Lecture 16: Dementia and Memory Flashcards

Question

What are the laboratory investigations for dementia?

Answer 1

complete blood count, thyroid function tests, B12 level, folate, serum electrolytes, glucose, urea, creatinine, calcium, liver function tests, toxicity screen for drugs (prescription and otherwise) test for syphilis and HIV optional: neuroimaging (CT/MRI), EEG, cerebrospinal fluid exam

Answer 2

there is usually an age-dependent progression and worsening of dementia reflecting loss of neurons and their connections in the CNS some parts of the brain and neurons within these regions are more vulnerable to the insult (whatever it happens to be) proteins, that are misfolded and abnormally deposited in specific brain areas seem to play a key role in these diseases for most part, precise cause(s) unknown and hence no definitive treatment available to stop progression of disease

Answer 3

is an irreversible, progressive brain disease that slowly destroys memory and thinking skills although the risk of developing AD increases with age (in most people with AD, symptoms first appear after age 60), AD is not a part of normal aging it is caused by a fatal disease that affects the brain

Answer 4

the brain has billions of neurons, each with an axon and many dendrites to stay healthy, neurons must communicate with each other, carry out metabolism, and repair themselves AD disrupts all three of these essential jobs affects neurons processes and ability to metabolize

Answer 5

most common cause (70-80%) 7-9% of Canadian population over 65 have AD, 35.5% of population over 85 have AD 4.5 million people in US and Canada have AD 40% of total health care cost associated with neurological diseases (billions of $)

Answer 6

impairment of memory and attention language and communication abstract thinking judgement personality changes depression visuo-spatial disorientation (difficulty orienting in space)

Answer 7

motor and gait disturbance poverty of movement and slowness falls problems with bladder and bowel control seizures

Answer 8

most cases occur usually late 60's or later

Answer 9

familial forms: less than 10% of cases sporadic (cause unknown): majority of cases >90% early onset (40s and 50s): usually familial and associated with susceptibility genes that include mutations of amyloid precursor protein (APP), Presenilin 1 & 2 mutations late onset (60s or later): mostly sporadic; Apolipoprotein E4 gene is the main susceptibility gene, some other genes identified recently

Answer 10

cortical atrophy synaptic and neuronal loss neurofibrillary tangles (NFTs) with paired helical filaments, abnormally hyperphosphorylated forms of microtubule-associated protein, tau neuritic plaques with amyloid core amyloid angiopathy tau and amyloid are key features

Answer 11

shrinkage of the brain not specific to AD

Answer 12

beta-amyloid plaques, which are dense deposits of protein and cellular material that accumulate outside and around nerve cells neurofibrillary tangles, which are twisted fibers that build up inside the nerve cell

Answer 13

membrane protein that sits in the membrane and extends outward, it is thought to be important for neural growth, survival and repair enzymes referred to as secretases (think of them as scissors) cut the APP into fragments, the most important of which for AD is called beta-amyloid beta-amyloid is "sticky" so fragments cling to together along with other materials outside of the cell, forming plaques seen in the AD brain and is toxic to neurons

Answer 14

decrease in chemical messengers in the brain especially acetylcholine (cortex, hippocampus)

Answer 15

increase release of Ach if AchE is inhibited then Ach will be broken down slower

Answer 16

cholinesterase inhibitors donepezil (Aricept) rivastigmine (Exelon) galantamine (Reminyl)

Answer 17

memantine (Namenda, Ebixa), a glutamate receptor (NMDA) blocker

Answer 18

amyloid vaccine secretase inhibitors anti-amyloid agents drugs that lower cholesterol

Answer 19

estrogens, NSAIDs, vasodilators, propentofylline

Answer 20

higher education intellectual stimulation exercise and diet (improves cardiovascular) red wine ?

Answer 21

fluctuating cognition with pronounced variation in attention and alertness recurrent visual hallucinations Parkinsonian features (rigidity or stiffness in muscles, slowness and poverty of movement, tremor) treatment with cholinesterase inhibitors, antipsychotic drugs (to control behavioral problems and agitation) loss of pigmented (dopamine-containing) neurons in the substantia nigra in PD and DLB

Answer 22

contain abnormal alpha-synuclein protein

Answer 23

female preponderance and at a younger age than AD focal frontal and temporal lobe atrophy disinhibition, apathy, perseveration, mental rigidity and affective symptoms Tau pathology most frequently observed familial forms: gene on chromosome 7 some forms associated with another neurodegenerative condition: ALS or Lou Gehrig's disease no curative treatment atrophy (shrinkage) of frontal and temporal lobes high number of Pick bodies (containing tau protein)

Answer 24

accounts for 10-15% of dementias dementia occurs "stroke by stroke" with progressive focal loss of function ("step-wise" function) risk factors that cause stroke are present: hypertension, diabetes, high cholesterol, smoking may occur concurrently with neurodegenerative dementia CT scan may show multiple areas of cerebral infarction treatment of hypertension and other vascular risk factors multiple small strokes