Aging & Dementia
Dementia
General
syndrome of cerebral dysfunction with many causes
usually cerebreal cortex
hippocampal formation, neostriatum, and talamus may play a role
incidence and prevalence increase with age
Clnical Characterization
deminished mental function in thought and memory
plus one of the following:
aphasia
language problems
apraxia
complex movement problems
agnosia
problem in executive functioning
making everyday descisions
Secondary
changes in feeling
changes in conduct
Maintained
alertness
motor and sensory
except in late Alzheimer's
Does not include
Coma
Dementia
Diagnosis
Aided byFolstein Minimental State Exam
CT and MRI used to visualize but not to diagnose
Alzheimer's
Clinical Diagnosis
no definitive test
Etiology
cause unknown
no clear evidence that alumimun intake causes
incidence higher (20-30x) in age 85 compared to 65
apolipoprotein E subtype E4 (4x risk)
history of head trauma
familial history comprises 10% or less of all cases
Down's Syndrome
those who can be tested, almost all get Alzheimer's
provides support for involvement of gene on Chromosome 21
Pathology
Neurofibrillary tangles
composed of prominent neurofibrils in perikaryon of neurons or extracellularly
appear as bundles of paired filaments in helical configuration
major constituent: abnormally phosphorylated protein called tau
normally associated in the cell with cytoskeletal neuronal microtubules
Senile (Amyloid) plaques
sine qua non for diagnosis
found in grey matter
Two Types
Diffuse plaques
deposits of A-beta amyloid
formed by cleavage of amyloid precursor protein
predominate in early disease
neuritic plaques
peripheral ring of:
abnormal accumulaions of A-beta amyloid
enlarged neural processes
plaques and tangles mostly found in cerebral neocortex and hippocampal formation
large numbers diagnostic
Neuronal loss
reduction of choline acetyltransferase (ChAT)
usually in nucleus basilis of Meynert
some hypothsize in entorhinal cortex (gateway to the hippocampus)
Genetic background
A-beta protein on Chromosome 21
familial forms have mutations on chromosomes 1-14 encoding presilin
presilin aids in forming A-beta peptide
Apolipoprotein E4 on Chromosome 19
Multi-Infarct dementia
bilateral or multiple infarcts of brain
accompanied by:
hemiparesis
visual field defect
other "focal" signs
step-wise deterioration as opposed to steady deterioration in Alzheimer's
Parkinson's and Lewy Body Dementia
dementia in 1/2 of PD patients if live past 75
demented PD show senile plaques in cerebral cortex
identical to Alzheimer's
Lewy bodies in cortical neurons may be a factor
Frontotemporal and Parkinsonism
autopsy shows loss of neocortical neurons (frontal and temporal) and hippocampal neurons
familial form involves tau protein (same as in NFT)
Pick's Disease
atrophy of brain confined to frontal and temporal
100x less common than Alzheimer's
Pick body found in cytoplasm of neuron
Other
Huntington's
caused by expanded CAG repeat on Chromosome 4p
dementia caused by degeneration of neostriatal neurons
ALS
disease of motor neurons
sometimes accompanied by changes similar to frontal lobe dementia
Infectious Dementia-Prion Diseases
Prions
agent of neurodegenerative damage
abnormal forms of glycoprotein found in brain, encoded by host
Genetically inherited forms of disease
familial CJD
Gerstman-Staussler-Scheinker disease
fatal familial insomnia
Kuru transmitted in New Guinea through ritualistic cannibalism
Transmission
rare
improperly decontaminated equipment
injestion of brain derived material
GH
human pituitary gland
usually species specific
by blood has not been confirmed
only infectious pathogen containing no nucleic acids
incubation periods of disease vary
transmissible spongiform encephalopathies
characterized by bubbles and holes in cortex or other regions
intracytoplasmic membrane-bound vacuoles in neuronal and glial processes
myoclonic jerks and pyramidal tract signs
transmission of prions by introduction of tissue into brain or by ingestion
Creutzfeldt-Jakob Disease (CJD)
most common disease of group, but overall rare
degenerative, fatal brain disorder
Mad Cow's Disease
bovine spongiform encephalopathy
Onset Age 60
Clinical Course
Rapidly progressive in months
death in one year
Clinical Signs
Early Clinical Signs
memory problems
behaviorial changes
lack of coordination
visual disturbances
Late Clinical
dementia
ataxia
insomnia
paraplegia
paresthesias
blindness
deviant behavior
Diagnosis
no single test
EEG may show specific abnormality in CJD
only confirmed by brain autopsy
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