Introduction:
Responsiveness to treatment with cholinesterase inhibitors (ChEIs) is difficult to predict in Alzheimer’s disease (AD). In the current review, vascular burden is considered as a potential moderator of treatment responsiveness. Cerebrovascular burden co-occurs in at least 30% of AD brains, although it is debated if vascular pathology plays a causal or synergistic role in AD pathogenesis. Vascular burden, therefore, could potentially limit response to treatment due to limited brain reserve or augment treatment efficacy as those with vascular pathology may represent a subgroup with comparable clinical expression but less progressed AD neurodegeneration.
Methods:
A systematic search of Web of Science, Pubmed, Scopus and EthoS identified 32 papers
which met the criteria for inclusion. Association of treatment response and vascular burden across
five broad markers are discussed: cerebral hypoperfusion, intima-media thickness, white matter
changes, cerebral microbleeds and co-existing diagnosis of cerebrovascular disease.
Results:
Analysis of frontal regional cerebral blood flow and intima-media thickness may have pre-
dictive ability to distinguish those with AD who may respond optimally to short-term treatment
with ChEIs. The impact of white matter changes is less consistent; the majority of studies demons-
trate no association with treatment response and those that do implicate changes in executive func-
tioning. There is preliminary evidence that deep cerebral microbleeds limit treatment response in
subcortical cognitive domains, but this requires replication. The use of diagnosis of co-occurring
cerebrovascular disease yields no robust variability in response to ChEIs in AD.
Conclusion:
There is limited evidence that markers of cerebral hypoperfusion, intima-media thick-
ness and cerebral microbleeds moderate response to ChEIs. Findings for other markers of vascular
burden are less consistent and do not support any moderating effect.
White Matter Changes in Cerebrovascular Disease: Leukoaraiosis