The featured article is ‘Acetylcholinesterase Inhibitors for Vascular Dementia and Alzheimer’s Disease Combined with Cerebrovascular Disease’ by John Bowler and freely available here. This is a brief article but useful because the author raises a number of points which can be used when examining other papers in this area although the paper was published in 2002 and is a response to an RCT published that year in the Lancet by Erkinjuntti and colleagues.
Firstly the authors comments that
Grouping vascular dementia (VaD) and ‘Alzheimer’s Disease (AD) combined with Cerebrovascular Disease’ has been used in more than one study and further that other authors remarked that ‘differentiation between AD and VaD on clinical grounds can be difficult’.
Bowler goes onto suggest that these two apparently disparate groups are similar as a result of diagnostic criteria. Thus he comments on two sets of critera:
a. NINDS-AIREN criteria for probable VaD
b. NINDS-ADRDA criteria for possible AD
In the process he argues that both criteria were created before the emerging consensus that mixed dementia is very common and that there is an interaction between AD and cerebrovascular disease.
Bowler then tells us that the NINDS-AIREN criteria require ‘an Alzheimer-like dementing process coupled with the presence of cerebrovascular disease’. As he moves quickly through this section, the essence of his argument seems to be that in cerebrovascular disease, a ‘subcortical cognitive impairment is now known to be the most prominent pattern’. However, ‘subcortical cognitive impairment’ itself is an unclear concept. There are numerous subcortical structures which are implicated in different parts of cognition and even the term cognition itself is unclear here. For instance the term ‘motor cognition’ was coined by Jeannerod, and there are subcortical structures which are clearly implicated in motor sequencing as well as a number of other motor tasks. Emotions are involved in cognition as discussed by Damasio and can again be affected by subcortical lesions. However memory itself is affected in subcortical lesions as well as in AD. The NINDS-AIREN criteria do require ‘dementia…and manifested by impairment of memory’ but also stipulate that the dementia process and the CVD are related either by a maximum period of 3 months or else the stepwise pattern of deterioration. The point is further emphasised in the NINDS-ADRDA criteria where ‘progressive memory worsening’ is included. Thus it is possible to separate out AD + CVD and VaD where the temporal sequence of vascular events is known according to this definition. The difficulty arises in looking retrospectively. Additionally within the criteria there are a number of other diagnostic aids such as the diagnosis being unlikely if there is an early memory deficit.
Bowler states that there is an absence of criteria for mixed dementia and that utilising this diagnosis is pragmatically useful. He then identifies a difficulty with the above criteria in that ‘fully developed dementia’ is required which he says takes the focus away from prevention. He suggests that dementia nomenclature should be applied to cognitive impairment e.g. vascular Alzheimer mixed cognitive impairment as an example, presumably so that a relationship can be made between the cognitive impairment and subsequent dementia. However subsequent research has shown that although some such relationships can be made, there is still no straightforward progression from one type of MCI to dementia. For instance, 50% of cases of vascular MCI were found to revert in one study.
Bowler then comments on the focus on NINDS criteria by regulatory authorities and subsequently the need for pharmaceutical companies to also focus on the use of these criteria. This is an interesting point as it suggests that the regulatory authorities are influential in establishing the recognition of certain definitions of a disease. Bowler also emphasises the need for identifying early disease and the use of diagnostic systems for doing so. Such criteria for MCI have been developed by Petersen.
Bowler then moves onto some really important points. He suggests that neuroprotective agents would include Memantine which could possibly be trialled if illness is detected at an early enough stage. This is an interesting suggestion as it infers designing trials to test this at the MCI stage rather than in dementia. However a number of ACHEI’s have been found to have varied effects on cognition in people without dementia and given the varied relationship between MCI and subsequent cognitive status, we could argue the case for the results of any trial in this area to go either way, although that is the point of needing a trial in the first place!
Bowler considers the actions of AChEI’s in cerebrovascular disease and states it is equivocal which makes sense of his discussion earlier in the article when he comments on the relative lack of data in vascular disease while also noting the cognitive impairment that has been noted in cases of cerebrovascular disease in the absence of any other overt pathology. The essence of Bowler’s article is that the AChEI’s for reasons outlined in his article could be used in the spectrum from AD to VaD and mixed included. However, the NINDS criteria are more stringent than suggested and the most meaningful way forward is for further understanding of VaD and Cerebrovascular cognitive impairment through research as well as an improved understanding of clinical decision making and protocols for diagnosis in these areas.
Steps to Treatment 5 (Theoretical discussion – Further Evidence Required – Improved Modelling – Care Protocols – Incorporation in Policy)
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