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Arterial Stiffness and Alzheimer Disease, a simple association?
- Pr. A. Benetos
Arterial Stiffness and Alzheimer Disease, a simple association? Pr. - - PowerPoint PPT Presentation
Arterial Stiffness and Alzheimer Disease, a simple association? Pr. - - PowerPoint PPT Presentation
Arterial Stiffness and Alzheimer Disease, a simple association? Pr. A. Benetos Universit de Lorraine Nancy, France 13 th EUGMS Congress Nice, 20-22 Septembre 2017 Disclosures Honoraria Fukuda Novartis No other conflict of
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“A man is as old as his arteries”
- Dr. Thomas Sydenham
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+ +
168/80 148/90
- Art. Stiffness
Arterial aging, stiffness, and blood pressure regulation
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- Heart Failure
- Stroke
- Coronary heart
disease
- Renal failure
And
- Vascular dementia
But also…
- Alzheimer disease
Arterial stiffness: A major determinant of morbidity/loss of autonomy/mortality
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Arterial stiffness and cognitive status in older adults
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Arterial stiffness is increased in patients with MCOI, AD and vasular dementia
Hanon et al, Stroke 2005
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Relationships between Aortic stiffness, Leucoaraïosis and Cognitive impairment: ADELAHYDE study
- A. Kearney-Schwartz et al, Stroke 2008
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Aortic stiffness, and leucoaraïosis are independent determinants of cognitive impairment in hypertensive subjetcs over 60 yo : The ADELAHYDE study
- A. Kearney-Schwartz et al, Stroke 2008
0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 4,5 5,0 Odds ratio
Hommes
Grade de Leucoaraîose VOP par m/s 1.43 (1.13-1.81) p = 0.003
1.22 (1.00-1.49) p = 0.05
MEN LEUCOARAIOSIS FAZEKAS PWV
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Baseline values of arterial stiffness and BP in « decliners » and « non-decliners » over a 2-year follow-up period. The PARTAGE study (>80 yo living in NHs)
- G. Watfa et al JAMDA 2015
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- G. Watfa et al JAMDA 2015
Baseline values of arterial stiffness and BP in « decliners » and « non-decliners » over a 2-year follow-up period. The PARTAGE study (>80 yo living in NHs)
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Arterial stiffness cognitive decline The Framingham cohort
Pase M et al, Stroke. 2016;47:2256-2261.
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… We demonstrate that high aortic stiffness, measured as CF-PWV, was an independent predictor of incident MCI in the whole sample and of incident dementia in nondiabetic
- patients. Limiting aortic stiffening with aging, through healthy
lifestyle, diet, and possible pharmacological therapy may thus help protect against later life vascular brain injury and cognitive impairment.
Pase M et al, Stroke. 2016;47:2256-2261.
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Possible mechanisms
- f these associations
- Hypoxia
- Inflammation
- ??
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Hypoperfusion et Maladie d’Alzheimer
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Hypoxia increases - secretase cleavage of APP and Amyloid deposition in APP23 transgenic mice.
PNAS , 2006; vol. 103, no. 49: 18727–18732
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- As vascular dysfunction is thought to occur years or
even decades ahead of the clinical manifestation of AD, quantitative measurements of cerebral vasomotion could predict microvascular dysfunction at an early stage of the disease, and contribute to assess the efficiency of therapeutic interventions.
Is Vasomotion in Cerebral Arteries Impaired in Alzheimer’s Disease ?
Luigi Yuri Di Marcoa, J Alzheimer’s Dis. 2015
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- E. Van Exel et al., Arch Gen Psych 2009
Inflammation and family history of Alzheimer Disease
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Amyloid intensifies VSM cell induced inflammatory response and de-differentiation.
Vascular smooth muscle cells treated with Aβ 1-40 exhibit higher inflammatory response to interleukin-1.
Vromman A et al, Aging Cell 2013
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Amyloid context intensifies VSM inflammatory response
Vromman A et al, Aging Cell 2013
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Risk factors for COGNITIVE DECLINE
- M. Baumgart et al Alzheimer’s & Dementia 11 (2015) 718-726
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Risk factors for DEMENTIA
- M. Baumgart et al Alzheimer’s & Dementia 11 (2015) 718-726
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- Fight against accelerated arterial