Diagnostic Criteria
DSM-IV Criteria for Dementia Diagnosis
- Impaired recent and remote memory
- One or more of the following:
- aphasia
- apraxia
- agnosia
- executive function impairment
- Decline in social occupational functioning
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Presenting Symptoms
Cognitive Function
- Learning new information
- Handling complex tasks
- Reasoning ability
- Spatial orientation
- Language
- Behavior
Source: Knopman D. Amer J Med 1998;104(4A):2S-12S.
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Example of Deficit
- Trouble remembering events
- Trouble with checkbook
- Inability to cope with change
- Disoriented in familiar places
- Word finding difficulty
- Irritable, apathetic, depressed
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Etiology
Primary Illnesses Causing Dementia
n=200 (age>60)
Source: Larson EB et al. J Gerontol 1985;40:536-543. |
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Differential Diagnosis
- Rapidly Progressive Dementia
- Dementia Associated with Stroke
- Dementia Associated with Parkinson
- Frontotemporal Dementia
- Alzheimer's Dementia
Source: Knopman D. Amer J Med 1998;104(4A):2S-12S.
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Rapidly Progressive Dementias
Causes
- Toxic disturbances
- Metabolic disturbances
- Depressive disorder
- CNS mass lesions
- Subacute/chronic meningitis
- Normal pressure hydrocephalus
- Other (Creutzfeldt-Jakob, paraneoplastic)
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Features
- Duration of weeks to months
- Younger age at presentation
- More responsive to treatment
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Dementias Associated with Stroke
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Causes
- Multiple infarctions
- Lacunar infarctions
- Single strategic infarctions
- CNS mass lesions
- Binswanger's disease
- Mixed Alzheimer's disease-vascular dementia
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Features
- Onset with a stroke
- Rapid stepwise deterioration
- Focal neurologic findings
- Infarcts on brain imaging
- Cognitive deficit corresponding with infarct
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Dementias Associated with Parkinsonism
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Causes
- Dementia with Lewy bodies
- Progressive supranuclear palsy
- Striatal infarctions
- Huntington's disease
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Features
- Extapyramidal symptoms and signs
- Fluctuations in alertness
- Early onset hallucinations and delusions
- Syncope and falls
- Adverse response to neuroleptics
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Frontotemporal Dementias
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Causes
- Pick's Disease
- Huntington's disease
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Features
- Impaired executive function
- Impaired reasoning and judgment
- Kluver-Bucy syndrome
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Dementia and Alzheimer's Disease
Epidemiology
4th leading cause of death in U.S. adults
women>men
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Dementia and Alzheimer's Disease
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NINCDS-ADRDA Diagnostic Criteria
for Alzheimer's Disease
- Dementia by clinical exam and mental status tests
- Deficits in two or more areas of cognition
- Progressive worsening of memory and other cognition
- No disturbance of consciousness
- Age of onset 40-90
- Absence of dementia due to systemic illness
| Histopathology
- Neurofibrillary tangles
- Neuritic plaques
- Other changes:
- cerebrovascular amyloid
- granulovacular bodies
- Hirona bodies
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Brain Areas Most Commonly Involved
with
Neurofibrillary Tangles and Neuritic Plaques
- Parietal-temporal cortex
- Prefrontal cortex
- Hippocampus
- Amygdala
| Neurotransmitter Changes
- Decrease in neurotrasmitter activity:
- acetylcholine>somatostatin>serotonin
- Norepinephrine possibly affected
- No change in neurotransmitter activity:
- dopamine
- GABA
- Glutamate
- neuropeptides
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Definite Risk Factors
Possible Risk Factors
- level of education
- female gender
- head injury
- family history
| Early Onset
Late Onset
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Genetic Factors
- Trisomy 21
- Early-onset familial AD: autosomal dominant genes on chromosomes 14>1>21
- Late-onset AD: gene on chromosome 19 encoding for apolipoprotein E
| Apolipoprotein E (apoE)
- Serum lipoprotein involved in cholesterol metabolism
- Three different alleles: E2, E3, E4
- Homozygous E4 (E4/E4) highest risk for Alzheimer's disease
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Percent of Subjects with apoE Alleles with and without AD
Source: Polvikoski T et al. N Engle J Med 1995;333:1242-1247 |
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Diagnostic Evaluation for Dementia
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Obtaining a History
- Confirm by proxy
- Establish educational level
- Investigate functional decline
- Quantify duration/qualify pattern of illness
- Detect risk factors
- Review medications
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Physical Examination
- Look for medical illness
- Elicit frontal release signs
- Detect focal neurologic signs
- Assess cognitive function
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Assessment of Cognitive Function
- Clock drawing test
- Mini-Mental State Examination
- Executive Function
- Neuropsychologic testing
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Rapid Progression (<6 Months) or Age < 70
- Complete Blood Count
- Chemistries
- Head CT or MRI
- Lumbar puncture
- EEG
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Dementia and Treatment of Alzheimer's Disease
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Acetycholinesterase Inhibitor
- Donezepil (Aricept) 5 - 10 mg po qd
- Galantamine (Remenyl) 4 - 12 mg po bid
- Risvastamine (Exelon) 1.5 - 6 mg po bid
- Tacrine (significant hepatoxicity)
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N-methyl-d-asparate (NMDA)
- Memantine (Namenda) approved for moderate to
severe Alzheimer's disease
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| Randomized Controlled Trial of High-Dose Tacrine in Patients with Alzheimer's Disease |
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Source: Knapp MJ et al. JAMA 1994;271:985-991 |
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Donepezil (Apricept)
- Noncompetitive, reversible cholinesterase inhibitor
- Peak plasma concentration 3 - 4 hours
- Metabolized in the liver (cytochrome P450)
- Half-life 70 hours
- Dose 5 or 10 mg QD for 12 to 24 weeks
- Adverse effects: nausea, vomiting, diarrhea, fatigue, muscle cramps, anorexia
Source: Knapp MJ et al. JAMA 1994;271:985-991
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Dementia - Summary
DSM-IV Criteria for Dementia Diagnosis
- Dementia can be caused by multiple conditions.
- It is an insidious process that affects not only the cognitive function but also the behavioral and functional capacity.
- Correct diagnosis along with education and treatment is essential.
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