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 Alzheimer’s 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 (Alzheimer’s 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 & Alzheimer’s 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

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

but independence maintained) • Not demented Albert et al. can take longer with more errors. 2011 .5SD below) • Preservation of independence in functional abilities (mild problems performing complex tasks.Mild Cognitive Impairment • Concern regarding a change in cognition • Impairment in one or more cognitive domains (1-1.

there were also positive changes in Alzheimer's biomarkers in spinal fluid. In those who showed benefits on memory tests. .New in 2010 ICAD (International Conference on Alzheimer’s 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 .

while veterans without PTSD had a dementia rate of 6. • There is a growing understanding of the links between depression and dementia http://news.New in 2009 • Veterans with PTSD are almost twice as likely to develop dementia • Veterans with PTSD had a dementia rate of 10.ucsf.6%.edu/releases/ptsd-linked-with-almost-double-dementia-risk-study-finds/ .6%.

What’s New? .

Learning objectives 1. neurovegetative signs b) differentiate depression from signs of dementia 2. Learn to recognize signs of depression in the elderly a) cognitive vs. emotional vs. 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 .

Learn the prevalence of depression across different types of dementia 5.Learning objectives con’t 4. Learn how to elicit key symptoms from clinical interview and cognitive testing results to aid in differentiation. . Learn to recognize the psychiatric and neuropsychological symptoms that differentiate pseudodementia from dementia 6.

lunch break • 1:45pm – 3pm.Agenda for this workshop 9am – 5pm. 10 min break • 11am . 4 periods. lunch & two breaks • 9am – 10:50am. 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! .12:30pm.

vegetative signs – EMOTIONAL – COGNITIVE – VEGETATIVE – ONSET . emotional.What do we know about the symptoms of depression? • Cognitive.

or decrease or increase in appetite.. . 5% of body weight in a month).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.

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 .

or suicidality . nearly every day 9) recurrent thoughts of death. or indecisiveness.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 other important areas of functioning.g.DSM-IV TR MDD con’t B) The symptoms do not meet criteria for a Mixed Episode C) The symptoms cause clinically significant distress or impairment in social.. D) The symptoms are not due to drugs/medication or a general medical condition (e. hypothyroidism) E) The symptoms are not better accounted for by Bereavement American Psychiatric Association . occupational.

Masked Facies? .Flat affect v.

Masked facies? .Flat affect v.

2003 . Wimo et al. 2011. up from 25 million in 2000 Alzheimer’s Assoc.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).

2011 . and as population growth increases in this age range. Alzheimer’s Association.Epidemiology of dementia • 5.000 people <65 years • predominantly elderly people.4 million in the US. expected to rise significantly. with 200.

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

(2010)An estimated 5.000 individuals < age 65 (“younger-onset”) • Vascular • FTD (12-15% of all dementias) – 30 – 50% of young onset .S.4 million Americans of all ages have Alzheimer’s disease (2011).U.Prevalence by type of dementia • Latest Alzheimer's Statistics .1 million people aged ≥ 65 (“late onset”) – 200. (70% of dementias) – 5.

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

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

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

Cerebral involvement .

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

dementia responds to ACE inhibitors • Sudden onset may result from subcortical infarcts • slow developing Late life depression atrophy .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.

Arrows point to subcortical infarcts .

Atrophy .

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

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

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

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.

are set ACUTE STRESS DISORDER Precipitated by a trauma . anxiety is generalized. no trigger Symptoms fluctuate.Delirium v. and include memory impairments and disorientation MOOD DISORDER WITH PSYCHOTIC FEATURES Hallucinations. delusions have themes. fragmented Fear. delusions are unsystematized. Mood Disorders DELIRIUM Hallucinations.

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

Huntington’s Progressive Suprabulbar Palsy Frontal Temporal Lobe Dementias – Picks. Semantic Dementia . MSA. CBGD.Types of Dementia • • • • • • Alzheimer’s Disease Vascular Dementia Lewy Body Disease Parkinsonism. Behavioral variant – Primary Progressive Aphasia.

including about 20% where dual LBD VaD pathology exists) • Dementia with Lewy bodies (15% of cases) • Fronto-temporal degeneration(1215%) .Most common types of dementia • Alzheimer’s disease (50-70% of cases) AD • Vascular dementia (30–40%.

2009 .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.

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 .

Surveys.Testing. 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 .

. 12 moderate (9+yrs edu) Laks et al.MMSE • 30 point scale. 24 mild. 2007 .

Key facts about AD Current U. http://knol.com/k/lara/alzheimers-disease/Ing3X-NE/g1JpHQ# .0% Heflin. L. prevalence: >5 million people U.8% Age 85-89: 26. age-related incidence of moderate AD – – – – – Age 65-69: 1.6% Age 70-74: 3.S.8% Age 80-84: 14.5% Age 75-79: 7.google.S.

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

Alzheimer’s severity .

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. onset. & course risk factors. executive functioning (judgment.Alzheimer’s diagnosis HISTORY family history of neurological disease education level and work history current symptoms. 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. . only recommended for patients in whom diagnosis is difficult.

Questions? .

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

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

triggers • • • • • Family history Medical history Psychiatric history Psychosocial history Academic/occupational history .History • History of current complaints – Onset. character.

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

Activities of Daily Living • • • • • • • • Ambulation Grooming Hygiene Dressing Pill taking Shopping Bill paying Bureaucracies: license renewal. etc • • • • • • • • Cooking Housekeeping Laundry DIY / home repairs Managing appointments Employment Bus/ drive Phone use Johnson et al 2004 . changing phone plan. getting parking permit. passport.

g. responsibilities in the context of those roles (e. never drove. never paid bills..Dementia is a change from prior ability levels • Quantity and quality of education • Occupational attainment • Roles. etc) .

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

Maria’s 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

Maria’s 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

Maria’s 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

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

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 .

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

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

but due to unforeseen family stressors. lives w daughter and 5 grandchildren .Psychosocial History II • Came to US age 73 for a visit. remained unexpectedly – Son who traveled w her died in car accident – Daughter leaving abusive husband required assistance w childcare • Currently.

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

concentration. decisions • Unclear thinking • Trouble getting out of bed in the AM • Lacks energy or motivation • Lacks initiative .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.

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 .Cognition .

• 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 .

slight reduction (16th – 50th %ile) – Mental arithmetic 50th %ile – Failed trails • Visual Memory – RCFT delayed recall 50th %ile .• 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.

Diagnosis? • Dementia? • Delirium? • Depression? • Other? .

31% depressive symptoms • More often referred for evaluations • Cognitive impairment = 17-36% of older adults .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 -.

retrieval. 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. learning. processing speed.Depression looks different in the elderly Symptom Mood Adult Presentation Depressed Anhedonic Suicidal thoughts Geriatric Presentation Weary. executive function Bierman 2007 . hopeless.

41% of women Landes et al.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. 2005 . 25% of women Age 95: 36% of men.

age . 2005 Family history Treatment effects Course Premorbid state History: diabetes. white matter changes. heart disease. ataxia.Distinguishing Dementia from Depression . HTN. high cholesterol. neuro findings Effort good Recognition poor DEPRESSION Onset follows a trigger.Background DEMENTIA Insidious (very slow) onset Apraxia. abrupt cognitive decline Effort less Recognition good Berger. urinary incontinence. nocturnal confusion.

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 .

mood lifts Butters 2008 .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.

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 .Depression and Rate of Progression to Dementia • Among people with MCI.

Severity of Depression & Anxiety over the Life Span Mood premorbid onset worsening Panza 2008 severe impairment .

& AD Severity Mood premorbid onset worsening severe impairment Panza 2008 Cognitive impairment . Anxiety.Depression.

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

2008 .. Young.Proposed mechanism of depression’s increased risk for AD Depression Glucocorticoids Cerebrovascular disease Hippocampal atrophy Generalized ischemia ↓ cognitive reserve Frontostriatal abnormalities AD Pathology Clinical AD Butters. Lopez. et al.

Risks for AD + Depression • • • • First degree relatives with depression History of depression Female Younger age of onset if dementia .

Obesity x Alzheimer’s .

NORMALS • Small differences • Motor related tasks • Attention • More “don’t know” responses.Neuropsychological Batteries DEPRESSION V. less guessing. NORMALS • Substantial differences • Less impairments on attention and motor related tasks • More intrusion errors . less effort DEMENTIA V.

New Learning. NORMALS • Mild attentional difficulty • Moderate to severe attentional difficulties. Immediate Memory DEPRESSION V. 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 . NORMALS DEMENTIA V.

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 .

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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 .

. mild.Normal COGNITIVE FUNCTION Within normal limits AFFECTIVE SYMPTOMS Within normal limits IMAGE FINDINGS Within normal limits (i. diffuse anomalies) .e.

Depressed / No Cognitive Dysfunction AFFECTIVE SYMPTOMS COGNITIVE FUNCTION Within normal limits Depressed affect. feelings of worthlessness & guilt IMAGE FINDINGS White matter hyperintensities. decreased tissue density. mild atrophy . increased ventricles. anhedonia. psychomotor retardation. vegetative signs.

decreased tissue density. vegetative signs. feelings of worthlessness & guilt Greater psychomotor retardation IMAGE FINDINGS White matter hyperintensities. increased ventricles. mild atrophy . anhedonia.Depressed / Motor-Related Cognitive Deficits COGNITIVE FUNCTION Mild-mod attentional and encoding deficits Generally slowed mentation AFFECTIVE SYMPTOMS Depressed affect.

perturbability IMAGE FINDINGS Widespread moderatesevere atrophy cortical & subcortical cell loss. increased ventricle-tobrain tissue ratio . motor. feelings of worthlessness & guilt Greater psychomotor retardation. language. agitation. anhedonia. vegetative signs.Depressed / Broad Cognitive Deficits COGNITIVE FUNCTION Pervasive cognitive deficits: IQ. memory. reasoning AFFECTIVE SYMPTOMS Depressed affect.

reasoning AFFECTIVE SYMPTOMS Flatness or lability Agitation IMAGE FINDINGS Widespread moderatesevere atrophy cortical & subcortical cell loss. memory. motor.Not Depressed / Broad Cognitive Deficits COGNITIVE FUNCTION Pervasive cognitive deficits: IQ. language. increased ventricle-tobrain tissue ratio .

but few intrusions Memory improves with antidepressants . Depression . incidental learning • Recency effect • Primacy effect • Intrusion errors • Semantic organization improves recall DEMENTIA DUE TO DEPRESSION Poor primacy effect.Neuropsychology DEPRESSION BETTER DEMENTIA BETTER • Olfaction (McCaffrey 2000) • Mood • Letter cancellation • Effort • Recognition.Alzheimer’s Dementia v.

50% of elderly in-patients • List learning adequate • Non-verbal memory remained impaired McNeil 1999 . irreversible • 15-40% of elderly • List learning impaired DSD • Reversible with treatment for depression • 20% of elderly out-patients. Dementia Syndrome of Depression BOTH • Older adults • Cognitive impairment • “don’t know” responses ALZHEIMERS with depression • Progressive.Alzheimer’s Dementia v.

Alzheimer’s 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. non-memory • Executive dysfunction • language – Multiple domain . but without functional impairments • Several subtypes – Amnestic – Single domain.

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

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

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

difficulty accepting criticism Irritable. imbalance Difficulty handling arguments Defensive.CCII & Activities of Daily Living • • • • • • • • Stopped driving 6 months ago Still pays her bills Still shops independently Stopped playing tennis due to falls. temper worse Feels despair .

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

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 .

running commentary which interfered w performance .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.

WNL GDS 7/30. WNL BNT 58/60. 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 .Test Results • • • • • • A+O x 4 BAI 7/63. WNL MoCA 17/30.

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 .

You don’t see them. 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. repetitions . Take his hand and look for the parents.Executive • What would you do if you saw thick black smoke coming from your neighbors window? Get them out of there. • Design fluency 75th %ile • Average for intrusions.

Diagnoses? • Memory disorder? • Mood disorder? .

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

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

hypothyroidism. atrial fibrillations. chronic pain.Extended Evaluation of Medical Risk Factors • Comorbid or contributing medical conditions – HTN. hyperlipidemia. TBI • Lab tests: B12/folate. diabetes. stroke history • Imaging: CT/MRI (preferable) • Medications: beta blockers . stenosis. cardiac conditions. TSH • Comprehensive history of vascular risk factors: atherosclerosis. obesity. CBC.

serious illness. marital discord. work or financial difficulties • Social support system • Community involvement: current level and recent changes .Psychosocial Risk Factors • Current stressors: recent losses.

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

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

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 . lack.Abulia Loss.

hopelessness) in AD ~ 38% • Both less common than apathy Potter 2007 . guilty feelings. low selfesteem.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.

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

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. and greater caregiver burden • Apathy is NOT associated with worse dysphoria . worse ADL functioning.

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 .

g.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. 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 .

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.Decreasing Depression Accompanied by Cognitive Impairment • Use redirection to maintain focus on positive experiences and memories – Maintain photo album. caregiver support groups .

including about 20% where dual pathology exists) • Dementia with Lewy bodies (15% of cases) • Fronto-temporal dementia (5%) . of cases) √ • Vascular dementia (30–40%.Most common types of dementia Alzheimer’s disease (60-70%.

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 Pick’s 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 .

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

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

concentration • Repeats conversations • Becomes disoriented • Checks w husband constantly . 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.Current Complaints • Misplaces keys. wallet • Locks herself out of house.

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

meningitis? . brother died age 19.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.

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

but picked up English at work .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.

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. farmwork Moved to big city age 18. very successful.Occupational History • • • • • Worked from young age: housework. gave it up last year because of difficulties w employees .

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

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

Psychiatric History • Pre-Menstrual Syndrome. gained weight (12lbs/6 months) in Brazil . 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”. severe mood swings with menstrual cycle.

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. pills. wouldn’t reveal) • Suicide attempt at 19. 5150’d in Brazil .

no good fit – 3-4 months – A few sessions • Open to therapy now. she feels she should cut back. tobacco • Drinks 3-6 beers a few nights a week when out w friends. no alcohol x 1 week • Racing thoughts. husband tells her it’s too much. Cymbalta 60mg • Denied drug use.Psychiatry III • Two different psychotherapists. denied mania .

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

borderline impaired . 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. her 2nd language w 4 y edu.Test Results • WTAR 19th %ile • Predicted IQ 10th %ile prediction on tests in English.

9 • Primacy effect • Encoding 53rd %ile • Delayed recall 100% • Recognition 100% • Story memory 2nd percentile • I can’t do this! • 100% retention • Visual memory 42nd %ile • Number sequencing slow • Letter sequencing impossible • Judgment adequate .Test Results II • Judgment of Line orientation 6th %ile • Complex figure 91st %ile • Acquisition on 10 word list: 3. 7. 6.

severe • Self depricating statements. delusions • Passive SI • Can’t cry • Feelings of guilt. dizzy. rapid heart beat • Unable to relax. fears the worst • BDI 48/63.Test Results III • BAI 42/63. severe • Denied hallucinations. decisions . restlessness. feels dumb • Nervous. self-blame. fatigue • Difficulties w concentration. punishment. scared • Hyperventilates.

Conclusions • Diagnoses – Memory disorder? – Mood disorder? • Recommendations – Medical • Referral to psychiatry • Referral to endocrinology – Psychological • Individual • Couples .

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

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 .Dysthymia • Relative to depression.

MCI & MMSE The earliest areas to decline • Orientation to time • Orientation to place • Delayed memory • Repetition • Following commands • Design copy .

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 .Early signs of depression • Dysphoria.

but not nec. specifically memory and language.Cognitive profiles of older adults with and without major depression • MD is associated with ↑ cognitive complaints. ↑ 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 .

those who went on to develop dementia had higher motivational BDI subtest scores Bartolini 2005 .Motivational Sx of MD mask MCI • Among people with cognitive and mood complaints.

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

progressive non-fluent aphasia . semantic dementia.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.

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

Distractibility Utilization behavior SPEECH DISORDERS Progressive reduction of speech (PFA) Stereotypy . modes of intonation Semantic Dementia (receptive aphasias) AFFECTIVE SYMPTOMS Depression.FTD Diagnosis CORE FEATURES Loss of social and personal awareness Mental rigidity Perseverative behavior Disinhibition. Anxiety Suicidal & fixed ideation Hypochondriasis Apathy PHYSICAL INDICATORS Early primitive reflexes (snout) Incontinence Rigidity. constantly recurring words and phrases..g.e. neologisms. 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. Unlike other impulse control disorders. even though the task may be to write a letter. patients with this disorder confabulate reasons for their actions. . if it is within reach. So in this case. a patient may pick up a spoon and stir a cup.

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

Brief Overview of Aphasias FLUENCY REPETITION COMPREHENSION APHASIA Fluent Yes Good Anomia Poor No TeleGraphic Yes No Transcortical sensory Conduction Wernicke’s Transcortical motor Transcortical mixed Broca’s 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. AD: animal naming < FAS . This disparity increased with increasing severity of dementia.

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

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. c) neurovegetative signs d) differentiate them from dementia . b) emotional vs.

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 .

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