Specialty Training for the New Era in Alzheimer’s Disease: Building Skills for Making an Early Diagnosis and Implementing Disease-Modifying Treatment

Chair, Sharon Cohen, MD, FRCPC, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/MOC/AAPA activity titled “Specialty Training for the New Era in Alzheimer’s Disease: Building Skills for Making an Early Diagnosis and Implementing Disease-Modifying Treatment.” For the full presentation, downloadable Practice Aids, monograph, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/472bp8g. CME/MOC/AAPA credit will be available until May 20, 2025.

1. Revised Criteria for Biomarker-Based Diagnosis
and Staging of AD
1

Full abbreviations, accreditation, and disclosure information available at PeerView.com/VQG40 Core 1 Biomarkers Core 2 Biomarkers Biomarkers of Nonspecific Processes Involved in AD Pathophysiology Biomarkers of Non-AD Co-Pathology Categorization of Fluid and Imaging Biomarkersβ Biomarker Category CSF Plasma Imaging
A (Aβ proteinopathy)
Hybrid ratios
T2 (AD tau proteinopathy)
N (injury, dysfunction, or degeneration
of neuropil)
I (inflammation) astrocytic activation
V (vascular brain injury)
S (α-synuclein)
–
–
– Amyloid PET
–
P-tau217/nP-tau217
pT205 Tau PET
P-tau181/Aβ42,
T-tau/Aβ42, Aβ42/Aβ40
pT205, MTBR-243,
nonphosphorylated
tau fragments
NfL NfL Anatomic MRI, FDG PET
Anatomic infarction,
WMH, abundant diluted
perivascular spaces
––
GFAP GFAP –
––αSyn-SAA
–
T
1
(phosphorylated and secreted AD tau)
• Core 1 biomarkers define
the initial stage of AD that
is detectable in vivo
• AD can be diagnosed with
any Core 1 biomarker
• Core 2 biomarkers
develop later than
Core 1 biomarkers, and
are closely tied to onset
of neurodegeneration and
clinical symptoms
• Core 2 biomarkers
can be combined with
Core 1 biomarkers
to stage biological
disease severity
P-tau217

2. Revised Criteria for Biomarker-Based Diagnosis
and Staging of AD
1

Full abbreviations, accreditation, and disclosure information available at PeerView.com/VQG40 Core 2 biomarkers can be combined with Core 1 biomarkers to stage biological disease severity and
• Provide information on the likelihood that clinical symptoms are associated with AD
• Inform the risk of clinical progression in people without symptoms
• Inform the likely rate of clinical progression in symptomatic individuals
Amyloid PET
Tau PET Medial
Temporal
Region
Tau PET
Moderate
Neocortical
Uptake
Tau PET High
Neocortical
Uptake
AT Notation
Stage A
(Initial)
+ - - - A+T-
+ + - - A+T
MTL
+
+ + + - A+T
MOD
+
+ + + + A+T
HIGH
+
Stage B
(Early)
Stage C
(Intermediate)
Stage D
(Advanced)Biological Staging of AD Using Amyloid PET and Tau PET

3. Revised Criteria for Biomarker-Based Diagnosis
and Staging of AD
1

Full abbreviations, accreditation, and disclosure information available at PeerView.com/VQG40 Preclinical AD
Stage 1: Clinically asymptomatic, biomarker evidence only  
Stage 2: Normal performance in expected range on cognitive tests, but decline from
previous level of cognitive function, with no or minimal impact on daily function 
Stage 3: Objective cognitive impairment with early functional impact insufficient to
result in significant functional loss
Stage 4 (mild dementia): Progressive cognitive and mild functional impairment on instrumental
ADLs with independence in basic ADLs
Stage 5 (moderate dementia): Progressive cognitive and moderate functional impairment
requiring assistance
Stage 6 (severe dementia): Progressive cognitive and severe functional impairment causing
dependence for basic ADLs
Mild Cognitive
Impairment
Alzheimer's
DementiaClinical Stages of Alzheimer?s Disease

4. Revised Criteria for Biomarker-Based Diagnosis
and Staging of AD
1

Full abbreviations, accreditation, and disclosure information available at PeerView.com/VQG40 • Typical relationship between biology and symptoms moves along an upper left to lower right diagonal (gray cells)
• Those in cells above diagonal (ie, worse clinical stage than expected for biological stage; blue cells) are expected
to have greater comorbid pathologic change
• Those in cells below diagonal (ie, better clinical stage than expected for biological stage; green cells) may have
exceptional resilience or cognitive reserve 
1. Jack CR et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. In progress. https://aaic.alz.org/diagnostic-criteria.asp.
Clinical
Stage 1
Clinical
Stage 2
Clinical
Stage 3
Clinical
Stage 4
Clinical
Stage 5
Clinical
Stage 6
Initial Biological
Stage (A)
1A
1B
1C 2C
1D 2D 3D
2A 3A 4A 5A 6A
Early Biological
Stage (B)
Intermediate
Biological Stage (C)
Advanced Biological
Stage (D)
2B 3B 4B
4C
4D
5B
5C
5D
6B
6C
6D
3CIntegrated Biological and Clinical Staging

5. Appropriate Use of AD Biomarkers by Modality
Full abbreviations, accreditation, and disclosure information available at PeerView.com/VQG40 Clinical Scenarios
Appropriate Use
for Amyloid PET
1
Appropriate Use
for Tau PET
1
Appropriate Use
for CSF Test
2
Patients with SCD (cognitively unimpaired based
on objective testing) who are at increased risk for
AD (eg, due to APOE4 positivity)
Patients with MCI or dementia which is consistent
with AD pathology (amnestic presentation) with
onset at 65 years or older
Patients with MCI younger than 65 years and in
whom AD pathology is suspected
Patients with MCI or dementia that could be consistent
with AD pathology but has atypical features
Patients with MCI or dementia with equivocal or
inconclusive results on recent CSF biomarkers
To inform the prognosis of patients presenting with MCI
due to clinically suspected AD pathology
To inform the prognosis of patients presenting with
dementia due to clinically suspected AD pathology
To determine eligibility for treatment with anapproved
amyloid-targeting therapy
To monitor response among patients that have received
an approved amyloid-targeting therapy
If patient has contraindication to lumbar puncture
No No Yes
Yes Yes Yes
Yes No No
Yes Yes Yes
Yes No No
Yes Yes No
No Yes No
Yes Yes Yes
Yes No -
Yes No No
1. Rabinovici GD et al. Updated Appropriate Use Criteria for Amyloid and Tau PET in Alzheimer’s Disease. In Progress. https://www.alz.org/media/Documents/AUC-Amyloid-Tau-PET-Alzheimers_Manuscript.pdf. 2. Shaw LM et al. Alzheimers Dement . 2018;14:1505 -1521.

6. Commercially Available Biomarkers for AD
1,2

Full abbreviations, accreditation, and disclosure information available at PeerView.com/VQG40 Test Name (Developer) Biomarker Modality Biomarkers Assay Platform
FDA-Approved/
CLIA-Certified/
Breakthrough Device Status
Florbetapir (Lilly)
Florbetaben (Life
Molecular Imaging)
Flutemetamol
(GE Healthcare)
Flortaucipir (Lilly)Flortaucipir (Lilly)
Elecsys AD (Roche)
Lumipulse G (Fujirebio)
AD-Detect (Quest
Diagnostics)
Amyloid Plasma Panel
(Roche, Lilly)
ATN Profile (Labcorp)
Lucent-AD (Lucent
Diagnostics)
PrecivityAD (C2N)
PrecivityAD2 (C2N)
Amyloid PET
Amyloid PET
Tau PET
CSF
CSF
Plasma
Plasma
Plasma
Plasma
Plasma
Plasma
Amyloid PET Amyloid plaques
Amyloid plaques
Amyloid plaques
Tau aggregates
P-tau181/Aβ42,
T-tau/Aβ42
Aβ42/40
Aβ42/40
Aβ42/Aβ40, P-tau181,
APOE4, P-tau217
Aβ42/Aβ40, P-tau181,
NfL
P-tau217
Aβ42/40, APOE4
status, age
Aβ42/40, P-tau217/
nP-tau217
FDA-approved
FDA-approved
FDA-approved
FDA-approved
FDA-approved
FDA-approved
CLIA-certified
CLIA-certified
CLIA-certified
CLIA-certified
CLIA/breakthrough
Breakthrough device
N/A
N/A
N/A
N/A
Elecsys
Lumipulse
IP-LC-MS/MS
Elecsys
Simoa
Simoa
IP-LC-MS/MS
IP-LC-MS/MS
1. Pleen J et al. Practical Neurology. 2024;23:27-42. 2. Hampel H et al. Neuron. 2 02 3 ;111: 27 81-27 9 9.

7. FDA-Approved Digital Cognitive Assessment Tools
1

Full abbreviations, accreditation, and disclosure information available at PeerView.com/VQG40 FDA-Approved Digital Cognitive Assessment Tools Can Assist With the Detection of Mild Cognitive Impairment
and Dementia in Primary and Specialty Care Settings Digital Cognitive
Assessment Tool
Domains Measured
Administration
Time
Website
Automated Neuropsychological
Assessment Metrics (ANAM)
Cambridge Neuropsychological
Test Automated Battery
(CANTAB Mobile®)
CognICA
Cognigram
Cognivue
25 min
35 min
5 min
<10 min
10 min
• Attention
• Concentration
• Reaction time
• Memory
• Attention
• Information
processing
• Memory
• Information processing speed
• Visual learning
• Working memory
• Memory
• Executive function/attention
• Discrimination
• Visuospatial
• Motor skills
• Processing speed
• Decision-making
• Executive function
• Executive function
• Motor skills
Scan to visit
https://vistalifesciences.com/
anam-intro
Scan to visit
https://cambridgecognition.com/
digital-cognitive-assessments
Scan to visit
https://cognetivity.com/cognica
Scan to visit
https://devcd-cognigram.esi-cms.com
Scan to visit
https://cognivue.com
1. https://www.alz.org/professionals/health-systems-medical-professionals/cognitive-assessment.