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Cited by 1,425Dementia and Cognitive Impairment ResearchAdvanced MRI Techniques and ApplicationsAging and Gerontology Research

Longitudinal Magnetic Resonance Imaging Studies of Older Adults: A Shrinking Brain

Open access
Resnick, Susan M., Pham, Dzung L., Kraut, Michael A., Zonderman, Alan B., Davatzikos, Christos·2003·The Journal of Neuroscience
DOI 10.1523/jneurosci.23-08-03295.2003PMC PMC6742337
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Abstract

Age-related loss of brain tissue has been inferred from cross-sectional neuroimaging studies, but direct measurements of gray and white matter changes from longitudinal studies are lacking. We quantified longitudinal magnetic resonance imaging (MRI) scans of 92 nondemented older adults (age 59-85 years at baseline) in the Baltimore Longitudinal Study of Aging to determine the rates and regional distribution of gray and white matter tissue loss in older adults. Using images from baseline, 2 year, and 4 year follow-up, we found significant age changes in gray (p < 0.001) and white (p < 0.001) volumes even in a subgroup of 24 very healthy elderly. Annual rates of tissue loss were 5.4 +/- 0.3, 2.4 +/- 0.4, and 3.1 +/- 0.4 cm3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 +/- 0.1 cm3 per year (3.7, 1.3, 2.4, and 1.2 cm3, respectively, in very healthy). Frontal and parietal, compared with temporal and occipital, lobar regions showed greater decline. Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread. In this first study of gray and white matter volume changes, we demonstrate significant longitudinal tissue loss for both gray and white matter even in very healthy older adults. These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated and suggest slower rates of brain atrophy in individuals who remain medically and cognitively healthy.

Integrity signals

Registry

Crossref · 10.1523/jneurosci.23-08-03295.2003

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 16 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The magnitudes of longitudinal changes in lobar regions were not significantly influenced by age and sex.

    “The magnitudes of longitudinal changes in the lobar regions were not significantly influenced by age and sex.”
    Quote in the paperSubstantial claim
  • Findingown data

    Analysis of lobar regions and voxel-based comparisons revealed regional patterns of vulnerability to age-related tissue loss.

    “analysis of lobar regions and voxel-based comparisons of local changes revealed regional patterns of vulnerability to agerelated tissue loss.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was a tendency for greater ventricular CSF increases in individuals with larger baseline volumes.

    “Although the magnitude of decline in brain volume appears relatively consistent across subjects, there is a tendency for greater V-CSF increases in individuals with larger baseline volumes.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the very healthy subgroup, the annual rate of ventricular volume increase was 1.2 cm3 per year.

    “Annual rates of tissue loss were 5.4 Ϯ 0.3, 2.4 Ϯ 0.4, and 3.1 Ϯ 0.4 cm 3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 Ϯ 0.1 cm 3 per year (3.7, 1.3, 2.4, and 1.2 cm 3 , respectively, in very healthy).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Longitudinal brain changes reached statistical significance for all regions examined.

    “As indicated by the significant effects of time, longitudinal brain changes reached statistical significance for all regions examined.”
    Quote in the paperSubstantial claim
  • May combine two claims. 25
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 5

  • May combine two claims.

    Findingown data

    Longitudinal changes remained significant after excluding four individuals with mild cognitive impairment and in analyses of 24 very healthy individuals.

    “Longitudinal changes remained significant excluding the four individuals with mild cognitive impairment and for the analyses based on 24 individuals free of medical problems and even very mild cognitive change.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For ventricular CSF, the main effect of time did not reach significance when the age-by-time interaction was present, but significant longitudinal increases appeared when the interaction was omitted.

    “In the presence of this interaction, the main effect of time for V-CSF did not reach significance, although significant longitudinal increases were evident when the interaction was omitted from the model.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Scatterplots showed declines in brain volumes and increases in ventricular CSF for the majority of individuals.

    “These scatterplots show declines in brain volumes and increases in V-CSF for the majority of individuals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    White matter tissue loss asymmetry was limited to the temporal lobe, with greater loss of left than right temporal white matter.

    “Although there is some asymmetry in the white matter tissue loss, this asymmetry appears limited to the temporal lobe, with greater loss of left than right temporal white matter.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The right-greater-than-left asymmetry was most pronounced in inferior frontal and anterior temporal regions, but reversed in the inferior parietal region.

    “The right greater than left asymmetry is most pronounced in inferior frontal and anterior temporal regions, but shows a reversed pattern in the inferior parietal region.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Voxel-based analyses indicated that cingulate, insular, orbital, and inferior frontal cortex, and to a lesser extent mesial temporal regions, showed longitudinal changes in gray matter.

    “Voxel-based analyses of local regions provided complementary information and indicated that cingulate, insular, orbital, and inferior frontal cortex, and, to a lesser extent, mesial temporal regions showed longitudinal changes in gray matter.”
    • Also stated in: § Discussion · plain
      “Gray matter volume loss in the insula (right Ͼ left; inferior and coronal views), orbital frontal cortex (inferior and sagittal views), and cingulate cortex (sagittal and coronal views) are highlighted.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Gray matter loss was most pronounced in orbital and inferior frontal, cingulate, insular, and inferior parietal regions, and less pronounced in mesial temporal regions.

    “Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the very healthy subsample, longitudinal changes were significant and did not differ by tissue type or lobar region.

    “MANOVA restricted to the very healthy subsample showed significant longitudinal changes that did not differ as a function of tissue type or lobar brain region.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Gray matter volume declined significantly over 4 years in nondemented older adults, including a subgroup of very healthy elderly.

    “we found significant age changes in gray ( p Ͻ 0.001) and white ( p Ͻ 0.001) volumes even in a subgroup of 24 very healthy elderly.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Rates of tissue loss were similar in men and women and in older and younger adults.

    “Rates of tissue loss were similar in men and women and in older and younger adults.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    White matter volume declined significantly over 4 years in nondemented older adults, including a subgroup of very healthy elderly.

    “we found significant age changes in gray ( p Ͻ 0.001) and white ( p Ͻ 0.001) volumes even in a subgroup of 24 very healthy elderly.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In the very healthy subgroup, the annual rate of white matter volume loss was 2.4 cm3 per year.

    “Annual rates of tissue loss were 5.4 Ϯ 0.3, 2.4 Ϯ 0.4, and 3.1 Ϯ 0.4 cm 3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 Ϯ 0.1 cm 3 per year (3.7, 1.3, 2.4, and 1.2 cm 3 , respectively, in very healthy).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The magnitude of brain tissue loss was somewhat reduced in the very healthy elderly, but these individuals still showed significant volume change.

    “The magnitude of brain tissue loss was somewhat reduced in the very healthy elderly, but these individuals still showed significant volume change.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the healthy subgroup, gray matter tissue loss was not significant in simple analysis but was significant in the more sensitive mixed-effects regression analysis.

    “All values are significant at p Ͻ 0.001 except gray (NS) and white (p Ͻ 0.05) in the healthy group.Note that the nonsignificant trend for gray matter tissue loss in the healthy subgroup is significant in the more sensitive mixed-effects regression analysis (see Results).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The sample is composed of relatively healthy individuals who have shown, on average, little cognitive change over the initial 4-year interval.

    “Our sample is composed of relatively healthy individuals, and they have shown, on average, little cognitive change over this initial 4 year interval.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Against a background of highly stable measurement, longitudinal decreases in brain tissue volume and increases in V-CSF occur across almost all individuals in this age range.

    “Inspection of Figure 1, top and bottom, indicates that, against a background of highly stable measurement, longitudinal decreases in brain tissue volume and increases in V-CSF occur across almost all individuals in this age range.”
    • Also stated in: § Discussion · plain
      “Against a background of highly stable measurement, brain volumes decrease and ventricular volumes increase over the 4 year interval.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Changes over the 4-year interval were 21.6 cm3 for cerebral tissue and 5.6 cm3 for V-CSF.

    “with changes over the 4-year interval of 21.6 and 5.6 cm 3 , respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Views of the right and left hemispheres highlight tissue loss in inferior frontal, insular, and posterior temporal regions (right greater than left) and the inferior parietal region (left greater than right).

    “Bottom, Views of the right and left hemispheres highlight tissue loss in inferior frontal, insular, and posterior temporal regions (right Ͼ left) and the inferior parietal (left Ͼ right) region.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    All measurements were highly stable over both 2-year and 4-year intervals, with test-retest correlations from 0.94 to 0.99.

    “All measurements were highly stable over both 2 and 4 year intervals, with test-retest correlations ranging from 0.94 to 0.99.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated.

    “These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    One-year stabilities for total gray, white, brain, ventricular CSF, and ventricle-to-brain ratio measures were all greater than 0.95.

    “Stabilities over 1 year for these measures are all Ͼ0.95.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Differences in age distributions between the two samples may account in part for the discrepancies.

    “Differences in age distributions for the two samples may account in part for these discrepancies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    The semi-automated image analysis approach used for MR volume quantitation has demonstrated validity and high reliability.

    “Quantitative analysis of MR volumes is accomplished using a semi-automated approach, with demonstrated validity and high reliability (Goldszal et al., 1998).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Goldszal et al., 1998

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The magnitude and age at which sex differences in ventricular size appear remain unclear.

    “the magnitude and age at which sex differences appear remain unclear.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kaye et al., 1992

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Few longitudinal neuroimaging studies exist, and none had examined global and regional changes in both gray and white matter using high-resolution MRI.

    “There have been few longitudinal neuroimaging studies, and none have examined global and regional changes in both gray and white matter using high-resolution magnetic resonance imaging (MRI).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There is already substantial evidence that loss of mesial temporal lobe tissue, particularly in hippocampus and entorhinal cortex, is associated with memory impairment and the development of Alzheimer's disease.

    “There is already substantial evidence that loss of mesial temporal lobe tissue, particularly in hippocampus and entorhinal cortex, is associated with memory impairment and the development of Alzheimer's disease (Convit et al., 1997;Petersen et al., 2000).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Convit et al., 1997

      Not checked in the free run.

    • cites Petersen et al., 2000

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The uniformity of findings across individuals argues against the interpretation that any tissue loss reflects preclinical dementia rather than normal aging, unless all are in a preclinical stage of dementia.

    “the uniformity of our findings across individuals argues against this interpretation unless all are in a preclinical stage of dementia.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The observed brain tissue loss is not entirely attributable to preclinical dementia in all participants.

  • May combine two claims.

    Study design and conductreasoning

    Registration errors limit the ability to detect change in voxel-based analyses, and these difficulties are most pronounced in regions of high cortical variability.

    “Registration errors limit our ability to detect change in voxel-based analyses, and these difficulties will be most pronounced in regions of high cortical variability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Initial amyloid pathology appears in basal neocortex, including perirhinal and orbital cortex, then spreads to adjacent neocortical association areas and hippocampal formation, and finally to primary neocortical areas.

    “Initial pathology appears in the basal neocortex, including perirhinal and orbital cortex, and next spreads into adjacent neocortical association areas and the hippocampal formation, followed finally by its appearance in primary neocortical areas.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Braak and Braak (1997)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    Findings from in vivo MRI studies can help direct more focused neuropathological studies of specific brain regions.

    “our findings from in vivo MRI studies can help direct more focused neuropathological studies of specific brain regions.”
    Quote in the paperNot a substantial claim
30 of 30

  • The paper relies on this without support.

    The 92 BLSA participants are representative of nondemented older adults aged 59–85, so the estimated rates and regional patterns generalize to that population.

    “This report provides the first evidence of substantial longitudinal declines in both gray and white matter brain volumes in older adults ranging in age from 59 to 85 years at baseline.”
    “this community-dwelling sample of older adults shows an average loss of 5.4 cm 3 of brain volume and increase of 1.4 cm 3 in ventricular volume each year.”

  • The paper relies on this without support.

    The observed 4-year longitudinal changes reflect aging rather than secular or cohort effects.

    “rates of brain changes can only be determined from longitudinal investigations.”
    “we found significant age changes in gray ( p Ͻ 0.001) and white ( p Ͻ 0.001) volumes even in a subgroup of 24 very healthy elderly.”

  • The paper relies on this without support.

    The observed brain tissue loss is not entirely attributable to preclinical dementia in all participants.

    “Although some argue that any tissue loss reflects pathological changes associated with preclinical dementia rather than normal aging, the uniformity of our findings across individuals argues against this interpretation unless all are in a preclinical stage of dementia.”

  • The paper relies on this without support.

    Increases in ventricular volume reflect central brain atrophy.

    “the rates of increase in ventricular volume, reflecting central brain atrophy”

  • The paper relies on this without support.

    The sample is representative of normal older adults without dementia.

    “Our sample is composed of relatively healthy individuals, and they have shown, on average, little cognitive change over this initial 4 year interval.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Prefrontal cortical regions that support executive functions are particularly vulnerable to declines at later ages.

    “Executive planning and organizational skills appear to be important to maintaining functional independence (4–7) and appear to be particularly vulnerable to declines at later ages (8–10) along with the prefrontal cortical regions of the brain that support them (11–14).”

    From Evidence for Neurocognitive Plasticity in At-Risk Older Adults: The Experience Corps Program (2009) · cites this paper as [12]

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Yan MXH, Karp JN (1995) An adaptive Bayesian approach to three- dimensional MR brain segmentation. In: Proceedings of XIVth Interna- tional Conference on Information Processing in Medical Imaging, pp 201-213. Ile de Berder, France, June.

Cited by

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Related

Authors
Resnick, S. M., Pham, D. L., Kraut, M. A., Zonderman, A. B., & Davatzikos, C.
Affiliations
  • National Institute on Aging (US)
  • Johns Hopkins University (US)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2003-04-15
Volume
23
Issue
8
Pages
3295-3301
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.23-08-03295.2003
PMC
PMC6742337
OpenAlex
W1929729372
Semantic Scholar
bfeb3d16a48b60458c19697495bc7dd17277f1e3
Cited by
1,425
References
46
Citations by year
2026: 24 · 2025: 33 · 2024: 54 · 2023: 54 · 2022: 66 · 2021: 90 · 2020: 77 · 2019: 72 · 2018: 79 · 2017: 68 · 2016: 71 · 2015: 65 · 2014: 79 · 2013: 68 · 2012: 72
FWCI
19.87
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
Keywords
brain atrophy, gray matter loss, white matter loss, brain volume changes, aging, older adults, ventriculomegaly, healthy older adults, Baltimore Longitudinal Study of Aging
MeSH terms
Age Factors, Aged, Aged, 80 and over, Aging, Brain, Brain Mapping, Cerebral Ventricles, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Reference Values, Regression Analysis, Sex Factors, Baltimore

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