Cognitive disorders

Question 1

Definition and current prevalence rates of dementia?

Answer 1

An acquired syndrome consisting of a decline in memory and other cognitive functions
6-8% if older than 65
30% if older than 80

Question 2

Diagnosis of dementia?

Answer 2

Memory impairment AND one of the following:
aphashia, apraxia, agnosia, or impaired executive functioning
Deficits cause significant impairment in social or occupational functioning

Question 3

Aphasia

Answer 3

Characterized initially by a fluent aphasia
- Able to initiate and maintain a conversation
- Impaired comprehension
- Intact grammar and syntax however the speech is vague with paraphasias, circumlocutions, tangential, and other using nonspecific phrases (“the thing”)
Later language can be severely impaired with mutism, echolalia

Question 4

Apraxia

Answer 4

Inability to carry out motor activities despite intact motor function
- Contributes to loss of ADLs

Question 5

Agnosia

Answer 5

The inability to recognize or identify objects despite intact sensory function

• Typically occurs later in the course of illness
• Can be visual or tactile

Question 6

Impaired executive function

Answer 6

Difficulty with planning, initiating, sequencing, monitoring or stopping complex behaviors

• Occurs early to midcourse
• Contributes to loss of instrumental activities of ADLs such as shopping, meal preparation, driving and managing finances

Question 7

Dementia subtypes?

Answer 7

• Early onset: before age 60
• Less than 5% of all cases of Alzheimer’s
• Strong genetic link
• Progresses more rapidly
• Late onset: after age 60
• Majority of cases

Question 8

Instrumental Activities of Daily Living (IADL’s) vs. Activities of Daily Living (ADL’s)

Answer 8

IADL’s are one step up from ADL’s in terms of complexity (e.g. using phone, traveling, shopping for oneself, preparing meals, taking medications, handling money)
ADL’s rudimentary tasks (e.g. bathing, dressing, grooming, toileting)

Question 9

Mini-Mental Status Exam

Answer 9

Orientation, Registration, Attention and Calculation, Recall, Language, Visuospatial (30 pts.) = if score less than 25, consider dementia
25 is the appropriate cutoff for an 80 y/o with a high school education, so score alone does NOT determine whether individual meets criteria for diagnosis or not

Question 10

MMSe pros and cons?

Answer 10

Pros:
- Widely used and therefore can track cognition over time and between clinicians
- 5-10 minutes
Cons:
- False positives: those with little education
- False negatives: those with high premorbid intellectual functioning
- Psychologically stressful–makes people angry!

Question 11

Clock Drawing Test (CDT)

Answer 11

Tests planning, visuospatial abilities, but NOT memory

Less stressful, less culture-bound

Question 12

Mini-Cog

Answer 12

Clock-Drawing Test + 3-item memory test

• More sensitive than CDT
• Same advantages as CDT
• Not as commonly used as MMSE, but fast and still quite sensitive
• Involves visuospatial, executive and planning, and memory functions

Question 13

What is a “positive” Mini-Cog?

Answer 13

2 word recall and/or abnormal clock

Question 14

Potentially reversible dementias?

Answer 14

Most attention given to normal pressure hydrocephalus, mass lesions, thyroid abnormalities, syphilis, and vitamin deficiencies

• Fewer than 13% of all dementia cases are reversible
• Most people do NOT return to normal or baseline cognitive functioning
• “Treatable” is more appropriate term

Question 15

Labs for dementia?

Answer 15

Electrolytes
CBC
Liver enzymes
TSH
B12 level
Syphilis?

Question 16

Neuroimaging for dementia?

Answer 16

CT is usually adequate
MRI if vascular dementia suspected
- “Small areas of white matter ischemic changes” commonly seen in VD, but also in normals
Functional imaging not in initial workup

Question 17

Alzheimer’s Disease prevalence

Answer 17

Most common form of dementia
Incidence age-related: 8% per year by 85 y/o
1/2 - 2/3 of all dementia is estimated to be AD

Question 18

Ultimate AD diagnosis?

Answer 18

Autopsy:
Extracellular senile plaques surrounding beta-amyloid core throughout cortex
Intracellular neurofibrillary tangles found within neurons composed of abnormally phosphorylated Tau proteins

Question 19

ACh in AD

Answer 19

AD is biochemically characterized by deficiency of ACh (cerebral cortex, amygdala, hippocampus)
Basal nucleus of Meynert (basal forebrain) depleted of ACh-containing neurons that project elsewhere

Question 20

Genetics of AD

Answer 20

Minority of cases there is autosomal dominant inheritance linked to chromosome 1, 14, or 21 (associated with early onset)
Presence of allele E4 on chromosome 19 increases risk, especially if homozygous
- 34-65% of those with the allele eventually get AD
AD is probably a common manifestation of multiple underlying disorders

Question 21

Course of AD

Answer 21

Insidious onset and progressive course with typical loss of 3 points on MMSE each year and death occurring 8-12 years after diagnosis

• Mild: MMSE 20-24, 2-3 yrs after diagnosis, primarily memory and visuospatial deficits, mild difficulty with executive functioning
• Moderate: MMSE 11-20, 3-6 yrs after diagnosis, aphasia and apraxia more pronounced, loss of IADLs and increased assistance with ADLs, start showing neuropsych symptoms (esp. paranoia)
• Severe: 6-10 yrs after diagnosis, severe language disturbances (mutism, echolalia, repetitive vocalizations), pronounced neuropsych manifestations (agitation, aggression), very late in course can see muscle rigidity, gait disturbances, incontinence, dysphagia

Question 22

Vascular Dementia prevalence

Answer 22

Second most common form of dementia

10-40% of all dementia cases

Question 23

Most common type of dementia including subtypes?

Answer 23

Azheimer’s Disease + Vascular Dementia

10-15% of AD cases are “mixed”

Question 24

Etiology of vascular dementia?

Answer 24

Caused by one or more strokes
- Diagnosis reserved for patients with clear evidence of stroke on imaging or physical exam
Global vascular changes in brain
Also called “multi-infarct dementia”

Question 25

Presentation of vascular dementia?

Answer 25

Abrupt onset and decline is classically stepwise (difficult to determine)
Two or more cognitive functions affected
Theoretically not as progressive as AD but if patients live long enough, can’t guarantee they won’t get AD as well

Question 26

Treatment of vascular dementia focused on?

Answer 26

Risk factors: smoking, a. fib, diabetes, HTN

Question 27

Lewy Body Dementia prevalence

Answer 27

Third most common form of dementia

Higher incidence than previously thought: 7-26%

Question 28

Lewy Body Dementia presentation?

Answer 28

Visual hallucinations, delirium, and parkinsonian symptoms
Memory impairment comes AFTER
Decline is faster than in AD
Sensitive to neuroleptics which have been associated with an increased mortality!

Question 29

Lewy Body Dementia pathology?

Answer 29

Cortical Lewy bodies

Question 30

Frontotemporal (Pick’s Disease) Dementia prevalence

Answer 30

Fourth most common form of dementia

Question 31

Frontotemporal (Pick’s Disease) Dementia presentation?

Answer 31

“Presenile” onset: 40-60 y/o
Personality changes, disinhibition, executive dysfunction
Memory impairment
More progressive and rapidly deteriorating than AD

Question 32

Frontotemporal (Pick’s Disease) Dementia imaging/pathology?

Answer 32

Frontotemporal atrophy, generally ASYMMETRIC
“Walnut brain” on gross examination
May have characteristic inclusion bodies on pathology

Question 33

First treatment for dementia?

Answer 33

Behavioral: reassurance, distraction, redirection, structure

Adult Day Care, Respite/Adult Family Homes, Caregiver Support Groups, Psychoeducation, SNF before crisis

Question 34

Pharmacologic treatment for dementia?

Answer 34

Behavioral problems often due to agitation, depression, delusions, aggression
Improvements are modest
Virtually every class of psychotropic medication has been used

Question 35

Neuroleptics for dementia

Answer 35

No gold standard - think about side effects
Very modest or no improvements compared to placebo
BLACK BOX WARNING: 1.6x increased risk of death
High-potency (haloperidol) more likely to cause parkinsonism
Low-potency (thorazine, thioridazine) more likely to cause sedation, hypotension, anticholinergic SE

Question 36

Anticonvulsants for dementia

Answer 36

Carbamazepine, valproate
Indications: dinhibited (YELLING) behavior in absence of psychosis or depression
Therapeutic drug levels apply to treatment of seizure, not behavioral control
Start at low doses

Question 37

Cognitive enhancers?

Answer 37

ACh esterase inhibitors - FDA approved for AD
Delay progression but do not reverse it, can delay nursing home placement by 12 months or more
SE (dose-related): GI upset, nausea, diarrhea, sleep disturbance, nightmares
Help with psychosis for Lewy Body dementia?
Expensive!

Question 38

Memantine

Answer 38

NMDA antagonist
Indicated for moderate-to-severe AD
Studies were add-on with an AChEi
Titrate by 5 mg per week up to 10 mg BID
Increase glutamate = overstimulation can cause excitotoxicity and neuronal cell death

Question 39

Vitamin E

Answer 39

1 randomized, controlled study showed some effectiveness in delaying SNF placement
Study used mega-dose of 2000 IU/day

Question 40

Prazosin

Answer 40

Alpha blocker
Demonstrated benefit for agitation
Very few side effects
Minimal effect on BP at therapeutic doses
Studied at 1-2 mg BID; higher doses probably safe
Can be used PRN

Question 41

When to refer to a specialist?

Answer 41

Early onset (<60)
Presentation is atypical
If severe parkinsonism, focal findings, or abnormal scan
Behaviors seemingly “untreatable”
To better document severity, consider neuropsychologist