Longitudinal Cerebral Blood Flow and Amyloid Deposition: An Emerging Pattern?

Although cerebral amyloid deposition may precede cognitive impairment by decades, the relationship between amyloid deposition and longitudinal change in neuronal function has not, to our knowledge, been studied. The aim of this article was to determine whether individuals without dementia with high and low amyloid burden show different patterns of longitudinal regional cerebral blood flow (rCBF) changes in the years preceding measurement of amyloid deposition. Methods: Twenty-eight participants without dementia (mean age ± SD, 82.5 ± 4.8 y; 6 mildly impaired) from the Baltimore Longitudinal Study of Aging underwent yearly resting-state 15O-H2O PET scans for up to 8 y. 11C-PIB images of amyloid deposition were acquired on average 10.8 ± 0.8 y after the first CBF scan. 11C-PIB distribution volume ratios of regions of interest were estimated by fitting a reference-tissue model to the measured time–activity curves. On the basis of mean cortical distribution volume ratios, participants were divided into groups with high or low 11C-PIB retention. Differences in longitudinal rCBF changes between high– and low–11C-PIB groups were investigated by voxel-based analysis. Results: Longitudinal rCBF changes differed significantly between high– (n = 10) and low– (n = 18) 11C-PIB groups (P ≤ 0.001). Greater longitudinal decreases in rCBF in the high–11C-PIB group than in the low–11C-PIB group were seen in right anterior to middle cingulate, right supramarginal gyrus, left thalamus, and midbrain bilaterally. Greater increases in rCBF over time in the high–11C-PIB group were found in left medial and inferior frontal gyri, right precuneus, left inferior parietal lobule, and left postcentral gyrus. Conclusion: In this group of older adults without dementia, those with high 11C-PIB show greater longitudinal declines in rCBF in certain areas, representing regions with greater decrements in neuronal function. Greater longitudinal increases in rCBF are also observed in those with higher amyloid load and may represent an attempt to preserve neuronal function in these regions.

[1]  J Nucl Med , 2010 .

[2]  A. Zonderman,et al.  Neuronal Hypertrophy in Asymptomatic Alzheimer Disease , 2008, Journal of neuropathology and experimental neurology.

[3]  H. Engler,et al.  PET imaging of amyloid deposition in patients with mild cognitive impairment , 2008, Neurobiology of Aging.

[4]  Bradford C. Dickerson,et al.  Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer's disease: Insights from functional MRI studies , 2008, Neuropsychologia.

[5]  S. Resnick,et al.  The Impact of Magnetic Resonance Imaging-Detected White Matter Hyperintensities on Longitudinal Changes in Regional Cerebral Blood Flow , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  A. Verma,et al.  Amyloid, hypometabolism, and cognition in Alzheimer disease: An [11C]PIB and [18F]FDG PET study , 2008 .

[7]  Yun Zhou,et al.  Using a reference tissue model with spatial constraint to quantify [11C]Pittsburgh compound B PET for early diagnosis of Alzheimer's disease , 2007, NeuroImage.

[8]  C. Rowe,et al.  Imaging β-amyloid burden in aging and dementia , 2007, Neurology.

[9]  M. Viitanen,et al.  PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment , 2007, Neurology.

[10]  Keith A. Johnson,et al.  Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. , 2007, Archives of neurology.

[11]  M. Albert,et al.  Single photon emission computed tomography perfusion differences in mild cognitive impairment , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[12]  Ira Driscoll,et al.  Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly , 2006, Annals of neurology.

[13]  M. Viitanen,et al.  Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease , 2006, Neurology.

[14]  H. Engler,et al.  Two-year follow-up of amyloid deposition in patients with Alzheimer's disease. , 2006, Brain : a journal of neurology.

[15]  Yvette I. Sheline,et al.  Potential antecedent marker of Alzheimer disease , 2006 .

[16]  Benjamin J. Shannon,et al.  Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory , 2005, The Journal of Neuroscience.

[17]  J. Morris,et al.  Mild cognitive impairment as a clinical entity and treatment target. , 2005, Archives of neurology.

[18]  S. DeKosky,et al.  Kinetic Modeling of Amyloid Binding in Humans using PET Imaging and Pittsburgh Compound-B , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  J. Morris,et al.  Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study. , 2005, Archives of neurology.

[20]  Yaakov Stern,et al.  Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance , 2004, NeuroImage.

[21]  Edward A. Stern,et al.  Cortical Synaptic Integration In Vivo Is Disrupted by Amyloid-β Plaques , 2004, The Journal of Neuroscience.

[22]  W. Klunk,et al.  Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B , 2004, Annals of neurology.

[23]  Brian J Bacskai,et al.  Cortical synaptic integration in vivo is disrupted by amyloid-beta plaques. , 2004, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  Ove Almkvist,et al.  Voxel- and VOI-based analysis of SPECT CBF in relation to clinical and psychological heterogeneity of mild cognitive impairment , 2003, NeuroImage.

[25]  Sanjiv Sam Gambhir,et al.  AMIDE: a free software tool for multimodality medical image analysis. , 2003, Molecular imaging.

[26]  Ann Marie Schmidt,et al.  RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain , 2003, Nature Medicine.

[27]  Sung-Cheng Huang,et al.  Linear regression with spatial constraint to generate parametric images of ligand-receptor dynamic PET studies with a simplified reference tissue model , 2003, NeuroImage.

[28]  S. Wisniewski,et al.  Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment , 2002, Annals of neurology.

[29]  H. Annoura,et al.  Progressive brain dysfunction following intracerebroventricular infusion of beta1–42-amyloid peptide , 2001, Brain Research.

[30]  George A. Carlson,et al.  Exogenous Aβ1–40 Reproduces Cerebrovascular Alterations Resulting from Amyloid Precursor Protein Overexpression in Mice , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[31]  T. Ohnishi,et al.  Longitudinal Evaluation of Early Alzheimer's Disease Using Brain Perfusion Spect the Recruitment Was For , 2000 .

[32]  R Brookmeyer,et al.  Age-specific incidence rates of Alzheimer’s disease , 2000, Neurology.

[33]  S. Resnick,et al.  One-year age changes in MRI brain volumes in older adults. , 2000, Cerebral cortex.

[34]  X. Tong,et al.  Regional cholinergic denervation of cortical microvessels and nitric oxide synthase-containing neurons in Alzheimer's disease , 1999, Neuroscience.

[35]  J. Hodges,et al.  Attention and executive deficits in Alzheimer's disease. A critical review. , 1999, Brain : a journal of neurology.

[36]  B L Holman,et al.  Preclinical prediction of Alzheimer's disease using SPECT , 1998, Neurology.

[37]  N. Foster,et al.  Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease , 1997, Annals of neurology.

[38]  E P Steinberg,et al.  Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study. , 1994, Stroke.

[39]  R. Kronmal,et al.  The Cardiovascular Health Study: design and rationale. , 1991, Annals of epidemiology.

[40]  M. Roth,et al.  The Association Between Quantitative Measures of Dementia and of Senile Change in the Cerebral Grey Matter of Elderly Subjects , 1968, British Journal of Psychiatry.