Dementia and Parkinson's Disease

serotonin is implicated in

migraine

anxiety

depressions

alzheimers

norepinephrine is implicated in

anxiety

depression

alzheimers

dopamine is implicated in

schizophrenia

parkinsons

alzheimers

depression

glutamate is implicated in

seizures

alzheimers

depression

GABA is implicated in

seizures

anxiety

depression

acetylcholine is implicated in

alzheimers

parkinsons

schizophrenia

histamine is implicated in

insomnia

CGRP is implicated in

migraine

dopamine activity in alzheimers

normal to low

acetylcholine activity in alzheimers

low

medication target for alzheimers

acetylcholine

dopamine activity in parkinsons

low; loss of dopaminergic neurons

acetylcholine activity in parkinsons

increased relative to dopamine

medication target for parkinsons

increase dopamine

dopamine activity in delirium

high

acetylcholine activity in delirium

potentially low

medication target for delirum

decrease dopamine

dopamine activity in schizophrenia

high mesolimbic

low mesocortical

medication target for schizophrenia

decrease dopamine

NT changes in alzheimers

decreased ACH

decreased dopamine and serotonin

increased glutamate

NT changes in Lewy body dementia

decreased ACh and dopamine

NT changes in frontotemporal dementia

decreased NE and serotonin

increased dopamine

treatment of other symptoms of lewy body dementia

quetiapine, clozapine

pimavanserin

treatment of other symptoms of frontotemporal dementia

valproate

amantadine

antidepressants

antipsychotics

core treatment of alzheimers

AChEIs

memantine

core treatment of lewy body dementia

AChEIs

normal cleavage of APP is done by

alpha secratase

abnormal cleavage of APP is done by

beta and gamma secretases

abnormal APP cleavage leads to

excess amyloid accumulation

dementia treatment goals

preserve cognitive function and patient independence as long as possible

lose < 2 points on MMSE per year

treating psychiatric and behavioral symptoms

donepezil indications

mild to severe alzheimers

donepezil titration timeline

4-6 weeks

donepezil should be dosed

daily in the morning

rivastigmine indications

mild to severe alzheimers

mild to moderate dementia associated with parkinsons

rivastigmine dosing

twice daily by mouth

daily transdermal

rivastigmine titration timeline

2-4 weeks

galantamine indication

mild to moderate alzheimers

galantamine titration schedule

every 4 weeks

galantamine dose adjustment

max 16 mg if CrCl < 60 or moderate hepatic impairment

memantine indication

moderate to severe alzheimers

memantine titration timeline

weekly

donepezil MoA

reversible inhibitor of AChE

rivastigmine MoA

pseudo-irreversible inhibitor of AChE and BChE

galantamine MoA

reversible inhibitor of AChe

allosteric modulation of nicotinic receptor sites

memantine MoA

NMDA antagonist

decrease over-activation of neurons

donepezil metabolism

2D6 and 3A4

rivastigmine metabolism

cholinesterases

galantamine metabolism

2D6 and 3A4

AChEI side effects

NVD

may increase gastric acid secretion

memantine adverse effects

fatigue, dizziness, somnolence, headache

agitation

medications for BPSD

brexpiprazole

citalopram

medications that should NOT be used in BPSD

valproate

melatonin

BZDs

first gen APDs

LAIs

clinical presentation of parkinsons

bradykinesia

resting tremor

muscle rigidity

postural/balance instability

parkinsons treatment inpatients under 65

may consider anticholinergic for tremors

dopamine agonist

carbidopa/levodopa

parkinsons treatment for patients over 65

carbidopa/levodopa

anticholinergic agents for parkinsons tremor, dystonia

benztropine

trihexyphenidyl

carbidopa/levodopa is effective for

5 years before motor complications

carbidopa/levodopa starting dose

25/100 mg TID

carbidopa/levodopa max tolerated daily dose

1000-1500 mg

carbidopa/levodopa absorption is decreased by

high fat, calorie, and protein meals

carbidopa/levodopa side effects

NV

postural hypotension

sedation, vivid dreams

dark discoloration of bodily fluids

amantadine is used for

managament of L-dopa induced dyskinesia

amantadine adverse effects

confusion

dizziness, orthostasis

dry mouth, nausea

hallucinations, nightmares, insomnia

reversible livedo reticularis

MAOI subtype used in parkinsosn

MAO-B

MAO-B inhibitors

selegiline, rasagiline

safinamide

COMT inhibitors

entacapone, opicapone, tolcapone

dopamine agonist agents

pramipexole

ropinirole

rotigotine

apomorphine

dopamine agonist side effects

sedation, confusion, vivid dreams, orthostasis

sleep attacks

compulsive behaviors

psychosis, hallucinations

pramipexole dosing

TID titrated weekly over 4 weeks

pramipexole dose adjustments

CrCl < 60 and < 35

ropinirole dosing

TID titrated weekly over 6-8 weeks

ropinirole metabolism

1A2 substrate

rotigotine dosing

daily, titrate after 1 week

apomorphine place in therapy

rescue med in advanced disease

apomorphine metabolism

1A2

avoid apomorphine if

CrCl < 30

Child-Pugh C

istradefylline MoA

adenosine receptor antagonist

istradefylline metabolism

1A2 and 3A4

istradefylline adverse effects

insomnia

nausea, constipation

hallucinations