Elsevier

Neurobiology of Aging

Volume 33, Issue 2, February 2012, Pages 215-225
Neurobiology of Aging

Regular paper
Cognition, glucose metabolism and amyloid burden in Alzheimer's disease

https://doi.org/10.1016/j.neurobiolaging.2010.03.011Get rights and content

Abstract

The authors investigated relationships between glucose metabolism, amyloid load, and measures of cognitive and functional impairment in Alzheimer's disease (AD). Patients meeting criteria for probable AD underwent 11C-labeled Pittsburgh Compound-B ([11C]PIB) and 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging and were assessed on a set of clinical measures. The Pittsburgh Compound-B (PIB) Distribution volume ratios and fluorodeoxyglucose (FDG) scans were spatially normalized and average PIB counts from regions-of-interest (ROI) were used to compute a measure of global PIB uptake. Separate voxel-wise regressions explored local and global relationships between metabolism, amyloid burden, and clinical measures. Regressions reflected cognitive domains assessed by individual measures, with visuospatial tests associated with more posterior metabolism, and language tests associated with metabolism in the left hemisphere. Correlating regional FDG uptake with these measures confirmed these findings. In contrast, no correlations were found between either voxel-wise or regional PIB uptake and any of the clinical measures. Finally, there were no associations between regional PIB and FDG uptake. We conclude that regional and global amyloid burden does not correlate with clinical status or glucose metabolism in AD.

Section snippets

Subject selection

Patients were recruited from an AD research cohort followed at the University of California, San Francisco Memory and Aging Center (UCSF-MAC). The clinical evaluation included a history and physical examination by a neurologist, a structured caregiver interview administered by a nurse, and a comprehensive battery of neuropsychological tests (Kramer et al., 2003). Clinical diagnoses were assigned by consensus at a multidisciplinary conference using standard research criteria (McKhann et al., 1984

Results

The patient cohort consisted of 39 AD patients (24 males) with a mean age of 68.3 ± 10.5 and 16.8 ± 2.8 years of education. Patients' mean scores for MMSE and CDRSB were 21.8 ± 5.7 and 5.5 ± 3.0, respectively. CDRSB data were only available for 34 patients. The cohort had an estimated average disease duration of 5.4 ± 2.8 years (Table 1) and a mean global PIB uptake of 1.67 with a range of 0.92–2.33.

Separate voxel-wise multiple regressions of FDG uptake with each of the cognitive/functional

Discussion

This study investigated in vivo relationships between Aβ plaque load, dementia severity and glucose metabolism in a cohort of 39 patients with probable AD. Consistent with the existing literature, we found cognitive decline to be strongly associated with decreased glucose metabolism in frontal and temporo-parietal regions (Heiss et al., 1991a, Heiss et al., 1991b, Herholz et al., 2002, Langbaum et al., 2009, Mielke et al., 1994, Minoshima et al., 1995b). The observed effects were not driven by

Disclosure statement

The authors have nothing to disclose.

Acknowledgements

This work was supported by National Institute on Aging grants NIA K23-AG031861 (GDR), NIA AG027859 (WJJ), NIA P01-AG1972403 and P50-AG023501 (BLM), Alzheimer's Association NIRG-07-59422 (GDR) and ZEN-08-87090 (WJJ), John Douglas French Alzheimer's Foundation (GDR).

References (101)

  • A. Ichimiya et al.

    Difference of regional cerebral metabolic pattern between presenile and senile dementia of the Alzheimer type: a factor analytic study

    J. Neurol. Sci

    (1994)
  • J.B. Langbaum et al.

    Categorical and Correlational Analyses of Baseline Fluorodeoxyglucose Positron Emission Tomography Images From the Alzheimer's Disease Neuroimaging Initiative

    ADNI. Neuroimage

    (2009)
  • J.E. McKenzie et al.

    Quantification of plaque types in sulci and gyri of the medial frontal lobe in patients with Alzheimer's disease

    Neurosci. Lett

    (1992)
  • S. Naruse et al.

    Mis-sense mutation Val–Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease

    Lancet

    (1991)
  • J.J. Palop et al.

    Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease

    Neuron

    (2007)
  • J.L. Price et al.

    The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease

    Neurobiol. Aging

    (1991)
  • A.B. Rocher et al.

    Resting-state brain glucose utilization as measured by PET is directly related to regional synaptophysin levels: a study in baboons

    Neuroimage

    (2003)
  • J.D. Schmahmann et al.

    Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space

    Neuroimage

    (1999)
  • R.A. Sperling et al.

    Amyloid deposition is associated with impaired default network function in older persons without dementia

    Neuron

    (2009)
  • N. Tzourio-Mazoyer et al.

    Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain

    Neuroimage

    (2002)
  • P.S. Aisen

    Alzheimer's disease therapeutic research: the path forward

    Alzheimers Rev. Ther

    (2009)
  • H.J. Aizenstein et al.

    Frequent amyloid deposition without significant cognitive impairment among the elderly

    Arch. Neurol

    (2008)
  • S.E. Arnold et al.

    The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease

    Cereb. Cortex

    (1991)
  • P.V. Arriagada et al.

    Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease

    Neurology

    (1992)
  • B.J. Bacskai et al.

    Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-beta ligand in transgenic mice

    Proc. Natl. Acad. Sci. USA

    (2003)
  • B.J. Bacskai et al.

    Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report

    Arch. Neurol

    (2007)
  • D.A. Bennett et al.

    Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function

    Arch. Neurol

    (2004)
  • L. Berg et al.

    Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older

    Arch. Neurol

    (1993)
  • L. Berg et al.

    Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype

    Arch. Neurol

    (1998)
  • L.M. Bierer et al.

    Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer's disease

    Arch. Neurol

    (1995)
  • A.L. Boxer et al.

    Amyloid imaging in distinguishing atypical prion disease from Alzheimer disease

    Neurology

    (2007)
  • H. Braak et al.

    Neuropathological staging of Alzheimer-related changes

    Acta Neuropathol

    (1991)
  • D.L. Brody et al.

    Amyloid-beta dynamics correlate with neurological status in the injured human brain

    Science

    (2008)
  • R.L. Buckner et al.

    Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory

    J. Neurosci

    (2005)
  • H. Crystal et al.

    Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease

    Neurology

    (1988)
  • P. Edison et al.

    Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study

    Neurology

    (2007)
  • G.N. Elston et al.

    Comparison of dendritic fields of layer III pyramidal neurons in striate and extrastriate visual areas of the marmoset: a Lucifer yellow intracellular injection

    Cereb. Cortex

    (1996)
  • G.N. Elston et al.

    The occipitoparietal pathway of the macaque monkey: comparison of pyramidal cell morphology in layer III of functionally related cortical visual areas

    Cereb. Cortex

    (1997)
  • G.N. Elston et al.

    Morphological variation of layer III pyramidal neurones in the occipitotemporal pathway of the macaque monkey visual cortex

    Cereb. Cortex

    (1998)
  • G.N. Elston et al.

    Complex dendritic fields of pyramidal cells in the frontal eye field of the macaque monkey: comparison with parietal areas 7a and LIP

    Neuroreport

    (1998)
  • H. Engler et al.

    Two-year follow-up of amyloid deposition in patients with Alzheimer's disease

    Brain

    (2006)
  • G.B. Frisoni et al.

    In vivo mapping of amyloid toxicity in Alzheimer disease

    Neurology

    (2009)
  • P. Giannakopoulos et al.

    Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease

    Neurology

    (2003)
  • A. Goate et al.

    Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease

    Nature

    (1991)
  • S.N. Gomperts et al.

    Imaging amyloid deposition in Lewy body diseases

    Neurology

    (2008)
  • T. Grimmer et al.

    Clinical severity of Alzheimer's disease is associated with PIB uptake in PET

    Neurobiol. Aging

    (2008)
  • C. Haass et al.

    Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide

    Nat. Rev. Mol. Cell Biol

    (2007)
  • J.A. Hardy et al.

    Alzheimer's disease: the amyloid cascade hypothesis

    Science

    (1992)
  • V. Haroutunian et al.

    Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease

    Arch. Neurol

    (1998)
  • W.D. Heiss et al.

    Positron emission tomography in the differential diagnosis of organic dementias

    J. Neural Transm. Suppl

    (1991)
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