages of Alzheimer’s Disease‘?
Stage 1: Clinically asymptomatic, biomarker evidence only
Screening for preclinical AD is not
currently recommended outside of
clinical trials
Preclinical AD Stage 2: Normal performance in expected range on
cognitive tests, but decline from previous level of cognitive
function, without functional impairment
Mild Cognitive
Impairment
Stage
: Objective cognitive impairment without functional
impairment
Amyloid-targeting therapies are
approved for patients with MCI or
mild dementia who also have
positive AD biomarkers
Stage 4 (Mild dementia): Progressive cognitive and mild
functional impairment on instrume
independence in basic ADLs
‘Stage 5 (Moderate dementia): Progressive cognitive and
moderate functional impairment requiring assistance c
basic ADLs
Alzheimer's
Dementia
Stage 6 (Severe dementia): Progressive cognitive and
severe functional impairment causing dependence for
basic ADLs
1.Jack Je GR e al Alzheimors Dement. 2024 Jun 27 (Epub ahead of pn. Jack GR etal. Alzheimers Doment, 2018; 18 535-562 PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Stage 1: Clinically asymptomatic, biomarker evidence only
Screening for preclinical AD is not
currently recommended outside of
clinical trials
Preclinical AD Stage 2: Normal performance in expected range on
cognitive tests, but decline from previous level of cognitive
function, without functional impairment
Mild Cognitive
Impairment
Stage
: Objective cognitive impairment without functional
impairment
Amyloid-targeting therapies are
approved for patients with MCI or
mild dementia who also have
positive AD biomarkers
Stage 4 (Mild dementia): Progressive cognitive and mild
functional impairment on instrume
independence in basic ADLs
‘Stage 5 (Moderate dementia): Progressive cognitive and
moderate functional impairment requiring assistance c
basic ADLs
Alzheimer's
Dementia
Stage 6 (Severe dementia): Progressive cognitive and
severe functional impairment causing dependence for
basic ADLs
1.Jack Je GR e al Alzheimors Dement. 2024 Jun 27 (Epub ahead of pn. Jack GR etal. Alzheimers Doment, 2018; 18 535-562 PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Temporal Evolution of AD Biomarkers
and Cognitive Impairment’
4
— AB fluid
— Amyloid PET
— Phosphorylated tau fluid
— Tau PET
— MRI + FDG PET
Biomarker Abnormality
9
8
à
8
E
E
3
=
Detection
threshold
Preclinical AD MCI AD Dementia
1.Jack Jr GR e al Lancet Neuro. 2022;10:886-869, PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
and Cognitive Impairment’
4
— AB fluid
— Amyloid PET
— Phosphorylated tau fluid
— Tau PET
— MRI + FDG PET
Biomarker Abnormality
9
8
à
8
E
E
3
=
Detection
threshold
Preclinical AD MCI AD Dementia
1.Jack Jr GR e al Lancet Neuro. 2022;10:886-869, PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Updated Biomarker Categorization From the Revised
Criteria for Diagnosis and Staging of AD (2024)!
|CSF or Plasma Analyte:
marker Categı Imaging
Core 1 Biomarkers
A (AB proteinopathy) AB42 Amyloid PET
T, (phosphorylated and P-tau217, P-taut81, _
secreted AD tau) P-tau231
Core 2 Biomarkers
Ta (AD tau proteinopathy) Porro Ena, Tau PET
nP-tau fragments
Biomarkers of Nonspecific Processes Involved in AD Pathophysiology
N (injury, dysfunction, or
dagenatation of neuropil) NL Anatomic MRI, FOG PET
1 (inflammation) astrocytic activation GFAP =
Biomarkers of Non-AD Copathology
= Infarction on MRI or CT, WMH
$ (a-synuclein) aSyn-SAA
1. Jack Je GR et al Alzheimers Dement 2024 Jun 27 (Epub ahead of print, PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Criteria for Diagnosis and Staging of AD (2024)!
|CSF or Plasma Analyte:
marker Categı Imaging
Core 1 Biomarkers
A (AB proteinopathy) AB42 Amyloid PET
T, (phosphorylated and P-tau217, P-taut81, _
secreted AD tau) P-tau231
Core 2 Biomarkers
Ta (AD tau proteinopathy) Porro Ena, Tau PET
nP-tau fragments
Biomarkers of Nonspecific Processes Involved in AD Pathophysiology
N (injury, dysfunction, or
dagenatation of neuropil) NL Anatomic MRI, FOG PET
1 (inflammation) astrocytic activation GFAP =
Biomarkers of Non-AD Copathology
= Infarction on MRI or CT, WMH
$ (a-synuclein) aSyn-SAA
1. Jack Je GR et al Alzheimers Dement 2024 Jun 27 (Epub ahead of print, PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Core Biomarkers of AD!
Imaging
Biomarker Category |
Core 1 Biomarkers
A (AB proteinopathy) Amyloid PET
P-tau217,
Ta (phosphorylated tau) P-tau181,
P-tau231
+ Core 1 biomarkers define the
initial stage of AD that is
detectable in vivo
+ AD can be diagnosed with any
Core 1 biomarker
Hybrid ratios of AB, ABAZIABAO, P-tau217/
tau181/AB4:
Pau: tall tau/AB42 Has + Core 2 biomarkers develop
later than Core 1 biomarkers,
Core 2 Biomarkers and are closely tied to onset of
Ta (AD tau neurodegeneration and clinical
proteinopathy) SER symptoms
+ Core 2 biomarkers can be
Biomarker confirmation of AB pathology required to be eligible for treatment with an ATT combined with Core 1
Biomarkers in red boxes are FDA-approved biomarkers to stage biological
+ Amyloid PET and CSF tests are covered by Medica disease severity
1. J GR ot al Aloinors Dement 2024 Jun 27 (Epub ahead of pin PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Imaging
Biomarker Category |
Core 1 Biomarkers
A (AB proteinopathy) Amyloid PET
P-tau217,
Ta (phosphorylated tau) P-tau181,
P-tau231
+ Core 1 biomarkers define the
initial stage of AD that is
detectable in vivo
+ AD can be diagnosed with any
Core 1 biomarker
Hybrid ratios of AB, ABAZIABAO, P-tau217/
tau181/AB4:
Pau: tall tau/AB42 Has + Core 2 biomarkers develop
later than Core 1 biomarkers,
Core 2 Biomarkers and are closely tied to onset of
Ta (AD tau neurodegeneration and clinical
proteinopathy) SER symptoms
+ Core 2 biomarkers can be
Biomarker confirmation of AB pathology required to be eligible for treatment with an ATT combined with Core 1
Biomarkers in red boxes are FDA-approved biomarkers to stage biological
+ Amyloid PET and CSF tests are covered by Medica disease severity
1. J GR ot al Aloinors Dement 2024 Jun 27 (Epub ahead of pin PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Amyloid PET!
1. Clark CM ot
4. Sporing RA
JAMA Nowrol 2015:72:207-294. 3. Sabri O eta Alzheimer
a JAMA, 2019.321:1206-1204.
PeerView.com/JNE827
Amyloid PET demonstrated 88%-98%
sensitivity and 80%-95% specificity
reliable proxy for amyloid accumulation
based on PET-to-autopsy studies
‘Accumulation of amyloid plaques
begins 10-20 years before onset of
clinical impairment
IDEAS study found that amyloid PET
can improve early diagnosis and
appropriate treatment of Alzheimer's
and other dementias
Three FDA-approved amyloid tracers
(florbetapir, florbetaben, flutemetamol),
and all have very similar clinical
performance
Dement. 2015:11:964-974
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Copyright © 2000-2024, Peer
1. Clark CM ot
4. Sporing RA
JAMA Nowrol 2015:72:207-294. 3. Sabri O eta Alzheimer
a JAMA, 2019.321:1206-1204.
PeerView.com/JNE827
Amyloid PET demonstrated 88%-98%
sensitivity and 80%-95% specificity
reliable proxy for amyloid accumulation
based on PET-to-autopsy studies
‘Accumulation of amyloid plaques
begins 10-20 years before onset of
clinical impairment
IDEAS study found that amyloid PET
can improve early diagnosis and
appropriate treatment of Alzheimer's
and other dementias
Three FDA-approved amyloid tracers
(florbetapir, florbetaben, flutemetamol),
and all have very similar clinical
performance
Dement. 2015:11:964-974
PeerView.com
Copyright © 2000-2024, Peer
Amyloid PET Quantitative Tool:
Centiloid Scale’
In clinical practice, amyloid PET is read
based on a qualitative interpretation of
activity in cerebral cortex versus white
matter
Reports designated positive or
negative
En 100
Negative
plaques
AB neuritic
<10= neurtic plaques absent de out AD
Neuropathology 29 al least moderate plaque densiy
Positive = moderate to frequent AB
plaque “Grey-Zone"
Visual Read
Alternatively, centiloid (CL) scale provide:
continuous measure of amyloid pathology
(range: 0-100)
80 = strongest emotion wth AD diagnosis
— 30 = equivocal, rom eariest detecablo (12) o established AR (30)
optimal visual ur-of fr highly experienced readers
26 = high correlation wah postive visual road
19 = velable worsening’ of CL rate of change
26 = optimal proditon of progression o dementia 6 years ator PET
le cutoff scor d 12 ———— 40 | >40= “elevated AB” (igh burden)
Clinical Trial Inclusion
amyloid positivity in res China AHEAD Sam)
intermediate AD
Early pretnical AD
typically have ranged
CL >20 correlates with moderate =
neuritic plaques at autopsy o : B 50 ÿ
1.Klunk WE et al. Alzheimers Dement. 2015:11:1-15.64. 2, Pemberton HG et al Eur J Nuc! Med Mol Imaging. 2022;49:9508-3520,
3. Su etal Neurolmage Cin, 2018:19:406-116. 4 Amador Seta Alzheimors Res The, 202012 1.8
PeerView.com/JNE827
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Copyright © 2000-2024, PeerView
Centiloid Scale’
In clinical practice, amyloid PET is read
based on a qualitative interpretation of
activity in cerebral cortex versus white
matter
Reports designated positive or
negative
En 100
Negative
plaques
AB neuritic
<10= neurtic plaques absent de out AD
Neuropathology 29 al least moderate plaque densiy
Positive = moderate to frequent AB
plaque “Grey-Zone"
Visual Read
Alternatively, centiloid (CL) scale provide:
continuous measure of amyloid pathology
(range: 0-100)
80 = strongest emotion wth AD diagnosis
— 30 = equivocal, rom eariest detecablo (12) o established AR (30)
optimal visual ur-of fr highly experienced readers
26 = high correlation wah postive visual road
19 = velable worsening’ of CL rate of change
26 = optimal proditon of progression o dementia 6 years ator PET
le cutoff scor d 12 ———— 40 | >40= “elevated AB” (igh burden)
Clinical Trial Inclusion
amyloid positivity in res China AHEAD Sam)
intermediate AD
Early pretnical AD
typically have ranged
CL >20 correlates with moderate =
neuritic plaques at autopsy o : B 50 ÿ
1.Klunk WE et al. Alzheimers Dement. 2015:11:1-15.64. 2, Pemberton HG et al Eur J Nuc! Med Mol Imaging. 2022;49:9508-3520,
3. Su etal Neurolmage Cin, 2018:19:406-116. 4 Amador Seta Alzheimors Res The, 202012 1.8
PeerView.com/JNE827
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Copyright © 2000-2024, PeerView
Positive Tau PET Pattern Predicts Progression
to MCI and Dementia‘
Progression to MCI Progression to All-Cause Dementia
NS
AtTueor*
Survival Probability
3
3
a
3
B
3
AdTueor*
36 72 24 36 48
Time, mo Time, mo
1. Ossonkoppete R et al 2922. Mat Mad. 2022:28:2381-2387 PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
to MCI and Dementia‘
Progression to MCI Progression to All-Cause Dementia
NS
AtTueor*
Survival Probability
3
3
a
3
B
3
AdTueor*
36 72 24 36 48
Time, mo Time, mo
1. Ossonkoppete R et al 2922. Mat Mad. 2022:28:2381-2387 PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Core AD CSF Biomarkers:
Performance Compared With Amyloid PET!
Fully automated Concordance
immunoassays Visual amyloid PET vs CSF
P-tau/Aß42 (OPA = 90%)
Visual amyloid PET vs CSF T-
tau/AB42 (OPA = 89.5%)
P-tau181/Aß42,
T-tau/ AB42
Study Cohorts
BioFINDER (n= 277) —]
ADNI (n = 646)
Concordance
‘Amyloid PET Visual amyloid PET
Visual read (three raters) inter-rater agreement
(OPA = 90%)
CSF biomarkers and amyloid PET can be used interchangeably for inclusion purposes or diagnostics
1. Hansson etal. Alzheimers Domont. 2018:14:1470-14B1. PeerView.com
Peer!
Copyright © 2000-2024, PeerView
Performance Compared With Amyloid PET!
Fully automated Concordance
immunoassays Visual amyloid PET vs CSF
P-tau/Aß42 (OPA = 90%)
Visual amyloid PET vs CSF T-
tau/AB42 (OPA = 89.5%)
P-tau181/Aß42,
T-tau/ AB42
Study Cohorts
BioFINDER (n= 277) —]
ADNI (n = 646)
Concordance
‘Amyloid PET Visual amyloid PET
Visual read (three raters) inter-rater agreement
(OPA = 90%)
CSF biomarkers and amyloid PET can be used interchangeably for inclusion purposes or diagnostics
1. Hansson etal. Alzheimers Domont. 2018:14:1470-14B1. PeerView.com
Peer!
Copyright © 2000-2024, PeerView
FDA-Approved In Vitro Diagnostics for AD:
CSF P-Tau181/Aß42 and T-Tau/Af4212
Individual Biomarkers Hybrid Ratio Biomarkers
10
o 075
prid ratio
os omarkers are
more accurate than
individu
True Positive Rate (Sensitivity)
True Positive Rate (Sensitivity)
— AB42/AB40: AUC = 0.936
— T-tau/A642: AUC = 0.941
— P-tau181/AB42: AUC = 0.94
0 05 os 0 o 0% 05 075 Yo
False Positive Rate (1-Specificity) False Positive Rate (1-Specificity)
1. ps M1 convousnes-nsights/plcy and-equlatoda-cesrancelarcle1S2040GBoche-nabss-clenranceortwoslneimer-dsea4e-classays, 7
2. Doecke JD at al Alzheimers Res Ther. 2020: 12:36 PeerView.com
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CSF P-Tau181/Aß42 and T-Tau/Af4212
Individual Biomarkers Hybrid Ratio Biomarkers
10
o 075
prid ratio
os omarkers are
more accurate than
individu
True Positive Rate (Sensitivity)
True Positive Rate (Sensitivity)
— AB42/AB40: AUC = 0.936
— T-tau/A642: AUC = 0.941
— P-tau181/AB42: AUC = 0.94
0 05 os 0 o 0% 05 075 Yo
False Positive Rate (1-Specificity) False Positive Rate (1-Specificity)
1. ps M1 convousnes-nsights/plcy and-equlatoda-cesrancelarcle1S2040GBoche-nabss-clenranceortwoslneimer-dsea4e-classays, 7
2. Doecke JD at al Alzheimers Res Ther. 2020: 12:36 PeerView.com
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Two-Cutoff Approach to Increase
Plasma-Based Biomarker Performance’?
Potential AD diagnosis
Initiate current treatments
Blood biomarker
Patients with
measurement
cognitive
impairment dE
=)
(0%-30% of patients)
Take CSF or perform
PET at specialist clinic
pathology
Pow Not AD |
probability
1. Hansson Det a. Not Aging. 2023::506-519, 2. Leuzy At a. Alzhoimers Dement. 2028:18 2994-3004, 3. Brum WS etal. Nat Aging. 2028::1078-1090, PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, Peerview
Plasma-Based Biomarker Performance’?
Potential AD diagnosis
Initiate current treatments
Blood biomarker
Patients with
measurement
cognitive
impairment dE
=)
(0%-30% of patients)
Take CSF or perform
PET at specialist clinic
pathology
Pow Not AD |
probability
1. Hansson Det a. Not Aging. 2023::506-519, 2. Leuzy At a. Alzhoimers Dement. 2028:18 2994-3004, 3. Brum WS etal. Nat Aging. 2028::1078-1090, PeerView.com
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Are Plasma Biomarkers Ready for Prime Time?1-5
» Plasma tests should have performance equivalent to FDA-approved
CSF tests
— 290% sensitivity and 290% specificity (amyloid status)
Plasma P-tau217 tests are the only plasma assays achieving
overall accuracy that exceeds 90%
1. Schindler SE eta. Nat Rev Neural 2024:20:426-439. 2. Rissman RA eta. Alzholmers Dement 2026:20:1214-1224. 3, Janeiro S et al. Gran. 2023;146:1592- y)
1601. 4. Palmgvit at a. JAMA. 2024 Jul 26 [Epub ahoad of prin. 5. Jack Jr CR eta. Alzheimers Dement. 2024 Jun 27 [Epub ahuad of prin) PeerView.com
NE827
» Plasma tests should have performance equivalent to FDA-approved
CSF tests
— 290% sensitivity and 290% specificity (amyloid status)
Plasma P-tau217 tests are the only plasma assays achieving
overall accuracy that exceeds 90%
1. Schindler SE eta. Nat Rev Neural 2024:20:426-439. 2. Rissman RA eta. Alzholmers Dement 2026:20:1214-1224. 3, Janeiro S et al. Gran. 2023;146:1592- y)
1601. 4. Palmgvit at a. JAMA. 2024 Jul 26 [Epub ahoad of prin. 5. Jack Jr CR eta. Alzheimers Dement. 2024 Jun 27 [Epub ahuad of prin) PeerView.com
NE827
Advantages and Limitations of
Three Modalities of AD Biomarkers
Limitat
+ Associated with changes in management of patients
+ Costly without coverage and stil difficult
with MCI and dementia
al + Long history of use and standardized interpretation te Get resnuraed by Medic In many
‘Amyloid PET, tau PET + Multiple FDA-approved tracers
Limited capacity and availability
+ Reflects spatial distribution and amount of pathology Invasive (radiation)
+ Medicare will now cover amyloid PET
+ Widely available + Test characteristics vary by method
gsFes + Reimbursed by CMS for certain diagnoses (sampling and measurement)
Bee a en en Ar un)
. © Muliple FDA-approved + Contraindications
+ Can be performed by a radiologist, neurologist, or advanced practice provider + Post LP complications
Plasmas E + Not yet FDA approved
The following tests are! a + Notreimbursed by CMS
avaiable as angl anales. Minimally invasivo 2 Test performance varies by assay and
or in combination panels: — ! Can be orderad by any provider ‘measurement method
P-1au217, AB42/AB40, analytically pd + Relatively new; lacking validation in a
P-tau181, APOES, NiL general population
1. Wong DF etaL Je! Med, 201051913920. 2 Rainovl OD ot al JAMA 2019321.1200-1284.2-Je GVM el Phamacautents, 2021:14:110
4: Chavez Fumagatl MA o a. JAlheimers Dis Rap 2021.519-30.8.Mps ww er govimotcare-covwragodatabovavanincacal-decson-
memo aeproropoeed=N&NCAld=00. 6, Date FH ea Alzhomers Doment 2010.12 184-160, 7. Bier Tet. Azhemers Demon. 2010.12517-520
8. danois S ot a. Ann Cin Trana Nowa. 2016.3:154-15, 9. Canovl Mts. Front Aging Nouros 2019; 11-262 10. Ou Y eta. Meurosc Biobahav Rev.
2624;128.479.405. 41, iY at a Neurology. 2022:98: 9688-0609. 12, Jack CR at al Alhamers Dement 2024-27. 13. Plan Jl al Practeal Neurology.
2024232742 14, Hampel Ht al. Neuron. 2023:1112781-279. 15 tps: way com convproiersneurocgyieurodegeneratw-dscasesazimere sense
{nips Mestitecoy qunsidagnostcs comtestinome specaly=Gonatestcr-AgosccoManagorent. 17 hie fa sigues Cabo cirio e
providers! 18. ps preciyad.com. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Three Modalities of AD Biomarkers
Limitat
+ Associated with changes in management of patients
+ Costly without coverage and stil difficult
with MCI and dementia
al + Long history of use and standardized interpretation te Get resnuraed by Medic In many
‘Amyloid PET, tau PET + Multiple FDA-approved tracers
Limited capacity and availability
+ Reflects spatial distribution and amount of pathology Invasive (radiation)
+ Medicare will now cover amyloid PET
+ Widely available + Test characteristics vary by method
gsFes + Reimbursed by CMS for certain diagnoses (sampling and measurement)
Bee a en en Ar un)
. © Muliple FDA-approved + Contraindications
+ Can be performed by a radiologist, neurologist, or advanced practice provider + Post LP complications
Plasmas E + Not yet FDA approved
The following tests are! a + Notreimbursed by CMS
avaiable as angl anales. Minimally invasivo 2 Test performance varies by assay and
or in combination panels: — ! Can be orderad by any provider ‘measurement method
P-1au217, AB42/AB40, analytically pd + Relatively new; lacking validation in a
P-tau181, APOES, NiL general population
1. Wong DF etaL Je! Med, 201051913920. 2 Rainovl OD ot al JAMA 2019321.1200-1284.2-Je GVM el Phamacautents, 2021:14:110
4: Chavez Fumagatl MA o a. JAlheimers Dis Rap 2021.519-30.8.Mps ww er govimotcare-covwragodatabovavanincacal-decson-
memo aeproropoeed=N&NCAld=00. 6, Date FH ea Alzhomers Doment 2010.12 184-160, 7. Bier Tet. Azhemers Demon. 2010.12517-520
8. danois S ot a. Ann Cin Trana Nowa. 2016.3:154-15, 9. Canovl Mts. Front Aging Nouros 2019; 11-262 10. Ou Y eta. Meurosc Biobahav Rev.
2624;128.479.405. 41, iY at a Neurology. 2022:98: 9688-0609. 12, Jack CR at al Alhamers Dement 2024-27. 13. Plan Jl al Practeal Neurology.
2024232742 14, Hampel Ht al. Neuron. 2023:1112781-279. 15 tps: way com convproiersneurocgyieurodegeneratw-dscasesazimere sense
{nips Mestitecoy qunsidagnostcs comtestinome specaly=Gonatestcr-AgosccoManagorent. 17 hie fa sigues Cabo cirio e
providers! 18. ps preciyad.com. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Commercially Available Biomarkers for AD!
Test Name (Develope
Florbetapir (Lily)
Florbetaben (Life Molecular Imaging)
Flutemetamol (GE Healthcare)
Flortaucipir (Lily)
Elecsys AD (Roche)
Lumipuise G (Fujrebio)
‘AD-Detect (Quest Diagnostics)
ALZpathDx (ALZpath, Quanterix)
LucentAD (Lucent Diagnostics)
‘Amyloid Plasma Panel (Roche, Lilly)
Phosphorylated Tau 217 (Labcorp)
Phospho-Tau 217 (Mayo Clinic)
PrecivityAD, PreciviyAD2 (C2N)
1. hips Mostgrctory quesidiagnosics contestes! uidesTS_AD_Detect_Plau217Pasmalquestod-coteciphosphontatedau217-p49u217-plasma?psta.
2. ips mw quantorx comvvancing alznaimors dsezso-pañoLay-doterion-wth simoo-alepat-p1au217.0588y/ . NOS rw lucontdagaostes comme
Biomarker Modality
‘Amyloid PET
Amyloid PET
Amyloid PET
Tau PET
CSF
csF
Plasma
Plasma
Plasma
Plasma
Plasma
Plasma
Plasma
Biomarkers
‘Amyloid plaques:
Amyloid plaques
Amyloid plaques.
Tau aggregates
P-taut81/AB42, T-
tauiApa2
Ap42/40
P-tau217, p-taut81,
‘AB42/40, ApoE isoform
P-tau217
P-tau217
P-tau217, ABADIAB4O,
P-tau181, APOE4
P-tau217
P-tau217
‘AB42/A40, APOEA,
P-tau217/nP-tau217
say Platform
NA
NA
NA
NA
Elecsys
Lumipuise
CLEIA,
LO-MSIMS
Simoa
Simoa
Elecsys
Lumipuise CLEIA
CLEIA
IP-LC-MSIMS
comentuplaade 2024004 07 LucantAD_White_Papor pd 4. hips ns labcorp comesta/484390/phosphoryatedtau-217-plau-217-plasma
5. hips preciviyod compreciiyad2-nep. 6. hips:alagnostes.rocne.convus/ennews-Bting/2024roche-grante{da-breakthrough-covion designation ptau217-
blood-lest-suppor-earier-alznemors-disease-diagnosis him. 7. nips raw mesoscale com envproducts_and_servicesservices!
ploxñau_p1217_and_p1181_sorvies. 8, Pleen Jet al. Practical Neurology. 2024;2327-42. 9. Hampel Het al. Nouron.2023,111:2781-2799,
PeerView.com/JNE827
Regulatory Status
FDA-approved
FDA-approved
FDA-approved
FDA-approved
FDA-approved
FDA-approved
CLIA-certified
CLIA-certifed &
FDA breakthrough
CLIA-cortified
Breakthrough device
CLIA-certified
CLIA-certified
CLIA/breakthrough
PeerView.com
Copyright O 2000-2024, Peerview
Test Name (Develope
Florbetapir (Lily)
Florbetaben (Life Molecular Imaging)
Flutemetamol (GE Healthcare)
Flortaucipir (Lily)
Elecsys AD (Roche)
Lumipuise G (Fujrebio)
‘AD-Detect (Quest Diagnostics)
ALZpathDx (ALZpath, Quanterix)
LucentAD (Lucent Diagnostics)
‘Amyloid Plasma Panel (Roche, Lilly)
Phosphorylated Tau 217 (Labcorp)
Phospho-Tau 217 (Mayo Clinic)
PrecivityAD, PreciviyAD2 (C2N)
1. hips Mostgrctory quesidiagnosics contestes! uidesTS_AD_Detect_Plau217Pasmalquestod-coteciphosphontatedau217-p49u217-plasma?psta.
2. ips mw quantorx comvvancing alznaimors dsezso-pañoLay-doterion-wth simoo-alepat-p1au217.0588y/ . NOS rw lucontdagaostes comme
Biomarker Modality
‘Amyloid PET
Amyloid PET
Amyloid PET
Tau PET
CSF
csF
Plasma
Plasma
Plasma
Plasma
Plasma
Plasma
Plasma
Biomarkers
‘Amyloid plaques:
Amyloid plaques
Amyloid plaques.
Tau aggregates
P-taut81/AB42, T-
tauiApa2
Ap42/40
P-tau217, p-taut81,
‘AB42/40, ApoE isoform
P-tau217
P-tau217
P-tau217, ABADIAB4O,
P-tau181, APOE4
P-tau217
P-tau217
‘AB42/A40, APOEA,
P-tau217/nP-tau217
say Platform
NA
NA
NA
NA
Elecsys
Lumipuise
CLEIA,
LO-MSIMS
Simoa
Simoa
Elecsys
Lumipuise CLEIA
CLEIA
IP-LC-MSIMS
comentuplaade 2024004 07 LucantAD_White_Papor pd 4. hips ns labcorp comesta/484390/phosphoryatedtau-217-plau-217-plasma
5. hips preciviyod compreciiyad2-nep. 6. hips:alagnostes.rocne.convus/ennews-Bting/2024roche-grante{da-breakthrough-covion designation ptau217-
blood-lest-suppor-earier-alznemors-disease-diagnosis him. 7. nips raw mesoscale com envproducts_and_servicesservices!
ploxñau_p1217_and_p1181_sorvies. 8, Pleen Jet al. Practical Neurology. 2024;2327-42. 9. Hampel Het al. Nouron.2023,111:2781-2799,
PeerView.com/JNE827
Regulatory Status
FDA-approved
FDA-approved
FDA-approved
FDA-approved
FDA-approved
FDA-approved
CLIA-certified
CLIA-certifed &
FDA breakthrough
CLIA-cortified
Breakthrough device
CLIA-certified
CLIA-certified
CLIA/breakthrough
PeerView.com
Copyright O 2000-2024, Peerview
Keeping PACE™ in the Management of
Alzheimer’s Disease
Integrating Disease-Modifying Therapies
Into Clinical Practice
Stephen Salloway, MD, MS \\
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of
Brown University
Associate Director of the Brown Center for
Alzheimer's Research
Providence, Rhode Island
Sharon J. Sha, MD, MS
Clinical Professor
Chief, Memory Disorders Division
Associate Vice Chair, Clinical Research
Neurology and Neurological Sciences
Stanford Center for Memory Disorders
Palo Alto, California à
à
Copyright © 2001
4, PeerView
Alzheimer’s Disease
Integrating Disease-Modifying Therapies
Into Clinical Practice
Stephen Salloway, MD, MS \\
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of
Brown University
Associate Director of the Brown Center for
Alzheimer's Research
Providence, Rhode Island
Sharon J. Sha, MD, MS
Clinical Professor
Chief, Memory Disorders Division
Associate Vice Chair, Clinical Research
Neurology and Neurological Sciences
Stanford Center for Memory Disorders
Palo Alto, California à
à
Copyright © 2001
4, PeerView
Amyloid-Targeting Therapies Are the First FDA-Approved
Disease-Modifying Treatment Options for AD!
July 2024
Donanemab received full
for
July 2023 traditional FDA approval
Lacan De received til the treatment of early AD
traditional FDA approval for
the treatment of early AD
June 2021
Aducanumab received FDA
accelerated approval for the
treatment of eariy AD
January 2024
Manufacturer announced
discontinuation of
January 2023 aducanumab
Lecanemab received FDA
accelerated approval for the
treatment of early AD
1. pe aw fa govinews-oventelpress-anrouncementsfds-ants-acolerated-approval-azhoimer-diug. 2. mps fa gounews-eventsiprss:
_ancuncementsféa-convers-novel-aaheimars disease reatman-radiional- approval. 3. IPS wwe bnightocus Orglalheimars nawslalzheimers.iug-
‘aduheln-e-discontinuedt~ text=Ons420Wednesday%20%20auary%2031%420%208i0gen tl: 204 20el90% 206% 20terminated.
4: nus Je da govldrugsinews-vens-haman-deuga/ea-approves-veatment-adis-alzeimers- disease
PeerView.com
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Disease-Modifying Treatment Options for AD!
July 2024
Donanemab received full
for
July 2023 traditional FDA approval
Lacan De received til the treatment of early AD
traditional FDA approval for
the treatment of early AD
June 2021
Aducanumab received FDA
accelerated approval for the
treatment of eariy AD
January 2024
Manufacturer announced
discontinuation of
January 2023 aducanumab
Lecanemab received FDA
accelerated approval for the
treatment of early AD
1. pe aw fa govinews-oventelpress-anrouncementsfds-ants-acolerated-approval-azhoimer-diug. 2. mps fa gounews-eventsiprss:
_ancuncementsféa-convers-novel-aaheimars disease reatman-radiional- approval. 3. IPS wwe bnightocus Orglalheimars nawslalzheimers.iug-
‘aduheln-e-discontinuedt~ text=Ons420Wednesday%20%20auary%2031%420%208i0gen tl: 204 20el90% 206% 20terminated.
4: nus Je da govldrugsinews-vens-haman-deuga/ea-approves-veatment-adis-alzeimers- disease
PeerView.com
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Anti-AB Monoclonal Antibodies: The First
Disease-Modifying Therapies to Be Approved in AD1-10
Impact on AD Pathobiology
+ Many patients “amyloid-negative” after 6-18 months of treatment
+ May improve other AD biomarkers (eg, tau, neuroinflammation, neurodegeneration)
Impact on Slowing of Clinical Decline
+ Slows declines in cognition, function, and health-related QOL
+ Moderate group-level efficacy in patients with MCI and mild dementia due to AD
+ Treatments save 5-7 months of expected decline compared to placebo over 18 months
(¡AULA Son Nal 2099927249 2 Cummins ll Aja Rs Tha 20211308 3 bn (étant) Poca
Papa accosedst 6a govrugaatés docs 20276 17880114 pl. & Loqombs(ucanamab) Prost Informati
Ios an sala gran soto teo HOOT Say Sea. Je Ath Ds 20220811542 8. Doody Rett. N
Engl J Med. 2014:970311:321,7. van Dyck ei. N Eng J Mod 2029300921. 8. Sms Jet a AAIC 2023. Oral presentation. 9, Sms Je al JAMA. 2023:350'512- m
527.10. Knuna(donanamap) Prost infomation ps accansata da gouts docalael2024781216:000b pa PeerView.com
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Disease-Modifying Therapies to Be Approved in AD1-10
Impact on AD Pathobiology
+ Many patients “amyloid-negative” after 6-18 months of treatment
+ May improve other AD biomarkers (eg, tau, neuroinflammation, neurodegeneration)
Impact on Slowing of Clinical Decline
+ Slows declines in cognition, function, and health-related QOL
+ Moderate group-level efficacy in patients with MCI and mild dementia due to AD
+ Treatments save 5-7 months of expected decline compared to placebo over 18 months
(¡AULA Son Nal 2099927249 2 Cummins ll Aja Rs Tha 20211308 3 bn (étant) Poca
Papa accosedst 6a govrugaatés docs 20276 17880114 pl. & Loqombs(ucanamab) Prost Informati
Ios an sala gran soto teo HOOT Say Sea. Je Ath Ds 20220811542 8. Doody Rett. N
Engl J Med. 2014:970311:321,7. van Dyck ei. N Eng J Mod 2029300921. 8. Sms Jet a AAIC 2023. Oral presentation. 9, Sms Je al JAMA. 2023:350'512- m
527.10. Knuna(donanamap) Prost infomation ps accansata da gouts docalael2024781216:000b pa PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Clinical Implementation of ATTs!
Patient Selection
Determine clinical status
Identify AD etiology
Assess treatment eligibility
Gauge risk
Engage in care goals (shared decision-making)
geriatricians, NPS/PAs, geneticists,
neuropsychologists, radiologists, pathologists
Treatment Monitoring
Design safety assessments
Track treatment response
Anticipate complications (eg, ARIA protocols)
Adapt to cumulative volumes
Drug Administration
Ensure drug access
Develop order sets and protocols
Identify infusion facilties/mechanisms
Plan for administrative burdens
Clinical stakeholders: neurologists, geriatricians,
NPsIPAs, neuropsychologists, radiologists, hospital
services
Clinical stakeholders: neurologists, nurses, social
workers, infusion therapists, pharmacists, EMR teams
1. Ramanon VK et al. Neurology. 2028;101:842-852 PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Patient Selection
Determine clinical status
Identify AD etiology
Assess treatment eligibility
Gauge risk
Engage in care goals (shared decision-making)
geriatricians, NPS/PAs, geneticists,
neuropsychologists, radiologists, pathologists
Treatment Monitoring
Design safety assessments
Track treatment response
Anticipate complications (eg, ARIA protocols)
Adapt to cumulative volumes
Drug Administration
Ensure drug access
Develop order sets and protocols
Identify infusion facilties/mechanisms
Plan for administrative burdens
Clinical stakeholders: neurologists, geriatricians,
NPsIPAs, neuropsychologists, radiologists, hospital
services
Clinical stakeholders: neurologists, nurses, social
workers, infusion therapists, pharmacists, EMR teams
1. Ramanon VK et al. Neurology. 2028;101:842-852 PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Practical Tips for Implementing ATTs for
Alzheimer’s ease in the Clinic
pecific protocols need to be developed to fa
+ Every clinic/institution will have unique barriers and challenges to address
Assess biomarker testing capabilities
+ Evaluate radiology/nuclear medicine capacity for performing and interpreting PET
+ Accessibility of CSF biomarker testing and interpretation
Be proactive about patient safety
+ Determine capacity for APOE genotype testing and genetic counseling
+ Identify and visit local infusion centers to meet with staff and medical directors
+ Educate emergency physicians and PCPs about signs and symptoms of ARIA
Assess financial burden of treatment
+ Determine costs/copays of each component (eg, medication copays, infusion center fees, amyloid PET
scans, APOE test, CSF tests, recurrent MRIs to monitor for ARIA)
+ Identify local processes and barriers to obtain reimbursement of expenses
PeerView.com
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Alzheimer’s ease in the Clinic
pecific protocols need to be developed to fa
+ Every clinic/institution will have unique barriers and challenges to address
Assess biomarker testing capabilities
+ Evaluate radiology/nuclear medicine capacity for performing and interpreting PET
+ Accessibility of CSF biomarker testing and interpretation
Be proactive about patient safety
+ Determine capacity for APOE genotype testing and genetic counseling
+ Identify and visit local infusion centers to meet with staff and medical directors
+ Educate emergency physicians and PCPs about signs and symptoms of ARIA
Assess financial burden of treatment
+ Determine costs/copays of each component (eg, medication copays, infusion center fees, amyloid PET
scans, APOE test, CSF tests, recurrent MRIs to monitor for ARIA)
+ Identify local processes and barriers to obtain reimbursement of expenses
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Selecting Patients to Treat With Anti-AB
Monoclonal Antibodies'+
A Presci g Info for Lecanemab and Donanemab
UR for lecanemab more than the FDA prescribing information
Inclusion: Exclusions
1. Clinical diagnosis of MCI or mild dementia 1. Contraindication to MRI procedure
due to AD 2. MRI with >4 microhemorrhages, >1 area of
2. Confirmed amyloid positivity superficial siderosis or significant cerebrovascular
(PET or CSF) disease, severe white matter changes on MRI,
3. MMSE = 22-30 or other cognitive screening | ™acrohemorrhage, >2 lacunar infarcts, a single
instrument with a score compatible with Tene) emp
early AD (eg, MoCA 218) (AUR) 3. Anticoagulant use (AUR restriction)
4. Unstable medical/psychiatric conditions
APOE £4 genotype testing is recommended for all patients considering treatment
with anti-AB monoclonal antibodies to inform discussion with patients and
care partners about risks/benefits of treatment
1. Cummings Jet at. J Prov Alzheimer Dis. 2023:10362.377.2.von Dyck Got. N Engl J Med. 2023:3689-21
3 Loge! Gecanema Preactnginfomaton hip vw acc ssdata a gowlvgstda, docsabel 2020761269010 1 pt a
4 Kuna (donanemab) Presrbin Information, pa ou accezadata ka govlengeatéa-docelabol2024/761246e0000 pa. PeerView.com
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Monoclonal Antibodies'+
A Presci g Info for Lecanemab and Donanemab
UR for lecanemab more than the FDA prescribing information
Inclusion: Exclusions
1. Clinical diagnosis of MCI or mild dementia 1. Contraindication to MRI procedure
due to AD 2. MRI with >4 microhemorrhages, >1 area of
2. Confirmed amyloid positivity superficial siderosis or significant cerebrovascular
(PET or CSF) disease, severe white matter changes on MRI,
3. MMSE = 22-30 or other cognitive screening | ™acrohemorrhage, >2 lacunar infarcts, a single
instrument with a score compatible with Tene) emp
early AD (eg, MoCA 218) (AUR) 3. Anticoagulant use (AUR restriction)
4. Unstable medical/psychiatric conditions
APOE £4 genotype testing is recommended for all patients considering treatment
with anti-AB monoclonal antibodies to inform discussion with patients and
care partners about risks/benefits of treatment
1. Cummings Jet at. J Prov Alzheimer Dis. 2023:10362.377.2.von Dyck Got. N Engl J Med. 2023:3689-21
3 Loge! Gecanema Preactnginfomaton hip vw acc ssdata a gowlvgstda, docsabel 2020761269010 1 pt a
4 Kuna (donanemab) Presrbin Information, pa ou accezadata ka govlengeatéa-docelabol2024/761246e0000 pa. PeerView.com
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Risk Factors for ARIA‘?
APOE e4 copy number
Dose of amyloid-targeting therapy
More common early in treatment; majority of ARIA
occurred within the first 7 doses
Presence of underlying cerebral amyloid angiopathy
1.Sporing RA etal. Alzhoimors Dement 2011:7367-385. 2. Cogswell PM ota, AJNR Am J Mourad 202243:£19-£35. PeerView.com
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APOE e4 copy number
Dose of amyloid-targeting therapy
More common early in treatment; majority of ARIA
occurred within the first 7 doses
Presence of underlying cerebral amyloid angiopathy
1.Sporing RA etal. Alzhoimors Dement 2011:7367-385. 2. Cogswell PM ota, AJNR Am J Mourad 202243:£19-£35. PeerView.com
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Scheduling ATT Infusions and Safety Monitoring MRIs‘?
Lecanemab Donanemab
Infusion schedule Every 2 weeks Every 4 weeks
Infusion times 60 min 30 min
Dose titration No Yes
700 mg (infusions 1-3)
Dose 10 mg/kg 1,400 mg (infusions 4+)
+ Schedule routine safety MRIs upfront at same time when booking infusions
+ Schedule MRI scan a few days before next scheduled infusion to ensure adequate time
for radiology to read and relay results to prescribing clinician
Monitoring MRIs
Donanemab
Safety MRI prior to 5th, 7th, 14th dose Safety MRI prior to 2nd, 3rd, 4th, 7th dose
+ Add 30.60 min monitoring tm forint infusions to monitor for infusion reactions,
Y Kisnla (Gonanomab) Prescrbiag Information. ps mma aecessdata da govirugsatida_ docs labe'2024/761248s0001D pd.
2. Legembi (ecanemat) Presrbng Information, ps ir accesedata (da goviérugatida_docs/abel20287612690rIg 150011 pdt PeerView.com
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Lecanemab Donanemab
Infusion schedule Every 2 weeks Every 4 weeks
Infusion times 60 min 30 min
Dose titration No Yes
700 mg (infusions 1-3)
Dose 10 mg/kg 1,400 mg (infusions 4+)
+ Schedule routine safety MRIs upfront at same time when booking infusions
+ Schedule MRI scan a few days before next scheduled infusion to ensure adequate time
for radiology to read and relay results to prescribing clinician
Monitoring MRIs
Donanemab
Safety MRI prior to 5th, 7th, 14th dose Safety MRI prior to 2nd, 3rd, 4th, 7th dose
+ Add 30.60 min monitoring tm forint infusions to monitor for infusion reactions,
Y Kisnla (Gonanomab) Prescrbiag Information. ps mma aecessdata da govirugsatida_ docs labe'2024/761248s0001D pd.
2. Legembi (ecanemat) Presrbng Information, ps ir accesedata (da goviérugatida_docs/abel20287612690rIg 150011 pdt PeerView.com
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Limited Duration Treatment Option With Donanemab!
In the TRAILBLAZER-ALZ 2 trial, amyloid PET was performed at week 24, week 52, and
week 76
If patients achieved amyloid plaque clearance based on PET scan, they had the option of
stopping treatment
Percentage of Donanemab-Treated Patients That Achieved
Treatment-Related Amyloid Clearance
Week 24 Week 52
Week 7
vay 29.7 (226/761) 66.1 (443/670) 76.4 (469/614)
Treatment-related amyloid clearance was defined as amyloid plaque levels <24.1 CL
on amyloid PET scan, whic! consistent a negative visual read
1. ps a fa govimosia’t79167/4owsload. PeerView.com
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In the TRAILBLAZER-ALZ 2 trial, amyloid PET was performed at week 24, week 52, and
week 76
If patients achieved amyloid plaque clearance based on PET scan, they had the option of
stopping treatment
Percentage of Donanemab-Treated Patients That Achieved
Treatment-Related Amyloid Clearance
Week 24 Week 52
Week 7
vay 29.7 (226/761) 66.1 (443/670) 76.4 (469/614)
Treatment-related amyloid clearance was defined as amyloid plaque levels <24.1 CL
on amyloid PET scan, whic! consistent a negative visual read
1. ps a fa govimosia’t79167/4owsload. PeerView.com
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Donanemab Demonstrated Efficacy in Patients Who Switched to
Placebo After Treatment-Related Amyloid Clearance’
Mean time in trial prior
to switch to placebo for
these participants:
47 weeks
Donanemab
A\o75
Placebo
CDR-SB
Adjusted Mean Change (SE)
Time, wk
+P 0001 >
Atsui fda govimedia’179167/download. PeerView.com
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Placebo After Treatment-Related Amyloid Clearance’
Mean time in trial prior
to switch to placebo for
these participants:
47 weeks
Donanemab
A\o75
Placebo
CDR-SB
Adjusted Mean Change (SE)
Time, wk
+P 0001 >
Atsui fda govimedia’179167/download. PeerView.com
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Shared Decision-Making Discussion
About ATTs for AD!
Goals and Expectations
Slow disease-related cognitive and functional
decline beginning at early symptoms
Clear AB plaques from the brain
Key
education:
points
Risks
Brain swelling or bleeding (ie, ARIA)
High burden of clinic visits for infusion
and testing
Potentially costly
Infusion-related reactions
1. Ramanan VK ota Neurology: 2028:101:842-852,
Caveats
Not a cure for AD
Not expected to improve cognition or function
Some patients benefit more than others
Underrepresentation of racial and ethnic
minorities in clinical trials
Alternatives
Existing oral medications for symptoms
Lifestyle modification
Clinical trials and potential for future approved
interventions
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Shared Decision-Making Discussion
About ATTs for AD!
Goals and Expectations
Slow disease-related cognitive and functional
decline beginning at early symptoms
Clear AB plaques from the brain
Key
education:
points
Risks
Brain swelling or bleeding (ie, ARIA)
High burden of clinic visits for infusion
and testing
Potentially costly
Infusion-related reactions
1. Ramanan VK ota Neurology: 2028:101:842-852,
Caveats
Not a cure for AD
Not expected to improve cognition or function
Some patients benefit more than others
Underrepresentation of racial and ethnic
minorities in clinical trials
Alternatives
Existing oral medications for symptoms
Lifestyle modification
Clinical trials and potential for future approved
interventions
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Patient Assistance Programs
https://www.legembi.com/eisai-patient-support >
El
https://kisunla.lilly.com/hcp/support-resources#supportprogram [> 3
El
Available resources can assist with
+ Locating infusion centers nearby
+ Reducing financial burden of treatment (eg, by conducting benefits investigations, appealing
insurance denials, facilitating reimbursement for treatment, providing savings card to eligible
patients)
+ Providing care coordination (eg, by navigating logistics associated with treatment such as linking
infusion appointments with MRI visits)
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https://www.legembi.com/eisai-patient-support >
El
https://kisunla.lilly.com/hcp/support-resources#supportprogram [> 3
El
Available resources can assist with
+ Locating infusion centers nearby
+ Reducing financial burden of treatment (eg, by conducting benefits investigations, appealing
insurance denials, facilitating reimbursement for treatment, providing savings card to eligible
patients)
+ Providing care coordination (eg, by navigating logistics associated with treatment such as linking
infusion appointments with MRI visits)
PeerView.com
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Amyloid-Related
Imaging Abnormalities
Imaging Abnormalities
ARIA Incidence Rates in Patients Receiving
Amyloid-Targeting Therapies’
In AD clinical trials
« Incidence of ARIA-E ranged from 0.9%-40.6%
« Incidence of ARIA-H ranged from 0.5%-28.4%
« 74%-89% of ARIA was asymptomatic
+ An estimated 4% of symptomatic ARIA was deemed
Clinically severe
1. Barakos Jet al. Prev Alzhoimors Dis. 2022:2.211.220 PeerView.com
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Amyloid-Targeting Therapies’
In AD clinical trials
« Incidence of ARIA-E ranged from 0.9%-40.6%
« Incidence of ARIA-H ranged from 0.5%-28.4%
« 74%-89% of ARIA was asymptomatic
+ An estimated 4% of symptomatic ARIA was deemed
Clinically severe
1. Barakos Jet al. Prev Alzhoimors Dis. 2022:2.211.220 PeerView.com
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Role of MRI in the Workup of MCI and AD‘?
+ MRI rules out other non-AD causes of cognitive impairment, including
>angiopathic changes and micro/lacunar infarcts
lesions: tumors, cysts, abscesses
= Traumatic brain injury: gliosis, hemorrhagic contusions, subdural hematomas
+ MRI identifies changes that are suggestive of AD
= Focal atrophy (ie, hippocampal atrophy, medial temporal lobe atrophy)
— Microbleeds that are suggestive of CAA
+ MRI needed to evaluate patient eligibility for ATTs
nues,
Normal control
1. htperadiclogyassstant neuroracologyidementialol-of- 5
2 Dickerson B, Att À. Dementia: Comprehensive Principles and Practices. Oxford, UK: Oxford University Press; 2014 PeerView.com
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+ MRI rules out other non-AD causes of cognitive impairment, including
>angiopathic changes and micro/lacunar infarcts
lesions: tumors, cysts, abscesses
= Traumatic brain injury: gliosis, hemorrhagic contusions, subdural hematomas
+ MRI identifies changes that are suggestive of AD
= Focal atrophy (ie, hippocampal atrophy, medial temporal lobe atrophy)
— Microbleeds that are suggestive of CAA
+ MRI needed to evaluate patient eligibility for ATTs
nues,
Normal control
1. htperadiclogyassstant neuroracologyidementialol-of- 5
2 Dickerson B, Att À. Dementia: Comprehensive Principles and Practices. Oxford, UK: Oxford University Press; 2014 PeerView.com
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Baseline MRI Findings That Make
Patients Ineligible for ATTs1-3
+ Findings suggestive of underlying cerebral amyloid angiopathy
— Any cerebral macrohemorrhage >10 mm in diameter
— >4 microhemorrhages
— Superficial siderosis?
— Vasogenic edema
+ Other lesions that increase the risk of intracerebral hemorrhage or serious ARIA
— Aneurysm
— Vascular malformation
— Cortical infarct
— Extensive diffuse white matter disease
+n he donanemab pressing information one area of super! sico is alowed a baseline.
ps an fda govinens-avorupress-anpourcamenttss-convets-novel-azemer-cseas-reatmentsrastion)-approval
2 Legen ecanemat) Proscrtng Informaton. ps ran accessóat da govrugseidedoc1b0V20237612000091500 1. fe
5. Kisunta(donanomab) Precrbing Information ips accessdata fa. gowarugsattsa_deesabo202475124830000 pl PeerView.com
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Patients Ineligible for ATTs1-3
+ Findings suggestive of underlying cerebral amyloid angiopathy
— Any cerebral macrohemorrhage >10 mm in diameter
— >4 microhemorrhages
— Superficial siderosis?
— Vasogenic edema
+ Other lesions that increase the risk of intracerebral hemorrhage or serious ARIA
— Aneurysm
— Vascular malformation
— Cortical infarct
— Extensive diffuse white matter disease
+n he donanemab pressing information one area of super! sico is alowed a baseline.
ps an fda govinens-avorupress-anpourcamenttss-convets-novel-azemer-cseas-reatmentsrastion)-approval
2 Legen ecanemat) Proscrtng Informaton. ps ran accessóat da govrugseidedoc1b0V20237612000091500 1. fe
5. Kisunta(donanomab) Precrbing Information ips accessdata fa. gowarugsattsa_deesabo202475124830000 pl PeerView.com
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Symptoms/Signs Consistent With ARIA That Should Trigger
Out-of-Sequence MRI for Patients Receiving an ATT'5
+ ARIAis asymptomatic in approximately 75% of patients
25% of patients with ARIA experience focal neurological signs or
symptoms, including
Headache
Confusion/altered mental status/delirium/disorientation
Dizziness/vertigo
Nausea
Vomiting
Fatigue
Blurred vision
Vision disturbance/impairment
Gait disturbance
Seizures
1. Cummings Jet a. J Prev Alzheimors Dis. 2023:10:362-377. 2. Cummings y etal. J Prev Alzholmors Dis, 2022:2-221.290
3 Cummings où Alzheimers Di 2021:4:398:10., Sporing RA el a. Althoimers Doment 2011.7:367.366 5
5. Cogswol PM etal. AUNR Am J Neuroradiol. 2022:43:E19-E35, PeerView.com
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Out-of-Sequence MRI for Patients Receiving an ATT'5
+ ARIAis asymptomatic in approximately 75% of patients
25% of patients with ARIA experience focal neurological signs or
symptoms, including
Headache
Confusion/altered mental status/delirium/disorientation
Dizziness/vertigo
Nausea
Vomiting
Fatigue
Blurred vision
Vision disturbance/impairment
Gait disturbance
Seizures
1. Cummings Jet a. J Prev Alzheimors Dis. 2023:10:362-377. 2. Cummings y etal. J Prev Alzholmors Dis, 2022:2-221.290
3 Cummings où Alzheimers Di 2021:4:398:10., Sporing RA el a. Althoimers Doment 2011.7:367.366 5
5. Cogswol PM etal. AUNR Am J Neuroradiol. 2022:43:E19-E35, PeerView.com
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ARIA-E and ARIA-H: Clinical Characteristics!
Primary MRI
features
Parenchymal edema in
the left parieto-occipital
lobe (T2-FLAIR)
Nature and Intravascular fluid and
location of protein into the
leakage parenchymal interstitial
products fluid compartment
1.Hampol He al. Brain 2023:146:4416-4424
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Leptomeningeal sulcal
effusions in several
sulci (T2-FLAIR)
Proteinaceous fluid into
the leptomeningeal/
subarachnoid space
ARIA-H
Microhemorrhage | Superficial Siderosis
Multiple punctate foci
of single loss
(GRE/T2* or SWI)
Blood degradation of
products into adjacent
brain parenchyma
Small leptomeningeal
hemosiderin deposit
(GRE/T2* or SWI)
Blood degradation of
products into
subarachnoid space
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Primary MRI
features
Parenchymal edema in
the left parieto-occipital
lobe (T2-FLAIR)
Nature and Intravascular fluid and
location of protein into the
leakage parenchymal interstitial
products fluid compartment
1.Hampol He al. Brain 2023:146:4416-4424
PeerView.com/JNE827
Leptomeningeal sulcal
effusions in several
sulci (T2-FLAIR)
Proteinaceous fluid into
the leptomeningeal/
subarachnoid space
ARIA-H
Microhemorrhage | Superficial Siderosis
Multiple punctate foci
of single loss
(GRE/T2* or SWI)
Blood degradation of
products into adjacent
brain parenchyma
Small leptomeningeal
hemosiderin deposit
(GRE/T2* or SWI)
Blood degradation of
products into
subarachnoid space
PeerView.com
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Characterizing ARIA Radiographic Severity’
ARIA MRI Classification Criteria
Radiographic Severity
ARIA Type
Moderate
FLAIR hyperintensity measures
FLAIR hyperintensity FLAIR hyperintensity 5-10 cm, — >10 cm, often with significant
ARIA-E confined to sulcus and/or or more than one site ‘subcortical white matter
cortex/subcortical white of involvement, each and/or sulcal involvement;
matter in one location <5 cm measuring <10 cm 21 separate sites of
involvement might be noted
ARIA-H 4 new incident 5-9 new incident 210 new incident
microhemorrhage microhemorrhages microhemorrhages microhemorrhages
ARIA-H superficial One focal area Two focal areas >2 focal areas
siderosis of superficial siderosis* of superficial siderosis® of superficial siderosis®
+ 1 donanemab prescrbing nomaton, regen Indng 1 12.072 naw or worzenng focal areas of sporti sero aro graded mid, moderate, and savre, rospocivoy
1 Adel fadieanumad) Prosi intoraton. tps rw ccessdat ta gowanogatsa,cocslabel 2029/76 178501 A pa
2 Legen fecanemab) Presertngifomaton ps wa acceswata da govigrugetida Jocafabel2023/7612800rg1s00 1 fs
3.Kisunla (donanemab) Prescbig Information. tos ly convusksunla epi pdf PeerView.com
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ARIA MRI Classification Criteria
Radiographic Severity
ARIA Type
Moderate
FLAIR hyperintensity measures
FLAIR hyperintensity FLAIR hyperintensity 5-10 cm, — >10 cm, often with significant
ARIA-E confined to sulcus and/or or more than one site ‘subcortical white matter
cortex/subcortical white of involvement, each and/or sulcal involvement;
matter in one location <5 cm measuring <10 cm 21 separate sites of
involvement might be noted
ARIA-H 4 new incident 5-9 new incident 210 new incident
microhemorrhage microhemorrhages microhemorrhages microhemorrhages
ARIA-H superficial One focal area Two focal areas >2 focal areas
siderosis of superficial siderosis* of superficial siderosis® of superficial siderosis®
+ 1 donanemab prescrbing nomaton, regen Indng 1 12.072 naw or worzenng focal areas of sporti sero aro graded mid, moderate, and savre, rospocivoy
1 Adel fadieanumad) Prosi intoraton. tps rw ccessdat ta gowanogatsa,cocslabel 2029/76 178501 A pa
2 Legen fecanemab) Presertngifomaton ps wa acceswata da govigrugetida Jocafabel2023/7612800rg1s00 1 fs
3.Kisunla (donanemab) Prescbig Information. tos ly convusksunla epi pdf PeerView.com
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ARIA Management Algorithm!-
Basoline MRI has no exclusion factors
MRI routine or conducted because of symptoms sugge
of ARIA
‘ARIE or ARIA-H detected
‘Symptomatic Asymptomatic
‘Suspend treatment; clinical assessment;
peat MRI monthly
Radlographically
moderatelsovere ARIA-E
or moderateisevere ARIA-H
|
‘Stop ATT for any of the following
Radiographically mild ARIA-E
y mild ARIA-H
MRI shows resolution of ARIA-E or.
stabilization of ARIA-H; symptoms
resolve; patient wishes to continue
Continue treatment with
ATT; monthly MRI
Continue treatment
discontinue monthly MRI
WARIA- resolves or
ARIA-H stabilizes
Resume treatment with ATT
+ Any macrohemonhage
+ >1 area of superficial siderosis
+ >10 microhemorthages since treatment tion
+ >2 episodes of ARIA
+ Sovere symptoms of ARIA
+ Patent requires treatment wäh an anticoagulant
1.Cummings Je a. Prev Alzheimer Ds. 2023:10:02:97.2. Cummings Jet al J Prov Alzheimers Dis, 2022:2221.230. :
3: Cummings Jot al. J Prev Alzheimers Dis. 2021 4:398-410. PeerView.com
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Basoline MRI has no exclusion factors
MRI routine or conducted because of symptoms sugge
of ARIA
‘ARIE or ARIA-H detected
‘Symptomatic Asymptomatic
‘Suspend treatment; clinical assessment;
peat MRI monthly
Radlographically
moderatelsovere ARIA-E
or moderateisevere ARIA-H
|
‘Stop ATT for any of the following
Radiographically mild ARIA-E
y mild ARIA-H
MRI shows resolution of ARIA-E or.
stabilization of ARIA-H; symptoms
resolve; patient wishes to continue
Continue treatment with
ATT; monthly MRI
Continue treatment
discontinue monthly MRI
WARIA- resolves or
ARIA-H stabilizes
Resume treatment with ATT
+ Any macrohemonhage
+ >1 area of superficial siderosis
+ >10 microhemorthages since treatment tion
+ >2 episodes of ARIA
+ Sovere symptoms of ARIA
+ Patent requires treatment wäh an anticoagulant
1.Cummings Je a. Prev Alzheimer Ds. 2023:10:02:97.2. Cummings Jet al J Prov Alzheimers Dis, 2022:2221.230. :
3: Cummings Jot al. J Prev Alzheimers Dis. 2021 4:398-410. PeerView.com
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Resuming Treatment After Resolution of ARIA‘
ARIA symptoms and radiographic ARIA-E changes
must resolve before considering restarting ATT
Decision to resume therapy should be based on a discussion of risks and
benefits with the patient and care partners, as ARIA can reoccur
Further considerations regarding ARIA management and whether to resume
treatment include: the severity of the radiographic changes, presence and
severity of any symptoms, patient’s APOE genotype,
comorbidities, and concurrent medications
1. Cummings J etal. J Prev Alzhoimors Dis. 2023:10-362-377, PeerView.com
Copyright © 2000-2024, PeerView
ARIA symptoms and radiographic ARIA-E changes
must resolve before considering restarting ATT
Decision to resume therapy should be based on a discussion of risks and
benefits with the patient and care partners, as ARIA can reoccur
Further considerations regarding ARIA management and whether to resume
treatment include: the severity of the radiographic changes, presence and
severity of any symptoms, patient’s APOE genotype,
comorbidities, and concurrent medications
1. Cummings J etal. J Prev Alzhoimors Dis. 2023:10-362-377, PeerView.com
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Management of Severe Neurological Symptoms
in Patients Being Treated With an ATT1-3
+ Severe focal symptoms in patients receiving ATTs should always trigger an urgent MRI
to look for ARIA
+ Decide whether symptoms can be managed in outpatient setting vs ED
- Weigh the risks and benefits of sending patient to ED
Benefits of Risks of ED
+ Could receive a CTA scan instead
+ Immediate evaluation to determine cause of an MRI
of symptoms + Could be misdiagnosed with stroke and
+ Higher level of care get treated with a thrombolytic, which
can be deadly
1. Cummings J eta. J Prev Alzheimers Dis. 2025:10:362:377. 2. Cummings J etal. J Prev Alzheimers Dis, 2022,2221.230 5
8. Cummings Jot a J Prov lcheimers Di. 2021:4:398-410. PeerView.com
Copyright © 2000-2024,
in Patients Being Treated With an ATT1-3
+ Severe focal symptoms in patients receiving ATTs should always trigger an urgent MRI
to look for ARIA
+ Decide whether symptoms can be managed in outpatient setting vs ED
- Weigh the risks and benefits of sending patient to ED
Benefits of Risks of ED
+ Could receive a CTA scan instead
+ Immediate evaluation to determine cause of an MRI
of symptoms + Could be misdiagnosed with stroke and
+ Higher level of care get treated with a thrombolytic, which
can be deadly
1. Cummings J eta. J Prev Alzheimers Dis. 2025:10:362:377. 2. Cummings J etal. J Prev Alzheimers Dis, 2022,2221.230 5
8. Cummings Jot a J Prov lcheimers Di. 2021:4:398-410. PeerView.com
Copyright © 2000-2024,
Key Information to Convey to the ED Prior to Arrival
The ED team needs to know the following details about the patient
and ARIA
+ Patient is being treated with an ATT for early-stage AD
+ The main adverse event with this treatment is ARIA, which can present with
stroke-like features
+ ARIA can also present with focal signs including seizures
+ Avoid tPA in patients being treated with ATTs, because it can cause
deadly hemorrhage in patients with ARIA
+ An early MRI with FLAIR, T2* GRE or SWI, and DWI sequences should be
performed for differential diagnosis
+ CT scans cannot adequately detect mild or moderate ARIA
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The ED team needs to know the following details about the patient
and ARIA
+ Patient is being treated with an ATT for early-stage AD
+ The main adverse event with this treatment is ARIA, which can present with
stroke-like features
+ ARIA can also present with focal signs including seizures
+ Avoid tPA in patients being treated with ATTs, because it can cause
deadly hemorrhage in patients with ARIA
+ An early MRI with FLAIR, T2* GRE or SWI, and DWI sequences should be
performed for differential diagnosis
+ CT scans cannot adequately detect mild or moderate ARIA
PeerView.com
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Provide Patient Wallet Card
sun epa aqua
ey uen Gauss
uo Sis es one apr
M tos] yes HA stan ut et
OO NDS 0 see es (a a Pete EY
“yay sones
‘bey pays pete ex pian vou na arpa
“peje apa anios AIS wm paunneree
ses wojny SUR poke 1 erp A
For Healthcare Professionals:
In Case of Emergency
Name:
Date of Bi
am current being treated with an amylid-targting
insen treatment ed — nn
cut
Foé
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PeerView.com/JNE827 Copyright © 2000-2024, PeerView
sun epa aqua
ey uen Gauss
uo Sis es one apr
M tos] yes HA stan ut et
OO NDS 0 see es (a a Pete EY
“yay sones
‘bey pays pete ex pian vou na arpa
“peje apa anios AIS wm paunneree
ses wojny SUR poke 1 erp A
For Healthcare Professionals:
In Case of Emergency
Name:
Date of Bi
am current being treated with an amylid-targting
insen treatment ed — nn
cut
Foé
PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Al-Based Quantitative Tools to Manage ARIA!
Sample ARIA-E and ARIA-H Al-Based Screening Reports
+ Several Al algorithms are in
development and under FDA review
that can assist in ARIA detection,
severity assessment, and
longitudinal tracking
— icobrain aria
— NeuroQuant ARIA
CPT III billing codes 0865T and
0866T for MRI brain scan
quantification have recently become
available, making it easier to get
reimbursed for these evaluations
4. Bash 8, Tanenbaum LN. App! Radio 2028:52:16:23, PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Sample ARIA-E and ARIA-H Al-Based Screening Reports
+ Several Al algorithms are in
development and under FDA review
that can assist in ARIA detection,
severity assessment, and
longitudinal tracking
— icobrain aria
— NeuroQuant ARIA
CPT III billing codes 0865T and
0866T for MRI brain scan
quantification have recently become
available, making it easier to get
reimbursed for these evaluations
4. Bash 8, Tanenbaum LN. App! Radio 2028:52:16:23, PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Case Discussion
Stephen Salloway, MD, MS
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of
Brown University
Associate Director of the Brown Center for
Alzheimer's Research
Providence, Rhode Island
\
Sharon J. Sha, MD, MS
Clinical Professor
Chief, Memory Disorders Division
Associate Vice Chair, Clinical Research
Neurology and Neurological Sciences
Stanford Center for Memory Disorders
Palo Alto, California
Copyright © 2001 , PeerView
Stephen Salloway, MD, MS
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of
Brown University
Associate Director of the Brown Center for
Alzheimer's Research
Providence, Rhode Island
\
Sharon J. Sha, MD, MS
Clinical Professor
Chief, Memory Disorders Division
Associate Vice Chair, Clinical Research
Neurology and Neurological Sciences
Stanford Center for Memory Disorders
Palo Alto, California
Copyright © 2001 , PeerView
re Patient Case: Derrick
86-year-old man FLAIR (baseline) SWI (baseline)
Mild Alzheimer's
disease dementia
MMSE = 25/30
CDR 0.5
Plasma amyloid
positive
APOE e3/€3
On antiplatelet therapy
No MRI exclusions
Unpubishod case, courtesy of Tammie LS. Benzing, MD, PhD. PeerView.com
m/JNEB27 Copyright © 2000-2024, PeerView
86-year-old man FLAIR (baseline) SWI (baseline)
Mild Alzheimer's
disease dementia
MMSE = 25/30
CDR 0.5
Plasma amyloid
positive
APOE e3/€3
On antiplatelet therapy
No MRI exclusions
Unpubishod case, courtesy of Tammie LS. Benzing, MD, PhD. PeerView.com
m/JNEB27 Copyright © 2000-2024, PeerView
Derrick (Cont’d)
86-year-old male patient with early dementia due to AD, APOE e3/e3
Weigh the risks and benefits of treatment for this patient
+ His AD was caught early, with mild symptoms; treatment may be more effective when it's
taken at this early stage in the disease course
Although the patients APOE genotype puts him at lower risk for ARIA and
symptomatic ARIA, there is a risk for all patients
= Will need to monitor him very closely with MRI scans
— Explain that ARIA is more likely to occur early in the course of treatment
— He will need to be vigilant about any symptoms of ARIA that may arise, and
immediately contact his physician about potential ARIA symptoms
+ Antiplatelet therapy is not a contraindication
PeerView.com
Unpubishod coso, courtesy of Tammie LS. Benzing, MD, PhD.
PeerView.com/JNES27 Copyright © 2000-2024, Peerview
86-year-old male patient with early dementia due to AD, APOE e3/e3
Weigh the risks and benefits of treatment for this patient
+ His AD was caught early, with mild symptoms; treatment may be more effective when it's
taken at this early stage in the disease course
Although the patients APOE genotype puts him at lower risk for ARIA and
symptomatic ARIA, there is a risk for all patients
= Will need to monitor him very closely with MRI scans
— Explain that ARIA is more likely to occur early in the course of treatment
— He will need to be vigilant about any symptoms of ARIA that may arise, and
immediately contact his physician about potential ARIA symptoms
+ Antiplatelet therapy is not a contraindication
PeerView.com
Unpubishod coso, courtesy of Tammie LS. Benzing, MD, PhD.
PeerView.com/JNES27 Copyright © 2000-2024, Peerview
Derrick (Cont'd)
FLAIR (baseline),
86-year-old male patient with MCI due
to AD, APOE e3/£3,
initiated treatment with lecanemab
+ Radiographic
— Moderate ARIA-E (two areas [left
and right occipital], <5 cm)
SWI(baseline)
— Mild ARIA-H MCH (one new MCH)
+ Symptoms
— Upon questioning, reports some
dizziness and recently fell off a chair
Unpubishod caso, courtesy of Tammie LS. Benzing, MD, PhD.
FLAIR (pre-inf #5)
#
>
\ SAME)
rView.com
Copyright © 2000-2024, PeerView
FLAIR (baseline),
86-year-old male patient with MCI due
to AD, APOE e3/£3,
initiated treatment with lecanemab
+ Radiographic
— Moderate ARIA-E (two areas [left
and right occipital], <5 cm)
SWI(baseline)
— Mild ARIA-H MCH (one new MCH)
+ Symptoms
— Upon questioning, reports some
dizziness and recently fell off a chair
Unpubishod caso, courtesy of Tammie LS. Benzing, MD, PhD.
FLAIR (pre-inf #5)
#
>
\ SAME)
rView.com
Copyright © 2000-2024, PeerView
Derrick (Cont'd)
Dose was held
Follow-up MRI shows
resolution of ARIA-E,
no new ARIA-H
Symptoms resolved
Treatment resumed
Unpubishod coso, courtesy of Tammie LS. Benzing, MD, PhD.
FLAIR (baelingy FLAIR (pre-inf #5)
À
e
SWI(baseline) %, SWIXBRESIAF#S)
rView.com
Copyright © 2000-2024, PeerView
Dose was held
Follow-up MRI shows
resolution of ARIA-E,
no new ARIA-H
Symptoms resolved
Treatment resumed
Unpubishod coso, courtesy of Tammie LS. Benzing, MD, PhD.
FLAIR (baelingy FLAIR (pre-inf #5)
À
e
SWI(baseline) %, SWIXBRESIAF#S)
rView.com
Copyright © 2000-2024, PeerView
Derrick Conclusion
+ Shared decision was made to resume ATT after the resolution of the
ARIA-E and dizziness
+ Factors that influenced this decision included
— Patients small number of microbleeds (1)
— His APOE e3/£3 genotype
— Patient and family's desire to continue
Unpublshed cose, courtesy of Tammie LS. Benzinger, MD, PhD. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
+ Shared decision was made to resume ATT after the resolution of the
ARIA-E and dizziness
+ Factors that influenced this decision included
— Patients small number of microbleeds (1)
— His APOE e3/£3 genotype
— Patient and family's desire to continue
Unpublshed cose, courtesy of Tammie LS. Benzinger, MD, PhD. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Patient Case: Amanda
61-year-old woman
Mild early-onset
dementia
MMSE = 24/30
CDR 0.5
CSF Amyloid +
APOE ¢4/e4
Strong family history
of AD
No medical exclusions
Unpubishod coso, courtesy of Tammie LS. Benzinge, MD, PhD. PeerView.com
om/JNE827 Copyright © 200
61-year-old woman
Mild early-onset
dementia
MMSE = 24/30
CDR 0.5
CSF Amyloid +
APOE ¢4/e4
Strong family history
of AD
No medical exclusions
Unpubishod coso, courtesy of Tammie LS. Benzinge, MD, PhD. PeerView.com
om/JNE827 Copyright © 200
Amanda (Cont’d)
GRE T2*
Unpubishod coso, courtesy of Tammie LS. Benzinge, MD, PhD. eerView.com
Copyright © 2000-2024, PeerView
GRE T2*
Unpubishod coso, courtesy of Tammie LS. Benzinge, MD, PhD. eerView.com
Copyright © 2000-2024, PeerView
Amanda (Cont’d)
61-year-old female patient with early-onset mild AD dementia, APOE ¢4/e4
This was a relatively young patient who had witnessed several family members succumb to AD, and she
was highly motivated to start treatment that may slow the rate of cognitive and functional decline
What are the key points to discuss with this patient about ATTs?
+ Weigh the potential benefits of treatment against the risk of developing ARIA, based on the specific
circumstances of each patient
Her APOE genotype greatly increased her risk for ARIA, as well as symptomatic ARIA;
discussed the potential risks associated with severe ARIA
Explained that early detection is key to minimizing harm from ARIA; she will need to be
monitored very closely with MRI scans to detect asymptomatic ARIA.
She will also need to be vigilant about any symptoms of ARIA that may arise, and immediately
contact her physician about potential ARIA symptoms
Unpubishod caso, courtesy of Tammie LS. Benzing, MD, PhD. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, Peerview
61-year-old female patient with early-onset mild AD dementia, APOE ¢4/e4
This was a relatively young patient who had witnessed several family members succumb to AD, and she
was highly motivated to start treatment that may slow the rate of cognitive and functional decline
What are the key points to discuss with this patient about ATTs?
+ Weigh the potential benefits of treatment against the risk of developing ARIA, based on the specific
circumstances of each patient
Her APOE genotype greatly increased her risk for ARIA, as well as symptomatic ARIA;
discussed the potential risks associated with severe ARIA
Explained that early detection is key to minimizing harm from ARIA; she will need to be
monitored very closely with MRI scans to detect asymptomatic ARIA.
She will also need to be vigilant about any symptoms of ARIA that may arise, and immediately
contact her physician about potential ARIA symptoms
Unpubishod caso, courtesy of Tammie LS. Benzing, MD, PhD. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, Peerview
Amanda (Cont’d)
What are the key points to discuss with this patient about ATTs? (cont'd)
+ Selecting the right ATT based on the specific circumstances of each patient
= This patient lives 2 hours away from the nearest infusion center, so the dosing schedule of the
treatment is a factor to consider
— The possibility of stopping treatment based on amyloid clearance that is verified with an amyloid
PET scan should also be discussed with the patient
+ The patient preferred the dosing schedule of donanemab (once-a-month vs twice-a-month infusions),
and she also wanted to have the option of stopping treatment if her amyloid plaques reduced to
minimal levels
An amyloid PET was ordered to have a baseline scan that could be compared to later scans while on
treatment
Unpubishod caso, courtesy of Tammie LS. Benzing, MD, PhD. PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
What are the key points to discuss with this patient about ATTs? (cont'd)
+ Selecting the right ATT based on the specific circumstances of each patient
= This patient lives 2 hours away from the nearest infusion center, so the dosing schedule of the
treatment is a factor to consider
— The possibility of stopping treatment based on amyloid clearance that is verified with an amyloid
PET scan should also be discussed with the patient
+ The patient preferred the dosing schedule of donanemab (once-a-month vs twice-a-month infusions),
and she also wanted to have the option of stopping treatment if her amyloid plaques reduced to
minimal levels
An amyloid PET was ordered to have a baseline scan that could be compared to later scans while on
treatment
Unpubishod caso, courtesy of Tammie LS. Benzing, MD, PhD. PeerView.com
PeerView.com/JNE827 Copyright © 2000-2024, PeerView
Amanda (Cont’d)
+ Amyloid PET was performed and analyzed using MIM, an FDA-approved quantitative tool
for amyloid PET
+ The patients Centiloid score was 50 (positive); the tracer was florbetapir
The patient
initiated treatment
with donanemab
Unpublshod caso, courtesy of Tammie LS. Benzing, MD, PhD. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
+ Amyloid PET was performed and analyzed using MIM, an FDA-approved quantitative tool
for amyloid PET
+ The patients Centiloid score was 50 (positive); the tracer was florbetapir
The patient
initiated treatment
with donanemab
Unpublshod caso, courtesy of Tammie LS. Benzing, MD, PhD. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Amanda Discussion
+ When should a patient being treated Percentage of Donanemab-Treated
with donanemab get an amyloid PET Patients That Achieved
to evaluate treatment response? Amyloid Clearance
Week 24 Week 52
If the patient achieves amyloid
clearance, how would you modify
their treatment regimen?
— Stop treatment?
— Extend the dosing interval?
— Something else?
29.7% 66.1%
Unpublshed case, courtesy of Tammie 8. Benzinger, MD, PRO. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
+ When should a patient being treated Percentage of Donanemab-Treated
with donanemab get an amyloid PET Patients That Achieved
to evaluate treatment response? Amyloid Clearance
Week 24 Week 52
If the patient achieves amyloid
clearance, how would you modify
their treatment regimen?
— Stop treatment?
— Extend the dosing interval?
— Something else?
29.7% 66.1%
Unpublshed case, courtesy of Tammie 8. Benzinger, MD, PRO. PeerView.com
PeerView.com/JNES27 Copyright © 2000-2024, PeerView
Conclusions
Stephen Salloway, MD, MS
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of Brown University
Associate Director of the Brown Center for Alzheimer’s Research
Providence, Rhode Island
Copyright © 200
Stephen Salloway, MD, MS
Professor, Psychiatry and Human Behavior
Professor of Neurology, Alpert Medical School of Brown University
Associate Director of the Brown Center for Alzheimer’s Research
Providence, Rhode Island
Copyright © 200
Key Takeaways
+ With multiple approved DMTs for AD, it has never been
more important to detect and diagnose AD early in the
disease course
+ Amyloid PET and CSF tests are both FDA approved and
reimbursed by Medicare
+» Reliability and accuracy of plasma biomarkers are rapidly
improving and some may be ready for prime time
+ ATTs are an exciting advancement in care for patients
with AD
+ Many complexities involved in selecting the right patients
for treatment and delivering ATTs safely and effectively
+ Incorporation of ATTs into clinical practice requires a team
approach (involving multiple specialties and professions)
+ Shared decision-making needs to include realistic
treatment expectations
+ Safety monitoring and appropriate management is critical
to successful utilization of these new therapies
PeerView.com/JNES27
Please make sure
to visit the Virtual
Training Center at
PACE-ALZ.com
and share the
resources with
your colleagues
For more information
about the CDC Training
of Trainers Model, visit
https://www.cde.gov/he
althyschools/tths/train_
trainers_model.htm
PeerView.com
Copyright © 2000-2024, Peerview
+ With multiple approved DMTs for AD, it has never been
more important to detect and diagnose AD early in the
disease course
+ Amyloid PET and CSF tests are both FDA approved and
reimbursed by Medicare
+» Reliability and accuracy of plasma biomarkers are rapidly
improving and some may be ready for prime time
+ ATTs are an exciting advancement in care for patients
with AD
+ Many complexities involved in selecting the right patients
for treatment and delivering ATTs safely and effectively
+ Incorporation of ATTs into clinical practice requires a team
approach (involving multiple specialties and professions)
+ Shared decision-making needs to include realistic
treatment expectations
+ Safety monitoring and appropriate management is critical
to successful utilization of these new therapies
PeerView.com/JNES27
Please make sure
to visit the Virtual
Training Center at
PACE-ALZ.com
and share the
resources with
your colleagues
For more information
about the CDC Training
of Trainers Model, visit
https://www.cde.gov/he
althyschools/tths/train_
trainers_model.htm
PeerView.com
Copyright © 2000-2024, Peerview
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