Mild Cognitive Impairment
and Other Early Diagnoses
Ronald C. Petersen, Ph.D., M.D.
Alzheimer’s Disease Research
Center
Mayo Clinic College of Medicine
Rochester, MN
Dementia: A Comprehensive Update
Boston
June 7, 2017
Disclosures
• Roche, Inc.
• Merck, Inc.
• Genentech, Inc.
• Biogen, Inc.
• Eli Lilly and Co.
• National Institute on
Aging:
• U01 AG006786
• P50 AG016574
• U01 AG011378
• R01 AG011378
• R01 AG041581
• GHR Foundation
• Mayo Foundation for
Education and Research
©2017 MFMER | 3636715-2
Introduction to the Recommendations
from the National Institute on
Aging-Alzheimer’s Association
Workgroups on Diagnostic Guidelines
for Alzheimer’s Disease
Clifford R. Jack, Jr, Marilyn S. Albert, David S. Knopman,
Guy M. McKhann, Reisa A. Sperling, Maria C. Carrillo,
Bill Thies, Creighton H. Phelps
Alz and Dementia, 2011
©2012 MFMER | 3238583-3
Hypothetical Model of Dynamic Biomarkers
of the Alzheimer’s Pathological Cascade
Biomarker magnitude
Abnormal
A
Tau-meditated neuronal injury and dysfunction
Brain structure
Memory
Clinical function
Normal
Cognitively normal
MCI
Dementia
Clinical disease stage
Jack et al: Lancet Neurol 2010
Neuroimaging in AD
Neuroimaging in AD
• Structural MRI
• Functional imaging
FDG PET
• Molecular imaging
Amyloid PET imaging
Tau PET imaging
Structural Imaging in AD
Structural MRI: Atrophy and AD
Stage
Control, 70, F
MCI, 72, F
AD, 74, F
AD Signature Cortical Thickness
©2017 MFMER | 3636715-9
Functional Imaging in AD
Molecular Neuroimaging
PIB Idealized
CN
aMCI
AD
3
2.5
00-863-895
02-310-847
06-209-892
2
1.5
1
0.5
0
PIB Examples – Full Spectrum
Low
CN
00-863-895
High
CN
aMCI
01-873-114
aMCI
02-155-940
3
2.5
2
1.5
1
0.5
0
02-310-847
AD
06-209-892
3001475-2
Tau PET
Brain tissue slides show the Tau
imaging agent is specific for the Tau
protein and not Amyloid
Stain of Tau
Imaging Agent
Amyloid
Tau PET
Clinically normal
84yo
AD dementia 71yo
Criteria Approach
• Clinical criteria
• Biomarkers
• Molecular neuropathology
• Measures of neuronal injury
Cognitive Continuum
Normal
MCI
Dementia
M
C
I
D
E
M
E
N
T
I
A
AD
FTD
DLB
VCI
MEDICAL
TRAUMA
•
•
•
©2015 MFMER | 3480518-20
M
C
I
DUE
TO
AD
D
D
E
E
M
E
M
N
E
T
NI
A
T
DUE
I
TO
A
AD
©2015 MFMER | 3480518-21
Old Conception of Alzheimer’s Disease
Cognitively Normal
Dementia
©2016 MFMER | 3505738-22
Cognitive Continuum
Normal
MCI
Dementia
Alzheimer’s Disease Spectrum
Preclinical AD
MCI Due to AD
Dementia Due to AD
©2016 MFMER | 3505738-24
Alzheimer’s Disease Spectrum
Asymptomatic
Preclinical AD
Symptomatic
MCI Due to AD
Dementia Due to AD
©2016 MFMER | 3505738-25
Mild Cognitive Impairment
Mild Cognitive Impairment
Cognitive complaint
Not normal for age
Not demented
Cognitive decline
Essentially normal functional activities
MCI
Memory impaired?
Yes
Yes
No
Amnestic MCI
Non-amnestic MCI
Memory
impairment only?
Single non-memory
cognitive domain
impaired?
Amnestic MCI
Single domain
No
Amnestic MCI
Multiple domain
Petersen: J Int Med, 2004
Yes
Non-amnestic MCI
Single domain
No
Non-amnestic MCI
Multiple domain
CP1265413-2
Mild Cognitive Impairment
Cognitive complaint
Not normal for age
Not demented
Cognitive decline
Essentially normal functional activities
MCI
Memory impaired?
Yes
Yes
No
Amnestic MCI
Non-amnestic MCI
Memory
impairment only?
Single non-memory
cognitive domain
impaired?
Amnestic MCI
Single domain
No
Amnestic MCI
Multiple domain
Petersen: J Int Med, 2004
Yes
Non-amnestic MCI
Single domain
No
Non-amnestic MCI
Multiple domain
CP1265413-3
Mild Cognitive Impairment
Cognitive complaint
Not normal for age
Not demented
Cognitive decline
Essentially normal functional activities
MCI
Memory impaired?
Yes
Yes
No
Amnestic MCI
Non-amnestic MCI
Memory
impairment only?
Single non-memory
cognitive domain
impaired?
Amnestic MCI
Single domain
No
Amnestic MCI
Multiple domain
Petersen: J Int Med, 2004
Yes
Non-amnestic MCI
Single domain
No
Non-amnestic MCI
Multiple domain
CP1265413-4
MCI Outcomes
Clinical classification
Degenerative
Amnestic
MCI
Nonamnestic
MCI
Single
domain
AD
Multiple
domain
AD
Single
domain
Multiple
domain
Etiology
Vascular
Psychiatric
Med Cond
Depr
VCI
Depr
FTD
DLB
VCI
CP1265413-5
MCI Outcomes
Clinical classification
Degenerative
Amnestic
MCI
Nonamnestic
MCI
Single
domain
AD
Multiple
domain
AD
Single
domain
FTD
AD
Multiple
domain
DLB
AD
Etiology
Vascular
Psychiatric
Med Cond
Depr
VCI
Depr
VCI
CP1265413-6
Mild Cognitive Impairment
Ronald C. Petersen, MD, PhD
N Engl J Med 2011:364-2227-34
©2012 MFMER | 3219504-32
The Diagnosis of Mild Cognitive
Impairment Due to Alzheimer’s Disease:
Recommendations from the National Institute on
Aging-Alzheimer’s Association Workgroups on
Diagnostic Guidelines for Alzheimer’s Disease
Marilyn S. Albert, Steven T. DeKosky, Dennis Dickson, Bruno Dubois,
Howard H. Feldman, Nick C. Fox, Anthony Gamst, David M.
Holtzman, William J. Jagust, Ronald C. Petersen, Peter J. Snyder,
Maria C. Carrillo, Bill Thies, Creighton H. Phelps
Alz and Dementia, 2011
©2012 MFMER | 3238583-33
MCI Criteria Incorporating Biomarkers
Diagnostic category
Biomarker
probability
of AD etiology
MCI
Uninformative
MCI due to AD –
intermediate likelihood
A
(PET or CSF)
Neuronal
injury (tau,
FDG, sMRI)
Conflicting/indeterminant
Untested
Intermediate
Intermediate
Positive
Untested
Untested
Positive
MCI due to AD –
high likelihood
Highest
Positive
Positive
MCI – unlikely due
to AD
Lowest
Negative
Negative
CASE
Case Study
• 64-year-old right-handed man
• Accompanied by his wife
• Has master’s degree and worked as
an engineer designing computer
chips
• Voluntarily retired at age 62
History (1)
• Over the past 1-2 years, patient and wife had
noticed gradual change in cognition
• Increasing forgetfulness and word-finding
difficulties
• Daily functioning normal
• On recent trip, had confusion regarding
instructions
• Ultimately able to complete the tasks
• Adult children noticed he had been behaving
differently than in the past
History (2)
•
•
•
•
•
Groping for words in midsentence
Lost interest in reading
Reading skills preserved
Driving without difficulty
Handling family’s finances although
somewhat more slowly
• Preserved insight into his difficulties
• Wife noted he would repeat himself, having
forgotten the answer to a previous question
Medical History
• Medical Conditions
Sleep apnea for the past three years, using
CPAP regularly, improved alertness
Mild hypertension
Mild hyperlipidemia
• Medications
Amlodipine, 5 mg
Rosuvastatin (Crestor), 40 mg daily
Metoprolol
Supplements: Fish oil, calcium and
multivitamin
Neuropsychiatric
• Mood appropriate, not depressed
• Some increase in irritability
particularly when aware of
forgetfulness
Family History
• Father alive at 91 with moderate dementia for
6-8 years
• Mother died age 83, had Parkinson’s disease
for 15 years
• Two maternal uncles and four maternal aunts
cognitively impaired in their 80s and 90s
• Maternal grandparents lived into 90s with
some degree of cognitive impairment
• Two brothers and one sister alive and well,
but younger
Neurological
• BP 118/62
• Kokmen Short Test of Mental Status,
36/38 (MMSE = 29/30)
• General neurologic exam
unremarkable
With normal and symmetrical
reflexes, normal strength and
sensation, no extrapyramidal
features or eye movement
abnormalities
Neuropsychological Exam
•
•
•
•
Standard scores: Age and education, mean = 10, SD = 3
Dementia Rating Scale: 143/144
Premorbid Intelligence Estimate: 113 (mean 100)
Memory
Logical Memory – Immediate recall: 26; Delayed recall: 18; 69% retention
Auditory Verbal Learning Test: Trials 1-5: 4, 6, 6, 8, 6
30-minute delayed recall 3
• Attention/concentration
Trail Making Test Part A, SS = 6; Part B, SS = 7
Stroop: Word, SS = 9, Color, SS = 7, Color-Word, SS = 10
• Language
Controlled Oral Word Association, SS = 10
Boston Naming Test, SS = 9
• Visuospatial Functioning
Rey O Figure, SS = 9
Diagnosis?
Amnestic Mild Cognitive
Impairment
MRI
Amyloid (PiB) PET
Tau (AV 1451) PET
Do the Criteria Work?
In the General Population
Mayo Clinic Study of Aging (MCSA)
3047674-49
Mayo Olmsted County
Study of Aging
(U01 AG006786)
CP1265413-14
Mayo Clinic Study of Aging
Population-based study of 5000+
(2800 active) nondemented persons age
30-89 years in Olmsted County, MN
©2017 MFMER | 3636715-51
MCSA Cycles of Recruitment and Follow-Up
70 Years Old
2004
2010
2008
2006
2012
2014
2016
October
Enrollment
F-U Cycle 2
F-U Cycle 3
F-U Cycle 4
F-U Cycle 5
F-U Cycle 6
F-U Cycle 7
F-U Cycle 8
50-69 Years Old
F-U Cycle 9, 10
2012
2013
2014
2015
2016
2017
Enrollment
F-U Cycle 2
F-U Cycle 3
30-49 Years Old
F-U Cycle 4
2015
2016
2017
2018
Enrollment
F-U Cycle 2
©2017 MFMER | 3636715-52
Evaluation
Consent form
Blood draw
Clinical evaluation
Nurse/SC interview
Neurological evaluation
Cognitive assessment
Participant
Family history
Current medications
Demographic information
Memory & orientation
Medical history &
risk assessment
Neuropsychiatric inventory
Study partner
Clinical dementia rating
Functional
assessment (FAQ)
Neurological history
Short test of mental status
Modified Hachinski scale
Prime MD (physician form)
Neurological examination
and modified UPDRS
Memory
Logical memory (delayed)
Visual reprod (delayed)
AVLT
Executive function
Trails A & B
Digit symbol substitution
Visuospatial
Picture completion
Block design
Language
Boston naming test
Category fluency
Consensus conference
©2017 MFMER | 3636715-53
Resources Acquired
• 5000+ non-demented subjects
•80% Cognitively normal
•18% MCI
• 2% Demented
• 5800 quantitative MRI scans
• ~ 5000 DNA samples
• ~ 5000 frozen plasma/serum samples
•plus annual samples
• Clinical and performance measures
©2017 MFMER | 3636715-54
Continuation of MCSA
• Add new subjects to cohort (500?)
• Continue annual clinical follow-ups
• Continue serial MRI/PET scans
• Collect annual plasma/serum
• Collected 1200 CSF’s
• Performed 2800 FDG-PET scans
• Performed 2800 PiB PET scans
• Performed 1100 tau PET scans
©2017 MFMER | 3636715-55
So, How Do the Criteria Fare in
the General Population?
Biomarker Prevalence
Mayo Clinic Study of Aging
Positive
Participate
Yes
Biomarker
Result
Biomarkers
Negative
SpAim 1a - 2a,b
Olmsted
County
Population
No
SpAim 1b
Refuse
SpAim 3
SpAim 1b
3c
3b
3a
©2016 MFMER | 3502180-58
Assessing Biomarkers in the
Community
• Biomarker negative (A- N-)
Amyloid neg
FDG PET/MRI neg
• Amyloid positive Neurodeg neg (A+ N-)
Amyloid pos
FDG PET/MRI neg
• Amyloid pos Neurodeg pos (A+ N+)
Amyloid pos
FDG PET/MRI pos
• Neurodegen only (A- N+) (SNAP)
Amyloid neg
FDG PET/MRI pos
Preclinical AD
Preclinical AD
Diagnostic
category
A
(PET or
CSF)
Neuronal
injury
Clinical
Stage 1
Positive
Negative
Negative
Stage 2
Positive
Positive
Negative
Stage 3
Positive
Positive
Positive
Stage 0
Negative
Negative
Negative
Sperling et al: 2011
Preclinical Stage
50
40
30
%
20
10
0
Stage 0
Stage 1
Stage 2
Stage 3
SNAP
Unclassified
Preclinical AD stage
©2014 MFMER | 3340705-62
NIA-AA Preclinical AD Staging
in Relation to Our Hypothetical Model
of Preclinical
Biomarkers
Stage
Biomarker magnitude
Abnormal
0
43%
1
2
3
16%
12%
3%
A
Neuronal
injury
Cognitive
symptoms
Cut points
Normal
Cognitively normal
Clinical disease stage
Jack et al: Lancet Neuro, 2010
MCI
Dementia
Preclinical Alzheimer’s Disease and Its
Outcome: A Longitudinal Cohort Study
Stephanie J. B. Vos; Chengjie Xiong; Pieter Jelle Visser;
Mateusz S. Jasielec; Jason Hassenstab;
Elizabeth A. Grant; Nigel J. Cairns; John C. Morris;
David M. Holtzman; Anne M. Fagan
Lancet Neurology, 12:957, Oct., 2013
©2013 MFMER | 3309417-64
Pre-Clinical AD Stages
Neuroimaging vs CSF
50
MCSA, Jack et al, 2012
Vos et al, 2013
40
30
%
20
10
0
Stage 0
Stage 1
Stage 2
Stage 3
SNAP
Uncl
Petersen: Lancet Neurol, 2013
©2013 MFMER | 3290921-65
Progression to CDR >/= 0.5
by Preclinical Alzheimer’s Disease Stage
Cumulative incidence
probability
1.0
Normal
Stage 1
Stage 2
Stage 3
SNAP Group
0.8
St 3
0.6
St 2
0.4
0.2
St 1
SNAP
NL
0.0
0
2
4
6
8
10
12
14
Follow-up (years)
Vos et al: Lancet Neurol 12:957, 2013
©2013 MFMER | 3309417-66
Biomarker Behavior in the
Population
Assessing Biomarkers in the
Community
• Biomarker negative (A- N-)
Amyloid neg
FDG PET/MRI neg
• Amyloid positive Neurodeg neg (A+ N-)
Amyloid pos
FDG PET/MRI neg
• Amyloid pos Neurodeg pos (A+ N+)
Amyloid pos
FDG PET/MRI pos
• Neurodegen only (A- N+) (SNAP)
Amyloid neg
FDG PET/MRI pos
Population Frequencies
of Biomarkers in Typical AD
Frequency (%)
100
A-NA+NA-N+
A+N+
80
60
40
20
0
50
60
70
80
90
Age (years)
Jack et al: Lancet Neurol 13:997, 2014
©2015 MFMER | 3414397-69
Cumulative Incidence of MCI
All
Fraction progressed
1.0
A+N+
A–N+
A+N–
A–N–
0.8
0.6
0.4
0.2
0.1
70
75
80
85
90
Age
©2016 MFMER | 3543139-70
Rates of Progression from CN to MCI Expressed
as Number of Events per 100 Person Years
Overall
Age 75
Age 80
Age 85
18
16
14
12
10
8
6
4
2
0
A–N–
A+N–
A+N+
A–N+
©2016 MFMER | 3543139-71
MCI Due to AD
Hypothetical Model of Dynamic Biomarkers
of the Alzheimer’s Pathological Cascade
Biomarker magnitude
Abnormal
A
Tau-meditated neuronal injury and dysfunction
Brain structure
Memory
Clinical function
Normal
Cognitively normal
MCI
Dementia
Clinical disease stage
Jack et al: Lancet Neurol 2010
MCI Due to AD
Diagnostic category
MCI
Biomarker
probability of AD
etiology
Uninformative
A
(PET or CSF)
Neuronal injury
(tau, FDG, sMRI)
Conflicting/
indeterminant or unavailable
MCI due to AD –
intermediate
likelihood
Intermediate
Intermediate
Positive
Untested
Untested
Positive
MCI due to AD –
high likelihood
Highest
Positive
Positive
MCI – unlikely due
to AD
Lowest
Negative
Negative
Albert et al: 2011
©2012 MFMER | 3219504-74
Assessing Biomarkers in the
Community
• Biomarker negative (A- N-)
Amyloid neg
FDG PET/MRI neg
• Amyloid positive Neurodeg neg (A+ N-)
Amyloid pos
FDG PET/MRI neg
• Amyloid pos Neurodeg pos (A+ N+)
Amyloid pos
FDG PET/MRI pos
• Neurodegen only (A- N+) (SNAP)
Amyloid neg
FDG PET/MRI pos
All MCI MCSA
Population Frequencies
50
40
30
%
20
10
0
Biom
neg
Amyloid
only
Amyloid +
neurodeg
Neurodeg
only
sNAP
Petersen et al: Ann Neuro , 2013
©2013 MFMER | 3270183-76
Practical Stuff
CLINICAL TRIALS IN MCI
Sponsor
Duration
Endpoint
Drugs
ADCS
3 yr
AD
Vitamin E
Donepezil
Merck
3-4 yr
AD
Rofecoxib
Novartis
4 yr
AD
Rivastigmine
Janssen
2 yr
AD
Galantamine
Pfizer
6 mo
Symptoms
Donepezil
UCB
1 yr
Symptoms
Piracetam
Cortex
4 wks
Symptoms
Ampakine
MCI Clinical Trials
Subjects
(no.)
Duration
(mo)
Progression
rate/yr (%)
Outcome
Rivastigmine
1,018
48
5-6
Neg
Galantamine
990
1,058
24
24
11-12
13
Neg
Neg
Rofecoxib
1,457
48
5-6
Neg
ADCS
Donepezil
Vitamin E
769
36
16
Neg*
ADNI
400
36
16
–
Compound
3001110-2
MCI Placebo Subjects in
Randomized Controlled Trials
Practice Parameter: Early Detection of
Dementia: Mild Cognitive Impairment
(an Evidence-Based Review)
Report of the Quality Standards Subcommittee
of the AmericanAcademy of Neurology
Ronald C. Petersen, PhD, MD; J. C. Stevens, MD;
M. Ganguli, MD, MPH; E. G. Tangalos, MD;
J. L. Cummings, MD; and S. T. DeKosky, MD
CP1186552-8
Publications on MCI
1600
1400
Articles (no.)
1200
1000
800
600
400
200
0
90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11
1990
Year
2011
©2012 MFMER | 3238583-82
American Acadmey of
Neurology
Practice Parameter on MCI
Petersen et al., Neurology, in press
Coding for MCI
3019717-84
Coding for MCI
• Nervous System (Medical) Codes
• (ICD 9)331.83; (ICD 10) G31.84
Mild cognitive impairment
3019717-85
DSM 5
Mild Neurocognitive
Disorder (MCI)
Major Neurocognitive
Disorder (Dementia)
Cognition
Independence
1. Cognitive decline
1. Cognitive decline
2. Single cognitive domain
impaired (usually)
2. Significant cognitive
impairment in one or
more often multiple
cognitive domains
3. Preservation of
independence
3. Loss of independence
3001109-1
NCD Etiologies
•
•
•
•
•
•
Alzheimer’s Disease
Frontotemporal degen
Lewy body disorders
Vascular cognitive imp
Traumatic brain injury
Substance/medications
•
•
•
•
•
•
HIV/AIDS
Prion disorders
Parkinson’s disease
Huntington disease
Other medical issues
Multiple causes
3023518-88
Prodromal AD
• Amnestic MCI
• Biomarker support
Amyloid PET
CSF amyloid and tau
Mild Cognitive Impairment
Cognitive complaint
Not normal for age
Not demented
Cognitive decline
Essentially normal functional activities
MCI
Memory impaired?
Yes
Amnestic MCI
MCI Criteria
Key Symposium
JIM, 2004
DSM-5
Amnestic MCI
Single domain
No
Non-amnestic MCI
Amnestic MCI
Multiple domain
Non-amnestic MCI
Single domain
Non-amnestic MCI
Multiple domain
Mild Neurocognitive Disorder
MCI due to AD
 Uncertain
No or conflicting A or MRI or FDG PET or tau
 Intermediate
Plus biomarker for A
OR
MRI or FDG PET or tau
 High
Plus biomarker for A
AND
MRI or FDG PET or tau
Prodromal AD
Plus biomarker for A or tau/A
Petersen et al., J Int Med, 2013
©2013 MFMER | slide-90
But…
Life is not simple
©2017 MFMER | 3636715-91
Tau PET
Clinically Normal 84-yo
AD Dementia 71-yo
©2017 MFMER | 3636715-92
Amyloid/Tau/Neurodegeneration
a descriptive classification scheme for AD
biomarkers
Adding Tau as a Biomarker
©2017 MFMER | 3636715-93
©2017 MFMER | 3636715-94
AD Biomarker Combinations
+
A
+
±
–
±
T
N
–
+
±
–
±
A
Amyloid
T
TAU
N
Neurodegeneration
©2017 MFMER | 3636715-95
ATN Biomarker Grouping
• B-amyloid plaques (A)
• CSF Ab 42 (low), or better low 42/40 ratio
• Amyloid PET
• Aggregated tau (T)
• CSF phosphorylated tau (high)
• Tau PET
• Neuronal injury and neurodegeneration (N)
• Structural MRI
• FDG PET
• CSF total tau (high)
©2017 MFMER | 3636715-96
TAU PET
Medial Temporal
Tau PET SUVR
2.0
PIBPIB+
1.5
1.0
CN
MCI
Dementia
©2017 MFMER | 3636715-97
TAU PET
Inferior Temporal
3.0
Tau PET SUVR
2.5
PIBPIB+
2.0
1.5
1.0
CN
MCI
Dementia
©2017 MFMER | 3636715-98
TAU PET
Lateral Temporal
Tau PET SUVR
3.0
PIBPIB+
2.5
2.0
1.5
1.0
CN
MCI
Dementia
©2017 MFMER | 3636715-99
Tau PET, SUVR
2.2
2.2
2.0
2.0
1.8
1.8
1.6
1.6
1.4
1.4
1.2
1.2
1.0
1.0
CN
MCI Dementia
CN
A–
CN
A+
MCI
A–
MCI
A+
Dem
A+
©2017 MFMER | 3635612-100
4
Memory z-score
3
2
1
0
-1
-2
-3
-4
A–T–
A+T–
A–T+
A+T+
©2017 MFMER | 3635612-101
ATN Framework
Summary
• Now can address defining features of AD in
life
• Plaques - amyloid
• Tangles - tau
• Temporal course variable
• Correlation with clinical spectrum to be
determined
©2017 MFMER | slide-102
Alzheimer’s Disease
New Conceptualization
• Alzheimer’s Disease refers to the underlying
presence of plaques (amyloid) and
neurofibrillary tangles (tau)
• Clinical spectrum is parallel but separate
from “Alzheimer’s Disease”
• Cognitively normal-MCI-dementia
• Alzheimer’s disease is no longer a clinicalpathological entity
©2017 MFMER | 3636715-103
How Early Can We Diagnose
Alzheimer’s Disease?
• Clinical spectrum
• Sensitive tools and criteria
for Preclinical-MCI stages
• Pathophysiology
• Biomarkers
• Imaging
• CSF
©2017 MFMER | 3636715-104
But…
©2016 MFMER | 3534461-105
But, at the end of the day…
©2017 MFMER | 3636715-106
Alzheimer’s
Disease
Aβ
TDP-43
Tau
Hippocampal
sclerosis
Clinical
Spectrum
CN – MCI – Dementia
Alpha
Synuclein
Other
Vascular
Disease
©2017 MFMER | 3636715-107
Rx?
PET/CSF
Rx?
Rx?
?CSF
Aβ
TDP-43
Tau
Hippocampal
Sclerosis
Clinical
Pathology
Biomarker
Therapy
PET/CSF
Clinical
Spectrum
CN – MCI
– Dementia
Alpha
Synuclein
?CSF
Other
Vascular
Disease
Rx?
?
Rx?
MRI
Rx?
©2017 MFMER | 3636715-108
Future Directions
Alzheimer’s disease as we know it today will
only be part of the total clinical/pathological
picture
We will describe clinical syndrome and
associate a variety of contributing etiologies
Treat our patients with combination therapies
depending on the biomarker/pathological
profile
©2017 MFMER | 3636715-109
Mayo Clinic AD Research
Rochester
Jacksonville
Brad Boeve
Neill Graff-Radford
Dave Knopman
Steve Younkin
Cliff Jack
Dennis Dickson
Val Lowe
John Lucas
Bob Ivnik
Tanis Ferman
Glenn Smith
Rosa Rademakers
Michelle Mielke
Nilufer Taner-Erketin
Rosebud Roberts
Len Petrucelli
Walter Rocca
Gojuin Bu
Shane Pankratz
Otto Pedraza
Jenny Whitwell
Scottsdale
Kejal Kantarci
Joe Parisi
Eric Tangalos
Rick Caselli
Bryan Woodruff
Yonas Geda
Thank You