Dementia (20.2) Flashcards
Gross neuropath changes associated with AD?
Cerebral atrophy especially affecting temporal, parietal, and frontal areas, together with ventricular enlargement
What are the microscopic neuropath changes associated with AD?
1- Amyloid plaques–> extracellular deposits of A-beta
2- A-Beta deposits in cortical and leptomeningeal arteries–> amyloid angiopathy
3- Neurofibrillary tangles/ Neuropil threads–> intracellular inclusions of tau protein
4- Granulovacuolar degeneration
5- Hirano bodies
What cleaves APP?
secretase proteases…gamma is most common
What is a major component of gamma secretase?
presenilin
What is the major component of neurofibrillary tangles?
HYPERphosphorylated tau protein
Name the major risk factors for AD?
1- Increasing age 2- Female 3- Family history of dementia 4- Lower income and education 5- Lower occulational status 6- Depression 7- Head injury 8- Postop delirium 9- Presence of apo E4 10- Elevated plasma homocystein levels
What are the THREE key features of AD?
Impaired cognition, impaired function, behavioral disturbance
Early symptoms of AD?
trouble keeping appointments, difficulty finding words, misplacing objects, difficulty driving, difficulty selecting clothes, missing appointments subtle changes in personality, social withdrawal, depression
How can you differentiate depression and dementia?
Depression has less motivation during cognitive testing, expresses cognitive complaints that exceed measured deficits, and they maintain language and motor skills
What is seen on brain imaging for AD?
Non specific findings are common–> lacunar infarcts, small vessel and white matter disease
What are some characteristics of frontotemporal dementia (pick’s disease)?
Insidious onset
Early decline in social interpersonal conduct and impairment of personal conduct with loss of insight
What can be used to treat frontotemporal dementia?
Divalproex for behavioral control
SSRI for irritability, depression, impulsive behaviors
What is used to treat alzheimers?
anticholinergic agents
NMDA receptor antagonists
What are the clinical characteristics of vascular dementia?
“step-wise progression”
emotional lability
What are the pathological characteristics of vascular dementia?
Multiple infarcts
Cerebral amyloid angiopathy
Hypertension related small vessel disease
Describe hypertensive small vessel disease?
Arteriosclerosis of small arteries and arterioles supplying deep gray and white matter–> lacunar infarcts and subcortical leukoencepholopathy
What are the symptoms that hypertensive small vessel disease can create?
Cognitive slowing, impaired problem solving, visuospatial abnormalities, disturbances of mood and affect
How is vascular dementia treated?
Controlling cardiovascular risk factors
Cholinesterase inhibitors
Name the two synucleinopathies:
1- Parkinson’s disease
2- Dementia with Lewy bodies
What are the symptoms of parkinson’s disease?
Resting tremor
Akinesia (difficulty initiating movement)
Bradykinesia
Rigidity
Shuffling gait
Postural instability
What is the deficit in Parkinsons?
Dopamine is deficient
What are the gross pathological changes in parkinsons?
Pallow of the substantia niagra
What are the microscopic changes seen in parkinsons?
Degneration and loss of the pigmaneted, dopaminergic neurons of the substantia nigra
Neurons contain inclusions of Lewy bodies
What are Lewy bodies made of?
fibrillar aggregates of alpha- synuclein
What are the clinical features of dementia with Lewy bodies?
Short term memory loss (gradual onset), Visual hallucinations, cognitive fluctuations, REM sleep disorder frequent falls, autonomic dysfunction
What are the gross pathological findings of lewy body dementia?
Nigral pallor and cortical atrophy
What are the microscopic pathological changes seen in lewy body dementia?
“Cortical” type LPs, Ligral LBs, LNs in the hippocampus
How is Lewy body dementia treated?
Cholinesterase inhibitors, REM sleep disorders
