Is the time ripe for new diagnostic criteria of cognitive impairment due to cerebrovascular disease? Consensus report of the International Congress on Vascular Dementia working group

Perneczky et al. BMC Medicine (2016) 14:162 DOI 10.1186/s12916-016-0719-y Vascular Dementia OPINION Open Access Is the time ripe for new diagnostic criteria of cognitive impairment due to cerebrovascular disease? Consensus report of the International Congress on Vascular Dementia working group Robert Perneczky1,2,3,4*, Oren Tene5,6, Johannes Attems7, Panteleimon Giannakopoulos8, M. Arfan Ikram9, Antonio Federico10, Marie Sarazin11 and Lefkos T. Middleton1* Abstract Background: Long before Alzheimer’s disease was established as the leading cause of dementia in old age, cerebrovascular lesions were known to cause cognitive deterioration and associated disability. Since the middle of the last century, different diagnostic concepts for vascular dementia and related syndromes were put forward, yet no widely accepted diagnostic consensus exists to date. Discussion: Several international efforts, reviewed herein, are ongoing to define cognitive impairment due to cerebrovascular disease in its different stages and subtypes. The role of biomarkers is also being discussed, including cerebrospinal fluid proteins, structural and functional brain imaging, and genetic markers. The influence of risk factors, such as diet, exercise and different comorbidities, is emphasised by population-based research, and lifestyle changes are considered for the treatment and prevention of dementia. Conclusion: To improve the diagnosis and management of vascular cognitive impairment, further progress has to be made in understanding the relevant pathomechanisms, including shared mechanisms with Alzheimer’s disease; bringing together fragmented research initiatives in coordinated international programs; testing if known risk factors are modifiable in prospective interventional studies; and defining the pre-dementia and pre-clinical stages in line with the concept of mild cognitive impairment due to Alzheimer’s disease. Keywords: Cerebrovascular disease, Dementia, Cognition, Biomarker, Risk factor, Neuroimaging, Cerebrospinal fluid, Magnetic resonance imaging, Genetics, CADASIL Background The current paper presents the consensus of the Diagnostic Criteria Working Group of the 9th International Congress on Vascular Dementia, held on October 16–18, 2015 in Ljubljana, Slovenia. The concept that late-life dementia can occur in the context of cerebrovascular disease has been known since the nineteenth century [1, 2], and * Correspondence: ; 1 Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, Charing Cross Hospital, St Dunstan’s Road, W6 8RP London, UK Full list of author information is available at the end of the article up until the 1960s, cerebral arteriosclerosis as well as widespread white matter lesions in patients with longstanding hypertension were seen as the main cause of dementia in older individuals [1]. This view was challenged by Blessed et al. [3] and others, who suggested that Alzheimer’s disease (AD) neuropathology is the landmark neuropathological feature in the majority of age-related dementia cases. This paradigm shift led to the development of the concept of multi-infarct dementia (e.g. dementia following multiple brain infracts), which subsequently was used to define vascular dementia (VaD) in several international classification systems such as the Diagnostic and © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Perneczky et al. BMC Medicine (2016) 14:162 Statistical Manual of Mental Disorders 4th edition (DSMIV) and the International Classification of Diseases and Related Health Problems, 10th edition (ICD-10). However, subsequent studies suggested that the majority of VaD cases were caused by subcortical cerebrovascular changes, rather than by large cortical infarcts [3]. As a result of these conflicting views, different sets of criteria for VaD were developed, including the National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDSAIREN) [4] and the State of California Alzheimer’s Disease Diagnostic and Treatment Centers criteria [4], as well as criteria for specific subtypes such as subcortical VaD [5]. Parallel to similar developments in the AD field, it was recognised that cerebrovascular disease frequently cooccurs with other pathological changes in the majority of patients over the age of 75 [6], which is the age group when over 70 % of dementia cases occur [7]. Simultaneously, there was controversy regarding the use of the term dementia, which became synonymous with the concept of AD dementia, requiring prominent memory deficits in addition to impairment in at least one other cognitive domain. Nevertheless, this pattern of cognitive decline is not necessarily applicable in patients with VaD [8]. Furthermore, the need for inclusion of pre-dementia changes within a broader nosological concept similar to mild cognitive impairment due to AD was also acknowledged. Based on these considerations, the term ‘vascular cognitive impairment’ (VCI) was proposed [9], which accounts for the heterogeneous nature (and degrees) of cognitive deficits related to prominent cerebrovascular pathologies. Vascular mild cognitive impairment [6] or vascular cognitive impairment, no dementia [7] were terms proposed to categorise the early clinical stages. However, despite VCI being clearly a step in the right direction, it has not been widely adopted and parallel classification systems are still being employed. Validated clinical diagnostic criteria are important to identify suitable subjects for clinical trials in order to develop new drugs for VCI. Their relevance increases further if treatment strategies are to be developed that target specific pathogenic cerebrovascular mechanisms leading to VCI [10]. Furthermore, lifestyle interventions and other non-pharmacological approaches can only be developed if the target populations are clearly defined [8]. Current efforts towards a consensus on diagnostic criteria and guidelines to account for the heterogeneous nature of VCI, such as the recent International Society for Vascular Behavioural and Cognitive Disorders statement [11], must be encouraged. However, despite considerable recent advances, there are significant gaps in our understanding of the neurobiological mechanisms underpinning the various dementia forms (...truncated)