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Advanced Neurology Anticoagulants as neuroprotective therapeutics

age of 65, but some studies also included individuals with For details on the prerequisites, framework conditions,
low AF risk or newly diagnosed AF, with no prior history of and diagnostic methods necessary for a clinical trial on
dementia or stroke. This observed anti-dementia potential DOAC use in AD, reference can be made to recent review
of thrombin-inhibiting OACs has raised the question of articles. 15,167 Ideally, in vivo staging of disease, selection
whether these anticoagulants, particularly DOACs, could of participants, and monitoring of treatment could
also use to treat vascular-driven neuropathogenesis and be conducted using a range of diagnostic techniques,
cognitive decline in AD. 15,16,22-24,26,27,90, 96,101,111 including imaging and biomarker tests from blood
At present, the most comprehensive clinical data on and CSF to assess amyloid, tau, and neurodegenerative
antithrombotic efficacy, bleeding risk, and anti-dementia changes. These assessments could be supplemented by
potential are available for the DOACs dabigatran, apixaban, tests evaluating procoagulant, proinflammatory, and
vasculopathic states.
In addition, these tools could
15,167
and rivaroxaban. 16,104,124-149,153-164 Collectively, studies suggest help track therapeutic outcomes and the emergence of side
a slight advantage for dabigatran and apixaban in reducing effects. 15,167
the risk of severe intracranial hemorrhage. However,
when it comes to anti-dementia potential, no particular The greatest cognitive benefit and safety would likely be
DOAC has demonstrated a clear advantage. Importantly, achieved if DOAC treatment was initiated in individuals
fast-acting antidotes are available for managing bleeding without cognitive symptoms, with a low bleeding risk
incidents with all three of these DOACs. 15,24,28 (HAS-BLED score), and with AD and CAA biomarkers
indicating an early disease stage. 10,11,14-16 In therapies
7. Future perspectives targeting brain Aβ deposition, the maximum benefit has
At present, a 7-year observational study in AF patients been suggested when treatment is administered during
(BRAIN-AF) compares the effects of rivaroxaban on pre-amyloid stages or before half-maximal amyloid
ischemic stroke and neurodegenerative events with those deposition is reached, which is when neurodegeneration
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of acetylsalicylic acid in participants with vascular disease typically begins. This time window may also be
or placebo in patients without vascular disease. In appropriate for initiating DOAC treatment in AD patients
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addition, a randomized, double-blind, placebo-controlled to timely counteract Aβ-triggered procoagulant and
clinical study (BEACON) was announced in 2018 to proinflammatory thrombin (Figure 2). However, detailed
investigate the effects of dabigatran in patients with mild investigations on the temporal dynamics of changes in the
cognitive impairment or AD. However, this study has procoagulant state, vascular and parenchymal amyloid
166
not yet been initiated. load, and the progression of neurovascular and cognitive
sequelae in AD are still needed. Studies in AD mouse
A clinical intervention study investigating the benefits models or patients could benefit from recent advances in
and risks of thrombin-inhibiting DOACs in AD patients in vivo biomarker-based AD staging methods, which use
would be a plausible step, ideally under the guidance of computational imaging and fluid (blood and CSF)-based
vascular neurologists. The aim of such treatment would diagnostics. 15,42,167
be to normalize the Aβ-induced procoagulant state in
AD, characterized by excessive thrombin formation, 8. Conclusion
thereby counteracting the associated inflammatory and Neurodegenerative diseases, including AD, are on the
vasculopathic sequelae that impair neuronal and cognitive rise globally, yet the availability of efficient drugs remains
function (Figure 2). For such a study, a detailed analysis limited. 12,14,19,70 The newly approved Aβ-targeting antibody
of each participant’s procoagulant state, bleeding risk, therapies for AD offer hope by slowing disease progression,
personalized drug dosing, and close medical monitoring but they cannot halt or cure the disease. 11,17,69,70 These
would be essential to prevent severe complications, therapies are also expensive, require elaborate screening
particularly intracranial hemorrhage.
for ARIA side effects, and present challenges in identifying
A postmortem study found that not all AD patients exhibit patients who are most likely to benefit. 11,17,19,70 Given these
a procoagulant state. As a result, DOAC treatment should limitations, other plausible approaches, particularly cost-
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not be prescribed in individuals without this procoagulant effective drug repurposing, remain valuable therapeutic
state to minimize the risk of bleeding. However, it remains options for AD. 5,13,15,16,19,21-24,26,27 OACs, particularly
16
unclear whether the AD patients without a procoagulant state DOACs, have shown disease-modifying potential for
in the study had been receiving anticoagulant treatment treating neurovascular dysfunction in AD, as supported
97
before the analysis. Special caution is also required in AD by both preclinical and clinical evidence. By targeting
patients undergoing Aβ-targeting antibody therapy due to excessive thrombin production caused by Aβ pathology,
the associated risk of ARIA. 11,17,69,70 DOACs could prevent, delay, or reduce vascular-triggered

Volume 3 Issue 4 (2024) 24 doi: 10.36922/an.3799