Quantitative measurement of cerebral haemodynamics in early vascular dementia and Alzheimer’s disease

Bateman, Grant A.; Levi, Christopher; Schofield, Peter W.; Wang, Yan; Lovett, Elizabeth

doi:10.1016/j.jocn.2005.04.017

Cited by 56 publications

(62 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, their findings support our MALDI data that these structures contain A␤ 1-42. Because A␤ in APP23 tg mice is of neuronal origin and present at high concentrations throughout the brain also in young mice (47), we suggest that during a removal process, A␤ is transported to the vasculature and may accumulate in or around endothelial cells (9,48,49). Our model describing the interplay between amyloid and the vasculature leading to the observed vascular alterations is described in Fig.…”

Section: Vascular Corrosion Casting Vascular Morphology and Networkmentioning

confidence: 99%

“…8). Reduced blood flow has been reported as one of the most consistent physiological deficits in AD (9,10); however, it remains unclear whether the reduced cerebral blood flow is a response to neuronal damage or a factor initiating the characteristic neuropathology. In vivo studies showed the effect of A␤ on cerebral blood flow and vessel architecture in a mouse model for AD (11,12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease

Meyer

Ulmann-Schuler

Staufenbiel

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

231

215

View full text Add to dashboard Cite

Substantial evidence from epidemiological, pathological, and clinical reports suggests that vascular factors are critical in the pathogenesis of Alzheimer's disease (AD), and changes in blood flow are currently the most reliable indicators of the disease. We previously reported that older APP23 transgenic (tg) mice have significant blood flow alterations correlated with structural modifications of blood vessels. For the present study, our objective was to analyze the age-dependent morphological and architectural changes of the cerebral vasculature of APP23 tg mice. To visualize the 3D arrangement of the entire brain vasculature, we used vascular corrosion casts. Already at young ages, when typically parenchymal amyloid plaques are not yet present, APP23 tg mice had significant alterations, particularly of the microvasculature, often accompanied by small deposits attached to the vessels. In older animals, vasculature abruptly ended at amyloid plaques, resulting in holes. Often, small deposits were sitting near or at the end of truncated vessels. Between such holes, the surrounding vascular array appeared more dense and showed features typical for angiogenesis. We propose that small amyloid aggregates associated with the microvasculature lead to morphological and architectural alterations of the vasculature, resulting in altered local blood flow. The characteristic early onset of vascular alterations suggests that imaging blood flow and/or vasculature architecture could be used as a tool for early diagnosis of the disease and to monitor therapies. amyloid precursor protein ͉ cerebral blood flow ͉ scanning electron microscopy ͉ vascular corrosion casting T he typical clinical picture of Alzheimer's disease (AD) includes a progressive decline of memory function, often accompanied by other clinical signs such as agitation, aggression, sleep disturbances, and social withdrawal. Nonetheless, brain autopsy is needed to positively confirm the diagnosis (1). A high density of neuritic plaques, neurofibrillary tangles, and vascular amyloid (A␤) is a characteristic neuropathological marker of AD (2, 3). Plaques and tangles in the neuropil may affect neuronal function and also contribute to the neuronal damage; however, it is unclear whether their incidence correlates with the clinical signs and symptoms of cognitive impairment characteristic of the disease (4). Evidence suggests that cerebrovascular pathologies, such as structural alterations (5), atherosclerotic lesions (6), and impaired hemodynamic responses (7), are early features of AD (for review, see ref. 8). Reduced blood flow has been reported as one of the most consistent physiological deficits in AD (9, 10); however, it remains unclear whether the reduced cerebral blood flow is a response to neuronal damage or a factor initiating the characteristic neuropathology. In vivo studies showed the effect of A␤ on cerebral blood flow and vessel architecture in a mouse model for AD (11,12). In other models, cerebrovascular regulatory mechanisms, such as endothelium-depende...

show abstract

Section: Vascular Corrosion Casting Vascular Morphology and Networkmentioning

confidence: 99%

mentioning

confidence: 99%

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease

Meyer

Ulmann-Schuler

Staufenbiel

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

231

215

View full text Add to dashboard Cite

show abstract

“…78 An emerging view is that many if not most cases of intellectual deterioration in older persons are due to microvascular lesions. 8,98 CT scanning enabled lacunar infarcts to be seen; they increase in frequency with age, particularly in persons with uncontrolled hypertension. 7 Magnetic resonance imaging studies probe deeper and have shown the frequency of white matter hyperintensities (leukoaraiosis) in the brains of older persons, and the greater frequency and severity in persons with dementia.…”

Section: (Ii) Effects Of Age On the Microcirculation In Brain And mentioning

confidence: 99%

Arterial aging: pathophysiological principles

2007

View full text Add to dashboard Cite

Abstract:In the nineteenth century, prior to the introduction of the cuff sphygmomanometer, arteriosclerosis (stiffening of arteries) was recognized by clinicians and by life insurance companies as an indicator of vascular aging and cardiovascular risk, even in asymptomatic individuals. Through the twentieth century, views on aging came to focus on values of systolic and diastolic pressure and on obstructive atherosclerotic disease. Such focus deflected attention from the primary aging change which occurs in all societies, and is represented by stiffening and dilation of the proximal aorta. This review emphasizes the cushioning function of elastic arteries -principally the aorta -and how in youth this results in optimal interaction with the heart, and optimal steady flow through peripheral resistance vessels. Aortic stiffening with age is principally due to fatigue and fracture of elastin lamellae, with transfer of stress to stiffer collagenous components. Stiffening increases left ventricular load and myocardial blood requirement, but limits the capacity for blood supply during diastole. Consequences are cardiac failure and predisposition to ischaemia. The second, under-appreciated effect of aortic stiffening is transmission of flow pulsations downstream into vasodilated organs, principally brain and kidney, where pulsatile energy is dissipated and fragile microvessels are damaged. This accounts for micro infarcts and microhaemorrhages, with specialized cell damage, cognitive decline and renal failure. The aging process can be best monitored by change in the arterial pressure wave rather than by reliance on the cuff sphygmomanometer. This reintroduces the approaches by clinicians and life insurance examiners of the nineteenth century, endorses modern treatments for established disease, and holds the promise of detecting premature arterial degeneration, and better applying lifestyle measures and vasoactive medications to modify the aging process.

show abstract

“…For example, increases in baseline cerebral blood flow (CBF) by use of vasodilators significantly decreases the amplitude of the BOLD response irrespective of task performance (Brown et al, 2003;Stefanovic et al, 2006). There is evidence that these neurovascular relationships may be altered in AD pathology, with increased vascular resistance (Bateman et al, 2006) and differences in coupling of the vascular response to neuronal activity (Iadecola, 2004;Zlokovic, 2005;Girouard and Iadecola, 2006). Therefore group differences in activation BOLD signal, in many cases, may be entirely due to differences in the cerebral perfusion states, not necessarily representative of increased neuronal activity or oxygen consumption.…”

Section: Introductionmentioning

confidence: 99%

Cerebral perfusion and oxygenation differences in Alzheimer's disease risk

Fleisher

Podraza

Bangen

et al. 2009

Neurobiology of Aging

164

138

View full text Add to dashboard Cite

Functional MRI has demonstrated differences in response to memory performance based on risk for Alzheimer's disease (AD). The current study compared blood oxygen level dependent (BOLD) functional MRI response with arterial spin labeling (ASL) perfusion response during an associative encoding task and resting perfusion signal in different risk groups for AD. Thirteen individuals with a positive family history of AD and at least one copy of the apolipoprotien E ε4 (APOE4) gene (high risk) were compared to ten individuals without these risk factors (low risk). In the medial temporal lobes (MTLs) the high risk group had an elevated level of resting perfusion, and demonstrated decreased fractional BOLD and perfusion responses to the encoding task. However, there was no difference in the absolute cerebral blood flow during the task. These data demonstrate that individuals with increased risk for Alzheimer's disease have elevated MTL resting cerebral blood flow, which significantly influences apparent differences in BOLD activations. BOLD activations should be interpreted with caution, and do not necessarily reflect differences in neuronal activation.

show abstract

Quantitative measurement of cerebral haemodynamics in early vascular dementia and Alzheimer’s disease

Cited by 56 publications

References 26 publications

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease

Arterial aging: pathophysiological principles

Cerebral perfusion and oxygenation differences in Alzheimer's disease risk

Contact Info

Product

Resources

About