DSM-5 DSM 5 and d Neurocognitive Disorders

Dilip V. Jeste, M.D.

University of California, San Diego

UCSD Geriatric Psychiatry

Disclosures
No financial relationship with the pharmaceutical industry p y

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OUTLINE

General Background
Neurocognitive g Disorders Mild Neurocognitive Disorder Major Neurocognitive Disorder (Dementia) Associated Behavioral Disturbances Future

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Global Aging
In 2000, 420 million p people p worldwide were > 65; this number is projected to y 2030 hit 1 billion by In 2000, 59% of the worlds seniors lived in developing nations; this is projected to reach 70% in 2030
S Source: 65+ in i the th United U it d States: St t US C Census B Bureau, 2005

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Prevalence of Alzheimers Disease Doubles Every 5 Years After Age 60

60-64: 65 69: 65-69: 70-74: 75-79: 80-84: > 85: 1% 2% 4% % 8% 16% 32%
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(Evans et al., 1988)

DSM-5 and Aging

No separate p Geriatric Disorders category g y Most relevant are Neurocognitive Disorders, which are listed toward the end of the book Section on Development and Course in the description of each disorder discusses onset and course over the lifespan

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What is Diagnosis?
Origin (Greek): Thorough Knowledge Determining g the nature and the cause/s of an illness by studying symptoms Diagnosis g is generally g y the first step p toward optimal treatment Model of acute infections vs. chronic, , complex diseases with varied course

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Primary Purpose of DSM vs. M lti l Practical Multiple P ti l Implications I li ti

Primary yp purpose: p to p provide criteria for diagnostic categories in order to enable clinicians y diagnose, g and researchers to reliably communicate about, study, and treat people with mental disorders Implications for clinical care access, social stigma, legal determinations, ethical considerations, and practical sequela job opportunities, insurance reimbursement Efforts to coordinate with ICD-11 UCSD Geriatric Psychiatry

Challenges in Changing Diagnoses

Uneven scientific progress in different areas (Alzheimers disease vs. Delirium) Stigma Diagnosing Mild Neurocognitive Disorder vs. Pre-cancerous conditions Varied and sometimes diametrically opposite input from different stakeholders Issues of conflicts of interest Practical issues objective neuropsychological evaluation
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OUTLINE
DSM DSM-5: 5: General Background

Neurocognitive g Disorders
Mild Neurocognitive Disorder M j Neurocognitive Major N iti Disorder Di d (Dementia) (D ti ) Associated Behavioral Disturbances Future

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Neurocognitive Neu ocog ve Disorders so de s Work Group

Dilip Jeste, MD (Chair Emeritus 20072007-2011) Dan Blazer, Blazer MD (Co(Co-Chair) Ronald Petersen, PhD, MD (Co(Co-Chair) D b h Bl Deborah Blacker, k MD Mary Ganguli, MD Igor Grant, MD Jane Paulsen, PhD Perminder Sachdev, MD

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DSM-5 DSM 5 Neurocognitive Disorders

A N A. New titl title Replaces DSM-IV-TR category of Dementia, Delirium, Amnestic and Other Cognitive Disorders B. Definition Primary clinical deficit in cognitive function Cognitive decline from previously attained level of functioning (Acquired) UCSD Geriatric Psychiatry

6 Neurocognitive N iti Domains D i

Complex attention Executive function Learning/Memory Language P Perceptual t l Motor M t Social cognition
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DSM-5 N Neurocognitive iti Di Disorders d (NCD)

Delirium D li i Major NCD ( = Dementia) Mild NCD Unspecified NCD

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Delirium: Response to Public Comments

Criteria: Substitute attention for awareness as the first symptom for delirium (more p precise) ) Subclassification by etiology: Clarify that the medical condition causing delirium cannot always be identified

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Delirium DSM-5 Criteria

Acute or subacute onset (over hours or days) of disturbance of attention and awareness, awareness with fluctuations in severity over the course of a day Associated feature: Cognitive disturbance (e (e.g., g memory, orientation, language, etc.) Not primarily explained by another neurocognitive disorder nor occurring in the context of severely reduced arousal as with coma Evidence of direct cause (specify)
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Delirium Specifications
Substance intoxication Substance withdrawal Medication-induced Due to another medical condition Due to multiple etiologies

Acute vs. Persistent Hyperactive vs. Hypoactive vs. Mixed level of activity Other Specified and Unspecified Delirium
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OUTLINE
DSM DSM-5: 5: General Background Neurocognitive Disorders

Mild Neurocognitive Di d Disorder

Major Neurocognitive Disorder (Dementia) Associated Behavioral Disturbances Future F t
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Mild Neurocognitive g Disorder

Major j Neurocognitive g Disorder Neurocognition Independence

1. Neurocognitive decline 2. Significant impairment in one neurocognitive domain (usually) 3 Preservation of 3. independence (albeit with extra effort, etc.)

1. Neurocognitive g decline 2. Significant impairment p in one, , or usually, multiple cognitive domains 3. Loss of independence
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3001109-1

Neurocognitive Disorders: Mild vs. Major M j

1. I 1 Independence d d i in f functioning ti i 2. Severity of neurocognitive impairment 3. Usually, but not always, a continuum with progression of decline 4. Subclassification by etiology

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DSM-5 Criteria for Mild NCD

A. Modest cognitive decline based on: 1. Report by patient, informant, clinician AND g impairment p on q quantified 2. Mild cognitive neuropsychological or another clinical assessment B. Does not interfere with independence p in IADLs although greater effort, accommodation, or compensatory strategies may be needed C. Not exclusively due to delirium D. Not primarily explained by another major mental disorder UCSD Geriatric Psychiatry

Specification by Etiology
Alzheimers disease Frontotemporal lobar degeneration Lewy body Disease Vascular disease Traumatic brain injury Substance/Medication Use HIV infection Multiple M ltiple etiologies Unspecified
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Specification by Behavioral Di t b Disturbance

Without behavioral disturbance With behavioral disturbance: Psychotic P h ti symptoms, t Mood M d disturbance, di t b Agitation, A it ti Apathy, or Other behavioral disturbance

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OUTLINE
DSM-5: DSM 5: General Background Neurocognitive Disorders Mild N Neurocognitive iti Disorder Di d

Major Neurocognitive Disorder (Dementia) ( )

Associated Behavioral Disturbances Future F t
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Major NCD (Dementia): Criteria

A. Significant cognitive decline based on: 1 R 1. Report tb by patient, ti t i informant, f t clinician li i i AND 2 S 2. Substantial b t ti l cognitive iti impairment i i t on standardized neuropsychological or another quantified tifi d clinical li i l assessment t B. Interference with independence in everyday activities i i i (IADLs (IADL such h as managing i medications) di i ) C. Not exclusively in the context of delirium D. Not primarily explained by another UCSD Geriatric Psychiatry major mental disorder

Specification by Etiology
Alzheimers disease Frontotemporal lobar degeneration Lewy body Disease Vascular disease Traumatic brain injury Substance/Medication Use HIV infection Multiple M ltiple etiologies Unspecified
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Othere Specifications
Without behavioral disturbance With behavioral disturbance: Psychotic symptoms, Mood disturbance, Agitation, p y, or Other behavioral disturbance Apathy, Current Severity (of difficulties with activities daily living): Mild vs. Moderate vs. Severe
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Example of Etiology: Alzheimers Disease

1. Neurodegenerative disease 2. Gradual onset and decline 3. Typically includes memory p impairment 4. ? Role of imaging and biomarkers
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Major or Mild NCD Due to Alzheimers Alzheimer s Disease: I

Criteria met for major j or mild NCD Insidious onset and gradual progression of g impairment p ( (for major j NCD, in at least cognitive 2 cognitive domains) probable or p possible Criteria met for p Alzheimers disease p by y Disturbance not better explained cerebrovascular or another neurodegenerative disease, effects of a substance, or another mental, neurologic, or systemic disorder
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Criteria for Probable or Possible Alzheimers Alzheimer s Disease: II

All 3 of the following g criteria must be present: p (1) Clear evidence of decline in memory and g learning (2) Steadily progressive, gradual decline in g without extended p plateaus cognition, (3) No evidence of mixed etiology (- absence of g cerebrovascular, or other neurodegenerative, another disease likely contributing to cognitive decline)
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Major or Mild NCD Due to Probable Alzheimer Alzheimers s Disease: III

Additional Criterion required q for diagnosing g g Mild NCD Due to Probable Alzheimers disease: g Evidence of a causative Alzheimers disease genetic mutation from family history or genetic testing This criterion is optional for Major NCD Due to Probable Alzheimers disease

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Issues Regarding Terminology: I

Disorder label: Cognitive vs Neurocognitive di d disorders We W preferred f d the h l latter term as i it identifies disorders where the primary deficit is cognitive, i i and d whose h relationship l i hi to CNS pathology is reasonbly established; similar to diff difference b between psychological h l i l& neuropsychological Minor vs. Mild: Risk of trivializing an NCD leading to inappropriate denial of service for a real and potentially treatable condition
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Issues Regarding Terminology:II

Dementia: Long history vs. Stigma (=loss of mind) Dementia used for Alzheimers & other neurodegenerative disorders, but not for HIV- or TBI-induced cognitive impairment, especially if in one domain only and in younger adults, and for the Amnestic syndrome Dementia as nearly synonymous Change: Use Dementia with the somewhat broader Major NCD UCSD Geriatric Psychiatry

Issues Regarding Continuum vs. vs Categorization

Although the underlying diseases/disorders may or may not be b progressive i or on a continuum, i there is a continuum of measurement along which hi h thresholds h h ld will ill b be i inevitably i bl arbitrary; bi Wide range of views as to how and whether this continuum i should h ld b be d defined fi d How should objective testing be included in the criteria (- more critical for mild than for major)?
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ICD-10 Dementia
Evidence of a decline in both memory and thinking, sufficient to impair personal Activities of Daily Living The impairment of memory typically affects the registration, storage, and retrieval of new i f information, i but b previously i l learned l d and d familiar f ili material may also be lost, particularly in later stages The above symptoms and impairments should have been evident for at least 6 months for a confident clinical diagnosis of dementia to be made .x0 Without additional symptoms .x1 Other symptoms, predominantly delusional .x2 Other symptoms, predominantly hallucinatory .x3 Other symptoms, predominantly depressive UCSD Geriatric Psychiatry .x4 Other mixed symptoms

DSM-IV-TR: Al h i Alzheimers Di Disease

Early E l onset t with behavioral disturbance Without behavioral disturbance Late Onset with vs. without behavioral disturbance Specify behavioral disturbance Uncomplicated With delirium With delusions With d depression i

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DSM-IV-TR:

th 5 -digit

Specifier

(1) Dementia without Behavioral Disturbance (2) Dementia with Behavioral Disturbance: Delirium Delusions D l i Depressed mood Other (3) Other syndromes of dementia to be coded as additional dxs under axis I e.g., Mood disorder due to AD, with depressive features; Personality change h d due t to AD AD, aggressive i t type
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Changes from DSM-IV

Changes in nomenclature Specification S ifi ti of f Mild NCD (i (included l d d in i DSM-IV DSM IV under Cognitive Disorder NOS) Need for objective neurocognitive assessment Removal of memory impairment as an essential criterion for Major NCD Better specification of associated behavioral symptoms Emerging role of biomarkers in future criteria
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OUTLINE
DSM 5: General Background DSM-5: Neurocognitive Disorders Mild N Neurocognitive iti Disorder Di d Major Neurocognitive Disorder (Dementia)

Associated Behavioral Disturbances

Future F t
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Prevalence of Behavioral Disturbances in Alzheimers Disease

Psychosis: y 40% - 60% Depression: 20% - 40% Agitation: 70% - 90%
(Wragg and Jeste, Am J Psychiatry, 1988; Ropacki and Jeste, Am J Psychiatry, 2005)
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Psychosis of AD: Diagnostic Criteria

A. Characteristics sxs: Delusions or Aud./Vis. Hallucinations B. Primary dx: AD C Chronology of onset of sx C. sxs s of dementia vs vs. psychosis D. Duration: >1 1 month Severity: Functional disruption E. Exclusion of: Schizophrenia, p , and Other causes of psychosis ; Delirium
(Jeste and Finkel, Am J Geriat Psychiatry, 2000)
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OUTLINE
DSM 5: General Background DSM-5: Neurocognitive Disorders Mild N Neurocognitive iti Disorder Di d Major Neurocognitive Disorder (Dementia) Associated Behavioral Disturbances

Future F t
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Neurocognitive Assessment: Issues

Objective j documentation of NCD Global vs. domain-specific assessment Specific measures: with norms, norms non non-patented patented Adequate norms: by age, education, language, culture, lt literacy lit Appropriate thresholds for Mild and Major NCD Bedside cognitive testing by primary care clinicians?
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Mild NCD: Issues

Should neuropsycholgical py g testing g be required q for its diagnosis? j cognitive g complaints p be Should subjective required for its diagnosis? y Alzheimers disease? Should it be labeled Early Should most Mild NCD be subtyped as NCD p Not Otherwise Specified?

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International Users
Coordination with ICD ICD-11 11 Cultural differences Political/ administrative aspects Cognitive g assessment Language/translation issues Norms Functional assessment: depends on local expectations t ti of f older ld people, l etc. t
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Biomarkers
Biomarkers such as MRI, amyloid imaging, APO-E, CSF a-beta/tau ratio are not yet recommended for clinical diagnosis and are still till in i the th realm l of f research h criteria it i Genetic testing not recommended at this stage t This field is moving fast, and one or more of th these bi biomarkers k may b be i incorporated t di into t the clinical diagnostic criteria in the foreseeable future
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DSM-5 Development: S i l Anthropolgy Social A th l

Long process Markedly changed social perceptions about psychiatry pharmaceutical industry psychiatry, industry, USA Impact on healthcare economics Stakeholder S groups with i conflicting f i i agendas personal and organizational Questions Q i about science i (R-DoC) ( C) Unprecedented scrutiny by media, public, and possibly ibl by b US C Congress re. objective bj i oversight, i h transparency, conflicts of interest UCSD Geriatric Psychiatry

Eventual Outcome
DSM-5 is more consonant with current scientific understanding of most psychiatric disorders Major changes can be difficult in the beginning, but are inevitable with progress Future revisions in DSM-5 will occur on a continual but small-scale basis, affecting specific di d disorders only l (DSM-5.1, (DSM 5 1 5.2, 5 2 .) ) Psychiatric diagnoses will be increasingly driven b scientific by i tifi advances, d with ith i instant t t feedback f db k from the community
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