DSM-5 Renaming Dementia (?)Neurocognitive Disorders A.New title • Replaces: delirium, dementia...
Transcript of DSM-5 Renaming Dementia (?)Neurocognitive Disorders A.New title • Replaces: delirium, dementia...
3023518-1
DSM-5 Renaming Dementia (?)DSM-5 Renaming Dementia (?)
Ronald C. Petersen, PhD, MDMayo Alzheimer’s Disease Research Center
Mayo Clinic College of MedicineRochester, MN
3023518-2
Disclosures
• Pfizer, Inc.: Chair DMC• Janssen Alzheimer’s Immunotherapy: Chair
DMC• GE Healthcare: Consultant• Funding
National Institute on Aging: U01 AG006786 P50 AG016574U01 AG011378
3023518-3
Neurocognitive Disorders Work GroupNeurocognitive Disorders Work Group
Dilip Jeste (Chair)Deborah BlackerDan Blazer (New Chair)Mary GanguliIgor GrantJane PaulsenRonald PetersenPerminder Sachdev
3023518-4
Neurocognitive Disorders
A. New title• Replaces: delirium, dementia
amnestic and geriatric cognitive disorders
B. Cognition• Core deficit in cognition• Decline from previous level
of function
Premises
3023518-5
Neurocognitive Disorders
• Delirium• Major Neurocognitive Disorder (NCD)• Mild Neurocognitive Disorder (NCD)
3023518-7
Delirium
• Disturbance of attention and awareness• Change over a short period of time• Includes disturbance in cognition• Not better explained by preexisting
condition• Caused by physiological consequence
of medical condition, substance use, or withdrawal
3023518-8
DSM-IV Definition
• "The essential feature of a delirium is a disturbance in consciousness that is accompanied by a change in cognition that cannot be better accounted for by a preexisting or evolving dementia."
3023518-9
Proposed Changes in DSM-5
ChangeA. Disturbance in level
of awareness or arousal with reduced ability to direct, focus, sustain, and shift attention.
Current A. Disturbance of
consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention
3023518-10
Addition
• Note : The following supportive features are commonly present in delirium but are not key diagnostic features: sleep-wake cycle disturbance, psychomotor disturbance, perceptual disturbances (e.g., hallucinations, illusions), emotional disturbances, delusions, labile affect, and EEG abnormalities (generalized slowing of background activity).
3023518-12
General Approach to NCD’s
• Characterize the patient syndromicallyMild NCDMajor NCD
• Determine etiology of syndrome
3023518-13
Major Change
• Now including a pre-dementia condition termed “Mild Neurocognitive Disorder”
• DSM IV characterized mostly conditions at the dementia stage and their subtypes
3023518-14
Neurocognitive Disorders
1. Severity2. Independence3. Usually a continuum with evolution
Not always4. Etiology
Major vs Mild
3023518-15
Neurocognitive DisordersDomains
Domain TasksComplex attention Major: diminished, multiple stimuli
Mild: takes longerExecutive abilities Major: abandon complex activities
Mild: ↑ effort, multi-taskingLearning/memory Major: repeat self in conversation
Mild: recent events, occas repeatLanguage Major: anomia, paraphasias
Mild: ↓ naming, word findingVisuoconstructionVisuoperception
Major: not driving, ↓ navigationMild: maps, effort
Social cognition Major: insensitivity social contextsMild: subtle personality, ↓ empathy
3001109-1
Mild Neurocognitive Disorder (MCI)
1. Cognitive decline
2. Single cognitive domain impaired (usually)
3. Preservation of independence
1. Cognitive decline
2. Single cognitive domain impaired (usually)
3. Preservation of independence
1. Cognitive decline
2. Significant cognitive impairment in one or more often multiple cognitive domains
3. Loss of independence
1. Cognitive decline
2. Significant cognitive impairment in one or more often multiple cognitive domains
3. Loss of independence
Major Neurocognitive Disorder (Dementia)
IndependenceIndependence
CognitionCognition
3023518-17
Major NCDDementia
A. Cognitive decline (1 or usually 2 cognitive domains)
1. Report by patient, informant, clinician
and
2. Deficits on assessment
B. Interfere with independence assistance in IADL’s
C. Not delirium
D. Not primarily attributable to another disorder
3023518-18
Mild NCDMCI
RationaleMild cognitive impairmentEarly recognitionInterventionClinical trials
CriteriaA. Cognitive decline
1. Report by patient, informant, clinicianand
2. Mild cognitive deficits
D. Not primarily attributable to other axis 1 disorderC. Not deliriumB. Not interfere with independence greater effort
3023518-19
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
3023518-20
Alzheimer’s Disease
General1. Neurodegenerative disease2. Gradual onset and decline3. Typically includes a
memory impairment4. ? role of imaging and
biomarkers
3023518-21
Alzheimer’s Disease
Major1. Meets criteria for Major NCD
Mild1. Meets criteria for Mild NCD
Probable and Possible AD
3023518-22
Alzheimer’s Disease
Major Probable AD1. Genetic mutation2. All 3
Memory + other domainProgressiveNo additional contributions
Mild Probable AD1. Genetic mutation
Mild Possible AD1. All 3
Memory disorderProgressiveNo additional contributions
3023518-23
Other Newish Criteria
• Alzheimer’s Disease SpectrumNIA-AA
• Prodromal Alzheimer’s DiseaseInternational Work Group
©2012 MFMER | 3219504-24
Hypothetical Model of Dynamic Biomarkers of the Alzheimer’s Pathological Cascade
Jack et al: Lancet Neurol, 2010
Normal
Bio
mar
ker m
agni
tude
AβTau-meditated neuronal injury and dysfunctionBrain structureAbnormal
Clinical disease stage
Cognitively normal MCI Dementia
MemoryClinical function
©2012 MFMER | 3219504-25
Alzheimer’s Disease Spectrum
MCI Due to AD
Preclinical AD
Dementia Due to AD
©2012 MFMER | 3219504-26
Dementia Due to AD
Diagnostic category
Biomarker probability of AD
etiologyAβ
(PET or CSF)Neuronal injury (tau, FDG, sMRI)
Probable AD dementia
Uninformative/available
Conflicting/indeterminant or unavailable
Probable AD with evidence of path AD
IntermediateHighest
?Positive
PositivePositive
Possible AD dementia atypical with path
High consider secondary
Positive Positive
Dementia unlikely AD
Lowest Negative Negative
McKhann et al: 2011
©2012 MFMER | 3219504-27
MCI Due to AD
Diagnostic category
Biomarker probability of AD
etiologyAβ
(PET or CSF)Neuronal injury (tau, FDG, sMRI)
MCI Uninformative Conflicting/indeterminant or unavailable
MCI due to AD –intermediate likelihood
IntermediateIntermediate
PositiveUntested
UntestedPositive
MCI due to AD –high likelihood
Highest Positive Positive
MCI – unlikely due to AD
Lowest Negative Negative
Albert et al: 2011
©2012 MFMER | 3219504-28
Preclinical ADDiagnostic category
Aβ(PET or CSF) Neuronal injury Clinical
Stage 1 Positive Negative Negative
Stage 2 Positive Positive Negative
Stage 3 Positive Positive Positive
Sage 0 Negative Negative Negative
Sperling et al: 2011
Prodromal Alzheimer’s Disease
• Episodic memory deficit• Supported by biomarkers• Essentially, amyloid by imaging or CSF
©2012 MFMER | 3219504-29
3047674-31
53 y/o woman• 1 ½ yr history loss of self-confidence• Not want to move• Says “can’t think”• Forgets rapidly in conversation• Daughters have noticed x 1 yr• Decreased reading comprehension• Family human compass• Sleep ok• Concerned but not depressed
3047674-32
53 y/o woman
• Family history negative for dementia• PMH: Good health, postpartum
hemorrhage• Med: supplements, Zoloft, ASA
3047674-33
53 y/o woman
• STMS: 37/38• VIQ: 107, PIQ: 97• Attention/Executive
Trails A and B: 50th %ileStroop: 50th %ile
• LanguageFluency: 90th %ileBNT: 59/60
3047674-34
53 y/o woman
• VisuospatialRey O copy: 50th %ileJLO: 50th %ile
• MemoryLogical Memory: 17/10Visual Reproductions: 64/21AVLT: 7,6,11,10,8; DR 3
©2012 MFMER | 3219504-35
MCI Due to AD
Diagnostic category
Biomarker probability of AD etiology
Aβ(PET or CSF)
Neuronal injury (tau, FDG,
sMRI)
MCI Uninformative Conflicting/indeterminant or unavailable
MCI due to AD –intermediate likelihood
IntermediateIntermediate
PositiveUntested
UntestedPositive
MCI due to AD –high likelihood
Highest Positive Positive
MCI – unlikely due to AD
Lowest Negative Negative
Albert et al: 2011
2008
Mayo MCI Subject
5/22/2008 MRI ScanHippvol in normal range
(-0.31; greater than -0.7 is normal)
3047674-40
©2012
MCI Due to AD
Diagnostic category
Biomarker probability of AD etiology
Aβ(PET or CSF)
Neuronal injury (tau, FDG,
sMRI)
MCI Uninformative Conflicting/indeterminantUntested
MCI due to AD –intermediate likelihood
IntermediateIntermediate
PositiveUntested
UntestedPositive
MCI due to AD –high likelihood
Highest Positive Positive
Albert et al: 2011
3047674-42
Clinical Progression 2 yr later
• Getting lost• Frequent forgetting• Not driving• Despondent• Needs assistance
3047674-43
55 y/o woman
• STMS: 32/38• VIQ: 107, PIQ: 97• Attention/Executive
Trails A and B: 25th %ileStroop: 30th %ile
• LanguageFluency: 60th %ileBNT: 50/60
3047674-44
55 y/o woman
• VisuospatialRey O copy: 30th %ileJLO: 25th %ile
• MemoryLogical Memory: 12/5Visual Reproductions: 32/15AVLT: 3,4,3,5,4; DR 0
3047674-49
©2012
Dementia Due to AD
Diagnostic category
Biomarker probability of AD etiology
Aβ(PET or CSF)
Neuronal injury (tau, FDG, sMRI)
Probable AD dementia
Uninformative/
available
Conflicting/indeterminant or unavailable
Probable AD with evidence of path AD
IntermediateHighest
?Positive
PositivePositive
McKhann et al: 2011
3023518-513001109-1
Mild Neurocognitive Disorder (MCI)
1. Cognitive decline
2. Single cognitive domain impaired (usually)
3. Preservation of independence
1. Cognitive decline
2. Single cognitive domain impaired (usually)
3. Preservation of independence
1. Cognitive decline
2. Significant cognitive impairment in one or more often multiple cognitive domains
3. Loss of independence
1. Cognitive decline
2. Significant cognitive impairment in one or more often multiple cognitive domains
3. Loss of independence
Major Neurocognitive Disorder (Dementia)
IndependenceIndependence
CognitionCognition
©2013 MFMER | slide-52
No
Non-amnestic MCINon-amnestic MCI
Cognitive complaintCognitive complaint
Not normal for ageNot demented
Cognitive declineEssentially normal functional activities
Yes
Amnestic MCIAmnestic MCI
MCIMCI
Memory impaired?Memory impaired?
Mild Neurocognitive DisorderMild Neurocognitive Disorder
Plus biomarker for ABPlus biomarker for AB MRI or FDG PETMRI or FDG PETor
Plus biomarker for ABPlus biomarker for AB MRI or FDG PETMRI or FDG PETand
MCI due to ADDMS-5
Plus biomarker for ABPlus biomarker for ABProdromal AD
No or conflicting AB and MRI or FDG PET No or conflicting AB and MRI or FDG PET § Uncertain
§ Intermediate
§ High
Non-amnestic MCISingle domain
Non-amnestic MCISingle domain
Non-amnestic MCIMultiple domain
Non-amnestic MCIMultiple domain
Amnestic MCISingle domainAmnestic MCISingle domain
Amnestic MCIMultiple domainAmnestic MCI
Multiple domain