Mind Mood and Memory in Parkinson's Disease

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Mind, Mood

and Memoryin Parkinsons

Disease

Robert B. Santulli, M.D.

Associate Professor of PsychiatryDartmouth Medical School

Director, Geriatric Psychiatry

Dartmouth-HitchcockMedical Center


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Disclosures

I am a member of theSpeakers Bureau for:

1. Eisai

2. Forest

3. Novartis

4. Pfizer


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Mind MoodCognitiveChanges

Memory


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Mind Mood

Depression

Memory

Depres-

sion


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Mind Mood

Dementia

Memory


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Mind MoodDepression

Dementia

Memory

Cognitive

Changes


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Mind Mood

Memory

The NeuropsychiatricSymptoms of

Parkinsons Disease


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The Neuropsychiatric Symptoms

of Parkinsons Disease

Generally, at least as disturbing to the patient and

the caregiver as the motor symptoms

More likely to be associated with poorer outcomesof the disease compared to the motor symptoms

Neuropsychiatric symptoms due to a combination of:

Brain pathology Psychological reactions to the disease

Medication side effects


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Mind Mood

Depression

Memory

Depres-

sion


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Depression

40 to 50% of persons with Parkinsonsdisease develop depression; = Major depressive disorder

= Minor depression

Depression associated with Faster progression of illness

Greater decline in cognitive skills

Poorer quality of life

Depression is more predictive ofoverall disability and distress thanthe motor symptoms of PD


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Causes of Depression

Biological:

Damage to serotonergic and noradrenergicsystems and to dopaminergic basal ganglia-limbic-

frontal systems which are involved in moodregulation, pleasure, reward

Psychological:

Loss of control Demoralization

Many other factors


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Symptoms of Depression in PD

Similar to depression in persons who donthave

Parkinsons disease

Diagnosis can be more difficult because many of

the symptoms could be due either to depression

or to Parkinsons disease


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DSM - IV Diagnosis of Major

Depressive Episode: Key Symptoms

Five (or more) of the following symptoms have been present during the same2-week period and represent a change from previous functioning; at leastone of the symptoms is either:

(1) Depressed moodmost of the day, nearly every day, as indicatedby either subjective report (e.g., feels sad or empty) orobservation made by others (e.g., appears tearful).

or:

(2) Markedly diminished interest or pleasure in all, or almost all,activities most of the day, nearly every day (as indicated by eithersubjective account or observation made by others)


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DSM - IV Diagnosis of

Depressive Episode: Other Symptoms

(3) Significant weight loss or weight gain (could be due to PD)

(4) Insomnia or hypersomnia (could be due to PD)

(5) Psychomotor agitation or retardation (could be due to PD)

(6) Fatigue or loss of energy (could be due to PD)

(7) Diminished ability to think or concentrate, or indecisiveness(could be due to PD)

(8) Recurrent thoughts of death (???? Probably a depression-specific symptom,

but could be due to PD)

7) Feelings of worthlessness or excessive or inappropriate guilt(DEPRESSION-SPECIFIC SYMPTOM)


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Critical Depression-Specific Symptoms

Markedly diminished interest or pleasure inall, or almost all, activities most of the day,nearly every day (as indicated by eithersubjective account or observation made byothers)

Feelings of worthlessness or excessive orinappropriate guilt


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Treatment of Depression in PD

Optimal treatment of the motor symptoms

(may or may not help mood)

More depression in patients with On-Offphenomena

Counselling to help cope with physical

limitations, dependency on others

Support Group


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Treatment of Depression in PD:Cognitive Behavioral Therapy


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Treatment of Depression in PD:Medication

Numerous antidepressants

can be helpful in treating

depression in PD

People with PD may be very

sensitive to side effects

SSRIs mayslightly worsentremor


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Other Critical Behavioral Concerns

Anxiety*

Sleep difficulties*

Psychotic signs andsymptoms**

Hallucinations (40%of persons with PD)

Delusional beliefs(10% of personswith PD)

Impulse control

disorders**

Hypersexuality Binge eating

Compulsive

shopping

Compulsive

gambling

*Can be induced or worsened by dopaminergic medications**Often (but not always) induced by dopaminergic medications


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Other Critical Behavioral Concerns

Anxiety*

Sleep difficulties*

Psychotic signs andsymptoms**

Hallucinations (40%of persons with PD)

Delusional beliefs(10% of personswith PD)

Impulse control

disorders**

Hypersexuality Binge eating

Compulsive

shopping

Compulsive

gambling

*Can be induced or worsened by dopaminergic medications**Often (but not always) induced by dopaminergic medications


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Mind CognitiveChangesin

PD


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Characteristic Cognitive Problems

1. Attention

2. Speed of mental processing

3. Executive functioning, problem-solving

4. Memory deficits

5. Visuospatial difficulties


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Simple Attention

Simple attention = being

able to repeat what was

just said; digit span test;Trails A test

May not be impaired in

someone withoutdementia

Trails A


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Complex Attention

Involves executive functioning (planning,

reasoning, judgment; a more complex

frontal lobe task overall)

Complex attention is essential for driving, or

other functions which require the ability to

alternate between two (or more) tasksquickly and accurately


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Impaired Complex Attention

Patients with

Parkinsons disease

withoutdementia domore poorly on tests of

complex attention than

do age-matched controlswithout PD

Trails B


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Bradyphrenia

Bradyphrenia = slowed thought processes

Due to frontal executive system impairment

Often mistaken for depression

Delay in responding to verbal or other stimuli

Take longer to complete tasks


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1. Attention



4. Memory deficits



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Executive Dysfunction

Problems with planning, executing, and

completing tasks

Difficulties generating, maintaining, shiftingand blending different ideas and concepts

Difficulties with problem solving

Impairment of judgment and social

appropriateness


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1. Attention



4. Memory deficits



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Memory Impairment

Characteristic memory difficulty in Parkinsons

disease is memory retrieval= being able to

recall a recent event without external cues

Parkinsons patients have better preserved

recognition memory relative to retrieval

Can pick out the object when presented with a

multiple - choice question


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Recognition Memory

People with PD are substantiallybetter at

being able to pick the item from a list

People with Alzheimers disease arent muchbetter at recognition than retrieval

The fact is in there in PD, but the trouble is

getting it out (retrieval) ; in AD, it does not

remain in memory at all.


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1. Attention



4. Memory deficits



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Visuospatial Difficulties

Poor ability to measure distance; poor depthperception even early in the disease;

may not be able to complete a

relatively simple jig saw puzzle

Progresses to more notable difficulty withsense of direction; loss ofinternal compass

Significant vulnerability to getting lost, even insimple or familiar settings (e.g., the house)


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CIND versus Dementia

The border between Cognitive Symptoms No

Dementia (CIND) and dementia is not well defined

No biomarker or other objective finding to indicatewhen someone has crossed over into dementia

Severity of symptoms, overall

Are the symptoms sufficiently severe to causeimpairment in daily functioning?


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Mind Mood

Dementia

Memory


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Parkinsons Disease Dementia (PDD)

Overall, about 40% of patients with

Parkinsons disease have dementia

After 9 years: 26%

After 13 years: 52%

After 17 years: 78%


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Core Diagnostic Features of

Parkinsons Disease Dementia (PDD)

Cognitive and motorslowing

Executivedysfunction

Impairment inmemory retrieval


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Typical Clinical Picture

Insidious onset

Slow progression over

years

Impairment in at least

one domain:

Attention

Executive function

Visuospatial function

Memory

A decline from previous

functioning

Deficits are sufficient

to impair daily life

Emde M et al: Clinical Diagnostic Criteria forDementia Associated with Parkinsons

Disease. Movement Disorders

Vol. 22, No. 12, 2007, pp. 1689-1707


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Dementia with Lewy Bodies (DLB):A Close Cousin of PDD

Central Feature:

Progressive cognitive decline (100%)

Core Features:

Fluctuating cognition (60-80%)

Recurrent, well-formed detailed visual hallucinations (50-75%)

Spontaneous parkinsonism (80-90%)

Suggestive features: REM Sleep Disorder (85%)

Neuroleptic sensitivity (30-50%)

Consensus criteria of the third report of the DLB consortium. McKeith, IG, Dickson, DW, Lowe, J, et al. Diagnosis and

management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology2005; 65:1863.


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How to Differentiate PDD, DLB and AD:

The Sequence of Symptomatology

In Parkinsons dementia, the motor symptoms

(tremor, stiffness, bradykinesia, etc.) begin at least

two years prior to the cognitive symptoms

In Lewy Body Dementia the cognitive and motor

symptoms begin around the same time

In Alzheimers disease the cognitive symptoms comefirst, and motor symptoms come years later, if at all

f ki


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Treatment of Parkinsons

Disease Dementia

Exelon (rivastigmine) is the only drugapproved by the US Food and DrugAdministration (FDA) for the treatment

of Parkinsons Disease Dementia

Original study done with oralrivastigmine; Exelon Patch now

available - has 1/3 the rate ofgastrointestinal side effects


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N Engl J Med2004;351:2509-18.

Ri i i Pl b


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Rivastigmine vs Placebo

ADAS-cog


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Results:

Rivastigmine (Exelon) caused significant

(p < 0.001) improvement in cognition, compared

to placebo, in 410 subjects, over 6 months

Clinically meaningful improvements in global

functioning were significantly greater, and clinically

significant worsening was significantly decreased in

the medication group, compared to placebo

(p


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