Chapter 10 Flashcards
dementia
loss of cognitive ability
Alzheimer’s disease (AD)
- leading cause of dementia
- degeneration of the brain, especially the cortex and limbic system (hippocampus)
- sulci especially wide, indicating degeneration of the cortex
preclinical AD
- no symptoms
- measurable brain changes
mild cognitive impairment due to AD
- very mild symptoms that do not interfere with everyday activities
- measurable brain changes plus subtle problems with memory and thinking
mild AD
- symptoms interfere with some everyday activities
- memory problems (especially new memories), word finding difficulties, trouble with planning/organization
moderate AD
- symptoms interfere with many everyday activities
- memory problems (personal history), feeling moody and/or withdrawn, wandering/getting lost, personality changes (e.g., suspiciousness and delusions)
severe AD
- symptoms interfere with most everyday activities
- loss of awareness (of recent events and surroundings), difficulty with communication, vulnerable to infections (especially pneumonia)
dementia memory lapses
- not recognizing family members
- forgetting to serve meal just prepared
- substituting inappropriate words
- getting lost in own neighborhood
key characteristics of AD
- cognitive deficits: profound memory loss (anterograde/retrograde), language (anomic, empty, circumlocutory), visuospatial disturbance
- behavioral deficits: no significant early changes in personality, unawareness or denial of illness, psychosis
- no sensory or motor deficits
- age of onset 70s-80s
pathology of AD
- neurofibrillary tangles (tau protein)
- amyloid plaques (beta amyloid)
beta-amyloid plaques (senile plaques)
- large amyloid precursor proteins (APP) are cut into fragments called beta-amyloid fragments via the enzyme beta-secretase
- the fragments clump into plaques outside of the cell and destroy dendrites, reducing dendritic branching affecting cognition
- they also initiate an immune response from the microglia that also increase the spread of plaques killing neurons
neurofibrillary tangles
- inside of the neuron
- microtubules are bound together with tau proteins
- if tau proteins change their structure, the microtubules fall apart
- the tau proteins clumps together in tangles, killing the neuron
cytoskeleton of neuron
- gives the neuron its shape
“bones” are: - microtubules: big, run longitudinally down neurites, made of tubulin, microtuble-associated proteins (MAPs) regulate microtuble assembly and function; changes in MAPs called tau implicated in AD
- microfilaments: solid, thinner, actin
- neurofilaments: intermediate filaments, individual long protein molecules
microtubule-associated proteins (MAPs)
- tau/MAPs can function as cross-bridges connecting microtubules
- can affect microtubule rigidity
- brain uses a transport system to help move around the nutrients it needs; system is made of proteins like railroad tracks guiding trains guide nutrients where they need to go; proteins that keep the tracks straight are tau proteins
causes of AD
- genetics (likely several genes)
- immune responses initiated by microglia
- sleep imbalance
genetics of AD
- amyloid precursor protein (APP) (familiar early onset of AD)
- presenilin (PS) 1 and 2 (familial early onset of AD)
- Down’s Trisomy 21
- ApoE4 increases risk of late onset of AD
microglia and AD
- microglia play a role in the immune system and in the brain
- release inflammatory proteins
- attempts to clean up damage caused by beta-amyloid plaques but may contribute to the spread
treatment of AD
- cholinergic replacement: treats symptoms
- anti-amyloid agents: tries to reduce the disease
cholinergic hypothesis
- loss of ACh activity correlates with the severity of AD
- acetylcholinesterase inhibitors: drugs used to treat Alzheimer’s disease, act by inhibiting acetylcholinesterase activity
- these drugs block the esterase-mediated metabolism of acetylcholine to choline and acetate; this results in: increased acetylcholine in the synaptic cleft, increased availability of acetylcholine for postsynaptic and presynaptic nicotinic (and muscarinic) acetylcholine receptors
acetylcholine (ACh)
an important neurotransmitter in areas of the brain involved in memory formation
fronto-temporal dementia (FTD)
- FTD is an umbrella term that encompasses several types of dementia primarily affecting the frontal and temporal lobes of the brain
- includes various subtypes, such as behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), and others
Pick’s disease
- specific subtype of FTD
- characterized by presence of abnormal brain cells known as Pick bodies and Pick cells
- mainly affects the frontal and temporal lobes and typically presents with symptoms similar to behavioral variant FTD
pathology of FTD
- can vary widely and may include tau protein inclusions, TDP-43 inclusions, or other forms of cellular degeneration
- does not always have Pick bodies
pathology of Pick’s disease
characterized specifically by the presence of Pick bodies, which are abnormal clumps of tau protein inside neurons
symptoms of FTD
- can vary depending on the subtype but typically include changes in personality, behavior, language, and sometimes motor skills
- behavioral variant is most common and can cause disinhibition, apathy, and loss of empathy
symptoms of Pick’s disease
often similar to the behavioral variant of FTD with early behavioral and personality changes such as impulsivity and lack of social awareness; language difficulties may also be present
age of onset of FTD
typically occurs in individuals under 65 years, most often in 50s or 60s but can occur earlier
age of onset of Pick’s disease
often appears in individuals in their 40s to 60s
genetics of FTD
can have a genetic component, with 1/3 to 1/2 of cases linked to inherited mutations in genes such as MAPTm GRN, C9orf72
genetics of Pick’s disease
- less well-understood genetic basis, though it may occasionally run in families
- not all cases genetically linked
some neuropsychological tests used to evaluate executive functions
- Wisconsin card sorting task
- Tower of Hanoi
Wisconsin card sorting task
- cards may be sorted on the basis of color, shape, or number
- patient not aware of the rules
- use trial-and0error to infer the rule
- after 10 accurate trials the rule will shift
- different types of errors to report: total number errors, perseveration errors (when you keep applying the old rule), non-perseveration errors
tower of Hanoi
- three pegs with three different colored rings on one end
- goal: move the tower from one end of the board to the opposite side with as few moves as possible
- rules: can only move one piece at a time, a larger piece is not allowed to be placed on top of a smaller piece
vascular dementia
- multi-infarct
- type of dementia caused by reduced blood flow to the brain, often due to strokes or other conditions that damage blood vessels, leading to brain cell death
- reduced blood flow to the brain can lead to symptoms that impact memory, reasoning, and sometimes movement
cause of vascular dementia
conditions that block or reduce blood flow to the brain, depriving brain cells of oxygen and nutrients
- may happen due to stroke or small vessel disease
small vessel disease
narrowing or blocking in the brain’s smaller blood vessels can lead to gradual brain cell damage
symptoms of vascular dementia
- vary depending on which parts of the brain are affected
- memory loss
- difficulty with problem-solving and organization
- slowed thinking
- difficulty with attention and concentration
- changes in mood or personality
- movement issues (e.g., unsteady gait)
acute dementia
- intoxications: delirium
- metabolic abnormalities: renal failure, substrate deficiencies (B12/folate deficiency)
- hypothyroidism
- depression (pseydodementia)
- infectious agents: neurosyphilis/fungal meningitis/HIV
delirium vs dementia
delirium and dementia often occur together in older hospitalized patients
distinguishing signs of delirium:
- acute onset
- cognitive fluctuations over hours or days
- impaired consciousness and attention
- altered sleep cycles
depression vs dementia
symptoms of depression and dementia often overlap, but patients with primary depression:
- demonstrate decreased motivation during cognitive testing
- express cognitive complaints that exceed measured deficits
- maintain langauge and motor skills
work-up of dementia
- careful history
- complete mental status and neurological exam
- blood studies CBC, electrolytes, LFTs, B12, folate levels, thyroid function tests, VDRL, FTA, HIV
- lumbar puncture
- EEG
- MRI
- PET
