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Received: 1 November 2023 Revised: 7 February 2024 Accepted: 9 February 2024
DOI: 10.1002/alz.13778
PERSPECTIVE
Adapting prescribing criteria for amyloid-targeted antibodies
for adults with Down syndrome
Hampus Hillerstrom1Richard Fisher1Matthew P. Janicki2,3Brian Chicoine4
Bradley T. Christian5Anna Esbensen6Lucille Esralew7Juan Fortea8,9
Sigan Hartley5Jason Hassenstab10 Seth M. Keller3,11 Sharon Krinsky-McHale12
Florence Lai13 Johannes Levin14,15 Mary McCarron16 Eric McDade10
Anne Sophie Rebillat17 Herminia Diana Rosas13,18 Wayne Silverman19
Andre Strydom20 Shahid H. Zaman21 Henrik Zetterberg22,23,24
1LuMind IDSC Foundation, Burlington, Massachusetts, USA
2Department of Disability and Human Development, University of Illinois Chicago, Chicago, Illinois, USA
3National Task Group on Intellectual Disabilities and Dementia Practices, Rockport, Maine, USA
4Advocate Health, Advocate Medical Group Adult Down Syndrome Center, Advocate Lutheran GeneralHospital Family Medicine Residency, Park Ridge, Illinois, USA
5Waisman Center IDDRC, University of Wisconsin, Madison, Wisconsin, USA
6Division of Developmental and Behavioral Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati
Children’s Hospital, Cincinnati, Ohio, USA
7California Department of Developmental Services, Sacramento, California, USA
8Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
9Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
10Departments of Neurology and Psychological & Brain Sciences, Knight Alzheimer Disease Research Center, Washington University, St. Louis, Missouri, USA
11Neurology Associates of South Jersey, Lumberton, New Jersey, USA
12Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Island, New York, USA
13MGH Neurology Research, Mass General Brigham Hospital, Massachusetts General Hospital, Boston, Massachusetts, USA
14Department of Neurology & German Center of Neurodegenerative Diseases (DZNE) e.V., Ludwig-Maximilians University, Munich, Germany
15Department of Neurology, Sahgrenska University Hospital, Mölndal, Sweden
16Trinity Centre for Ageing and Intellectual Disability, TrinityCollege, University of Dublin, Dublin, Ireland
17Outpatient Department, Institut Jerome Lejeune, Paris, France
18Department of Radiology, Athinoula Martinos Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA
19Department of Pediatrics, University of California Irvine, Irvine, California, USA
20Institute of Psychiatry, Psychology and Neuroscience, Kings College, London, UK
21Department of Psychiatry, Cambridge Intellectual and Developmental Disabilities Research Group, Cambridge University, Cambridge, UK
22Institute for Stroke and Dementia Research, Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden
23Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, Sweden
24Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided
the original work is properly cited.
© 2024 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Alzheimer’s Dement. 2024;20:3649–3656. wileyonlinelibrary.com/journal/alz 3649
3650 HILLERSTROM ET AL.
Correspondence
Matthew P. Janicki, Ph.D., PO Box 862,
Rockport, ME 04856, USA.
Email: janickimp@gmail.com
Funding information
Centers for Disease Control and Prevention;
National Center for Chronic Disease
Prevention and Health Promotion; Healthy
Brain Initiative, Grant/Award Numbers:
NU58DP006782-01-00, U19 AG068054;
National Institutes of Health
Abstract
Prior authorization criteria for Federal Drug Administration (FDA) approved
immunotherapeutics, among the class of anti-amyloid monoclonal antibodies (mAbs),
established by state drug formulary committees, are tailored for adults with late-onset
Alzheimer’s disease. This overlooks adults with Down syndrome (DS), who often expe-
rience dementia at a younger age and with different diagnostic assessment outcomes.
This exclusion may deny DS adults access to potential disease-modifying treatments.
To address this issue, an international expert panel convened to establish adaptations
of prescribing criteria suitable for DS patients and parameters for access to Centers
for Medicare & Medicaid Services (CMS) registries. The panel proposed mitigating
disparities by modifying CMS and payer criteria to account for younger onset age,
using alternative language and assessment instruments validated for cognitive decline
in the DS population. The panel also recommended enhancing prescribing clinicians’
diagnostic capabilities for DS and initiated awareness-raising activities within health-
care organizations. These efforts facilitated discussions with federal officials, aimed
at achieving equity in access to anti-amyloid immunotherapeutics, with implications
for national authorities worldwide evaluating these and other new disease-modifying
therapeutics for Alzheimer’s disease.
KEYWORDS
Alzheimer’s disease, anti-amyloid immunotherapeutics, dementia, Down syndrome, drug formu-
laries, prescribing criteria
1INTRODUCTION
Adults with Down syndrome (DS) have a genetic predisposition to
early onset brain amyloid deposition and face a cumulative lifetime
risk of approximately 90% for DS-associated Alzheimer’s disease (DS-
AD). Risk for exhibiting clinical symptoms of DS-AD increases prior
to age 60,1,2 contributing to 70% to 80% of deaths in adults with
DS.3,4 Adults with DS are the largest population with an increased
risk for Alzheimer’s disease (AD) associated with a specific genotype,
as an extra copy of the gene coding for amyloid precursor protein
(APP) located on chromosome 21 leads to its overproduction and con-
sequent atypical deposition of amyloid beta (Aβ).5,6 Adults with DS
typically show Aβplaque buildup by their fourth decade of life, initi-
ating the cascade of AD neuropathology some 15 to 20 years earlier
than is typical for sporadic or late-onset AD (LOAD).2,7,8 Therefore,
there is a compelling case for this high-risk population to have equi-
table and timely access to new anti-amyloid monoclonal antibodies
(mAbs), which are considered disease-modifying therapies (DMTs) that
slow AD progression.9,10
Current prior authorization criteria for the use of anti-amyloid
mAbs, as established by drug formulary committees in the United
States, have focused on LOAD in its early stages,11,12 and therefore,
some of the recommended criteria for prescribing these agents would
effectively bar adults with DS-AD from having access to these inno-
vative treatments. To address this issue, it is necessary to adapt the
current inclusionary prior authorization criteria as follows: (1) mod-
ify the current age criteria in recognition of average onset of DS-AD
at a younger age compared to LOAD; (2) remove exclusions for adults
with pre-existing lifelong cognitive impairments; (3) allow for diag-
nostic findings based on neurocognitive and behavioral assessments
validated for measuring cognitive and functional decline for adults with
DS and other comparable developmental disorders; and (4) address
inappropriate contraindications for co-occurring conditions in adults
with DS-AD, if safety is not affected.
Drug formulary committees have the primary objective of over-
seeing and designating preferred drugs to guide rational prescrib-
ing practices.13 State drug formulary committees have assumed the
responsibility of selecting precise wording and criteria for Leqembi and
any other anti-amyloid antibodies that gain approval, derived from lan-
guage from the Food and Drug Administration (FDA) approval label
that defines clinical trial patient inclusion criteria. These state commit-
tees determine the eligibility for anti-amyloid mAbs treatment through
so-called prior authorization prescribing criteria, which vary among
individual states in defining the eligible LOAD population. These crite-
ria consider factors such as age, exclusionof non-Alzheimer’s dementia,
demonstrated cognitive decline or impairment caused by mild cogni-
tive impairment or mild AD, and biomarker indicators for the presence
of amyloid plaques (see Appendix C in Hillerstrom et al. 14). Addition-
ally, there are variations among states in the applications and provi-
sions for use, only some of which allow for the inclusion and assessment
of individuals with a history of intellectual disability (ID), including
adults with DS. In fact, some state prior authorization prescribing
HILLERSTROM ET AL.3651
criteria specifically exclude individuals with DS due to their pre-
existing cognitive impairments (see Appendix C in Hillerstrom et al.14).
Most state drug formulary committees’ prescribing criteria refer-
ence specific assessments for identifying cognitive impairment in the
sporadic AD population. However, these assessments are not suit-
able for quantifying cognitive decline in the presence of pre-existing
intellectual impairments, highlighting the need for alternative meth-
ods specifically tailored for adults with DS.12 The typical process for
assessing adults with DS and other people with ID entails gather-
ing information from both adults with DS or ID and their caregivers
regarding physical and mental health, determining overall adaptive
functioning, and utilizing a range of directly administered neuropsy-
chological tests that assess memory and other domains of cognition
and signs of cognitive decline.15 Furthermore, state prescribing guides
direct physicians to adhere to protocols for conducting comprehen-
sive clinical workups and medication reviews to identify and rule out
alternative or treatable causes for cognitive decline. Since many adults
with DS may have co-occurring conditions that havebeen present since
childhood,16 monitoring these conditions for any potential adverse
effects on behavior and/or function is crucial.
Obtaining magnetic resonance imaging (MRI) and positron emis-
sion tomography (PET) scans or collection of cerebral spinal fluid (CSF)
to meet brain imaging and fluid biomarker AD diagnostic criteria,
respectively, in adults with DS can be challenging under the best of
circumstances, but it is feasible for specialized clinics or by clinicians
highly familiar with this population and depending on the patient’s level
of tolerance. Given the extremely high likelihood of early-age amyloid
neuropathology in adults with DS,1,7 consideration should be given to
empirically supported alternatives that can be more easily obtained,
such as validated blood biomarkers.17,18
Given the high risk for AD-mediated early-onset dementia in adults
with DS and the potential therapeutic value of anti-amyloid DMTs,
the Working Group on Criteria for Access to Alzheimer’s Therapeu-
tics for Adults with Down Syndrome (“Working Group”) determined
that there was an urgent need to adapt and enact reasonable accom-
modations to the current prescribing criteria, while at the same
time ensuring that safety risks are managed, consistent with best
clinical practice guidelines. While similar concerns have been raised
for sporadic AD,19 this effort is focused on adaptations specific to
DS. Thus, the Working Group comprised a set of evidence-based
and evidence-informed recommendations for modifying wording in
prior authorization prescribing criteria to address this inequity. This
report, thus, is intended to (1) propose alternative inclusionary word-
ing and suggested accommodations, and (2) serve as a roadmap or
guide for prescribers when determining eligibility for adults with
DS.
2WORKING GROUP PROCESS TO GENERATE
THE ADVISORY
Under the auspices of the LuMind IDSC Foundation and the National
Task Group on Intellectual Disabilities and Dementia Practices, a
multinational working group of experts specializing in the clinical,
biomarker, and cognitive and behavioral assessment aspects of DS-
AD was convened in February 2023. The participants represented
diverse perspectives and expertise related to prescribing criteria for
assessing adults with DS-AD. Their objective was to examine the exist-
ing prescribing criteria utilized in various US states for the sporadic
AD population and to determine which criteria were applicable to
adults with DS-AD and which required additional wording or modifi-
cations. The panel also took into consideration the criteria employed
by the US Department of Veterans Affairs and the appropriate use
criteria for Leqembi.20 At the time, the FDA had given conditional
approval for Aduhelm and Leqembi; subsequently, in July 2023, the
FDA gave Leqembi traditional (full) approval.1The group’s work com-
prised four phases: defining parameters, reviewing existing criteria,
collating perspectives and comments, and reaching a consensus on
recommendations.
2.1 Derivative data
A search for available state drug formulary information resulted in the
compilation of 12 states’ criteria, considered a representative sample,
based upon geography, content, and breadth of wording. The crite-
ria of the Veterans Affairs National Formulary were also included as
the US Department of Veterans Affairs maintains its own prescribing
and insuring processes.20 Lastly, the working group considered use and
contraindication criteria in the Appropriate Use Criteria published for
Aduhelm and for Leqembi.11,12 The working group reviewed the cri-
teria based on aspect focus, language, breadth of specification, and
presence of formal exclusionary language related to DS (see Appendix
C in Hillerstrom et al.14).
2.2 Consensus
Comments and recommendations for adaptations were discussed dur-
ing several virtual meetings and via written commentary over the
course of approximately 90 days. It culminated with the issuance of
an extensive report containing an expanded advisory and consensus
statement.14
2.3 Advisory outcomes
2.3.1 Current criteria
The Working Group conducted an examination of the criteria from
12 representative state drug formulary committees to assess their
content and applicability. The categories typically encompassed in the
prescribing use criteria include (1) age, (2) prescriber qualifications,
1In January 2024, Biogen withdrew support for Aduhelm and terminated any ongoing clinical
trials.
3652 HILLERSTROM ET AL.
TAB LE 1 Recommended language modifications or additions to state prescribing criteria for Alzheimer’s disease treatment medications for
adults with Down syndrome.
Criteria Recommendations and commentary
State authorization criteria
Age Recommendation: Patient with Down syndrome may be 50 to 85 years old – or younger and
meets other criteria for early DS-AD.
Prescriber Recommendation: For patients with Down syndrome, prescriber should consult with specialist
health provider/clinician knowledgeable in DS-AD or in dementia with intellectual disability, if
feasible.
Validated MCI/mild AD diagnosis
assessment scales
Recommendation: For patients with DS, provider attestation for diagnosis of early DS-AD via
evidence of cognitive, functional, and behavioral decline from DS-appropriate assessments
and/or caregiver/informant/clinician interview reports.
Biomarkers for amyloid positivity Recommendation: For patients with DS, PET scan is positive for amyloid beta plaque indicative of
AD.
Test evidence of cognitive
impairment
Recommendation: For patients with Down syndrome, evidence of cognitive decline relative to
premorbid cognitive functioning level, as evidenced by informant-reported and directly
administered assessment measures showing poorer than expected performance.
MRI at baseline Recommendation: For patients with Down syndrome, baseline brain MRI scan to assess
amyloid-related imaging abnormalities (ARIA) prior to initiating treatment (within 1 year prior).
Exclusion of other causes of
cognitive impairment
Recommendation: Patients with Down syndrome (DS) are not to be excluded based on lifelong
DS-associated pre-existing cognitive impairment.
Abbreviations: AD, Alzheimer’s disease; DS, Down syndrome; DS-AD, Down syndrome-associated Alzheimer’s disease; MCI, mild cognitive impairment;MRI,
magnetic resonance imaging; PET, positron emission tomography.
(3) validated assessment scales for early AD diagnosis, (4) biomark-
ers indicating amyloid positivity, (5) evidence of progressive cognitive
impairment based on testing, (6) baseline MRI requirements, and
(7) exclusion of non-Alzheimer’s causes for cognitive decline. Some
states opted for a concise approach, presenting criteria in a terse,
straightforward manner, while others provided expanded descrip-
tors for improved clinical precision and measures. Consistencies were
found across many of the criteria, but variations and omissions
were also noted, pointing to a need for discussions leading to a
national consensus, perhaps spearheaded by an appropriate federal
agency.
2.3.2 Wording adaptations
The Working Group concluded that the prior authorization prescrib-
ing criteria, as defined by states, should be adapted or supplemented
to enable the inclusion of adults with DS-AD. These included seek-
ing, when feasible, guidance from clinical consultants with expertise in
diagnosing and managing dementia in adults with DS (or comparable
developmental disorders). The Working Group produced the recom-
mended wording (as shown in Tables 1and 2) for use by state drug
formulary committees when modifying or supplementing criteria to
accommodate prescribing for adults with DS-AD (or LOAD-affected
adults with histories of other developmental disorders). As many states
have suggested the age of 50 as the floor for drug recipients, the
Working Group also recommended either removing the floor age or
providing exceptions for DS-AD as some adults are diagnosed with
earlyADintheir40s.
21
3COMMENTARY
The Working Group recommends that the prior authorization pre-
scribing criteria established by states for equivalency be adjusted or
supplemented to promote equity by granting access to the emerging
class of amyloid targeting AD therapies for adults with DS-AD and pre-
venting exclusion of adults with DS. The Working Group recognizes
concerns related to safety and to better understanding the risks and
benefits of the anti-amyloid DMTs for adults with DS, but to serve
its stated primary objective, it limited its focus to drug access equity.
The need for specific attention to and adaptations for inclusion and
equity for adults with DS-AD is supported by two key factors: (1) the
well-documented high lifetime risk and early onset of DS-AD com-
pared to LOAD and (2) the potential efficacy of new mAbs for reducing
Aβaccumulation during middle age and the possibility of enhancing
both lifespan and brain health in later years. It is not expected that
all adults with DS/ID will qualify using clinical trial eligibility crite-
ria for the DMTs, analogous to the LOAD population for which only
a small proportion of potentially eligible adults qualified recently due
to exclusions.22 Such exclusions include some related to other chronic
conditions and neuroimaging findings or due to an inability to tol-
erate essential procedures such as blood draws, injections, or MRI
to monitor for the development of potential complications.22 On a
broader scale, the Working Group recommendations may also have rel-
evance to the work of the Alzheimer’s Association and National Insti-
tute for Aging’s revised diagnostic criteria for a biological definition
of AD.23,24
The Working Group’s efforts identified critical needs to adapt
and supplement state-established prior authorization prescribing
HILLERSTROM ET AL.3653
TAB LE 2 Recommended language modifications or additions to other criteria related from Department of Veterans Affairs authorization or to
Leqembi appropriate use criteria for adults with Down syndrome.
Criteria Recommendations and commentary
Thyroid levels Recommendation: For patients with DS, hypothyroidism is diagnosed and treated according
to standard of care with thyroid stimulating hormone (TSH) levels monitored.
The following are taken from additional Leqembi appropriate use criteria
BMI Recommendation: No significant difference in DS.
Care partner Recommendation: No significant difference in DS.
Understand requirements for therapy Recommendation: No significant difference in DS.
Recent history of stroke, transient ischemic
attacks, and seizures
Recommendation: For patients with DS, no significant difference of criteria for stroke or
transient ischemic attacks; however, as a history of seizures is more likely for individuals
with DS and adult-onset seizures can occur with AD progression, their presence should
not be a contraindication for treatment with immunotherapies.
Mental issues Recommendation: For patients with DS, mental health criteria are not appropriate as
contraindication for immunotherapy treatment, as severe mental illness comorbiditiesare
uncommon.
Depression Recommendation: No significant difference in DS.
Bleeding disorder Recommendation: No significant difference in DS.
Anticoagulants Recommendation: No significant difference in DS.
Immunological disease Recommendation: For patients with DS, rheumatoid arthritis, celiac disease, and alopecia
areata or totalis, should not be exclusionary in DS-AD when these conditionsare stable.
Otherwise, no significant difference in DS for the other immunological diseases referred
to in the Appropriate Use Criteria.
Medications Recommendation: No significant difference in DS.
Abbreviations: AD, Alzheimer’s disease; DS, Down syndrome; DS-AD, Down syndrome-associated Alzheimer’s disease; DVA, US Department of Veterans
Affairs.
criteria, stemming from clinical trial eligibility, to ensure fair access
to treatment for adults with DS-AD. These recommended prescribing
adjustments are aimed at not only promoting inclusion and equity but
also preventing the exclusion of individuals with DS (or other develop-
mental disorders) from accessing emerging AD therapies. The Working
Group’s primary focus was on ensuring access equity, although they
acknowledged concerns related to the safety and efficacy of DMTs for
adults with DS-AD.25
One significant challenge highlighted by the Working Group is the
scarcity of experts specializing in DS-AD in the United States, mak-
ing it difficult to find clinical consultants. To bridge this gap, the group
recommend two key actions:
1. Governmental entities and academic health sciences/medical
institutions should establish resources easily and broadly acces-
sible to prospective prescribers, providing them with sufficient
information needed to inform their diagnostic and treatment deci-
sions. These resources could be integrated with existing national,
state, and other non-profit organizations focused on public
health.
2. Non-profit organizations and professional/interdisciplinary associ-
ations associated with DS/ID and the geriatric medicine community
should develop technical resources (such as practice guidelines and
help lines). These resources could serve as alternatives to consult-
ing clinical experts related to assessing assessment scale instru-
ments or conducting clinical evaluations, particularly in regions
with limited consultants.
Additionally, given the vagaries of prescribing behaviors and
resources within the general population,26 there is a need to orga-
nize continuing education programs tailored specifically for cognitive
assessment of adults with DS (eg, via ECHO, telehealth, webinars)
and provide for the distribution of guidelines for assessing adults with
DS and cognitive decline or recognizable early dementia (eg, Moran
et al.27;Tsouetal.
28). See Hillerstrom et al.14 on activities that could
be undertaken.
Mattke et al.29 noted the general difficulties in undertaking brief
cognitive assessments (BCAs) in adults. However, even if clinicians can
effectively undertake such BCAs with adults with LOAD, they must
also be alert to the unique characteristics of DS-AD and DS cogni-
tive phenotypes. Further, prescribing clinicians need to be able to
differentiate between DS-AD-related decline and lifelong cognitive
limitations. While a small minority of adults with DS may have cog-
nitive capabilities aligning closely with average intellectual capacities,
the majority have lifelong impairments, possibly severe, complicating
recognition of changes that accompany the transition from the preclin-
ical to prodromal stage of DS-AD. Informant-reported brief screening
measures, commonly used in this population, can help caregivers eval-
uate cognition, daily functioning, and behavior, but the need for easily
administered, empirically supported direct tests with high sensitivity
3654 HILLERSTROM ET AL.
and specificity persists. The Working Group acknowledged that meth-
ods used in research focused on DS-AD, while highly effective, would
need to be streamlined for use in most clinical settings and that longi-
tudinal studies are ongoing that may validate methods that can be more
easily completed during routine patient visits.30
A pressing concern is the potential delay in adapting prior authoriza-
tion prescribing criteria for adults with DS-AD. This delays treatment
access to anti-amyloid mAb therapeutics that have already received
FDA approval and to future treatment innovations, as well as extending
lack of recognition to be enrolled in clinical trials.31 The upside of such
a delay is time gained for gathering more treatment experience and for
addressing safety issues arising from the general LOAD population32
and for new DMTs, such as a third anti-amyloid mAb, donanemab,33
pending approval.34 The Working Group also acknowledges the poten-
tial for added risks of anti-amyloid mAb-induced adverse events,
compared to the LOAD population, arising from brain edema and
microhemorrhage due to higher rates of cerebral amyloid angiopathy
in adults with DS.35 To address this additional risk factor, the Working
Group’s prescribing recommendations presuppose the establishment
of safety with anti-amyloid mAb treatments through clinical study in
the DS-AD population, as also implied by current recommended use
guidelines for approved anti-amyloid mAbs.11,12
When the Centers for Medicare & Medicaid Services (CMS)
announced its insurance coverage commitment in July 2023 for
patients prescribed fully approved anti-amyloid mAbs for early AD,36
provided these patients entered an approved registry, it created an
opportunity to engage in critical discussions with CMS officials. These
conversations aimed to secure accommodations within the CMS-
approved registries for adults with DS and to verify eligibility for
coverage under Medicare and Medicaid. As previously noted,19 the
current registry structure has limits, as it may have insufficient robust-
ness to permit “a comprehensive analysis of the benefits and harms of
drugs in the diverse population of Medicare beneficiaries with comor-
bidities, disabilities, and who are from demographic categories not
adequately represented in clinical trials.” Further, the authors recog-
nized that there are “multiple cognitive, function, and amyloid test
options, and every effort should be made to standardize outcome data.”
Thus, our effort has been directed at adding a DS-AD pull-down option
for dementia type and introducing standardization in the test options
relevant to adults with DS. This is the direct result of the Working
Group’s translation of recommendations into practical solutions that
would produce equitable access for individuals with DS-AD to essen-
tial therapies after safety issues are addressed, as described above for
anti-amyloid mAbs.
Considering the acknowledgement from CMS of coverage for AD
DMTs for patients eligible for Medicare/Medicaid, we propose that
state drug formulary committees should revise their prescribing lan-
guage to be more inclusive and that CMS-approved registries incorpo-
rate applicable instruments for use with patients with DS-AD. CMS has
acknowledged that current coverage policy does not prohibit adults
with DS-AD from accessing approved DMTs.37 Consequently, as some
adults with DS-AD will seek access to approved DMTs and be entered
into CMS-approved registries prior to a complete understanding of the
safety and efficacy for this specific population,37,25 registries should
include in their collected data the impact of each specific drug on cog-
nitive improvement and adverse events.19 Upon request from CMS,
the Working Group is currently engaged in recommending DS-specific
instruments as equivalents for the CMS approved registries.
Overall, the efforts of the Working Group led to extensive outreach
to various stakeholders on the imperative of achievingequitable access
to new AD therapies, coupled with the necessary language modifica-
tions to move that equity toward a reality. This multifaceted outreach
strategy encompassed a series of informational sessions and meetings
that brought together an array of influential entities and stakeholders.
These included the federal Advisory Council on Alzheimer’s Research,
Care, and Supports, which is responsible for developing the National
Plan to Address Alzheimer’s Disease,38 and an “in conjunction with”
meeting held at the 2023 Conference of the American Academy of
Neurology.39 The engagement also extended to prominent federal
agencies such as the National Institutes for Health, the National Insti-
tute on Aging, the Administration on Community Living, FDA, and
CMS, fostering a collaborative environment to align policies and prac-
tices with the project’s goals. Simultaneously, efforts were undertaken
with stakeholder organizations, such as the National Association of
Medicaid Directors, the National Association of State Directors of
Developmental Disability Services, the Alzheimer’s Association, the
LEAD Coalition, and others, to amplify the reach and impact of the
advocacy efforts.
Additionally, the process undertaken by the Working Group to
address language and criteria modifications in the United States may
offer valuable insights for other countries as jurisdictions approve
anti-amyloid mAbs use.40,41,42,43 Since drug approval and prescribing
criteria decisions often occur at the national level, the Working Group’s
experience can serve as a model for advocating for equity in access
within other countries,44 especially through advocacy by intellectual
disability or DS advocacy organizations.45 Its recommendations and
insights can also serve as a valuable resource for policymakers, health-
care providers, and advocates working toward improving the quality of
care and life for this at-risk population.
ACKNOWLEDGMENTS
This project was underwritten by the LuMind IDSC Foundation (www.
lumindIDSC.org) and the National Task Group on Intellectual Disabili-
ties and Dementia Practices (www.the-ntg.org). We acknowledge the
specific contributions of Hampus Hillerstrom and Dr. Richard Fisher
of the LuMind IDSC Foundation and Dr. Matthew P. Janicki of the
National Task Group in their roles as organizers and facilitators of
this effort. Partial support for MPJ was provided by a grant from the
Centers for Disease Control and Prevention (CDC), National Center
for Chronic Disease Prevention and Health Promotion, the Healthy
Brain Initiative Award No. 1 NU58DP006782-01-00, to the Univer-
sity of Illinois Chicago. Additional support for the contributions for
BTC, SH, SKM, FL, HDR, WS, and SHZ was provided by grant U19
AG068054 from the National Institutes of Health (NIH). Contents are
solely the responsibility of the authors and do not represent the offi-
cial views of the CDC or the NIH. No funding was specifically provided
HILLERSTROM ET AL.3655
for this effort or the development of the information contained in this
manuscript, except for individual institutional support for participant
time commitments.
CONFLICT OF INTEREST STATEMENT
HZ has served on scientific advisory boards and/or as a consul-
tant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apel-
lis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx,
Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pin-
teon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche,
Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has
given lectures at symposia sponsored by Alzecure, Biogen, Cellectri-
con, Fujirebio, Lilly, and Roche, and is a co-founder of Brain Biomarker
Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures
Incubator Program (outside submitted work). The other authors report
not having any conflicts of interest. Author disclosures are available in
the supporting information.
ORCID
Matthew P.Janicki https://orcid.org/0000-0003-1053-1748
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SUPPORTING INFORMATION
Additional supporting information can be found online in the Support-
ing Information section at the end of this article.
How to cite this article: Hillerstrom H, Fisher R, Janicki MP,
et al. Adapting prescribing criteria for amyloid-targeted
antibodies for adults with Down syndrome. Alzheimer’s Dement.
2024;20:3649–3656. https://doi.org/10.1002/alz.13778
