Autoregulation of Cerebral Blood Flow to Changes in Arterial Pressure in Mild Alzheimer's Disease

Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent 15O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107±13 to 92±9 mm Hg with intravenous nicardipine; 11C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (−0.9±5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=−3.4 to 1.5), cortical borderzones (−1.9±5.0 mL per 100 g per minute, P=0.10, 95% CI=−4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (−0.3±4.4 mL per 100 g per minute, P=0.85, 95% CI=−3.3 to 3.9), or regions of peak 11C-PIB uptake (−2.5±7.7 mL per 100 g per minute, P=0.30, 95% CI=−7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD.

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Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer’s disease

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-04831-w ◽

2020 ◽

Vol 47 (13) ◽

pp. 3165-3175 ◽

Cited By ~ 2

Author(s):

Denise Visser ◽

Emma E. Wolters ◽

Sander C. J. Verfaillie ◽

Emma M. Coomans ◽

Tessa Timmers ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Executive Functioning ◽

Pet Scan ◽

Binding Potential ◽

Tau Pathology ◽

Positron Emission ◽

Composite Scores

Abstract Purpose We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer’s disease (AD), by using a single dynamic [18F]flortaucipir positron emission tomography (PET) scan. Methods Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [18F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. For tau pathology and rCBF, receptor parametric mapping (cerebellar gray matter reference region) was used to create uncorrected and partial volume-corrected parametric images of non-displaceable binding potential (BPND) and R1, respectively. (Voxel-wise) linear regressions were used to investigate associations between BPND and/or R1 and cognition. Results Higher [18F]flortaucipir BPND was associated with lower R1 in the lateral temporal, parietal and occipital regions. Higher medial temporal BPND was associated with worse memory, and higher lateral temporal BPND with worse executive functioning and language. Higher parietal BPND was associated with worse executive functioning, language and attention, and higher occipital BPND with lower cognitive scores across all domains. Higher frontal BPND was associated with worse executive function and attention. For [18F]flortaucipir R1, lower values in the lateral temporal and parietal ROIs were associated with worse executive functioning, language and attention, and lower occipital R1 with lower language and attention scores. When [18F]flortaucipir BPND and R1 were modelled simultaneously, associations between lower R1 in the lateral temporal ROI and worse attention remained, as well as for lower parietal R1 and worse executive functioning and attention. Conclusion Tau pathology was associated with locally reduced rCBF. Tau pathology and low rCBF were both independently associated with worse cognitive performance. For tau pathology, these associations spanned widespread neocortex, while for rCBF, independent associations were restricted to lateral temporal and parietal regions and the executive functioning and attention domains. These findings indicate that each biomarker may independently contribute to cognitive impairment in AD.

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Cerebral blood flow abnormality in clinically diagnosed Alzheimer's disease patients with or without amyloid β accumulation on positron emission tomography

Neurology and Clinical Neuroscience ◽

10.1111/ncn3.12107 ◽

2016 ◽

Vol 5 (2) ◽

pp. 55-59 ◽

Cited By ~ 4

Author(s):

Toshikazu Mino ◽

Haruna Saito ◽

Jun Takeuchi ◽

Kazuhiro Ito ◽

Akitoshi Takeda ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Amyloid Β ◽

Emission Tomography ◽

Positron Emission

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Hypertension Impairs Cerebral Blood Flow in a Mouse Model for Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205012666151027130135 ◽

2015 ◽

Vol 12 (10) ◽

pp. 914-922 ◽

Cited By ~ 14

Author(s):

Maximilian Wiesmann ◽

Carmen Capone ◽

Valerio Zerbi ◽

Laura Mellendijk ◽

Arend Heerschap ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Mouse Model

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Reversal of Focal Misery Perfusion after Intracranial Angioplasty: Case Report

Neurosurgery ◽

10.1097/00006123-200102000-00042 ◽

2001 ◽

Vol 48 (2) ◽

pp. 436-440 ◽

Cited By ~ 1

Author(s):

Colin P. Derdeyn ◽

DeWitte T. Cross ◽

Christopher J. Moran ◽

Ralph G. Dacey

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Carotid Artery ◽

Intracranial Stenosis ◽

Oxygen Extraction Fraction ◽

Oxygen Extraction ◽

Positron Emission ◽

Misery Perfusion ◽

Before And After ◽

Hemodynamic Measurements

Abstract OBJECTIVE AND IMPORTANCE The presence of reduced blood flow and increased oxygen extraction fraction (OEF) (misery perfusion) in the hemisphere distal to an occluded carotid artery is a proven risk factor for subsequent stroke. Whether angioplasty of intracranial stenosis is sufficient to reverse this condition has not been documented. CLINICAL PRESENTATION A 67-year-old man exhibited progressive right hemispheric ischemic symptoms despite maximal antiplatelet and antithrombotic therapy. Angiography demonstrated focal 80% stenosis of the supraclinoid segment of the ipsilateral internal carotid artery. TECHNIQUE 15O positron emission tomographic measurements of cerebral blood flow and OEF were made before and after transfemoral percutaneous angioplasty. OEF values measured before angioplasty were elevated in the middle cerebral artery distal to the stenosis. Angioplasty reduced the degree of luminal stenosis to 40% (linear diameter). OEF values measured 36 hours after angioplasty were normal. CONCLUSION Angioplasty of intracranial stenosis can restore normal cerebral blood flow and oxygen extraction, despite mild residual stenosis after the procedure. Hemodynamic measurements may be useful for the identification of patients with the greatest potential to benefit from angioplasty.

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