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Advanced Neurology Anticoagulants as neuroprotective therapeutics

retrospective observational study involving nearly 450,000 (2012 – 2018) has also concluded that DOAC treatment
AF patients in Sweden (2006 – 2014). In an on-treatment reduced the risk of dementia. In the study, first-time
144
104
analysis, OAC users had a 48% lower risk of developing DOAC users (apixaban, dabigatran, and rivaroxaban)
dementia compared to non-OAC users (hazard ratio [HR] showed a 16% reduction in newly diagnosed all-cause
= 0.52; 95% CI = 0.50 – 0.55). Particularly noteworthy, dementia (HR = 0.84; 95% CI = 0.73–0.98; P = 0.02) and a
104
even patients with a low risk of AF, as well as those aged 26% reduction in mild cognitive impairment (HR = 0.74;
over 65 years, benefited from OAC use, irrespective of 95% CI = 0.65 – 0.84; P = 0.009) compared to VKA users
their stroke risk score. Likewise, retrospective cohort (acenocoumarol, phenprocoumon, and warfarin). 144
126
studies from the United Kingdom (UK) have concluded In addition, three retrospective studies conducted
that OAC treatment (DOACs or warfarin) reduces the in elderly AF patients from Korea (2014 – 2017) 137,139
risk of cognitive impairment and dementia (including AD, and Taiwan (2012 – 2016) have demonstrated that the
138
vascular dementia, and unspecified dementia) compared use of DOACs (apixaban, dabigatran, edoxaban, and
to non-OAC users or patients on antiplatelet therapy. 127,128 rivaroxaban) was associated with a lower risk of incident

Comparable findings were reported in an Australia- dementia, including vascular dementia and AD, 137,139
wide retrospective study (2010 – 2018) that included compared to warfarin.
nearly 19,000 patients with newly diagnosed AF and no Four large systematic reviews and meta-analyses
140
prior history of dementia or stroke. OAC users had a of comparative studies have also recently confirmed
significantly lower incidence of dementia compared to the superiority of DOACs over VKAs in lowering the
non-users (HR = 0.59; 95% CI = 0.44 – 0.80; P < 0.001), risk of composite dementia. 141,142,145,146 Specific DOACs,
with DOACs (apixaban, dabigatran, and rivaroxaban) such as apixaban and rivaroxaban, dabigatran and
141
offering greater protective effects compared to warfarin. rivaroxaban, 142,146 and edoxaban, 137 demonstrated
140
Likewise, a meta-analysis of nearly 480,000 AF patients has particularly strong protective effects. For dabigatran
found that OACs significantly reduced the occurrence of users, beneficial effects on cognitive and psychological
cognitive impairment compared to non-users (HR = 0.71; function, as well as a reduced incidence of dementia, were
95% CI = 0.69 – 0.74; P < 0.00001). Recent systematic highlighted in a literature search in PubMed/Medline data
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reviews and meta-analyses of observational and controlled updated through 2021. 133
studies have consistently reiterated the anti-dementia
benefits of OAC use. 131,132 Most recently, a Belgian study of first-time OAC users,
involving approximately 240,000 AF patients (2013 –
A number of observational studies have compared the 2019), assessed the risk of new-onset dementia, classified as
efficacy of DOACs versus VKA in reducing dementia risk in AD, vascular dementia, or other/unspecified dementia.
143
AF patients. For instance, a retrospective US trial involving The study found that DOAC use (apixaban, dabigatran,
approximately 5000 elderly AF patients (2010 – 2014) has edoxaban, and rivaroxaban) was associated with a slightly
revealed that individuals on long-term anticoagulation lower risk of vascular dementia and other/unspecified
with DOACs (apixaban, dabigatran, and rivaroxaban) had dementia compared to VKAs (warfarin, acenocoumarol,
a 51% reduced risk of dementia (including AD, vascular, and phenprocoumon). However, the risk of AD was similar
senile, and unspecified dementia) or subsequent stroke/ between the DOAC and VKA groups. 143
transient ischemic attack, compared to warfarin users (HR
= 0.49; 95% CI = 0.35 – 0.69; P < 0.0001). No significant Worldwide clinical observational studies have
129
differences in dementia rates were found between the demonstrated that the administration of OACs is beneficial
various DOACs. 129 for cognitive health in AF patients. 104,124-149 Individual
studies have shown that the risk of dementia after OAC
Similarly, analyses of both controlled and real-world treatment could be reduced by up to 48% compared
studies in AF patients have demonstrated that treatment to non-OAC users. 104,140 When comparing DOACs to
with DOACs was associated with a lower risk of cognitive VKA-type anticoagulants, DOACs generally appeared
impairment and all-cause dementia compared to VKAs or to provide a more pronounced reduction in the risk of
acetylsalicylic acid. 134,135 Furthermore, an analysis of US cognitive impairment and dementia. 128,129,134-146 However,
health-care databases has revealed lower rates of incident some studies revealed similar efficiency between DOACs
dementia in AF patients treated with DOACs (apixaban, and VKAs in reducing dementia risk, suggesting that
dabigatran, and rivaroxaban) compared to warfarin, either treatment strategy may be acceptable. 104,124,127,147-149
136
with no apparent advantage for any specific DOAC. 136 These studies include recent long-term retrospective
A recent historical cohort study involving nearly observations in incident AF cohorts of elderly patients
149
40,000 AF patients aged 40 years and older from the UK as well as prospective 24-month observational trials. 124,147

Volume 3 Issue 4 (2024) 20 doi: 10.36922/an.3799