Cerebrum & Dementia Flashcards
What are the two broad parts of the cerebrum?
- the cerebrum/forebrain/prosencephalon develops into two sub groups: the telencephalon (hemispheres, basal ganglia, lateral ventricles, etc.) and the diencephalon (epithalamus, thalamus, hypothalamus, and ventral thalamus, and 3rd ventricle)
What separates the two cerebral hemispheres? What connects them?
- they are separated by the great longitudinal fissure
- they are connected by the corpus callosum (commissural fibers)
What separates the frontal lobe from the parietal lobe? What separates the frontal and parietal lobes from the temporal lobe?
- central sulcus separates frontal from parietal
- lateral fissure separates frontal and parietal from temporal
What is the gyrus just anterior to the central sulcus called? What about that just posterior to the central sulcus?
- anterior: precentral gryus - contains the primary motor cortex
- posterior: postcentral gyrus - contains the primary somatosensory cortex
Where is the primary auditory cortex located?
- in the superior temporal gyrus of the temporal lobe
What are the three types of signs/symptoms that focal cerebral lesions can cause?
- focal epileptic seizures (due to repetitive discharging of the affected neurons)
- sensory/motor deficits (due to involvement of respective cortices)
- psychological deficits (due to loss of brain matter dealing with language, memory, perception, etc.)
What does a unilateral cerebral hemisphere lesion result in? What can rapidly cause such a lesion?
- mental impairment, contralateral spastic hemiparesis + hyperreflexia + Babinski positive (extensor plantar response), contralateral hemisensory loss
- a stroke can cause a rapid unilateral cerebral hemisphere lesion
How many layers does the cerebral cortex have? In which layer do afferents from the thalamic nuclei project to? From which layer do projection fibers/tracts (to subcortical structures) originate?
- cortex has 6 layers (I to VI, running superficial to deep)
- thalamic nuclei project to layer IV
- projection fibers originate in layer V
What are association centers/cortices?
- these are areas between adjacent gyri/lobes that permit multimodal identification of objects, sensations, etc.
What do the medial portions of the cerebrum deal with?
- this is the limbic system (made up of the hippocampus, cingulate gyrus, and parahippocampal gyrus); it enables storage and retrieval of information
Which hemisphere is usually responsible for language?
- most individuals are left hemisphere dominant, meaning language is generated in the left hemisphere’s association cortices
Describe the layout of the primary motor homunculus in the primary motor cortex.
- moving superiorly/medially: larynx, pharynx, tongue, nose, eyes, neck, fingers, hands, shoulders, trunk, hips, knees, legs, foot, genitals
- the larynx, tongue, face, and fingers have the largest regions
The primary motor cortex receives afferents from mainly which thalamic nuclei? What about the premotor cortex?
- primary motor cortex: ventral lateral (VL) nucleus of thalamus
- premotor cortex: ventral anterior (VA) nucleus of thalamus
Where is the premotor cortex? Which cortex is contained within it?
- premotor cortex is immediately anterior to the primary motor cortex
- within the premotor cortex lies the supplementary motor cortex
What lies anterior to the premotor cortex?
- in both hemispheres, the frontal eye field gyrus is found anterior to the premotor cortex
- in the dominant hemisphere, Broca’s area is also found here (this is the motor speech gyrus, deals with word formation)
What will result from a left frontal lobe lesion?
- right-sided focal seizures, right-sided UMN lesions, speech deficit (expressive/Broca’s aphasia: patient understands language, knows what he wants to say, but is unable to do so; extremely poor articulation and loss of fluency; they are aware of their disability), dementia
What lies anterior to the all the motor cortices?
- the prefrontal cortex: controls intellectual, judgmental, and predictive faculties and behavior (executive function)
The primary somatosensory cortex receives afferents from mainly which thalamic nuclei?
- the ventral posterolateral (VPL) nucleus of the thalamus
What will result from a left parietal lobe lesion? A right parietal lobe lesion?
- left: right-sided focal seizures, right-sided hemisensory loss, right-sided inferior visual field loss, inability to name objects, loss of literacy (reading and writing) and calculation
- right: left-sided focal seizures, left-sided hemisensory loss, left-sided inferior visual field loss, spatial disorientation
The primary auditory cortex (in the temporal lobe) receives afferents from mainly which thalamic nuclei? What is unique about these afferent fibers?
- the medial geniculate nucleus (MGN) of the thalamus
- these fibers partially decussate as they ascend to the cortex, meaning that they have bilateral representation; a lesion in one temporal lobe will, therefore, result in partial deafness in both ears
What is located posteriorly to and surrounding the primary auditory cortex in the temporal lobe?
- the auditory association cortex; in the dominant hemisphere (usually left) this is called Wernicke’s area (deals with language comprehension and word choice)
What will result from a left temporal lobe lesion?
- right-sided focal seizures, right-sided superior visual field loss, bilateral partial deafness, speech deficit (receptive/Wernicke’s aphasia: patient can’t understand written or spoken language; speech is fluent but non-sensical; often they are unaware of their difficulty speaking)
What is found in the calcarine sulcus in the occipital lobe? What’s found in the rest of the lobe?
- the primary visual cortex
- the rest of the occipital lobe contains the visual association cortex
The primary visual cortex receives afferents from mainly which thalamic nuclei?
- the lateral geniculate nucleus (LGN) of the thalamus
What is represented in each primary visual cortex?
- each primary visual cortex deals with the lateral half of the visual field of the contralateral eye
What will result from a left-sided occipital lobe lesion? A bilateral lesion?
- focal seizures and right-sided lateral visual field loss
- if bilateral: cortical blindness (partial or total bilateral vision loss; often the patient will deny the vision loss!)
The left hemisphere is usually dominant for what processes? What about the right hemisphere?
- left: language and mathematics (logical), recognition of local features
- right: spatial perception, emotion, and musical proficiency (creative), recognition of global features
What are the three types of fibers found in the white matter of the cerebral hemispheres?
- association fibers: connecting cortical sites within one hemisphere (back and forth)
- commissural fibers: connecting related sites of one hemisphere to the other (left and right)
- projection fibers: connecting subcortical structures with the cortex (up and down)
What are the major association fibers of the cortex?
- superior longitudinal fasciculus: connects frontal, temporal, and occipital
- arcuate fasciculus: connects frontal and temporal (connects Broca’s and Wernicke’s areas; important for language)
- inferior longitudinal fasciculus: connects occipital and temporal (important for visual recognition)
- uncinate fasciculus: connects frontal and temporal (important for behavior)
- cingulum: connects lobes with limbic system
What is the anterior commissure?
- essentially a smaller version of the corpus callosum
- this is made up of commissural fibers that link the two temporal lobes
- the temporal lobes are not connected via the corpus callosum!
What does damage to the corpus callosum result in?
- results in relatively normal function, but in a disconnected fashion
- (ex: patient can write normally, but can’t read)
- (ex: visual info to the non-dominant side will not evoke a verbal response)
What is prosody?
- prosody is the concept of language conveying emotion
- this means that lesions of the right hemisphere WILL impact the patient’s language (flattened intonation and difficulty in judging other’s emotional tone, sarcasm, etc.)
How long is short-term memory? What about long-term? Which lobes are involved in each?
- short-term: seconds to minutes; frontal lobe (the prefrontal cortex)
- long-term: hours to years; temporal lobes (with the hippocampus)
What are the two types of long-term memory?
- explicit (AKA declarative) memory: facts, events, autobiographical memory; knowledge, reflective tasks, conscious recall
- implicit (AKA non-declarative) memory: habits, skills, priming and conditioning; motor skills, reflexive tasks, unconscious recall
Which structure plays a vital role in developing learned emotional responses (such as fear)?
- the amygdala (plays a role in recognizing our own and others’ emotional responses)
Alzheimer’s Disease
- the most common cause of dementia (60%) in the elderly population
- this is diffuse degeneration of the brain parenchyma resulting in an insidious onset of impaired higher intellectual function and altered mood/behavior that progresses to disorientation, memory loss, and profound disability + muteness
- most common deficits: short-term memory loss with variable dysfunction of executive function, visuospatial function, and language
What gross morphology do we see in Alzheimer’s Disease? What microscopic characteristics?
- gross: widening of the sulci and gyral atrophy due to loss of brain parenchyma, with resulting dilated ventricles (hyrdocephalus ex vacuo)
- microscopic: beta amyloid plaques (extracellular) and tangles of Tau (intracellular)
- (Tau is a neuronal microtubule binding protein; when it is phosphorylated it relocates from the axons to the cell bodies, where it aggregates into tangles)
What is dementia? In contrast, what is delirium?
- dementia: a progressive degradation in intellectual function that impairs social/occupational functioning
- delirium (AKA acute confusional state or acute brain syndrome): a transient state of confusion due to some underlying cause (infection, drugs, intoxication, etc.)
- (EEG for delirium: classic wide-spread slow-wave activity)
- patients with dementia have an increased susceptibility to developing delirium
When does Alzheimer’s classically begin? How common is it? What are the main risk factors? Is anything thought to be protective?
- Alzheimer’s usually begins after 60
- it initially has a 1% prevalence, but this doubles every 5 years (so by 85 it’s between 30 and 50%)
- risk factors: age, family history, diabetes (and other vascular disorders), history of significant/repeated head trauma, ApoE epsilon 4 isotope, Down syndrome, poor education, depression
- protective: ApoE epsilon 2 isotope, good education, social interaction, NSAIDs, statins, light alcohol consumption
Degeneration of the hippocampus will result in what? What about the left tempoparietal junction? The right parietal lobe? The left parietal lobe? The frontal lobe?
- hippocampus: short-term memory loss
- left tempoparietal junction (Wernicke’s area): word-finding difficulty, receptive dysarthria)
- right parietal lobe: visuospatial dysfunction (getting lost, not recognizing faces, etc.)
- left parietal lobe: apraxia
- frontal lobe: executive dysfunction (easily distracted, mentally inflexible, etc)
What investigations should be done in a patient presenting with a new cognitive complaint?
- brain imaging is indicated in all cases; the goal here is to rule out cerebrovascular disease, tumor, or other structural abnormality (rather than to confirm Alzheimer’s)
- MRI is the best, but CT is OK as well; can do a PET scan as well to show hypometabolic areas of Alzheimer’s)
How do we treat Alzheimer’s Disease?
- encourage aerobic exercise, social/community involvement, and frequent mental stimulation
- 1st line drug therapy: cholinesterase inhibitors (donepezil, rivastigamine, galantamine): mildly treat the cognitive impairment (these will NOT prevent disease progression); side effects: nausea and diarrhea are common, syncope and arrhythmia are uncommon
- NMDA-receptor antagonists (memantine) work similarly
- can give selective serotonin reuptake inhibitors (SSRIs) to treat depression, anxiety, and agitation; also give anticonvulsants (carbamazepine) and antipsychotics
What can cause an immensely rapidly progressive dementia (weeks to months)?
- Creutzfeldt-Jakob disease (CJD) via an “infection” with a prion (can also arise sporadically)
- the normal degradable protein is PrPc; prion form is PrPsc (forms beta-pleated sheets; which are resistant to proteases)
- (CJD is the most common form of spongiform encephalopathy, which is degeneration due to prion protein accumulation)
- (vCJD is variant CJD, due to consumption of contaminated meat; “mad cow disease”)
What are the two major causes of dementia? What are some others? What percent of cases are reversible?
- degenerative disorders (AD alone makes up 50-60% of all cases) and vascular disruptions (11% of all cases); 21% are mixed Alzheimer’s + vascular
- others: infection (CJD), systemic inflammatory disease, neoplasm, trauma, iatrogenic (anticholinergics and antihistamines), normal pressure hydrocephalus, etc.
- 10-20% of cases are due to reversible causes
What are the major degenerative disorders leading to dementia?
- Alzheimer’s disease (AD) is the major one
- dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), end-stage Parkinson’s disease, end-stage Huntington’s disease
- (DLB is essentially dementia and Parkinsonism developing at the same time)
What type of heterogeneity is involved in Alzheimer’s Disease?
- locus heterogeneity (where several genes can cause the disease)
- as opposed to allelic heterogeneity (where only a single gene causes the disease) as seen in Huntington’s
What is the proposed pathogenesis of Alzheimer’s disease?
- accumulation of beta amyloid proteins
- these result from alternative cleavage of the APPs (amyloid precursor proteins); normally, APP is cleaved by alpha-secretase into a degradable byproduct, but occasionally, they get cleaved by beta-secretase, generating Abeta40/42 fragments (these are unable to be cleared, and accumulate into plaques)
- the Abeta40 fragment tends to be more benign, while the Abeta42 fragment is associated with a more rapid onset and progression of the disease
What percentage of Alzheimer’s cases are clearly familial? Which genes are mainly involved?
- less than 2-5% of cases of AD are clearly familial; all cases so far are A.D. and involve chromosome 1, 19, or 21
- chromosome 14’s PSEN1 gene is most commonly mutated
- chromosome 1’s PSEN2 gene is more rare
- chromosome 21 contains the APP gene (thus patients with Down syndrome - trisomy 21 - nearly always develop Alzheimer’s)
- (mutated PSENs or APP genes result in altered processing of the APP protein)
Explain the role of ApoE in Alzheimer’s disease.
- (apolipoprotein E)
- three variants: epsilon2, epsilon3, and epsilon4
- epsilon3 is the wild type, with 1 cysteine and 1 arginine
- epsilon2 protects against AD, with 2 cysteines
- epsilon4 predisposes to AD, with 2 arginines (increases the conversion of APP to the non-degradable form)
DDx of Dementia
- delirium, aphasic stroke, severe depression with pseudodementia, amnestic disorder (such as Wernicke-Korsakoff), intellectual impairment
How do we diagnose Alzheimer’s Disease? How about vascular dementia?
1) patient has memory impairment and at least one of the following: aphasia, apraxia, agnosia (difficulty recognizing objects/faces), executive dysfunction
2) dysfunction must impair social/occupational setting
3) must not be due to delirium or another disease
- vascular: above 2 points + focal neurological signs or lab evidence of cerebrovascular disease
Vaccine for Dementia
- (not yet approved)
- vaccine against the Abeta42 protein results in clearing of the neuritic plaques!
- this works in mice
- works in humans, BUT 6% developed meningoencephalitis with an auto-antibody reaction to brain tissue
What do most patients with Alzheimer’s Disease die from?
- 57% die from pneumonia
- 16% from cardiovascular disease
- 14% from PE
What characterizes an amnestic disorder? What are common causes?
- severe impairment of new learning ability and an inability to recall previous memories WITHOUT a general loss of intellectual ability (vs. dementia) and WITHOUT clouding of consciousness (vs. delirium)
- common causes: Wernicke-Korsakoff syndrome, head trauma, brain tumor, subarachnoid hemorrhage, CO poisoning, encephalitis
What is Pick disease?
- a type of frontotemporal dementia characterized by Pick bodies (round aggregates - NOT tangles - of Tau)
What is the Charcot classic triad of presentation of multiple sclerosis?
- “S.I.N.”
- Scanning speech
- Intention tremor (or Incontinence, or Internuclear ophthalmoplegia)
- Nystagmus
