Does vascular pathology contribute to Alzheimer changes?

Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi

doi:10.1016/j.jns.2012.07.032

Cited by 217 publications

(185 citation statements)

References 89 publications

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“…However, VCI with concomitant AD pathology has also emerged as an increasing cause of age‐related cognitive impairment 3. Cerebral hypoperfusion is also presumed to accelerate AD pathology 4. Therefore, the mechanisms through which vascular factors affect dementias, including AD, warrant further examination.…”

Section: Introductionmentioning

confidence: 99%

Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans

Hattori

Enmi

Iguchi

et al. 2016

JAHA

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BackgroundExisting rodent models of vascular cognitive impairment (VCI) show abrupt changes in cerebral blood flow (CBF) and do not reliably replicate the clinical pathogenesis of VCI. We therefore aimed to develop a mouse model of VCI where CBF is gradually reduced, followed by subsequent progressive motor and cognitive impairment, after surgical intervention.Methods and ResultsAdult C57BL/6J male mice were subjected to gradual common carotid artery stenosis (GCAS) surgery by using an ameroid constrictor vessel‐constricting device with an inner diameter of 0.75 mm. The common carotid arteries narrowed gradually after gradual constriction of ameroid constrictors over 28 days after GCAS, with subsequent 79.3% area stenosis as a result of smooth muscle cell proliferation and macrophage infiltration in the tunica intima. The 28‐day survival rate was 91%. Arterial spin labeling demonstrated gradual and continuous reduction of cortical and subcortical CBF (ratio to the preoperative value) to 54.6% and 51.5%, respectively, over 28 days. However, magnetic resonance angiography showed increment of collateral flow signals in the leptomeningeal artery. Rarefaction and proliferation of astrocytes and microglia, with loss of oligodendrocytes, were found in the white matter at 32 days. Hippocampal neuronal loss was observed in only 25% of GCAS mice, consistent with lack of abnormalities in the Morris water maze test. The rotarod test showed motor impairment, and the Y‐maze test showed working memory deficits.ConclusionsThe GCAS model successfully generated gradual and continuous CBF reduction over 28 days, with replication of key histological, radiological, and behavioral features associated with cerebral hypoperfusion leading to VCI.

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Section: Introductionmentioning

confidence: 99%

Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans

Hattori

Enmi

Iguchi

et al. 2016

JAHA

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“…6,7 Crosssectional investigations in several population studies suggest the association of higher arterial stiffness and abnormal vascular hemodynamics with subclinical neurovascular injury detected both by brain MRI and a standard neurocognitive battery. [8][9][10][11] Given the progressive nature of CVD, we reasoned that arterial hemodynamics at any given time point may be associated with longitudinal progression of measures of brain vascular injury and neurocognitive function.…”

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confidence: 99%

Association of arterial stiffness with progression of subclinical brain and cognitive disease

et al. 2016

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Objective: We tested whether abnormal arterial stiffness and blood pressure would be associated with progression of brain aging measured by brain MRI and neurocognitive testing.Methods: Framingham Offspring Cohort participants (n 5 1,223, 61 6 9 years, 56% women) without previous stroke or dementia underwent applanation tonometry, brain MRI, and neurocognitive testing at examination 7 (1998-2001). Follow-up brain MRI and neurocognitive testing was performed at examination 8 (2005-2008, mean interval 6.4 6 1.3 years). We related examination 7 inverse-transformed carotid-femoral pulse wave velocity (iCFPWV), central pulse pressure (CPP), and mean arterial pressure to changes in the following variables between examinations 7 and 8: total cerebral brain volume, white matter hyperintensity volume, and performance on executive function and abstraction tasks, the Trail Making Test, Parts B and A (DTrails B-A), and Similarities tests.

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“…Vascular risk factors such as hypertension, arteriosclerosis, and diabetes can have an impact on the structure of vessels and, consequently, play a role in blood flow. 14 There is a relationship between blood pressure and blood flow. The flow in an artery depends on the blood pressure at each RESUMO INTRODUÇÃO: Estudos demonstram a potencial deterioração da vascularização cerebral e a provável relação da hipertensão na doença de Alzheimer (DA).…”

Section: Introductionmentioning

confidence: 99%

Arterial hypertension impact on cerebral blood flow in patients with Alzheimer’s disease

Zmudka¹,

Bouzerar²,

Gondry³

et al. 2017

Geriatr., Gerontol. Aging

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BACKGROUND: Studies show the potential deterioration of brain vascularization and probable involvement of hypertension in Alzheimer disease (AD). OBJECTIVE: The objective was to evaluate the potential impact of hypertension on cerebral vascular flows in a sample of Alzheimer's patients. METHODS: 19 patients with AD, including 10 with hypertension (aHT+) and 9 without hypertension (aHT-) were recruited. They underwent clinical evaluation and phase-contrast MRI protocol for flow assessment. Cerebral arterial flow distributions were evaluated using kurtosis and skewness indices at the intracranial and extracranial levels. RESULTS: No significant differences were found in the mean arterial flow, pulse flow and kurtosis between the levels in the AD aHT+ population. There was a significant difference in skewness between extra-and intracranial levels (p = 0.01). No significant differences were found in the mean arterial flow between the levels in the AD aHT-population. A significant difference was observed in the pulse flow (p = 0.03), kurtosis (p = 0.02) and skewness (p = 0.008) between the levels. At the extracranial level we did not find any significant differences in the mean arterial flow, pulse flow or skewness between aHT+ and aHT-. There was a significant difference in kurtosis at the extracranial level between the aHT+ and aHT-(p = 0.03). At the intracranial level, there were no significant differences in all parameters. CONCLUSION: Results showed a difference between cerebral vasculature in AD for aHT+ and aHT-groups. This is probably related to the loss of arterial compliance induced by the degradation of the vascular system.

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Does vascular pathology contribute to Alzheimer changes?

Cited by 217 publications

References 89 publications

Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans

Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans

Association of arterial stiffness with progression of subclinical brain and cognitive disease

Arterial hypertension impact on cerebral blood flow in patients with Alzheimer’s disease

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