Dementia Flashcards
Define dementia
An acquired persistent (often slowly progredient)
– Loss of intellectual function due to a brain disorder
Define aging
An acquired, persistent, slowly progredient disorder
– Leads to loss of various organ functions over time
Define Alzheimer’s disease
"senile dementia" Gradual memory loss Decline in ability to perform routine tasks Disordientation Difficulty in learning Loss of language skills Impairment of judgement Personality changes Age associated
What is the pathophysiology of Alzheimer’s?
- Amyloid plaques formed by false processing of APP (Amyloid precursor protein) – genetically or environmental contributions
- Neurofibrillary tangles in neurons due to hyper-phosphorylation of the tau-protein — changes signal transduction; loss of axonal transport
- Neuronal cell death, primarily of cholinergic neurons (severe memory loss and loss of cognitive functioning)
- –Accelerated aging
Treatment of Alzheimer’s?
Enhancement of cholinergic function to improve cognition (low does prevents activity but high causes toxicity)
- Reduction of amyloid and NFT formation (inhibits abnormal enzymatic pathways by enzyme inhibitors, antioxidative strategies)
- – Stem cell and gene therapies
What does it mean enhancement of cholinergic function?
Inhibition of AChE and muscarinic agonists
What is arecoline?
Brain-permeable muscarinic agonists of botanical origin
What is physostigma venenosum (Calabar bean)?
West African climbing herb
Source of “Ordeal bean of Calabar”
First anticholinesterase known
What are other acetycholinesterase inhibitors from plants?
Galanthamine
Huperzine A
What is Huperzine A?
Inhibits acetylcholine esterase reversibly
- Placebo-controlled double blind trail: 50% AD patients showed improvement after 8 weeks at 200 micro but 36% placebo did as well
What is ginkgo?
Fossil
150-300 mil yo
Resistant to insects and microbes
What is ginkgo biloba?
Resistant to environmental conditions (pH, salt, air, pollution)
Biloba: two lobes
Quality is not guaranteed –> but best selling herbal remedy
What is EGb761?
Extract Ginkgo biloba Flavone glycosides (rutin 25-30%) Terpenoids: ginkgolides, bilobalide (3% each) Organic acid, ascorbic acid Bitter taste
What do extraction procedure eliminate?
Ginkgolic acids Tannins Steroids Proteins Minerals
Cardiovascular effects of EGb761
Potent antioxidative properties Reduction of blood viscosity PAF- antagonistic properties Inhibits platelet aggregation Arterial occlusive disease and tinnitus
What are acute neuroprotective effects of EGb761?
Increase tolerance to brain hypoxia
Inhibition of edema formation
Inhibition of membrane breakdown during ischemia
Interactions with various neurotransmitters and receptors
Active in stroke, brain, trauma
What are problems with anti-dementia drugs?
Dead neurons cannot be replaced by drug treatment–> therapy goal is prevention further degeneration
- Trials must be very long
What are the criteria for improvement in dementia?
Level of daily activities (social interactions, care needs via social interactions, care needs)
Level of performance activities (psychometric tests via psychologists, staff)
Level of psychopathology (complaints and symptoms via physician)
Placebo-controlled clinical trials?
Placebo-treated group gets worse
Ginkgo-treated group remains stable for 6-9 months
Meta-analysis of clinical trials?
Small but significant improvement of AD with Ginkgo extract
Efficacy comparable to esterase inhibitor but overall efficacy rather limited
Not effect for benign age-associated memory impairment
What shows oxidative stress in its brain in the mouse model?
Study used a Tg2576, which over express APP, acquires A-beta plaque deposits
Indications for Ginkgo extracts WITHOUT clinical evidence of effectiveness?
Hypercholesterolemia, hypertension Asthma, bronchitis Angina pectoris Regulation of gastric acidity Improvement of liver function Premenstrual syndrome Improvement of sexual performance Eye problems Dysentery, filariasis
What is the toxicity of Ginkgo extract EGb761?
- Lethal dose could not be detmined in rats after oral administration
- No organ damage during chronic application, no carcinogenicity, no teratogenicity
- Clinical toxicity is very low
- Rare cases of allergenicity, GI disturbances (with nausea and vomiting) and bleeding disorders
- Do not use in patients with coagulopathies
Define curcumin
Recently been reported to reduce amyloid formation in vitro
