You'll have to ask your doctors how they will use this to prevent your likely chance of Alzheimers/dementia.
Your chances of getting dementia.
2. Then this study came out and seems to have a range from 17-66%. December 2013.
The latest here:
Alzheimer’s disease (AD) is the most common form of dementia,
a condition in which the individual suffers the loss of cognitive
faculties such as thinking, logic, judgment, language, problem-solving,
and memory.
Image Credit: Lightspring/Shutterstock.com
It is a progressive condition and is thought to be linked to a reduced number of interneuronal connections in the brain.
Fibrinogen and AD
The brain in a patient with AD is the presence of abnormal proteins
within and around the neurons, called beta-amyloid plaques and tau
neurofibrillary plaques. The accumulation of these proteins is
correlated with synaptic degeneration and cognitive decline.
Earlier studies have demonstrated abnormalities in the complex
vascular network of the brain, but scientists have not been able to
clarify if the vascular deficit caused the synaptic breakdown or if it
only led to inflammation in the nervous system. Both of these conditions
end in cognitive deterioration.
A study from the Gladstone Institutes demonstrated that
fibrinogen,
a key blood coagulation component, is involved in a cascade of events
at both molecular and cellular events which lead to the loss of memory
storage neurons within the brain. This is the pathophysiological basis
of memory loss, according to the researchers.
The fibrinogen comes from the blood within the brain’s blood vessels.
It leaks out of the blood, leading to activation of the microglia,
which are the brain’s immune cells. This leads to their attack on the
neurons at the synapses, causing their destruction.
The study employed cutting-edge technology to generate the first 3D
volume images of AD, from humans and mouse experiments. The researchers
then manipulated the mice, preventing the leakage of fibrinogen, which
in turn kept the brain’s immune cells quiescent. This protected the
brain against memory loss.
In a healthy brain, too, the presence of fibrinogen induced the same
type of changes as in AD, but without any evidence of amyloid plaques.
This was surprising, as amyloid has been the target of many research
efforts to find a therapy that works for AD.
These findings lend support to the hypothesis that dementia is caused
by two separate mechanisms. Or in other words, the symptoms of AD and
vascular dementia could be due to independently operating underlying
disease processes.
Vascular and Amyloid Hypotheses
On the one hand, vascular insufficiency causes dementia, as is seen
in elderly people following a stroke. On the other hand, AD occurs in
people whose brains show the appearance of amyloid plaques.
Alternatively, both could be part of a linked process. Both sets of
people show the deterioration of cognitive abilities and when both
pathologies are present, the decline in cognition is more profound than
for either alone.
How are Amyloid-Beta and Fibrinogen Linked?
The additive effect of fibrinogen in AD could be partly explained by
the fact that when amyloid interacts with fibrinogen or its successor,
fibrin, increased amounts of fibrin are deposited within the blood
vessels of the brain.
The amyloid-fibrinogen interaction leads to the formation of clots
that are resistant to the thrombolytic action of tissue plasminogen
activator (tPA) when they are formed directly from thrombin.
This resistance to breakdown could be due to the formation of a
tighter fibrin network when associated with amyloid, or because amyloid
interferes with the binding of plasminogen to fibrin.
In short, the interaction of fibrinogen or fibrin with amyloid could
initiate or aggravate the hypoperfusion and inflammation in the brain.
Fibrin build-up interferes with the normal cerebral perfusion and
induces microinfarcts, which lead to neuroinflammation, disruption of
the blood-brain barrier, and dysfunction of the neurons.
Simultaneously, the amyloid activates fibrinogen, causing more fibrin
to be generated via the intrinsic coagulation pathway. Amyloid also
activates factor XII which triggers thrombosis, besides increasing the
level of inflammation and vascular permeability through other soluble
inflammatory mediators like kallikrein and bradykinin.
Fibrinogen-Linked Prothrombotic State in AD
AD patients may have a higher risk of thrombosis, as shown by higher
levels of activated factors VII and V, factor V Leiden (a mutant and
more degradation-resistant form of factor V), von Willebrand factor, and
prothrombin fragments.
Patients with AD were tested for the risk of spontaneous emboli
within the cerebral circulation, compared to healthy age-matched
controls. A full 40% of them showed such events, vs only 15% in the
controls, and this subset showed a faster cognitive decline over the
next 6 months.
Again, microbleeds from cerebral blood vessels occur more frequently
in AD than with non-AD controls, perhaps due to ischemia-induced
hemorrhage.
Research in mice shows that by reducing the fibrinogen levels, the
incidence of cerebral amyloid angiopathy (CAA) declines. With CAA,
amyloid is deposited around cerebral blood vessels, causing narrowing
and ischemia, as well as blood-brain barrier damage. CAA is present in
up to 90% of AD patients.
Reduction in the level of fibrinogen also reduces microglial
activation and improves cognitive performance in mouse models. On the
other hand, AD is associated with a prothrombotic state: there is a
higher tendency to form clots, reduced fibrin degradation, increased
platelet activation, and higher levels of clotting factors.
Platelet activation might deliver fibrin directly to forming clots, contributing to the formation of resistant clots.
Directions for Future Therapy in AD
The presence of fibrin in cerebrospinal fluid helps distinguish a
patient with AD from mild dementia, or non-dementia patients, and is
linked with a more severe disease course. These findings could change
the way the condition is perceived and treated.
The use of coagulation data in AD patients could be a novel
biomarker, and research suggests that the inhibition of fibrinogen
effects in AD could be a new therapeutic target.
Since anticoagulant therapy is a challenge in elderly patients, and
AD
increases the risk of major cerebral bleeds due to the presence of CAA,
novel inhibitors that act on the amyloid-fibrinogen interaction could
be useful in the therapy of this devastating condition.
Image Credit: Juan Gaertner/Shutterstock.com
Source
- Strickland, S. (2017). Impact of the Coagulation System on the Pathogenesis of Alzheimer's Disease. Blood (2017) 130 (Supplement 1): SCI-3. https://doi.org/10.1182/blood.V130.Suppl_1.SCI-3.SCI-3. ashpublications.org/.../Impact-of-the-Coagulation-System-on-the
- Suidan, G. L., et al. (2018). Abnormal Clotting of the
Intrinsic/Contact Pathway in Alzheimer Disease Patients Is Related to
Cognitive Ability. Blood Advances; 2(9): 954–963. doi: 10.1182/bloodadvances.2018017798. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942003/
- Cortes-Cantelli, et al. (2012). Fibrinogen and Altered Hemostasis in Alzheimer's Disease. Journal of Alzheimer's disease: JAD 32(3). DOI: 10.3233/JAD-2012-120820.
- Merlini, M. et al. (2019). Fibrinogen Induces Microglia-Mediated
Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease
Model. Neuron. DOI: https://doi.org/10.1016/j.neuron.2019.01.014
Changchun Lin
Hui Pan†, 
Yuan Qiao
Jingjing Su
Jianren Liu
