Differentiating Effects of Depression & Dementia

Shelley Peery, PhD

Introductions
Shelley Peery, PhD Neuropsychologist 760 Market Street, #712 San Francisco, CA 94102 shelleypeeryphd@gmail.com 415-627-9095 Your background in working with elders, your setting, your role, your population What you hope to gain from this talk

Hot off the Presses!

Pre-clinical Alzheimers disease guidelines published for research participants (Sperling et al 2011)

Hypothetical Model of AD

Sperling et al, 2011

Suggested diagnostic criteria revisions

Dementia definition that captures major disease entities (Alzheimers disease, dementia with Lewy bodies, vascular and frontotemporal dementia) MCI clinical definition that unambiguously fills gap between normal and dementia Retain core NINCD & SADRDA criteria Biomarkers to be part of augmented criteria Quantitative clinical and pathological criteria used in parallel with categoricals
DeKosky et al, 2011

NINDS & Alzheimers Association Core Criteria

Definite Alzheimer's disease: meets the criteria for probable Alzheimer's disease and has histopathologic evidence of AD via autopsy or biopsy. Probable Alzheimer's disease: Dementia established by clinical and neuropsychological examination. Cognitive impairments are progressive and present in two or more areas of cognition. Absence of other causes of dementia.
McKhann et al, 1984

 Possible Alzheimer's disease: There is a dementia syndrome with an atypical onset, presentation or progression; and without a known etiology; but no co-morbid diseases capable of producing dementia are believed to be in the origin of it. Unlikely Alzheimer's disease: The patient presents a dementia syndrome with a sudden onset, focal neurologic signs, seizures, or gait disturbance early in the course of the illness.
McKhann et al, 1984

Mild Cognitive Impairment

Concern regarding a change in cognition Impairment in one or more cognitive domains (1-1.5SD below) Preservation of independence in functional abilities (mild problems performing complex tasks, can take longer with more errors, but independence maintained) Not demented
Albert et al, 2011

New in 2010
ICAD (International Conference on Alzheimers Disease) 2010: Increased risk of seizures, anemia Intranasal insulin showed significant benefits on certain tests of memory and functioning for some with Alzheimer's and MCI . In those who showed benefits on memory tests, there were also positive changes in Alzheimer's biomarkers in spinal fluid.

New in 2009
Veterans with PTSD are almost twice as likely to develop dementia Veterans with PTSD had a dementia rate of 10.6%, while veterans without PTSD had a dementia rate of 6.6%. There is a growing understanding of the links between depression and dementia

http://news.ucsf.edu/releases/ptsd-linked-with-almost-double-dementia-risk-study-finds/

Whats New?

Learning objectives
1. Learn to recognize signs of depression in the elderly a) cognitive vs. emotional vs. neurovegetative signs b) differentiate depression from signs of dementia 2. Examine the criteria for diagnosis of dementia 3. Learn about the varying courses of disease progression a) depression heralding dementia b) depression co-morbid with dementia c) depression as a consequence of having dementia

Learning objectives cont

4. Learn the prevalence of depression across different types of dementia 5. Learn to recognize the psychiatric and neuropsychological symptoms that differentiate pseudodementia from dementia 6. Learn how to elicit key symptoms from clinical interview and cognitive testing results to aid in differentiation.

Agenda for this workshop

9am 5pm, 4 periods, lunch & two breaks 9am 10:50am, 10 min break 11am - 12:30pm, lunch break 1:45pm 3pm, 10 min break 3:10pm 5pm Last 15 minutes to be used for evaluations

Please be sure to sign in and out on the correct sheet for your license!

What do we know about the symptoms of depression?

Cognitive, emotional, vegetative signs
EMOTIONAL
COGNITIVE VEGETATIVE ONSET

DSM-IV TR Major Depression

A)5+ symptoms x 2-week period & represent a change At least one * *1) depressed mood *2) markedly diminished interest or pleasure in almost all activities 3) significant weight loss when not dieting or weight gain (e.g., 5% of body weight in a month), or decrease or increase in appetite.

DSM-IV TR Major Depression

4) insomnia or hypersomnia nearly every day 5) psychomotor agitation or retardation nearly every day 6) fatigue or loss of energy nearly every day

DSM-IV TR Major Depression

7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) 8) diminished ability to think or concentrate, or indecisiveness, nearly every day 9) recurrent thoughts of death, or suicidality

DSM-IV TR MDD cont

B) The symptoms do not meet criteria for a Mixed Episode C) The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D) The symptoms are not due to drugs/medication or a general medical condition (e.g., hypothyroidism) E) The symptoms are not better accounted for by Bereavement
American Psychiatric Association

Flat affect v. Masked Facies?

Flat affect v. Masked facies?

Epidemiology of dementia
Sixth leading cause of death in US Fifth leading cause of death in Americans aged 65 years Dementia affecting 37 million people worldwide (2010), up from 25 million in 2000
Alzheimers Assoc, 2011; Wimo et al, 2003

Epidemiology of dementia
5.4 million in the US, with 200,000 people <65 years predominantly elderly people, and as population growth increases in this age range, expected to rise significantly.

Alzheimers Association, 2011

Prevalence of dementia
over the age of 65 is 5% over 80, 20% 85 and older, 30% + over the age of 85 26% of women and 21% of men have some form of dementia
Lyketsos, 2002; Matthews, 2010

Prevalence by type of dementia

Latest Alzheimer's Statistics - U.S. (2010)An estimated 5.4 million Americans of all ages have Alzheimers disease (2011). (70% of dementias)
5.1 million people aged 65 (late onset) 200,000 individuals < age 65 (younger-onset)

Vascular FTD (12-15% of all dementias)

30 50% of young onset

DSM-IV TR Dementia
1. Memory impairment, plus 2. One or more of the following cognitive disturbances: a) Aphasia: Ability to generate coherent speech or understand spoken or written language is disrupted

DSM-IV TR Dementia
b) Apraxia: Ability to execute motor activities, assuming intact motor abilities, sensory function, and comprehension of the required task; c) Agnosia: Failure to recognize or identify objects despite intact sensory function

DSM-IV TR Dementia
e) disturbance in executive functioning (i.e., planning, organizing, sequencing, initiation, abstracting): Ability to think abstractly, make sound judgments, and plan and carry out complex tasks. The decline in cognitive abilities must be severe enough to interfere with daily life.

Cerebral involvement

DSM-IV TR Dementia
3. The deficits do not occur exclusively during the course of delirium.
Some symptoms can be reversed if they are caused by treatable conditions such as depression, delirium, drug interaction, thyroid problems, excess use of alcohol, or certain vitamin deficiencies (e.g. B12).

Cognition in depression
Cognitive loss can distinguish depressed mood from depressive episode Executive function can become impaired during SDE and not recover even after mood lifts Depression responds to antidepressants; dementia responds to ACE inhibitors Sudden onset may result from subcortical infarcts slow developing Late life
depression

atrophy

Arrows point to subcortical infarcts

Atrophy

Delirium
A. Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain, and shift attention B. Change in cognition (e.g., memory, language, orientation) that is not better accounted for by a preexisting dementia C. Rapid onset: Develops over a short period of time (hours-days) and fluctuates during the day D. Due to a general medical condition as evidenced by history, physical exam, and/or lab findings

Prevalence of Delirium
At any given point, 1.1% of those 55yo and older are experiencing delirium Of hospitalized medically ill, 10% - 30% Of hospitalized elderly, 10% - 15% upon admission and 10% - 40% at some time during their stay Nursing home, 75yo and older, 60%

Course of Delirium
Rapid onset (hours to days) Prodrome of restlessness, anxiety, irritability, disorientation, distractibility, sleep disturbance Lasts up to 3 days, but may last months in people with dementia Untreated etiologies can lead to seizure, stupor, coma, death

Delirium v. Dementia
BOTH Memory impairment Disorientation (Word finding difficulties)
DELIRIUM Change in level of consciousness (clarity of awareness re: environment) Rapid onset (hours-days) Symptom severity fluctuates DEMENTIA Alert Insidious onset Severity stable

Delirium v. Mood Disorders

DELIRIUM Hallucinations, delusions are unsystematized, fragmented Fear, anxiety is generalized, no trigger Symptoms fluctuate, and include memory impairments and disorientation
MOOD DISORDER WITH PSYCHOTIC FEATURES Hallucinations, delusions have themes, are set

ACUTE STRESS DISORDER Precipitated by a trauma

Causes of Delirium
Head trauma, seizure, stroke, tumors, dehydration, electrolyte imbalance, anemia, hypoxia, hypoglycemia, thiamine deficiency, heart attack, congestive heart failure, arrhythmia, shock, septicemia, pneumonia, urinary tract infections, substances, substance withdrawal, medications (digoxin toxicity [for CHF])

Types of Dementia
Alzheimers Disease Vascular Dementia Lewy Body Disease Parkinsonism, CBGD, MSA, Huntingtons Progressive Suprabulbar Palsy Frontal Temporal Lobe Dementias
Picks, Behavioral variant Primary Progressive Aphasia, Semantic Dementia

Most common types of dementia

Alzheimers disease (50-70% of cases) AD Vascular dementia (3040%; including about 20% where dual LBD VaD pathology exists) Dementia with Lewy bodies (15% of cases) Fronto-temporal degeneration(1215%)

Questionable Dementia
MCI: Mild Cognitive Impairment:
subjective complaints re: cognitive decline Without change in ADL/IADLs Positive findings on neuropsychological evals Impaired sense of smell

Pseudodementia
DRCD: depression-related cognitive dysfunction (reversible) Dementia syndrome of depression
Edwards, 2009

Pseudodementia
Cognitive changes in the elderly blur the distinction between normal aging and early signs of dementia Cognitive impairment often accompanies depression when severe enough Overlapping symptoms between depression & dementia Co-existence of depression and dementia
Bartolini et al, 2005

Testing, Surveys, Questionnaires

Many instruments designed to identify symptoms of depression were not designed for use with people with dementia or any healthcompromised group Symptoms due to illness may spuriously inflate depression ratings

MMSE
30 point scale, 24 mild, 12 moderate (9+yrs edu)

Laks et al., 2007

Key facts about AD

Current U.S. prevalence: >5 million people U.S. age-related incidence of moderate AD
Age 65-69: 1.6% Age 70-74: 3.5% Age 75-79: 7.8% Age 80-84: 14.8% Age 85-89: 26.0%

Heflin, L. http://knol.google.com/k/lara/alzheimers-disease/Ing3X-NE/g1JpHQ#

AD risk factors
Older age e4 allele of apolipoprotein gene Family history of dementia Family history of Parkinsons disease Downs syndrome Head injury with loss of consciousness Very low education (< 6 years) Female gender (mildly increases the risk) Diabetes

Alzheimers severity

Alzheimers diagnosis
HISTORY family history of neurological disease education level and work history current symptoms, onset, & course risk factors, drug and alcohol use medical history, current medications sleep habits NEUROPSYCHOLOGY verbal and nonverbal learning and memory visuospatial perception and copying/drawing ability speech and language skills Attention, executive functioning (judgment, insight) motor speed, processing speed Mood and vegetative state

BLOOD WORK Infection kidney dysfunction liver dysfunction B12 or folic acid deficiency thyroid dysfunction autoimmune disorders

NEUROIMAGING CT or MRI examines brain structure for places of

atrophy characteristic of AD
PET or SPECT examine brain function for places of hypometabolism or hypoperfusion characteristic of AD. only recommended for patients in whom diagnosis is difficult.

Questions?

Clinical approach
Identify the referral question Your clinical history will include an assessment of mood as well as questions to identify the course, history, and nature of any cognitive complaints Testing Hypothesis testing think of all possible diagnoses, and systematically rule these in or out

Referral questions
New onset memory disorder Is this dementia, depression, or delirium? If dementia, what kind of dementia is it? Treatment recommendations
Medicine Therapy Environmental supports Other

History
History of current complaints
Onset, character, triggers

Family history Medical history Psychiatric history Psychosocial history Academic/occupational history

Current Complaints
Mood, behavioral observations of affect, prosody, speech patterns, eye contact, rhythm Sleep, appetite, vision, hearing, smell When did these problems begin? What kinds of things do you forget? Activities of daily living Interview a significant other

Activities of Daily Living

Ambulation Grooming Hygiene Dressing Pill taking Shopping Bill paying Bureaucracies: license renewal,
passport, changing phone plan, getting parking permit, etc

Cooking Housekeeping Laundry DIY / home repairs Managing appointments Employment Bus/ drive Phone use
Johnson et al 2004

Dementia is a change from prior ability levels

Quantity and quality of education Occupational attainment Roles, responsibilities in the context of those roles (e.g., never drove, never paid bills, etc)

Case 1: Maria C.
You have been asked to see an 80 year old woman who has developed memory complaints over the past year and a half. What questions will you ask in the clinical interview and why?

Marias Current Complaints

Fell out of bed 6 weeks ago (motive for referral) Son died 18 months ago Fearful to leave house (new) Mobility, balance, and decision making all declining Now requires in home support services (IHSS) for housekeeping

Marias Family History

3rd of 5 children to a farmer and his wife in Mexico Older brother died of cancer, younger brother has prostate cancer, father died of stroke, hypertension runs in the family Sisters healthy, mother 97 healthy No known family history of memory disorders, or other neurologic, psychiatric, developmental disorders

Marias Medical History I

Current diagnoses: motion sickness, hypertension, poor balance, anemia, tinnitus, dizziness, headaches, R/O depression Health care at Emergency Dept only Medications: calcium. Although prescribed meds for HTN and anemia, not filled Remote hx: gall bladder removal, hernia repair, multiple blows to the head

Marias Medical History II

Fell out of bed: after standing up while getting out of bed, felt dizzy, lost balance, and fell to the floor. Hit head on nightstand. No loss of consciousness. More trouble w grooming, ambulates w a cane, difficulties keeping appointments Hearing impaired, wears glasses, sleep interrupted, appetite stable, denied alcohol/drugs/smoking

Psychiatric History
Hx c/w PTSD secondary to long history of domestic violence, ending decades ago No mental health care ever No history of serious mental illness Denied hallucinations/delusions/SI

Academic History
Informally taught to read and write over two years when she was a child from a woman in her village Bright student No ESL in US

Occupational History
Beginning age 7: domestic servant Adolescence: cooking, cleaning, caring for younger children both in and out of the home Adult: vendor of fruits/nuts at market

Psychosocial History I
Married age 17, husband sold jewelry, was abusive, widowed 20 years ago 1st child age 18, last age 44 15 births, 3 infants died, 5 miscarriages 6 daughters, 4 sons living 3 in SF, 4 in US not SF, 3 in Mexico 2 adult sons died in car accidents: 7 and 1.5y ago About 40 grandchildren

Psychosocial History II
Came to US age 73 for a visit, but due to unforeseen family stressors, remained unexpectedly
Son who traveled w her died in car accident Daughter leaving abusive husband required assistance w childcare

Currently, lives w daughter and 5 grandchildren

Mood
GDS: 17/30 (Moderate) Gracious, polite, warm Tearful describing sons death, affect restricted in range otherwise Fluent rate, soft spoken When 2nd son died, new onset of pain symptoms, fatigue, social withdrawal, stopped shopping & running errands

Mood current symptoms

Lonely Dissatisfied w life Prefers to stay home Worries about little things Worries about the future Feels helpless Disheartened Crying Problems w memory, concentration, decisions Unclear thinking Trouble getting out of bed in the AM Lacks energy or motivation Lacks initiative

Cognition - adjusted for age & edu

Orientation x 4 Attention Digit Span 93rd %ile Sustained attn 16th %ile Calculations Mental arithmetic average Subtraction 16th %ile Verbal Naming 50th %ile Sentence Rep 50th %ile Commands 50th %ile Similarities 68th %ile Animals 30th %ile Phonemic 16th %ile

 Visual/Construction RCFT copy 7th %ile Clock 2/3 could not place the hands Could not copy cube

Motor/ Processing Speed Motor planning Right hand 30th %ile Left hand 84th %ile Visual scanning 0 errors 2nd %ile for speed

 Verbal Memory
List learning 50th %ile Delayed recall 50th %ile 75% retention/ 20 min Recognition 6/6 Poor discriminability

Executive
Motor planning 50th %ile Alternating motor movements 68th %ile Initiation within broad limits of normal, slight reduction (16th 50th %ile) Mental arithmetic 50th %ile Failed trails

Visual Memory
RCFT delayed recall 50th %ile

Diagnosis?
Dementia? Delirium? Depression? Other?

Prevalence
Occurrence of depressive symptoms in the elderly: 5-40%, average: 12-15% Major Depressive Disorder much lower: 1-4% Comparable to general population Institutionalized show much higher rates
12% MDD -- 31% depressive symptoms

More often referred for evaluations Cognitive impairment = 17-36% of older adults

Depression looks different in the elderly

Symptom Mood Adult Presentation Depressed Anhedonic Suicidal thoughts Geriatric Presentation Weary, hopeless, angry Anxious Thoughts of death

Somatic

Cognitive

Sleep Appetite Psychomotor Pain Concentration Indecisiveness

Pain Somatic symptoms v. Comorbid disease Effects of medications attention, working memory, retrieval, learning, processing speed, executive function
Bierman 2007

Distinguishing Dementia from Depression - Prevalence

DEPRESSION (MDD) Lifetime: 10-25% for women 12-15% for men Point prevalence 5-9% for women 2-3% for men DEMENTIA (AD) Lifetime: 15% Age 65: <1% Age 85: 11% of men, 14% of women Age 90: 21% of men, 25% of women Age 95: 36% of men, 41% of women

Landes et al, 2005

Distinguishing Dementia from Depression - Background

DEMENTIA Insidious (very slow) onset Apraxia, neuro findings Effort good Recognition poor DEPRESSION Onset follows a trigger; abrupt cognitive decline Effort less Recognition good
Berger, 2005

Family history Treatment effects Course Premorbid state History: diabetes, HTN, high cholesterol, nocturnal confusion, white matter changes, ataxia, urinary incontinence, heart disease, age

Vegetative symptoms
Both depression and dementia may cause Hypersomnia or sleep disturbances Appetite and Weight changes Fatigue As distinct from social withdrawal and reduced initiation

Depression: Old Age v. Middle Age

Remission rates similar between middle aged and older patients Relapse rates higher for elderly Earlier onset x more total Number of episodes of depression Medical comorbidity worsens outcomes from depression Cognitive impairment is seen in 14% of depressed patients
Mirchell 2005

Late-life Depression as a Risk Factor for Dementia

Increasing evidence suggests that depression contributes to persistent cognitive deficits Late-life 1st episode of depression increases risk of developing AD within 4-18 years: 89% Depression confers a risk for developing AD Depression more severe in vascular dementia Total days depressed Slowed information processing & decreased working memory (tx resistance) Cognitive deficits persist after tx, mood lifts
Butters 2008

Depression and Rate of Progression to Dementia

Among people with MCI, rate of progression to dementia was greater for those with depression Depressive symptoms may be the earliest signs of MCI An acceleration of age-related cognitive decline in people with depression Reduced smell is predictor of progression from MCI to AD
Panza 2008

Severity of Depression & Anxiety over the Life Span

Mood

premorbid

onset

worsening

Panza 2008

severe impairment

Depression, Anxiety, & AD Severity

Mood

premorbid

onset

worsening

severe impairment
Panza 2008

Cognitive impairment

Depression In AD
90% of people with AD have psychiatric disturbances (24-50% depression) (agitation, hallucinations, delusions, mania, sleep disturbances, aggression, wandering, apathy) 20% dysphoria, 20% irritability stemming from depression In long term care, 6% of people with AD have depression Mood sx are common in mild-moderate dementia, less so later on (severe dementia, less depressed) Not reactive; autopsy reveals atrophy in locus coeruleus less norepinphrine Atrophy in raphe nuclei less serotonin

Proposed mechanism of depressions increased risk for AD

Depression
Glucocorticoids Cerebrovascular disease

Hippocampal atrophy

Generalized ischemia cognitive reserve

Frontostriatal abnormalities

AD Pathology

Clinical AD
Butters, Young, Lopez, et al., 2008

Risks for AD + Depression

First degree relatives with depression History of depression Female Younger age of onset if dementia

Obesity x Alzheimers

Neuropsychological Batteries
DEPRESSION V. NORMALS Small differences Motor related tasks Attention More dont know responses, less guessing, less effort DEMENTIA V. NORMALS Substantial differences Less impairments on attention and motor related tasks More intrusion errors

New Learning, Immediate Memory

DEPRESSION V. NORMALS DEMENTIA V. NORMALS Mild attentional difficulty Moderate to severe attentional difficulties, especially on more Shallow encoding of complex tasks information Decreased response latency Lack of ability to encode new information even with (mildly impulsive; not taking repetition the time to consider answer before responding) Random learning (no serial position effects) or recency Encoding benefits from effects predominate with span repetition consistent with basic attention Normal serial position effects

Memory & Retention

DEPRESSION Near normal rate of forgetting on delayed recall Delayed recall not significantly different from normals DEMENTIA Accelerated rate of forgetting NO retention on delayed recall Deficient immediate recall

Language Functioning
DEPRESSION Essentially normal receptive and expressive abilities Reduced verbal fluency

DEMENTIA Decline in expressive and receptive abilities as a function of state of progression

Range of Clinical/ Affective Presentations

Normal Depressed / no cognitive dysfunction Depressed + motor-related cognitive deficits Depressed + broad cognitive deficits Not depressed / Broad cognitive deficits

Normal

COGNITIVE FUNCTION Within normal limits

AFFECTIVE SYMPTOMS Within normal limits

IMAGE FINDINGS Within normal limits (i.e., mild, diffuse anomalies)

Depressed / No Cognitive Dysfunction

AFFECTIVE SYMPTOMS COGNITIVE FUNCTION

Within normal limits

Depressed affect, anhedonia, vegetative signs, psychomotor retardation, feelings of worthlessness & guilt

IMAGE FINDINGS White matter hyperintensities, increased ventricles, decreased tissue density, mild atrophy

Depressed / Motor-Related Cognitive Deficits

COGNITIVE FUNCTION Mild-mod attentional and encoding deficits Generally slowed mentation AFFECTIVE SYMPTOMS Depressed affect, anhedonia, vegetative signs, feelings of worthlessness & guilt Greater psychomotor retardation

IMAGE FINDINGS White matter hyperintensities, increased ventricles, decreased tissue density, mild atrophy

Depressed / Broad Cognitive Deficits

COGNITIVE FUNCTION Pervasive cognitive deficits: IQ, language, memory, motor, reasoning AFFECTIVE SYMPTOMS Depressed affect, anhedonia, vegetative signs, feelings of worthlessness & guilt Greater psychomotor retardation, agitation, perturbability

IMAGE FINDINGS Widespread moderatesevere atrophy cortical & subcortical cell loss, increased ventricle-tobrain tissue ratio

Not Depressed / Broad Cognitive Deficits

COGNITIVE FUNCTION Pervasive cognitive deficits: IQ, language, memory, motor, reasoning

AFFECTIVE SYMPTOMS Flatness or lability Agitation

IMAGE FINDINGS Widespread moderatesevere atrophy cortical & subcortical cell loss, increased ventricle-tobrain tissue ratio

Alzheimers Dementia v. Depression - Neuropsychology

DEPRESSION BETTER DEMENTIA BETTER Olfaction (McCaffrey 2000) Mood Letter cancellation Effort Recognition, incidental learning Recency effect Primacy effect Intrusion errors Semantic organization improves recall

DEMENTIA DUE TO DEPRESSION

Poor primacy effect, but few intrusions Memory improves with antidepressants

Alzheimers Dementia v. Dementia Syndrome of Depression

BOTH Older adults Cognitive impairment dont know responses ALZHEIMERS with depression Progressive, irreversible 15-40% of elderly List learning impaired

DSD Reversible with treatment for depression 20% of elderly out-patients, 50% of elderly in-patients List learning adequate Non-verbal memory remained impaired
McNeil 1999

Alzheimers Dementia v. Dementia Syndrome of Depression

BOTH Poor memory scores ALZHEIMERS with depression Cortical dementia qualities agnosia aphasia apraxia

DSD Subcortical dementia qualities poor attention poor encoding poor memory Motor speed Course fluctuates with mood

Mild Cognitive Impairment (MCI)

Complaints of cognitive deficits confirmed on np testing, but without functional impairments Several subtypes
Amnestic Single domain, non-memory
Executive dysfunction language

Multiple domain

MCI outcomes
MCI with neuropsychiatric symptoms (NPS) are 2-3 times more likely to convert to dementia in 10 years Anxiety, sleep changes, depression most common NPS Those with more NPS were more likely to have the amnestic subtype of MCI

Extended Evaluation of Psychiatric symptoms

Anosognosia: performance is worse than selfassessment Effort: usually normal History of episodes of depression, possible untreated episodes, prior response to treatment Suicidal ideation, intention; history of attempts Family history, age of onset Performance on ADLs: focus on changes (insidious v. abrupt?)

Case 2: Joan C.
79 year old woman with a history of memory loss and anxious feelings How would you approach this case?

Medical History
hypothyroidism, high cholesterol, history of falls Hit head, stitches to hand, no loss of consciousness or other effects MRI: multiple white matter hyperintensities (50) slightly more than usual for age Cataract surgery, wears glasses Synthroid, plavix, baby aspirin, lipitor Hearing WNL, smell reduced x 20 years

Psychiatric History
Frequent anxious feelings Denied delusions, hallucinations, SI Remote history of psychotherapy for marital issues sleep, appetite adequate by report

Current complaints
Long, slow decline Difficulty remembering peoples names both familiar and unfamiliar people Forgets appointments, to take medication, where she put her keys, wallet, phone, glasses Loses train of thought, forgets what she was doing, forgets what she just read, forgets plans for the day, easily distracted Spelling problems, problems w new instructions

CCII & Activities of Daily Living

Stopped driving 6 months ago Still pays her bills Still shops independently Stopped playing tennis due to falls, imbalance Difficulty handling arguments Defensive; difficulty accepting criticism Irritable, temper worse Feels despair

Psychosocial History
Lives w husband in an independent living community Artist, goes to studio daily (BA in Art) Socializes over meals w other residents, and w husband on planned outings to plays and concerts Denied significant alcohol, drugs, tobacco

Family History
Older of 2 girls to pilot and homemaker Father died from occluded artery Mother & sister demented before dying Daughter has autism and seizure disorder, lives in group home

Behavioral Observations
Speech rate & rhythm WNL Well groomed Anxious about her performance on testing Accompanied by her husband to all sessions No abnormal behaviors Frequently second guessed herself, running commentary which interfered w performance

Test Results
A+O x 4 BAI 7/63; WNL GDS 7/30; WNL BNT 58/60; WNL MoCA 17/30; low WTAR 79th %ile Predicted IQ = 84th %ile Current IQ = 7th %ile 6 digits Forward = 33rd 4 digits Backward = 2nd Sentence Rep impaired Picture completion 9th Visual scanning 37th Sustained attention ok

Results
Could not copy a cube Line bisection WNL Animals 9th %ile Phonemic 16th %ile Switching 5th %ile Motor speed 75th %ile Utility errors Coding 9th %ile 0/5 words after 5 minutes 9-word list x 4: 21st %ile Story memory
immediately 25th %ile Delay 16th %ile Retention 36th %ile

Picture memory
Immediately 25th %ile Delayed 75th %ile

Executive
What would you do if you saw thick black smoke coming from your neighbors window? Get them out of there. What else? DK What would you do if you saw a 3-year-old child walking alone at the end of a pier? Look for the parents. You dont see them. Take his hand and look for the parents. Design fluency 75th %ile Average for intrusions, repetitions

Diagnoses?
Memory disorder? Mood disorder?

Causes of dementia
Degenerative disorders: Alzheimers disease (AD); fronto-temporal dementias (FTD); dementia with Lewy bodies (DLB); Parkinson disease dementia; Huntingtons disease; progressive supranuclear palsy. Vascular causes: multi-infarct dementia (MID); vasculitis (eg, lupus erythematosus). Trauma: major head injury; subdural hematoma; boxing. Intracranial tumors: primary tumors; metastatic tumors.

More causes of dementia

Infection: bacterial (eg, Lyme disease and syphilis); fungal; viral (eg, post-encephalitic HIV). Other infectious agents (eg, Creutzfeldt-Jakob disease [CJD], neurocysticercosis; tuberculosis). Hydrocephalus: obstructive, normal pressure hydrocephalus (NPH). Toxic, endocrine and metabolic causes: heavy metals; drug intoxication; hypothyroidism; hypercalcemia; B12 and folate deficiencies; hepatic and renal failure; paraneoplastic/limbic encephalitis; inherited metabolic disorders (eg, Wilsons disease, leukodystrophies). Anoxia: post-cardiac arrest; carbon monoxide poisoning.

Extended Evaluation of Medical Risk Factors

Comorbid or contributing medical conditions
HTN, hypothyroidism, chronic pain, cardiac conditions, diabetes, obesity, hyperlipidemia, TBI

Lab tests: B12/folate, CBC, TSH Comprehensive history of vascular risk factors: atherosclerosis, atrial fibrillations, stenosis, stroke history Imaging: CT/MRI (preferable) Medications: beta blockers

Psychosocial Risk Factors

Current stressors: recent losses, serious illness, marital discord, work or financial difficulties Social support system Community involvement: current level and recent changes

Severity of AD & Presence of Depressive Symptoms

Apathy is more prevalent than dysphoria or depression Apathy was more closely associated with severity of AD, cognitive impairment, & functional deficits Differential diagnosis of apathy and depression bears on family education & effective treatment
Starskein 2009

Apathy
Loss of motivation, manifested by reduced initiation, poor persistence, lowered interest, indifference, low social engagement, blunted emotional response, lack of insight 61-92% of AD patients ADL participation caregiver burden Viewed as laziness, opposition, lack of caring

Abulia
Loss, lack, or impairment of the power to will to execute what is in mind Overlaps with apathy Dependency on others to structure activity Lack of effort to perform every day activities

Prevalence of Depression Comorbid with Dementia

20% of people with AD meet criteria for MDD 13% of community-dwelling people with dementia meet criteria for MDD Depressed mood in AD (41%) is more common than MDD in AD (20%) Dysphoria (sad mood, guilty feelings, low selfesteem, hopelessness) in AD ~ 38% Both less common than apathy
Potter 2007

Apathy versus Depression in Dementia

DSM-IV: Loss of interest or pleasure instead of depressed mood may qualify as MDD In people with dementia: loss of pleasure
Loss of motivation or ability -- OR - Depression

Both: hypersomnia, fatigue, weight loss Dysphoria does not correlate with apathy Apathy is more closely associated than dysphoria with severity of AD, cognitive impairment, & functional deficits

Hamilton Depression Rating Scale: 2 Factors

APATHY Psychomotor retardation Loss of interest Poor energy Agitation Poor appetite DEPRESSION (dysphoria) Sad mood Guilt Suicidal ideation Anxiety Insomnia

Apathy & Depression in Dementia

Presence of apathy in criteria for depression may artificially increase depression scores on standardized instruments Coexistence of apathy and depression does not increase depression scores on standardized instruments Apathy is consistently associated with worse cognitive impairment, worse ADL functioning, and greater caregiver burden Apathy is NOT associated with worse dysphoria

Prevalence of Apathy & Depression in Mild Dementia

People with Mild Dementia

19% have Apathy

12%

42% have Depression

62% of those with Apathy have Depression

28% of those with Depression have Apathy

Medications
Patients with apathy and NO depression are often treated with antidepressants (the majority) Confusion re: the overlap of behavioral features between apathy and depression (e.g., social withdrawal)

Benoit 2008

Goal: Characterize affect as depressed versus apathetic

Need to distinguish apathy from depression to guide treatment Loss of interest is not a valid sx in dementia Apathy: cholinergic deficits (respond to methylphenidate and cholinesterase inhibitors) SSRIs may increase apathy Depression: serotonergic deficits or an imbalance of dopamine & norepinephrine

Recommendations
Behavioral strategies for decreasing depression accompanied by cognitive impairment
enjoyable activities based on previous interests Modify activity by level of current ability
Attend garden shows instead of gardening Decrease duration & intensity of physical activity

Structure activities for patient; arrange rides Modify or eliminate activities that cause frustration due to impairment
Arrange for help with finances or household repairs

Decreasing Depression Accompanied by Cognitive Impairment

Use redirection to maintain focus on positive experiences and memories
Maintain photo album, encourage discussion of favorite memories (life review)

Caregivers must monitor and nourish own state of well-being for best response to challenging behavior from patient
Respite care, daytime care programs, caregiver support groups

Most common types of dementia

Alzheimers disease (60-70%; of cases) Vascular dementia (3040%; including about 20% where dual pathology exists) Dementia with Lewy bodies (15% of cases) Fronto-temporal dementia (5%)

Crowe 1999

Vascular dementia
Presence of clinical dementia Evidence of cerebrovascular disease Exclusion of other conditions capable of producing dementia A score 7 is suggestive of vascular dementia.

Dementia with Lewy bodies (DLB)

Typical presenting features fluctuating dementia prominent deficits in
attention frontal executive tasks visuospatial abilities

both cortical and subcortical features

Clinical Features of DLB

Dementia of six months duration with: Periods of confusion Fluctuations in cognition (especially attention and alertness) Visual hallucinations Spontaneous extrapyramidal signs such as rigidity or slowing (mild parkinsonism) Bradykinesia (paucity of movement)

Supportive features of DLB

Frequent or unexplained falls, syncope or transient loss of consciousness Increased sensitivity to neuroleptics Hallucinations in other modalities Systematized delusions

Fronto-temporal dementia
sometimes called Picks complex characterized by
focal frontal atrophy with personality and behavioral disturbances (bvFTD = behavioral variant) temporal atrophy with either
progressive aphasia or semantic dementia

Onset is in a younger age group than other dementias diagnosis may be difficult in the early stages
Kertesz 2010

Presenting features of FTD

Insidious onset and slow progression Early and prominent personality changes (eg, apathy, irritability, jocularity, euphoria, loss of personal and social awareness) Loss of tact and concern Hypochondriasis Unrestrained exploration of objects and the environment (hypermetamorphosis) Distractability and impulsivity, depression and anxiety Inertia

Case 3: Ana D.
54 year old Brazilian woman with memory problems over the past 7 years, getting worse 3 years ago, and really bad in the last several months Hypotheses? Testing?

Current Complaints
Misplaces keys, wallet Locks herself out of house, car Tries to change the TV channel w her cell phone or tried to make a call w the TV remote Word finding difficulties, language mistakes Difficulties w decision making, concentration Repeats conversations Becomes disoriented Checks w husband constantly

ADLs
Can use cell phone properly No longer working, living off savings Can manage finances Shops independently Drives and takes bus, gets lost Cooks, burns food

Early History
3rd of 7 children born on a ranch in Brazil to an agricultural laborer and homemaker Very religious Catholic parents At times, not enough food No medical care; brother died age 19, meningitis?

Family Medical History

Several strokes in family (grandparents, aunts & uncles) Family hx of depression (parents, sister) Mother died of pulmonary embolism Father alive w hypertension, high cholesterol, depression

Academic History
Father taught her to read and write Portuguese 1st grade starting age 9 4 years of school One of the best students Worked part time throughout school No ESL courses, but picked up English at work

Occupational History
Worked from young age: housework, farmwork Moved to big city age 18, by herself Vendor in the market selling clothes Began her own clothing store in her mid-20s Age 35 moved to US, housekeeping for other womens businesses 15 years ago started her own housekeeping business, very successful, gave it up last year because of difficulties w employees

Recent Personal History

Married husband 7 years ago, hotel clerk, speaks English and Spanish, verbally & emotionally abusive Mother-in-law lived with them from 4 years ago to 1 year ago, verbally abusive Should have never gotten married Lived in Brazil much of last year Friends are Brazilian, 2 siblings live in US, no children, spiritual but not religious, no legal issues

Medical History
Chemical (cleaning agents) and pesticide exposure, prolonged High cholesterol Fell backwards and hit head 9 months ago, no loss of consciousness, daily headaches MRI results unknown

Psychiatric History
Pre-Menstrual Syndrome, severe mood swings with menstrual cycle; Menopause began last year with increased irritability Disturbed sleep
An hour to fall asleep (rumination) Wakes up 3-4 times/ night for 15-30 minutes Nightmares x 4 years Wakes unrefreshed

Appetite good, gained weight (12lbs/6 months) in Brazil

Psychiatry II
Isolated, detached as a child never really felt parents were my parents Mother verbally abusive Developed symptoms of PTSD at age 12 after being abused by male head of household where she was a domestic servant (tearful, wouldnt reveal) Suicide attempt at 19, pills, 5150d in Brazil

Psychiatry III
Two different psychotherapists, no good fit
3-4 months A few sessions

Open to therapy now, Cymbalta 60mg Denied drug use, tobacco Drinks 3-6 beers a few nights a week when out w friends, husband tells her its too much, she feels she should cut back, no alcohol x 1 week Racing thoughts, denied mania

Behavioral Observations
Arrived on time Appeared younger than her age, fashionable, very attractive, very well groomed/dressed/ hair, make up, nails, casual but nicely put together I'm terrible at this! Affect restricted in range Word finding difficulties Good effort

Test Results
WTAR 19th %ile Predicted IQ 10th %ile prediction on tests in English, her 2nd language w 4 y edu; inference re true IQ invalid Current IQ = 10th %ile 5 digits forward 16th %ile Letter Number Sequence 4 digits = 16th %ile Symbol Search multiple errors 5th %ile Picture Completion 10th but 25th %ile w more time Similarities 25th %ile Animals 9th %ile Naming in any language, borderline impaired

Test Results II
Judgment of Line orientation 6th %ile Complex figure 91st %ile Acquisition on 10 word list: 3, 6, 7, 9 Primacy effect Encoding 53rd %ile Delayed recall 100% Recognition 100% Story memory 2nd percentile I cant do this! 100% retention Visual memory 42nd %ile Number sequencing slow Letter sequencing impossible Judgment adequate

Test Results III

BAI 42/63; severe Self depricating statements, feels dumb Nervous, scared Hyperventilates, dizzy, rapid heart beat Unable to relax, fears the worst BDI 48/63; severe Denied hallucinations, delusions Passive SI Cant cry Feelings of guilt, punishment, self-blame, restlessness, fatigue Difficulties w concentration, decisions

Conclusions
Diagnoses
Memory disorder? Mood disorder?

Recommendations
Medical
Referral to psychiatry Referral to endocrinology

Psychological
Individual Couples

Preclinical distinctions
Preclinical depression includes dysphoria (sadness, guilt, thoughts of death, pessimism, irritability) Preclinical memory disorders (MCI) include signs of apathy & poor motivation
Lack of interest, Social isolation, Loss of libido Poor concentration Poor sustained attention & divided attention, Indecision, Associated with cognitive declines

Dysthymia
Relative to depression, people with dysthymia had better insight/ awareness regarding functional limitations Dysthymia in AD may be reactionary to loss of functions Major depression in AD may be more related to underlying physiology

MCI & MMSE

The earliest areas to decline Orientation to time Orientation to place Delayed memory Repetition Following commands Design copy

Early signs of depression

Dysphoria, loss of energy Cause difficulty with automatic tasks when very severe Motivation-related symptoms are more detrimental to cognitive performance than mood-related symptoms Those with comorbid depression & MCI are more likely to convert to AD in 3 years

Cognitive profiles of older adults with and without major depression

MD is associated with cognitive complaints, specifically memory and language, but not nec. np test findings for those domains Executive functioning may be more sensitive to effects of depression on cognition Presence of cognitive impairment before development of depressive symptoms heralds further cognitive decline Memory and language complaints in elders without np findings is a strong indicator of depression
Fisher 2008

Motivational Sx of MD mask MCI

Among people with cognitive and mood complaints, those who went on to develop dementia had higher motivational BDI subtest scores

Bartolini 2005

Frontotemporal Dementia
Social errors or abuses Hyperorality Personality changes Early on, few behavioral manifestations Less interest in professional, social, personal lives Withdrawal from previously pleasurable activities Impaired decision making Mood changes
Elderkin-Thomson, Boone, Hwang, & Kumar, 2004

FTD course & prevalence

15-20% of dementia Starts in 5th 7th decade of life (40 60yo) Insidious onset Disruptive after 2-3 years 3 types: behavioral variant, semantic dementia, progressive non-fluent aphasia

Neuropsychology of FTD
Preservation of memory to late-stage disease making diagnosis difficult Impaired judgment and insight Mental rigidity and inflexibility Language difficulties (eg, problems with word recall, circumlocution, word repetition also known as gramophone syndrome)
Rascovsky et al, 2007

FTD Diagnosis
CORE FEATURES
Loss of social and personal awareness Mental rigidity Perseverative behavior Disinhibition, Distractibility Utilization behavior

SPEECH DISORDERS
Progressive reduction of speech (PFA) Stereotypy - e.g., neologisms, constantly recurring words and phrases, modes of intonation Semantic Dementia (receptive aphasias)

AFFECTIVE SYMPTOMS
Depression, Anxiety Suicidal & fixed ideation Hypochondriasis Apathy

PHYSICAL INDICATORS
Early primitive reflexes (snout) Incontinence Rigidity, Tremor Hypoperfusion Accelerated frontal atrophy

Utilization behavior
a frontal lobe disorder in which the patient has difficulty resisting their impulse to operate or manipulate objects which are in their visual field and within reach. So in this case, a patient may pick up a spoon and stir a cup, if it is within reach, even though the task may be to write a letter. Unlike other impulse control disorders, patients with this disorder confabulate reasons for their actions.

Confabulation
the formation of false memories, perceptions, or beliefs about the self or the environment as a result of neurological or psychological dysfunction. When it is a matter of memory, confabulation is the confusion of imagination with memory, or the confused application of true memories. Confabulations are difficult to differentiate from delusions and from lying.

Brief Overview of Aphasias

FLUENCY REPETITION COMPREHENSION APHASIA

Fluent

Yes

Good

Anomia

Poor No
TeleGraphic Yes No

Transcortical sensory Conduction Wernickes

Transcortical motor Transcortical mixed Brocas Global

Good Poor
Good Poor Good Poor

AD versus FTD
FTD patients performed worse overall and showed similar impairment in letter and semantic category fluency, whereas AD patients showed greater impairment in semantic category than letter fluency. This disparity increased with increasing severity of dementia. AD: animal naming < FAS

FTDL v. MDD
Prefrontal cortex orbital , dorsolateral Frontal hypoperfusion on PET Cognitive loss Semantic memory FTD < MDD Boston Naming Test Size, shape, habits of animals, eg, Does a zebra eat meat? Verbal fluency FTD Greater cognitive impairment, esp. for language and executive functions (planning)

cortical
MDD late onset Limbic hypometabolism Amygdala hypermetabolism

subcortical

Dorso Lateral Pre Frontal Cortex

Ventro Lateral Pre Frontal Orbito Cortex Frontal Cortex

Amygdala

Case 4

Summary
1. signs of depression in the elderly a) cognitive vs. b) emotional vs. c) neurovegetative signs d) differentiate them from dementia

Summary
diagnosis of dementia prevalence rate of depression across different types of dementia

Summary
1. Learn about the varying courses of disease progression a) depression heralding dementia b) depression co-morbid with dementia c) depression as a consequence of having dementia

Summary
Psychiatric and neuropsychological symptoms that differentiate pseudodementia from dementia What to ask in the clinical interview What to look for in cognitive test results

Acknowledgements
Simon Tan, PsyD Seoni Llanes, PhD