Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD
Abstract
OBJECTIVE: To test the hypotheses 1) that whole-brain volume decline begins in early adulthood, 2) that cross-sectional and longitudinal atrophy estimates agree in older, nondemented individuals, and 3) that longitudinal atrophy accelerates in the earliest stages of Alzheimer disease (AD). METHODS: High-resolution, high-contrast structural MRIs were obtained from 370 adults (age 18 to 97). Participants over 65 (n = 192) were characterized using the Clinical Dementia Rating (CDR) as either nondemented (CDR 0, n = 94) or with very mild to mild dementia of the Alzheimer type (DAT, CDR 0.5 and 1, n = 98). Of these older participants, 79 belonged to a longitudinal cohort and were imaged again a mean 1.8 years after baseline. Estimates of gray matter (nGM), white matter (nWM), and whole-brain volume (nWBV) normalized for head sizes were generated based on atlas registration and image segmentation. RESULTS: Hierarchical regression of nWBV estimates from nondemented individuals across the adult lifespan revealed a strong linear, moderate quadratic pattern of decline beginning in early adulthood, with later onset of nWM than nGM loss. Whole-brain volume differences were detected by age 30. The cross-sectional atrophy model overlapped with the rates measured longitudinally in older, nondemented individuals (mean decline of -0.45% per year). In those individuals with very mild DAT, atrophy rate more than doubled (-0.98% per year). CONCLUSIONS: Nondemented individuals exhibit a slow rate of whole-brain atrophy from early in adulthood with white-matter loss beginning in middle age; in older adults, the onset of dementia of the Alzheimer type is associated with a markedly accelerated atrophy rate.
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The advantage of a longitudinal PET-MR combined study relative to cross-sectional designs has been occasionally but not consistently shown.
“Although a longitudinal PET-MR combined study would obviously be of considerable interest, the advantage of this approach relative to cross-sectional designs has been occasionally [40,65], but not consistently [27,75], shown.”
From Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging (2009) · cites this paper as [27]
The very mild/mild DAT group has significantly reduced whole brain and hippocampal volumes compared with non-demented controls.
“The very mild/mild DAT group also exhibited significantly reduced whole brain (nWBV) and hippocampal (HC) volumes, as has been reported previously.6, 27”
From Decreased cerebrospinal fluid Aβ <sub>42</sub> correlates with brain atrophy in cognitively normal elderly (2009) · cites this paper as [27]
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Dadar, M., Camicioli, R., Duchesne, S., Collins, D. L., & Initiative, F. T. A. D. N. (2020) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1002/dad2.12091 · Cited by 64 · see citing works
Clinical Epidemiology, Risk Factors, and Outcomes of Encephalitis in Older Adults
Hansen, M. A., Samannodi, M. S., Castelblanco, R. L., & Hasbun, R. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciz635 · Cited by 48 · see citing works
Diagnostic biomarkers in Alzheimer’s disease
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Episodic Memory in Healthy Older Adults: The Role of Prefrontal and Parietal Cortices
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Aging Mindfully to Minimize Cognitive Decline
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- Authors
- Fotenos, A. F., Snyder, A. Z., Girton, L. E., Morris, J. C., & Buckner, R. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Neurology
- Published
- 2005-03-22
- Volume
- 64
- Issue
- 6
- Pages
- 1032-1039
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2084177652
- Cited by
- 579
- References
- 54
- Citations by year
- 2026: 17 · 2025: 26 · 2024: 26 · 2023: 28 · 2022: 37 · 2021: 31 · 2020: 43 · 2019: 39 · 2018: 18 · 2017: 26 · 2016: 26 · 2015: 28 · 2014: 30 · 2013: 20 · 2012: 25
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P 50 AG05681, P50AG005681, P01 AG0 3991, P01AG003991)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- brain atrophy, Alzheimer's disease, aging, white matter loss, gray matter loss, total brain volume, mild cognitive impairment, dementia onset
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Atrophy, Brain, Brain Mapping, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Reference Values, Regression Analysis, Disease Progression
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