What is the most common Dementing Disorder

ad, frontal temporal dimentia, PD, AIDS, Huntington, AD

1. Progressive decline in mental ability 
2. impairment in 2 cognitive domains
3. presence of dementing syndrome 
4. absence of acute confusion 

-Episodic memory imapirment 

- executive/self monitoring deficits

and both of these are progressive - super gradual 

Neuritic plaques and neurofibril tangles

neuronal and synaptic loss 

proceeds temporal --> parietal-->frontal 

loss of acetylcholine 

Plaques - spongelike aggregates of amyloid beta with cell elements, invoke glial response 

Tangles are made of microtubule associated tau, very phosphorylated 

3 implicated chromosomes - 14, 21, 1 - autosomal dominant 

cause either increase in amyloid or decrease in its clearance as well as increase in number of tangles 

• Anti amyloid
• anti tau 
• antiinflammatory?
• immunization?
• beat secretase inhibitors 

• Hippocampal volume 
• Medial temporal lobe atrophy 
• pet.spect perfusion patterns (topography and its changes)

uses water as a standars to measure matter density -

absorb more rays--> appear light--> more dense

hmorrage - light 

edema -dark now since fluid filled

- huge magnet, huge radio frequency coil, huge gradient cord 

they can image across time and do diff pulses simultaneously 

use stronge magnet to align proton and radiowaves to change spin axis. then record energy release in deccay time or time for electrons to return to normal

spindensity -  long reptition time, (tr) short echo time (TE) 

T2 - long TR and TE - CSF looks white (transverse mag )

T1 short TR andTE (longitudinal mags)

can also perfuse and get MTT called TTP in MRI

DTI predicts infarcts 

DWI takes a real time snap shot - no accumulation or predictive measures 

ADC threshold can predict extent of damage - know when to treat people more aggressively

DTI uses anisotropies to determine bath of beaded filament cloumps and white matter bundles

it can separate bundles and determine which axons go where - allowing us to predict which fiber tracts may deviate and which alrready have

we can also just view how axons change and grow 

-flocculus and nodulus 

vermis

intermediate zone 

lateral hemispheres

what does the flocculo noduclar region do?

what does damage to it cause?

what does the vermis do?

what does damage to it cause?

its the midline, recieve spinal and vestibular input 

damage causes poor posture, eye motion deficits and locomotion/gait problems 

what does the intermediate zone do?

what does damage to it cause?

converges cortical and spinal inputs

damage causes limb movement issues 

floccular nodular doesnt have deep nuclei 

vermis --> fastigial 

intermediate --> interposed

lateral hemisphere - dentate gyrus 

purpose of the inferior olivary nucleurs 

WHat does damage to anterior inferior cerebral artery

 cause?

more common in children then adults, but resolve better in children than in adults 

- usually from paraneoplastic syndrome because of autoimmune effects 

• ataxia
• dysmetria 
• abnormal movement paths
• action tremors 
• bad VOR - cant stabalize eyes when head moving 

Late onset - 60 yrs 

no known cause

no racial/geo distribution

Pathology of PD?

1. Bradykinesia (slow)

2. resting tremor) 

3. Cogwheel rigidity (spasticity) 

4. impaired balance 

• striatum
• caudate 
• putamen
• nucleus accumbens
• globus pallidus 

-subthalamic nucleus for action selection 

-substantia nigra  - Pr like Gpi for eyes - goes to thalamus 

SNpc - dominergic 

What bio molecules is thought to be related to the pathology? 

Go (direct pathway) Motor cortex activates Putamen --I gpi(body)/snpc(eye) --I thalamus

disinhibiton of the thalamus allows thal to function 

No Go( indirect) 

motor cortex--> putamen --I Gpe --I STN --> Gpi (gabaergic) --I thalamus 

disinhibiton of the subthalmic nuceus allows gpi to inhibit thalamus 

motor program of specific speed force and direction is decided - go path for this must be activated and the no go suppressed 

at the same time - for all other motor programs no go must be active and go must be suppressed 

DA release from nigrostriatal axons does the motor training - without these neurons there will be deficits beacause of an increase in STN +GPi activation leading to an increase in thalamus inhibition (less motor cortext activiation 

(over excitation of no-go pathway - weak/ lack of movements ) 

D1 receptors in go pathway 

d2 in no go path way 

What are the motor deficits that can arise from this throw of balance in DA release 

lack of movement - akinesia 

slowness - brady kineasia

rhythmic basal ganglia activation 

only 5% is familial monogenetic - aging and environment may also have an effect 

MPTP impuriteis 

pecistides and well water 

decreased risk with smoking and and caffeine

MEDS- antipsychotics and aniemetics 

toxins, MPTP, Carbon monoxide 

vascular issues

PD syndromes like progressive supranuclear palsy and multisystem atrophy 

replace dopamine  through polypharmacological ways 

- agonists are weaker treatments 

anticholinergics to restore balance 

antivirals, anti esterases to keep things around longer. 

works on the Pallidus and subthalamic nucleus, it increases on time withot drugs, good as refractory for when leodopa fails, good for the youth 

doesn't coincide with current bgang lit but may explain b gabg 

- long term trt rough - levodopa because less efficient the more you use it - off time increases between time for drug to start and time when it wears off before next dose 

dyskinesia and hallucinations because of DA over sensitivity, doesnt help DA's are dying

dimentia occurs with age 

transcytosis through capilaries - use epitope tag recognized by receptors 

osmotic shock to open barriers 

cannula into brain

polymer chip for local release 

what does auc stand for and mean?

• no polymers existed
• drug syst toxic in brain
• no fda
• no$ 
• now need better chips
• not good enough 

cost too much to make and wouldnt be able to turn large profitds 

the drug itself is not the agent - metabolized into something succesful after it crosses the bbb

it modifies DNA