NeurologyMIRANDA – MOLINA – MONZON – MORALES – MUSNI – NALLAS - NAVAL

Batch 2011 - Section C

History A 63 y/o woman was brought by her husband for consult because of increasing forgetfulness. 

The husband reports that his wife had completed a degree in BS Education.  She has been teaching for the past 25 yrs. Confidentially, he reports that she has increasing difficulty remembering her class schedules and examinations as well as conversations with coworkers over the past year. 

He likewise noted reduced interest and withdrawal from many long-standing social activities.

Recently, she left food cooking on the stove, which resulted in a small kitchen fire.

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History The patient has no significant current medical problems and takes no medications.  The patient's older brother has recently been diagnosed with the same illness.

There were no significant PE findings. 

On mental status testing, the patient was noted to be disoriented to time and person. She had difficulty with calculation and had impaired short-term verbal memory.  Visuospatial abilities, however, were intact. 

Cranial CT scan done revealed normal findings. 

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Salient FeaturesPertinent Positive

• 63 year old, female• CC: Increasing forgetfulness over the past

year– Difficulty remembering class schedules and

exams and conversations with co-workers– Left food cooking on the stove small

kitchen fire• Impaired short-term verbal memory• Reduced interest ; withdrawal from social

activities• Disoriented to person and time• Difficulty with calculation• Brother: diagnosed with same illness

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Salient FeaturesPertinent Negative

• No significant medical problems • No medications taken• No significant PE findings• Visuospatial abilities intact• Normal CT

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Salient FeaturesPertinent Positive

• 63 year old, female• CC: Increasing forgetfulness

over the past year• Impaired short-term verbal

memory• Reduced interest;

withdrawal from social activities

• Disoriented to person and time

• Difficulty with calculation• Brother: diagnosed with

same illness

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Memory Impairment

DEMENTIA DELIRIUM AMNESIA

Stable level of consciousness

Impairment in consciousness

Stable level of consciousness

Multiple cognitive defects

Attention deficits

Insidious onset Abrupt onset Onset depends on etiology

Behavioral abnormality

Behavioral abnormality

Behavioral abnormality

8Reference

Salient FeaturesPertinent Positive

• 63 year old, female• CC: Increasing forgetfulness

over the past year• Impaired short-term verbal

memory• Reduced interest;

withdrawal from social activities

• Disoriented to person and time

• Difficulty with calculation• Brother: diagnosed with

same illness

9Reference

DEMENTIA

Stable level of consciousness

Multiple cognitive defects

Insidious onset

Behavioral abnormality

Pseudodementia is a depression-

related cognitive dysfunction

Clinical Impression

Dementia• Syndrome of cognitive decline

with variable non-cognitive features of behavioral and psychiatric symptoms and disturbance in activities of daily living

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Criteria for DementiaDSM –IV criteria

• Multiple Cognitive Deficits1. Memory Impairment

2. One or more• Aphasia

• Apraxia

• Agnosia

• Executive

• Impaired Social/Occupational function

• Gradual and progressive course

Patient

• Increasing forgetfulness over the past year

– Difficulty remembering – class schedules – exams – conversations with co-workers

– Attention: Left food cooking on the stove small kitchen fire

• Reduced interest ; withdrawal from social activities

• Disoriented to person and time• Difficulty with calculation

• Impaired short-term verbal memory

ClassificationDisease in which Dementia is:• Associated with clinical and laboratory signs of

other medical diseases • Associated with other neurological signs but not

with other obvious medical disorders– Invariable associated with other neurologic signs

– Often associated with other neurologic signs

• Usually the only evidence of neurologic or medical diseases

13Principles of Neurology , 8th Edition

Pertinent Negatives•No significant medical problems•No medications taken•No significant PE findings•Normal CT

DementiaDementia is usually the only evidence

of neurologic or medical disease • Alzheimers Disease• Diffuse Lewy Body Dementia• Pick Disease• Frontotemporal and frontal lobe dementias

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Dementia• Diffuse Cerebral Atrophy

– Alzheimers Disease– Diffuse Lewy Body Dementia

• Circumscribed Cerebral Atrophy– Pick Disease– Frontotemporal and frontal lobe dementias

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Alzheimer’s Disease

Lewy Body Disease

Pick’s Disease

Frontotemporal Dementia

≥ 60 years old;3x higher in women

Memory impairment

Aphasia, apraxia, agnosia, executive dysfunction

Early aphasia; Dysexecutive syndrome

Speech deterioration;Poor judgment and abstraction

Impaired social or occupational function

Marked psychiatric Sx

Prominent alteration in personality behavior;Neglect of personal hygiene and grooming

Early personality changes;Ritualistic & repetitive behavior; Disinhibition

Fluctuating confusionVisual HallucinationsParanoid delusions

Hallucinations

(+) Family History

(+) Family History

Insidious onset 2-5 years course of illness

Dementia: Usually the only evidence of neurologic or medical diseases

Patient

63 year old woman

Memory impairment

Difficulty with calculation

Withdrawal from social activities

Disoriented to person and time

Her brother diagnosed with same illness

Symptoms noted over the past year

Alzheimer’s Disease

A. The development of multiple cognitive deficits manifested by both:

-1.Memory impairment (impaired ability to learn new information or to recall previously learned information)

-2.One or more of the following cognitive disturbances:

(a) aphasia (language disturbance)

(b) apraxia (impaired ability to carry out motor activities depite intact motor function)

(c) agnosia (failure to recognize or identify objects despite intact sensory function)

(d) disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)

B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.

C. The course is characterized by gradual onset and continuing cognitive decline.

D. The cognitive deficits in Criteria A1 and A2 are not due to any of the following:

(a) other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)

(b) systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)

(d) substance-induced conditions  

E. The deficits do not occur exclusively during the course of a delirium.

F. The disturbance is not better accounted for by an Axis I disorder 

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Alzheimer’s DiseaseDSM IV Criteria

Alzheimer’s DiseaseDSM IV Criteria

A. The development of multiple cognitive deficits manifested by both:

-1.Memory impairment (impaired ability to learn new information or to recall previously learned information)

-2.One or more of the following cognitive disturbances:

(a) aphasia (language disturbance)

(b) apraxia (impaired ability to carry out motor activities despite intact motor function)

(c) agnosia (failure to recognize or identify objects despite intact sensory function)

(d) disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)

B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.

C. The course is characterized by gradual onset and continuing cognitive decline.

D. The cognitive deficits in Criteria A1 and A2 are not due to any of the following:

(a) other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)

(b) systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)

(d) substance-induced conditions  

E. The deficits do not occur exclusively during the course of a delirium.

F. The disturbance is not better accounted for by an Axis I disorder 

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Alzheimer’s Disease• Most common cause of

dementia

• Incidence increases with age– 60 years and above

• 3x higher in women

• (+) Family History– Chromosome 21 – amyloid gene – senile plaques– Chromosome 19 – ApoE4 gene – inherited predisposition– Chromosome 1, 14 – Presenilins 1 and 2

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Alzheimer’s DiseaseRisk Factors

• Old age• Family history• Low education• Head trauma• High cholesterol• Hypothyroidism• Exposure to metals

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Alzheimer’s DiseaseRisk Factors

• Old age – 63 yrs old• Family history – older brother• Low education• Head trauma• High cholesterol• Hypothyroidism• Exposure to metals

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Alzheimer’s DiseaseClinical Features• Gradual development of forgetfulness• Cognitive Dysfunctions

– Language: expression, comprehension, reading, writing

– Decline in arithmetic skills (acalculia/dyscalculia)

– Visuospatial orientation• 4 A’s: amnesia, aphasia, apraxia, agnosia

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Alzheimer’s DiseaseClinical Features• Gradual development of forgetfulness• Cognitive Dysfunctions

– Language: expression, comprehension, reading, writing

– Decline in arithmetic skills (acalculia/dyscalculia)

– Visuospatial orientation• 4 A’s: amnesia, aphasia, apraxia, agnosia

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Alzheimer’s DiseaseClinical Features• Executive Dysfunction

– Planning– Organizing– Sequencing– Abstract thinking

• Behavioral and personality change• Decline in ADL

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Alzheimer’s DiseaseClinical Features• Executive Dysfunction

– Planning– Organizing– Sequencing– Abstract thinking

• Behavioral and personality change– Withdrawal from social activities

• Decline in ADL – Disturbance in the household and workplace

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Alzheimer’s DiseasePathophysiology

• Generalized brain atrophy• Loss of neurons• Astrocytic proliferation

- inflammation

• Microscopic changes- Neurofibrillary tangles

• Histological marker

- Amyloid deposition • Histological marker

- Granulovacuolar degeneration29Reference

Alzheimer’s Disease• Diagnostic Procedures

• Cranial CT or MRI scan- Mild AD: normal or MTL atrophy

- Advanced AD– Generalized atrophy

• EEG- Diffuse slowing (theta/delta range) in

late disease

• CSF analysis- Normal, slight increase in total protein

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Alzheimer’s DiseaseDiagnostic Procedures

• Neuropsychological Tests- Poor memory, verbal skills in early

to moderate stages

• Biologic Markers- CSF tau and β amyloid

- Inflammatory markers– Isopostane (serum & CSF)

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Diagnostic Procedures

Diagnostic Procedures

• Mini-Mental State Examination• Blood tests• Cranial CT scan or MRI• Single-photon emission CT (SPECT) • EEG• CSF analysis

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Mini-Mental State Examination

• assesses cognitive abilities such as orientation to time and place, use of language, memory, attention, and abilities to carry out various tasks and follow instructions

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Blood tests• check for infections or conditions

such as vitamin deficiency, anemia, medication levels, disorders of the thyroid, kidneys or liver  

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Cranial CT scan or MRI

• reveals reduction in the size of the brain (atrophy), widened indentations in the tissues, and enlargement of the cerebral ventricles

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Single-photon emission CT (SPECT)

• imaging detects blood flow in the brain

• used in some medical centers to distinguish Alzheimer’s disease from vascular dementia

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EEG• diffuse slowing (theta/delta range) in

late disease

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CSF analysis• normal, slight increase in total

protein• biologic markers: amyloid beta or

tau proteins

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Thank you!