Download Objectives 49

DEMENTIA
1. Major causes, types, and symptoms of dementia and the clinical course of dementias
Symptoms
- dementia is a decline in cognitive function measured in relationship to previous levels
- general, progressive deficit in memory areas, learning of new information, ability to
communicate, and motor coordination
- loss of intellect, memory, or mental capacity accompanied by personality and behavior
changes
- definition of dementia requires presence of multiple deficits including memory impairment
and one of the following: aphasia, apraxia, agnosia, or executive functioning deficits (higher
cortical); other criterion includes impaired occupational/social functioning
Causes/Types
- most common causes of dementia include Alzheimer’s disease (50%) and vascular dementia
(25%); other causes (25%): degenerative diseases such as Parkinson’s disease, multiple
sclerosis, substance abuse, alcohol-induced dementia (Korsakoff Syndrome), infectious
diseases, AIDS, encephalitis, autoimmune problems (Lupus), and Down’s Syndrome
- Cortical dementia due to damage to neocortex (Alzheimer’s); slowing on tasks and memory
encoding
- Subcortical dementia due to damage to subcortical structures, such as basal ganglia
(Parkinson’s disease); cognitive slowing and memory retrieval problems
- Vascular disorders (strokes) cause damage to both cortical and subcortical structures
Clinical course
- some dementias are reversible (brain tumor), while others are not reversible (Alzheimer’s)
- early stages  cognitive deficits in 2-3 of areas mentioned above; problems are noticeable,
but overall function is good
- middle stages  more severe cognitive deficits seen in several areas; problems noticeable
- late stages  almost all cognitive functions impaired with loss of effective motor control;
patient requires total care at this point
2. Neuropathological changes that characterize Alzheimer’s disease
Neurofibrillary tangles
- abnormal meshwork of filamentous material
- tangles consist of an abnormally phosphorylated microtubule associated protein called tau
- tangles occur within cytoplasm of neuron and impair axonal transport
- tangle containing neurons lack functional MTs  neural dysfunction and death
Senile plaques
- extracellular deposits of amyloid proteins surrounded by activated microglia, cytokines,
complement proteins, neurites, apolipoprotein E, swollen synaptic terminals and cellular debris
- Beta amyloid protein secreted by many cells; it is created from amyloid precursor protein
(APP), through protease action
- tangles and senile plaques develop with temporal lobe structures initially  hippocampus,
entorhinal cortex and parahippocampal gyrus; parietal lobe also effected
- later  frontal cortex and association cortices show pathology; not much damage to
subcortical structures
- number of synapses in cortex decreases and increased neurofibrillary tangles  decline in
intellectual function
3. Brain regions that demonstrate prominent changes in dementia
- diagnostic changes  decrease in blood flow and decrease in glucose utilization in cingulate
gyrus, parietal lobes and posterior temporal lobes bilaterally
4. Roles of genes for Alzheimer’s disease
- genes located on chromosomes 1, 14, and 21  contribute to development of early-onset
Alzheimer’s disease
- Almost all Down’s syndrome (trisomy 21) individuals who survive until age 50 develop
plaques and tangles
- gene for APP (amyloid precursor protein - plaques) on chromosome 21 (may be mutated)
- Down’s syndrome  more beta amyloid produced  earlier onset of plaque formation 
earlier formation of neuropathological changes
- chromosome 19  gene for apolipoprotein E (ApoE): protein involved in lipid transport
accounts for 45% of Alzheimer’s cases
- 3 alleles E2, E3, E4; E4 allele increases risk for Alzheimer’s; E2 allele has neuroprotective
effect
- ApoE genotype predicts when, not whether, one is predisposed to develop Alzheimer’s
- E4 allele  develop symptoms earlier; ApoE effects clearance of beta amyloid produced by
neurons; if E4 is present  less beta amyloid cleared from brain  beta amyloid aggregates
into plaques
- more amyloid load in brain  age of onset of symptoms becomes earlier
5. PET and SPECT findings in Alzheimer’s patients
- diagnostic changes  decrease in blood flow and decrease in glucose utilization in cingulate
gyrus, parietal lobes and posterior temporal lobes bilaterally
- can be identified in PET and SPECT scans; can also be used to differentiate Alzheimer’s from
other forms of dementia
- decrease in glucose utilization precedes cognitive decline and neuropathological changes by
30-40 years
- later in illness  frontal lobes demonstrate decreased blood flow
- primary motor and sensory cortices, and subcortical structures spared