VasCog 2015

VasCog 2015 hosts (Nagata and Abe) with the VasCog Society Executive Committee
and Distinguished VasCog Japan members.

Nagata-Abe 'kabuki' team at the VasCog 2015 Conference dinner party with the past
and present VasCog Society Secretary-Generals (Kalaria and Skoog).

Highlights of the meeting

by Donna Wilcock


VasCog was held in the beautiful city of Tokyo. The meeting was co-organized by Prof. Koji Abe and Prof. Ken Nagata, both from Japan. The conference spotlighted the exciting work being done in Japan, and internationally, to advance the study of vascular contributions to cognitive impairment and dementia (VCID). There were many presentations given to regarding better diagnosis of post-stroke dementia, characterization of the dementia trajectories, and risk factor characterization for VCID. While a brief report like this cannot possibly highlight all the wonderful work that was presented at this three day conference, some themes were apparent and will be highlighted below.

Scientific sessions

Day one of the scientific sessions opened with a wonderful presentation by Dr. Sandra Black presenting her elegant data on the venular network in the brain and the prevalence of periventricular white matter hyperintensities (WMH) in the elderly. Given the density close to the periventricular spaces. Dr. Black hypothesizes that the thickening of the venule walls in this region contributes significantly to the presence of WMH, and will also disrupt the pervientricular clearance of solutes, such as Abeta. Along the lines of clearance, Dr. Roxana Carare, and her PhD student Alan William Joe Morris, both presented exciting data regarding the perivascular drainage pathways in the brain and potential mechanisms by which the process can be disrupted leading to Abeta accumulation in the brain parenchyma and the brain. Abeta is shown to accumulate along basement membranes in between circular layers of smooth muscle cells. Loss of perivascular cholinergic innervation appears to disrupt solute drainage, as does maternal high fat diet administration. It is suggested that there may be therapeutic potential in increasing this perivascular drainage pathway.

Post-stroke dementia

There were many presentations surrounding the diagnosis and trajectory of post-stroke dementia. Dr. Olivier Goderfroy asked what the prevalence of post-stroke dementia was in hospitalized cohorts. By performing a meta-analysis he found a 53.8% prevalence of post-stroke cognitive impairment across 11 cohorts. Dr. Bonnie Yin Ka Lam is interested in the differences between early-onset (within a few months) and late-onset (many months later) post-stroke dementia. Data was presented on ApoE and some PiB PET imaging was performed. Dr. Koji Abe presented several talks describing the prevalence of white matter hyperintensities and prevalence of dementia in stroke populations and aging mild cognitive impairment individuals. Dr. Louise Marie Allen presented a poster studying 355 stroke survivors in the Newcastle COGFAST study. Of the 355 participants, 25% of stroke survivors had cognitive impairment without dementia 3 months post stroke, and at the first annual follow up 13.7%% of participants had cognitive impairment without dementia, and 9.6% had dementia. Over the first 5 year follow up the percentage with any form of cognitive impairment remained stable, however, the transition from cognitive impairment without dementia to full dementia. It was noted, however, that over the 10 year follow ups there was a lot of transition between states of individuals indicating that vascular cognitive impairment is highly variable and extremely fluid. Another poster presented by Dr. XinXin Guo examined a population study in 1460 women without stroke or dementia at baseline who were followed for 38 years. Of these, 321 women developed stroke or transient ischemic attacks (TIA) and 244 developed dementia. Cumulative incidence of dementia was significantly higher in those women with stroke / TIA than those without, even when adjusted for age. Additionally, risk of first stroke / TIA was increased in those women with dementia, even age adjusted. Therefore, these data present intriguing findings that there is a bidirectional relationship between stroke and dementia over the lifetime.


A particular highlight of the meeting was the debate surrounding the question; “Do vascular risk factors make a major contribution to the etiology of Alzheimer’s disease?”. Presenting their thoughts on this question were Dr. Deborah Gustafson, Dr. Koji Abe, Dr. Shinichiro Uchiyama and Dr. Marije Benedictus. All presented intriguing data regarding vascular risk factors and the relationship to Alzheimer’s disease. The debate centered around the incidence of Alzheimer’s disease in individuals with risk factors such as stroke, hypertension, obesity and high BMI, as well as cholesterol and lipid profiles. The data strongly supports increased risk of Alzheimer’s disease when vascular risk factors are present. However, as the question was posed regarding etiology of Alzheimer’s disease, it was noted by delegate that etiology, by definition, indicates cause. The data is correlative but not causative at this point. Also, the risk factor influence may be affected by whether the Alzheimer’s diagnosis is clinical or neuropathological, since the vascular factors could likely be leading to vascular cognitive impairment and not plaques and tangles of Alzheimer’s disease. Therefore, there was encouragement to re-phrase the question to “Do vascular risk factors make a major contribution to the clinical syndrome of dementia?”.

Characterizing vascular pathologies that are contributing to vascular cognitive impairment and dementia remains a challenge for the field and is being addressed on several fronts, from imaging to neuropathologically and preclinically in animal models. Dr. Geert Van Biessels gave a wonderful talk describing small vessel disease as characterized through 7T MRI imaging. He showed that he now has methods to examine tortuosity of vessels and perivascular spaces, which opens up MRI imaging to the assessment of these vascular changes that have previously only been observed in animal models or post-mortem brain samples. Further, he showed that using 2D Qflow technology on the 7T MRI he can measure single beat blood flow in small vessels and this could be a readout for vascular stiffness in small vessel disease. Dr. J Matthjis Biesbroek presented a poster characterizing small vessel disease, specifically focusing on white matter hyperintensities (WMH) as detected by MRI in a cohort of 167 patients with small vessel disease. The group found that strategically localized WMH impacted executive functioning and visuomotor speed and that WMH associated with individual tracts appear to have significant impact on these cognitive functions. Dr. Aiqing Chen presented neuropathological data examining astrocytes in post-stroke brains. Clasmatodendrosis, the irreversible damage of perivascular astrocytes, was a significant characteristic of the post-stroke dementia group as compared to the post-stroke non-demented group. This could further add to the hypothesis that astrocyte damage at the neurovascular unit is a significant pathological event in cerebrovascular disease that contributes to cognitive impairment. In a mouse model, Dr. Masafumi Ihara presented data on both his bilateral carotid artery stenosis model, which applies microcoils to the common carotid arteries, restricting blood flow to the brain to about 80% of normal. This model develops cognitive impairment and white matter hyperintensities in a time-dependent manner over several months. Dr. Ihara has also developed a model of white matter infarcts that uses an ameroid constrictor applied to the right common carotid artery. Multiple infarct damage is observed over 28 days post-surgery with impaired performance on both motor and cognitive tasks.


There were several presentations directly addressing the co-morbidity of vascular cognitive impairment and Alzheimer’s disease. Dr. William Jagust gave a very good talk highlighting the relationships between brain amyloid burden, cerebrovascular disease and cognition. As has been published, the relationship between Alzheimer’s pathology and dementia in the oldest of old is weak, which suggests multiple pathological processes leading to dementia. Using the Framingham Cardiovascular Risk Profile (FCRP) Dr. Jagust showed that the higher the FCRP, the higher the risk of seeing amyloid in the brain by PET ligand imaging. Dr. Susanne Janneke Van Veluw presented a poster describing post-mortem MRI studies in 5 cases with pathological CAA. These brains with significant CAA also show increased dilation of the perivascular spaces. Importantly, while CAA correlated to the perivascular space dilation, parenchymal amyloid load did not correlate. Dr. Jessica Duncombe presented a poster showing a study in the TgSwDI mosue model of CAA. By modeling chronic cerebral hypoperfusion through microcoil application on the common carotid arteries, the group showed that brain amyloid load increased significantly. Dr. Christian Bocti presented data showing that there are additive effects of brain amyloid load as measured by PiB PET imaging and white matter hyperintensities in a normal cognitive aging cohort of 76 healthy older adults (mean age of 73 years).

Overall, this was a very interesting meeting with lots of interesting data. This review is not comprehensive at all, but touches on some of the highlights from the meeting. The next VasCog meeting will be held in Amsterdam, The Netherlands, 12-15 October 2016. Please join us.