Cited by 393Dementia and Cognitive Impairment ResearchFunctional Brain Connectivity StudiesAging and Gerontology Research

The DOI matches its Crossref record; 95 of the 111 references it cites were found in a registry or an index; none of the 121 sources its claims cite is checked for support yet.

Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging

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Abstract

With age, the brain undergoes both structural and functional alterations, probably resulting in reported cognitive declines. Relatively few investigations have sought to identify those areas that remain intact with aging, or undergo the least deterioration, which might underlie cognitive preservations. Our aim here was to establish a comprehensive profile of both structural and functional changes in the aging brain, using up-to-date voxel-based methodology (i.e. optimized voxel-based morphometry (VBM) procedure; resting-state (18)FDG-PET with correction for partial volume effects (PVE)) in 45 optimally healthy subjects aged 20-83 years. Negative and positive correlations between age and both gray matter (GM) volume and (18)FDG uptake were assessed. The frontal cortex manifested the greatest deterioration, both structurally and functionally, whereas the anterior hippocampus, the thalamus and (functionally) the posterior cingulate cortex were the least affected. Our results support the developmental theory which postulates that the first regions to emerge phylogenetically and ontogenetically are the most resistant to age effects, and the last ones the most vulnerable. Furthermore, the lesser affected anterior hippocampal region, together with the lesser functional alteration of the posterior cingulate cortex, appear to mark the parting of the ways between normal aging and Alzheimer's disease, which is characterized by early and prominent deterioration of both structures.

Overview

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TL;DR

In 45 optimally healthy adults aged 20–83, normal aging showed the greatest structural and metabolic deterioration in frontal cortex, while anterior hippocampus, thalamus, and posterior cingulate cortex were among the least affected. The authors interpret this pattern as supporting developmental theory and as distinguishing normal aging from Alzheimer’s disease.

Key findings

  • Absolute gray matter (GM) loss was mainly bilateral frontal (dorsolateral prefrontal, sensorimotor, orbitofrontal), with additional loss in superior occipital/parietal cortices, insula, posterior hippocampus, cerebellum, and periventricular/caudate/anterior thalamic regions.
  • Highest 18FDG uptake decreases were bilateral superior medial frontal, motor, anterior/middle cingulate, parietal regions (left-predominant), and superior temporal pole encroaching on insular/orbitofrontal cortex.
  • Least GM decline was mainly right anterior mesial temporal structures (anterior hippocampus, entorhinal cortex, amygdala), lateral thalamic nuclei, right calcarine region, and brainstem; least 18FDG decrease was bilateral mesial temporal (hippocampus, amygdala, parahippocampal gyrus), putamen/pallidum/lateral thalamic nuclei, right posterior cingulate/precuneus, occipito-temporal cortex, and cerebellum.
  • Complementary analyses: right hippocampal head volume vs age was r = .07 (p = .65); HipMask relative metabolic hippocampal ratios vs age was r = .51 (p < .001), and HipMask measures correlated with SPM hippocampal peaks at r = .73 left and r = .70 right (p < .001 for both).

Methods

  • Cross-sectional study of 45 right-handed healthy subjects aged 20–83 years (mean 49.4 ± 18; 24 females, 21 males), screened with stringent clinical, MRI, and neuropsychological criteria; MRI and resting 18FDG-PET were completed within two months.
  • MRI analyzed with optimized voxel-based morphometry (VBM); PET corrected for partial volume effects using a modified Müller-Gärtner method, coregistered/normalized to a customized template, and smoothed with a 14-mm isotropic Gaussian filter.
  • SPM2 voxelwise correlations with age used p < .01 FDR corrected, minimum cluster size k = 20; proportional scaling assessed relative GM and relative 18FDG changes, with complementary ROI and HipMask analyses for hippocampus.

Limitations

  • The paper states that PET and MR spatial resolution differed, preventing direct comparison of atrophy and hypometabolism; possible age effects on intrinsic MR signal/contrast; PVE correction accuracy depends on MRI-PET realignment and MRI segmentation; and the cross-sectional design cannot definitively resolve hippocampal impairment because of possible cohort effects.
  • The text also makes evident that PET data were relative rather than CMRglc because raw FDG uptake has no physiological meaning and CMRglc requires invasive arterial blood sampling.
  • A formal psychiatric interview was not performed, as noted in the inclusion criteria.

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Integrity signals

Registry

Crossref · 10.1016/j.neurobiolaging.2007.05.019

Cites

95 of 95 references verified0 citation errors · 0 not checkable

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  • It may state two separate claims as one. 27
  • The quote only partly states this claim. 16
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54 of 54
  • The paper relies on this without support.

    No prior study has assessed both structural and functional deterioration and relative preservation in normal aging in the same sample using voxel-based analyses, optimized VBM and PVEc.

    “To our knowledge, no study has assessed both structural and functional deterioration and relative preservation in normal aging in the same sample and using up-to-date methodology, i.e. voxel-based analyses, the optimized-VBM procedure and PVEc.”
  • The paper relies on this without support.

    Cross-sectional age-related differences in brain structure and metabolism reflect true aging effects rather than cohort effects.

    “Forty-five healthy subjects aged between 20 and 83 years (mean: 49.4 ± 18 years, 24 females and 21 males) were selected according to stringent prospective inclusion/exclusion criteria.”
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Citations

Cites

Research works printed but not linked: 2

  1. Cardebat, 1990, Evocation lexicale formelle et sémantique chez des sujets normaux: performances et dynamiques de production en fonction du sexe, de l’âge et du niveau d’étude, Acta Neurol. Belg., 90, 207
  2. Eustache, 1998, L’évaluation clinique de la mémoire. Revue Neurologique (Paris), 154, 18

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Metadata

Authors
Kalpouzos, G., Chételat, G., Baron, J.-C., Landeau, B., Mevel, K., Godeau, C., Barré, L., Constans, J.-M., Viader, F., Eustache, F., & Desgranges, B.
Affiliations
  • Inserm (FR)
  • Centre National de la Recherche Scientifique (FR)
  • Centre Hospitalier Universitaire de Caen Normandie (FR)
Corresponding author
Desgranges, Béatrice
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2009-01
Volume
30
Issue
1
Pages
112-124
ISSN
0197-4580 (ISSN-L)
OpenAlex
W2067165730
Cited by
392
References
111
Citations by year
2026: 5 · 2025: 10 · 2024: 17 · 2023: 14 · 2022: 25 · 2021: 21 · 2020: 21 · 2019: 26 · 2018: 27 · 2017: 28 · 2016: 22 · 2015: 24 · 2014: 29 · 2013: 33 · 2012: 19
FWCI
9.46
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Social Sciences › Psychology › Developmental and Educational Psychology › Aging and Gerontology Research
Keywords
normal brain aging, gray matter volume, glucose metabolism, voxel-based morphometry, FDG-PET, partial volume correction, frontal cortex, hippocampus, thalamus, posterior cingulate cortex, cognitive preservation, Alzheimer's disease, brain aging
MeSH terms
Adult, Aged, Aged, 80 and over, Aging, Brain, Female, Humans, Male, Metabolic Clearance Rate, Middle Aged, Neurons, Organ Size, Radionuclide Imaging, Tissue Distribution, Radiopharmaceuticals, Fluorodeoxyglucose F18, Young Adult

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