Lecture 16: Dementia and Memory Flashcards
What is dementia?
global deterioration of intellectual function in the face of unimpaired consciousness
impossible to tell if they have dementia if they re unconscious
How do we approach and evaluate someone with dementia?
general medical history
general neurological history
neurobehavioral history
psychiatric history
toxic, nutritional and drug history
family history
objective examination: physical, neurological, neuropsychological
family members bring them in for treatment, not the patients
What are bedside tests for the assessment of mental state?
administer at clinic, objective measure of decline over time
mini-mental status examination (MMSE) and Montreal objective cognitive assessment (MOCA)
MOCA: score of 30 is max, lower the score the greater the impairment
What are the domains of cognition that are tested when assessed a patients mental state?
level of consciousness: i.e. alert, drowsy, stuporous, etc.
orientation: time, place, person
memory: remote, recent, immediate (3 object recall), same thing they do at bedside
attention and concentration: (serial 7’s, digit span), ability to concentrate on the task at hand
knowledge, insight
language: fluency, comprehension, repetition, object naming, tests for apraxia, reading, writing
What are some general characteristics of the symptoms of dementia?
symptoms of dementia reflect the part of the brain that is affected
patients with dementia frequently exhibit visual-spatial difficulties indicating involvement of the parietal cortex
How do reflexes indicate dementia symptoms?
neurological examination frequently reveals abnormal reflexes related to dysfunction of the frontal lobes
primitive reflexes found in infants return in dementia
frontal lobe dysfunction
What is the pout reflex?
tap lips with tendon and hammer, a pout response is observed
What is the glabellar reflex?
patient cannot inhibit blinking in response to stimulation (tapping between eyes)
What is the grasp reflex?
stroking palm of hand induces “grasp”
What is the plamo-mental reflex?
quick scratch on palm of hand induces sudden contraction of mentalis muscle in face
What are two ways to think of causes and types of dementia?
the part of the brain that is mostly affected, e.g. frontal (anterior) versus parietal (posterior) lobes/cortex
that rapidity of progression of the dementias
What does damage to the anterior (frontal) lobe cause in terms of dementia?
frontal pre-motor cortex
behavioral changes/loss of inhibition, antisocial behavior, facile and irresponsible (less executive function)
other dementias, frontotemporal dementia (Pick’s), Huntington’s disease (areas deep in the brain are affected)
What does damage to the posterior (parietal) lobe cause in terms of dementia?
parietal and temporal lobes
disturbance of cognitive function (memory and language) without marked changes in behavior
Alzheimer’s disease (in the end if affects the whole brain)
What is the intellectual decline pattern of encephalitis?
acute (weeks)
What is the intellectual decline pattern of Creutzfeldt-Jackob (mad cow disease)?
subacute (months)
What is the intellectual decline pattern of normal pressure hydrocephalus?
chronic (years)
difficulty controlling bladder and walking affects ventricles and CSF
What is the intellectual decline pattern of Alzheimer’s disease?
chronic (years)
What are examples of degenerative dementias?
Alzheimer’s disease
Lewy body dementia
Tauopathies, frontotemporal dementia (Pick’s disease, progressive supranuclear palsy)
Huntington’s disease
Parkinson’s disease
Wilson’s disease (problem with copper binding proteins)
What are examples of cerebrovascular dementias?
vascular dementia (multi-infarct dementia)
CNS vasculitis
What are examples of structural dementias?
normal pressure hydrocephalus
brain tumor
head injury
subdural hematoma
What are examples of infection caused dementias?
Creutzfeldt-Jacob disease
neurosyphilis, others
HIV
sequelae of viral encephalitis
What are examples of toxic/metabolic dementias?
drug induced, treatable
alcoholism
toxins, heavy metals, CO
vitamin deficiencies (B12, thiamine, folate)
hypothyroidism
uremia and dialysis-related
hepatic encepgalopathy
What are examples of immune disorder and cancer caused dementias?
lupus, paraneoplastic disease
What is the relationship between dementia and depression?
frequently accompanies and clouds assessment of dementia
What are the laboratory investigations for dementia?
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
What are common themes that run in neurodegenerative dementias?
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
What is Alzheimer’s disease?
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
How does Alzheimer’s affect neurons?
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
What is the prevalence of Alzheimer’s disease?
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 $)
What are the symptoms of Alzheimer’s?
impairment of memory and attention
language and communication
abstract thinking
judgement
personality changes
depression
visuo-spatial disorientation (difficulty orienting in space)
What are the signs of Alzheimer’s?
motor and gait disturbance
poverty of movement and slowness
falls
problems with bladder and bowel control
seizures
What is the age of occurrence of Alzheimer’s?
most cases occur usually late 60’s or later
What is the etiology of Alzheimer’s?
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
What is the neuropathology of Alzheimer’s?
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
What is cortical atrophy?
shrinkage of the brain
not specific to AD
What are the two abnormal structures that people with Alzheimer’s disease?
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
How are amyloid depositions formed?
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
What are neurotransmitter abnormalities in Alzheimer’s disease?
decrease in chemical messengers in the brain especially acetylcholine (cortex, hippocampus)
How to cholinergic drugs treat Alzheimer’s?
increase release of Ach
if AchE is inhibited then Ach will be broken down slower
What are examples of cholinergic agents?
cholinesterase inhibitors
donepezil (Aricept)
rivastigmine (Exelon)
galantamine (Reminyl)
What are examples of non-cholinergic agents?
memantine (Namenda, Ebixa), a glutamate receptor (NMDA) blocker
What are other possible treatments for Alzheimer’s?
amyloid vaccine
secretase inhibitors
anti-amyloid agents
drugs that lower cholesterol
What are unproven treatments for Alzheimer’s?
estrogens, NSAIDs, vasodilators, propentofylline
What are some non-drug approaches to treating Alzheimer’s?
higher education
intellectual stimulation
exercise and diet (improves cardiovascular)
red wine ?
What is dementia with Lewy bodies?
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
What are Lewy bodies?
contain abnormal 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 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)
What is vascular dementia?
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
