Dementia and Alzheimer's Disease Flashcards
What is Dementia?
dementia is global deterioration of intellectual function in the face of unimpaired consciousness
What are 7 steps in evaluating someone with dementia?
- general medical history
- general neurological history
- neurobehavioral history (i.e. personality issues)
- psychiatric history
- toxic, nutritional and drug history
- family history
- objective examination … (physical, neurological and neuropsychological)
What are bedside tests? what do they include?
type of comprehensive assessment of mental state… includes mini-mental status examination (MMSE) and Montreal Objective Cognitive Assessment (MOCA) .. these rate patients on a scale
what are 6 domains of cognition that are tested in the bedside tests?
- level of consciousness: i.e. alert, drowsy …etc..
- orientation: time, place, person
- memory, remote, recent, immediate (3 object recall… such as repeating, recalling 3 objects)
- attention and concentration (serial 7’s –> subtraction by 7, and digit span)
- Knowledge and insight
- language: fluency, comprehension, repetition, objecting naming, tests for apraxia, and reading & writing
What is one condition that involves the parietal cortex that patients with dementia frequently exhibit?
visual-spatial difficulties involving the parietal cortex…
construction of apraxia –> they can draw (have motor capability) but they cannot construct something… lesions in parietal lobe reflect this
What are some abnormal reflexes shown in people with dementia in neurological exams?
they are reflexes related to frontal lobe dysfunction
- pout reflex –> tap lips with tendon hammer -> a pout response is observed
- glabellar reflex –> patient cannot inhibit blinking in response to stimulation of tapping between eyes
- grasp reflex –> stroking palm of hand induces ‘grasp’
- palmo-mental reflex –> quick scratch on palm of hand induces sudden contraction of mentalist muscle in the face
what two ways can we think of causes and types of dementias?
- the part of the brain that is mostly affect.. ie. frontal (anterior) vs. parietal (posterior) lobes/cortex [anatomically]
- the rapidity of progression of the dementia
location and rate of progression
what changes are noticed when theres dysfunction in the anterior area of the brain?
includes the frontal and pre-motor cortex
behavioural changes/loss of inhibition, antisocial behaviour, facile and irresponsible
includes: frontotemporal dementia (pick’s disease)
and huntington’s disease
what changes are noticed when theres dysfunction in the posterior area of the brain?
includes the parietal and temporal lobes
disturbance of cognitive function (memory and language) without marked changes in behaviour
includes: alzheimer’s disease
What is an example of a chronic disorder based on its temporal progression and intellectual function?
Alzheimer’s disease –> its slow, and the symptoms don’t come right away… usually takes years
What is an example of a Subacute based on its temporal progression and intellectual function?
includes normal pressure hydrocephalus –> CSF cavities in the brain not clear CSF properly and the ICP of the brain starts to rise.. this is slow but not slow enough to be chronic .. it takes about months to notice
also Creutzfeldt-Jakob syndrome is also a subacute disorder however, its quicker in development than hydrocephalus …
What is an example of a acute disorder based on its temporal progression and intellectual function?
These are quick showing disorders that show up within weeks and have a lot of damage to the brain… these include encephalitis (brain infections) and rapid decline in intellectual function
what are 7 causes of dementia?
- degenerative
- cerebrovascular
- Structural
- infections
- toxic/metabolic
- immune disorders and cancer
- depession
What are some ways that neurodegernativity can cause dementia?
- caused by 80% of dementias
- includes alzheimer’s disease
- lewy body dementia
- taupathies like pick’s disease and progressive supra nuclear palsy
- huntington’s disease
- parkinson’s disease
- wilson’s disease
what are some ways that dementia can be cerebrovascular in cause
- vascular dementia (multi-infarct dementia) and CNS vasculitis
What are some ways that dementia can be structural disorder and in cause?
- normal pressure hydrocephalus
- brain tumour
- head injury
- subdural hematoma (collections of blood in the brain)
What are some ways dementia can be caused by infections?
- creutzfeld-jacob disease …
- neurosesyphilis, others
- HIV
- sequelae of viral encephalitis (Herpes)
these are more rapidly progressing dementias
what are some ways dementia can be caused by toxic/metabolic problems?
- drug induced
- alcoholism
- toxins, heavy metals and carbon monoxide
- vitamin defiendes, like b12, thiamine and folate
- hypothyroidism
- uremia and dialysis-related
- hepatic encephalopathy
these are the most treatable and has some sort of cure to it
what are some ways dementia can be caused by immune disorders and cancer?
lupus
paraneioplastic disease
What are 4 common themes that run in neurodegenerative dementias?
- 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 is) –> i.e. for alzheimer’s it affects the basal forebrain area, parkinson’s affects the substantia nigra and huntingon’s affects the caudate nucleus area
- proteins that are misfiled and abnormally deposited in the specific brain areas, seem to play a key role in these diseases
- for the most part, precise causes unknown and hence no definitive treatment available to stop progression of disease
What is alzheimer’s disease?
alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills… affects mainly hippocampal and basal ganglia area
in most people with AD, symptoms first appear after age 60 AD is not a normal part of aging
it is caused by a fatal disease that affects the brain
How many number of neurons does the brain have?
100 billion
how many number of synapses does the brain have?
100 trillion
What three essential jobs of the neurons does AD disrupt?
- communication between neurons
- metabolic functions of neurons
- repair functions of neurons
What are some alzheimer’s facts?
- 70-80% cause of dementia (most common cause)
2. a lot in canada
What are some clinical features of signs and symptoms of alzheimer’s disease?
symptoms:
- impairment of memory and attention
- language and communication
- abstract thinking
- judgement
- personality changes
- depression
- visuospatial disorientation (difficulty orienting in space)
signs:
- motor and gait disturbance (balance)
- poverty of movement and slowness
- falls
- problems with bladder and bowel control
- seizures
What are the three time course events in alzhiemers?
- early diagnosis –> shows increasing number of cognitive symptoms
- mild-moderate –> loss of functional independence, behavioural problems
- severe –> nursing home placements and death
What is the aetiology and occurrence of alzheimers?
occurrence: most cases occur usually late 60’s or later
etiology:
1. familial forms: less than 10% of cases
2. sporadic (unknown case) –> over 90% of cases
3. early onset like 40s and 50s is usually familial and associated with susceptibility genes that include mutations of amyloid precursor protein (APP), presenilin 1 and 2 mutations
3. late onset (60s and later) –> mostly sporadic (unknown cause)
- E4 gene is the main susceptibility gene, some other genes include SORL1, Clustering CLU, complement receptor 1 CR1 and TREM2
What are the 5 neuropathology’s associated with alzheimer’s disease?
- cortical atrophy (brain shrinkage)
- synaptic and neuronal loss
- neurofibrillary tangles (NFTs) with paired helical filaments, abnormally hyperphosphorylated forms of microtubule associated TAU protein
- neuritic plaques with amyloid core
- amyloid angiopathy
What are some signs of cortical atrophy in the brain?
its not specific to AD
but it shows widening of sulk and thinning of cortex
What are plaques and tangles?
the brains of people with AD have an abidance of two abnormal structures
- beta-amyloid plaques: these are dense deposits of proteins and cellular material that accumulate outside and around nerve cells
- neurofibrillary tangles –> which are twisted fibres that build up inside the nerve cell
What is Amyloid precursor protein (APP) and how does it form beta-amyloid plaques?
APP is a membrane protein that sits in the membrane end and extends outwards
it is thought to be important for neuronal growth, survival and repair
enzymes cut the APP into fragments, the most important of which for AD is called the beta-amyloid enzyme
Beta-amyloid is “sticky” so the fragments that are cut cling together along with other materials in the cell forming the plaques seen the AD brain
how can alzheimer’s disease be described in terms of neurotransmitter abnormalities?
- low chemical messengers in the brain especially acetylcholine from the cortex and hippocampus areas
what is the cholinergic basal forebrain and its connections?
aCH lives in the basal forebrain and spreads through the cortex
- when the basal forebrain areas die, it produces less ACH
what are some symptomatic cholinergic agents/drugs for alzheimer’s disease?
- choleninergic drugs act to block reuptake sites for aCH and increase release of it, and keep it longer in the synapse
also has selective m1 agonists
drugs include: cholinesterase inhibitors: donepezil (accept), rivastigmine (exelon), galatamine (reminyl) … these stop the enzyme cholinesterase from eating the aCH
what are some non cholinergic agents of alzheimer’s disease?
memantine, which is a glutamate receptor modulator
What are some other approaches for treating AD?
- amyloid vaccine
- secretase inhibitors
- anti amyloid agents
- drugs that lower cholesterol
what are some unproven treatments for AD?
- estrogens
- NSAID’s
- vasodilators
- propentofylline
what are some non drug approaches to treating DA?
- higher education
- intellectual stimulation
- excersize and diet
these are not backed up by science though
What is dementia with lewy bodies?
- involves fluctuating cognition with pronounced variation in attention and alertness (one day they have good cognition and the other day they don’t)
- recurrent visual hallucinations
- parkingsonian features like rigidity, stiffness in muscles, slowness, and poverty of movement and tremors
- treatment with cholinesterase inhibitors, antipsychotic drugs to control behavioural problems and agitation and hallucinations
it is represented in the brain by loss of pigmented (dopamine containing) neurons in the substantia nigra in parking sons and dementia with lewy bodies which look similar
also its the presence of lewy bodies which contain alpha synuclein protein
What is frontotemporal dementia (pick’s disease)?
- 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 is most frequently observed
- gene on chromosome 17 is apparently mutated
- ALS or lou gherig disease are either forms associated with neurodegenerative condition
the pick bodies that are present are called tau
theres no cure
What is vascular dementia?
- accounts for 1-015% of dementias
- dementia occurs stroke by stroke with progressive focal loss of function
- risk factors that cause stroke are present in patients such as hypertension, diabetes, high cholesterol, smoking
- may occur concurrently with neurodegenerative dementia
- CT scan may show multiple areas of cerebral infarction (obstruction of blood supply)
- treatment of hypertension and other vascular risk factors
MRI scan shows multiple small strokes
