patho II section 1

what is the function of the supplemental motor area

store the thought of motion

what is the pathway through the brain for motion

input > area 6 (basal ganglia, thalamus, cerebellum) > area 4 (brainstem) > spinal cord > movement

what part of the brain is responsible for the refinement of movement

basal ganglia

what makes up the basal ganglia

substantia nigra, putamen, globus pallidus

what is the overall function of the basal ganglia

regulate start, amplitude, and speed of movement

what is involuntary oscillating contractions of opposite muscles around a joint

tremor

what is reduced range and force of movement with slow initiation

bradykinesia

what is irregular writhing

chorea

what are tiwsting and turning movements

athetosis

what are flinging motions

ballismus

what are simultaneous contractions of agonist and antagonist muscles

dystonia

what is bizarre wriggling and writhing

dyskinesia

what age range is parkinsons most common in

>65

which gender is parkinsons most common in

men

what are the 3 pathologic processes for parkinson's

oxidative stress, apoptosis, mitochondrial disorder

what are risk factors for parkinson's

rural living, TBI, age >60

what is drug induced parkinsonism

dopamine blocking agents cause reversible parkinsonian tremors

what are the common genetic mutations that can cause parkinsons

PARK2, LRRK2, GBA

what is the course of pathophysiology that leads to parkinson's

destruction of dopaminergic neurons in substantia nigra > depletion of dopamine stores > imbalance of ACh and dopamine NT > impairment of control of complex body movements

what role does dopamine play in movement

inhibitory

what role does ACh play in movement

excitatory

what can be found in histology of the brain post-mortem

lewy bodies

what is the essential cardinal feature for parkinson's diagnosis

bradykinesia

what other criteria lead to a parkinson's diagnosis

asymmetric resting tremor or rigidity

what are other features seen in parkinson's disease

micrographia, diminished arm swing, shuffling gait, fall risk

what are the 4 absolute exclusion criteria

confirmed cerebellar, visual, or cortical abnormalities; medication induced; no response to high-dose levodopa; features only in lower limbs >3 years

what are red flags at the time of diagnosis

bilateral presentation, respiratory dysfunction

what are red flags within 3-5 years of diagnosis

recurrent falls w/i 3 years; wheelchair use w/i 5 years; autonomic failure w/i 5 years

what are red flags w/i 5 years

absence of common non-motor features after 5 years; absence of progression in 5 years w/o treatment; contractures of hands/feet w/i 5 years

when do you consider alternative diagnosis

symmetrical presentation, no response to DA challenge, no bradykinesia, history of TBI, concurrent dementia

what is a DaT scan

visualization of dopamine transport to support diagnosis

ioflupane binds to DA transporter, shown in PET scan

what are common things that lead to falls in parkinson's

postural instability, orthostatic hypotension, levodopa induced dyskinesia

what are symptoms of autonomic dysfunction in parkinson's

constipation, urinary retention, sexual problems, pain, dysphagia

what are neuropsychiatric symptoms in parkinson's

cognitive impairment, hallucinations, depression, sleep disorders

what is a 1 on hoehn/yahr staging

asymmetrical symptoms

what is a 2 on hoehn/yahr staging

bilateral symptoms, no trouble ambulating

what is a 3 on hoehn/yahr staging

bilateral symptoms, some trouble ambulating

what is a 4 on hoehn/yahr staging

bilateral symptoms, moderate trouble ambulating

what is a 5 on hoehn/yahr staging

bilateral symptoms, inability to walk

what is a hallmark symptom of early parkinson's

olfactory impairment

what are the 4 pain types of dementia

dementia, lewy body, vascular, frontotemporal

what is alzheimers

progressive, fatal neurogenerative disorder

what does alzheimers affect

cognition, behavior, functional status

what are reversible causes of dementia

normal pressure hydrocephalus, hypothyroidism, B12 deficiency, delirium, depression, B1 deficiency

what are the most common med associated with cognitive impairment

anticholinergics, benzos, sedative hypnotics, opioids, antipsychotics

what are the non-modifiable risk factors for alzheimers

age, female gender

what are the modifiable risk factors for alzheimers

hearing loss, physical inactivity, diabetes, hypertension, obesity, depression, cigarette smoking, low education attainment, excessive alcohol use

what influences a persons likelihood of getting AD

environmental/lifestyle factors/genetics/medical comorbidities

what is the leading theory for the reason behind AD

proteinopathies: aggregation and accumulation of misfolded proteins

what are the two types of lesions

amyloid plaques and neurofibrillary tangles

what type of pathways are destroyed in AD

cholinergic

which type of lesion is outside the neuron

amyloid plaques

what type of lesion in inside the neuron

neurofibrillary tangles

what are APP required for

helps neuro grow and repair

what recycles APP

alpha and gamma secretase

in AD, what recycles APP

beta and gamma secretase

what is the consequence of production of beta amyloid

it is insoluble and sticky and forms plaques

what composes neurofibrillary tangles

abnormally hyperphosphorylated tau proteins

what is the normal function of tau proteins

stabilize microtubules in the neurons

what is the consequence of having phosphorylated tau proteins

microtubules collapse and tau proteins clump together to create tangles

what biomarker is first seen in AD

amyloid PET

what are the second and third biomarkers seen

MTL tau, then neocortical tau

what is the secondary cause of AD

nueroinflammation

what are the physical changes that happen to the brain in AD

brain atrophy, gyri narrow, sulci widen, ventricles become larger

which of the following is true regarding the pathophysiology of AD

a. AD can be caused by amyloid plaques

b. AD can be caused by neurofibrillary tangles

c. AD can be caused by inflammatory brain processes

d. the cause of AD is not completely understood

e. all of the above

e. all of the above

what neurotransmitter is depleted in alzheimers disease

a. dopamine

b. ACh

c. serotonin

d. NE

b. ACh

why is the advantage of using blood biomarkers of plaque/tangle PET scans

can be used in early stages, less invasive, decreased cost

what are the core 1 biomarkers

A and T1

what is the core 2 biomarkers

T2

when do core 1 biomarkers become abnormal

around the same time as amyloid PET

what is core 1 used for

can identify presence of AD in symptomatic and asymptomatic patients

when does core 2 become abnormal

close to the onset of symptoms

what are the clinical presentations of AD

memory loss, aphasia, disorientation, impaired executive function, depression, psychotic symptoms, inability to perform ADLs

what is the loss of ability to understand or express speech

aphasia

what is apraxia

loss of ability to execute skilled movement despite having the physical ability to do so

what is agnosia

inability to recognize and identify objects or persons using one or more senses

what is the difference between ADLs and IADLs

ADLs: toileting, feeding, bathing

IADLs: paying bills, remembering appointments

what are the 6 stages of AD

1. biomarker evidence, no symptoms

2. transitional decline

3. objective cognitive impairment

4. mild functional impairment

5. moderate functional impairment

6. severe functional impairment

how does stage 1 AD present

normal performance on cognitive tests, no cognitive decline

biomarkers are positive

how does stage 2 AD present

decline from previous cognition but still within expected range on cognitive tests

fully independent

how does stage 3 AD present

performance is abnormal on cognitive tests, decline from baseline, can perform ADLs independently but may have impact on complex activities

how does stage 4 AD present

progressive cognitive and mild impairment in IADLs, independence with ADLs

how does stage 5 AD present

progressive cognitive and mild function impairment. requires assistance for basic ADLs

how does stage 6 AD present

complete dependence on others for basic ADLs

what is the main test of cognition for AD

MMSE, mini mental state exam

what is the MMSE used for

score determines appropriateness for drug therapy and staging of illness

what is the MMSE range for mild AD

18-26

what is the MMSE range for moderate AD

10-17

what is the MMSE range for severe AD

0-9

what are behavioral Sx associated with dementia

delusions, hallucinations, depression, sundowning

what are the DSM-5 criteria for a major depressive episode

-at least 1 of these 2: depressed mood or loss of pleasure

-at least 4 of these: weigh change, sleep disturbance, agitation/retardation, fatigue, guilt, decreased concentration, or suicidal ideation

-symptoms present nearly every day for at least 2 weeks

what is required for diagnosis of MDD

symptoms must be causing clinically significant distress or impairment in areas of functioning that is not attributable to other conditions

what are medical conditions associated with depressive symptoms

anemia, heart failure, HIV, hypothyroidism, cancer, MS, parkinson's, seizure disorders

what are medications that are associated with depressive symptoms

acyclovir, anti-seizure meds, ARVs, barbiturates, benzos, b-blockers, corticosteroids, accutane, hormonal products, opioids, varenicline

what are risk factors for depression

female, middle-aged, widowed/separated/divorced, low income, unemployment, disability, stressful life events, first degree relative with MDD

what is the monoamine hypothesis of depression

depression due to deficiency of NE and serotonin

causes upregulation of receptors

according to the monoamine hypothesis, when do anti-depressants take effect

when receptors downregulate toward normal

what is BDNF required for

growth and development of neurons, survival of adult neurons, maintenance of connections (essentially your brains fertilizer)

what happens to BDNF in depression

levels are lower

what occurs due to low levels of BDNF in depression

neurons undergo apoptosis which leads to loss of dendritic spines