What are the characteristics of Alzheimer's disease? Supervision of family: feeding, hygiene; Social isolation; Most common: sporadic form - age o...

What are the characteristics of Alzheimer's disease?

Supervision of family: feeding, hygiene;
Social isolation;
Most common: sporadic form - age of 80 years, but 20 to 30% with age of 60 years;
Duration of 4 to 10 years;
1% represents genetic factors;
Common: polymorphism of Apo E (catalyzing lipoproteins of amyloid plaque) - causing formation of amyloid protein plaques and Tau proteins;
Monoclonal antibodies: Solanezumab, Gantenerumab, Crenezumab? Cognitive improvements??
Few advances!
Neuronal death due to excessive activity of glutamate and accumulation of beta-amyloid, Tau proteins;
Monoclonal antibodies > slightly improve the patient's cognitive response, but were not effective, studies stopped;
There is no effective therapy to control the progression of the disease, of accumulation of Tau and beta-amyloid proteins in neurons;
Relation with hippocampus, low glucose that can hinder mitochondrial activity and ATP in cellular activity;
We have vesicles containing glutamate, when generating AP, it is released in the synaptic cleft, acts on 2 receptors: at the level of AMPA receptors: they cause opening of sodium channels, rapid action, membrane depolarization, when they act at the level of NMDA receptors: they cause opening of calcium channels, slow action, but also open sodium channels but much less intense than with AMPA opening, for calcium to open vesicles containing glutamate - neurotransmitter, to fall into the synaptic cleft again, when there is an NMDA receptor> there is a magnesium ion blocking the channel, when magnesium leaves, it leaves calcium to enter, then magnesium closes the channel, so that glutamate is not released, and in Alzheimer's there is excess release of glutamate, memantine will block NMDA receptors, mimicking the action of the magnesium ion, but the difference is that with its use, the channel it blocks can reach AP, which does not displace, does not enter calcium;
Ionotropic KAINATE (cerebellum and cortex) and AMPA (cortex and hippocampus) receptors * Na entry, rapid action, depolarization;
NMDA receptors * Ca entry, slow action, cell death (excess glutamate);
Memantine: helps to minimize neurotoxicity caused by glutamate, does not improve neuroplasticity - memory, only avoids neuronal death caused by glutamate;
Protection against neurotoxicity;
Blocking of Ca ions by blocking NMDA-type receptors, and the release of glutamate;
Reduces neuronal apoptosis and prevents damage, in addition to promoting improvement in the symptoms of Alzheimer's disease (AD) by acting on hippocampal neurons;
Blocks glutamatergic receptors when they are at rest;
Can be used as monotherapy in advanced stage or associated;
Does not turn off receptors: improves cognitive and behavioral clinical;
Oral route without influence of food;
Half-life: 100 hours;
Adverse effect: lethargy, drowsiness, dizziness, constipation;
Doses of 5 mg/day: increasing 5 mg/week until reaching 20 mg/day, divided into doses of 10 mg up to 2 x day;
Acetylcholinesterase inhibitors: inhibit the enzyme that degrades acetylcholine, which remains in the vesicles with the process of acetyl conjugation with Co-A, related to the activity of the parasympathetic SN, when released in the synaptic cleft, has acetylcholinesterase enzyme degrading the rest that remained in the cleft and butyrylcholinesterase;
When acetylcholine interacts: it has 2 receptors> muscarinic and nicotinic;
Acetylcholine, deficiency and lost activity in patients with Alzheimer's> loss of memory, inhibits the enzyme that degrades acetylcholine, to improve action on muscarinic and nicotinic receptors;
It is necessary to start with a minimum dose and increase according to the need, always waiting.