Leaky Blood-Brain Barrier a Harbinger of Alzheimer s Disease - presentation made at Alzforum's live webinar of February 17, 2015. See details at: http://www.alzforum.org/webinars/leaky-blood-brain-barrier-harbinger-alzheimers

1. Vascular Contributions to Cognitive Impairment
and Dementia (VCID) is proposed as a distinct
discipline on the stroke spectrum, closely
related to and in part embedded in Alzheimer’s,
that is scientifically and clinically poised for
impact on disease burden.
Proposal:
Roderick A. Corriveau, Ph.D.
Program Director, NINDS

2. Years of follow-up
3,53,02,52,01,51,0,50,0
Dementia-freesurvival
100%
95%
90%
85%
no SBI
with SBI
HR (adj) =2.3
Dementia-freesurvival
Vermeer, Breteler NEJM 2003;348:1215
(=21% of stroke-free
individuals age 60-90)
Years Follow-Up (Population-Based Imaging)
Vermeer, Breteler NEJM 2003;348:1215
Decades of Studies Reveal
Vascular Disease/Dementia links
No Impairment Dementia
Alzheimer alone 29% 42%
Alzheimer + small strokes 8% 30%
Schneider Ann Neurol 2009;66:200

3. Vascular Contributions to Cognitive
Impairment & Dementia (VCID)
cardiac disease
micro-infarct
micro-bleed
small vessel ischemic stroke
silent stroke
small vessel hemorrhagic strokeCADASIL
cerebral amyloid angiopathy (CAA)
large vessel ischemic stroke
TIA
large vessel hemorrhagic stroke
• VCID recognizes & unifies as a discipline the spectrum of
Vascular Contributions to Cognitive Impairment & Dementia
• VCID was historically siloed among disciplines with various
names & inclusivity; scientific progress impacted
• Separating VCI & dementia not advantageous for
mechanisms focused research; e.g., a person may progress
from VCI to dementia
~multi-infarct dementia
~vascular brain injury

4. Co-Morbidities are the Norm in Dementia:
VCID is the Most Common Co-Morbidity
Attems and Jellinger, 2013, Neuropathology. In: Dening T, Thomas A (eds) Oxford
textbook of old age psychiatry, 2 edn., Oxford University Press., pp 87-105.

5. cardiac disease
micro-infarct
micro-bleed
small vessel ischemic stroke
silent stroke
small vessel hemorrhagic strokeCADASIL
cerebral amyloid angiopathy (CAA)
large vessel ischemic stroke
TIA
large vessel hemorrhagic stroke
• VCID recognizes & unifies as a discipline the spectrum of
Vascular Contributions to Cognitive Impairment & Dementia
• VCID includes & embraces its largely comorbid nature
AD Pathology
~multi-infarct dementia
~vascular brain injury

6. Stroke AD Dementia
Stroke and AD Dementia:
Overlapping Fields

7. Stroke AD Dementia
VCID
Vascular Contributions to
Cognitive Impairment and
Dementia (VCID) as a Discipline

8. Stroke AD Dementia
VCID
Vascular Contributions to
Cognitive Impairment and
Dementia (VCID) as a Discipline
Cognitively Normal
Cognitive Impairment
(e.g. MCI, VCI)
Dementia

9. VCID Recognizes/Unifies the Biological Spectrum of
Vascular Contributions to Cognitive Impairment & Dementia
Sugar + Lipid
Metabolism
Immune Function
AD Biology
Stroke + Vascular Biology
Neurovascular Unit

10.  Congressional Task Force on Alzheimer’s (1999, US)
 Plan Alzheimer et Maladies Apparentées (2001-12, FR)
 Evaluation du Plan Alzheimer 2013
«Elargir le champ du plan au-delà de la maladie d’Alzheimer»
 England’s National Dementia Strategy (2009)
 National Alzheimer’s Project Law (2011, US)
 includes AD, vascular dementia, FTD, and LBD
 2013: G8 Dementia Summit (London)
VCID Poised as Distinct Scientific Discipline:
International Recognition of the Relationship
Between Dementia and the Vasculature