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Trajectories of brain loss in aging and the development of cognitive impairment
Abstract
Background The use of volumetric MRI as a biomarker for assessing transitions to dementia presumes that more rapid brain loss marks the clinical transition from benign aging to mild cognitive impairment (MCI). The trajectory of this volume loss relative to the timing of the clinical transition to dementia has not been established. Methods The authors annually evaluated 79 healthy elderly subjects for up to 15 consecutive years with standardized clinical examinations and volumetric brain MRI assessments of ventricular volume. During the study period, 37 subjects developed MCI. A mixed effects model with a change point modeled the pattern of brain volume loss in healthy aging compared with subjects diagnosed with MCI. Results The brain loss trajectory of subjects developing MCI during follow-up differed from healthy aging in a two-phase process. First, the annual rate of expansion of ventricular volume decreased with age; however, the annual rates of expansion were greater in those who developed cognitive impairment during follow-up compared with those who did not. Further, subjects who developed MCI had an acceleration of ventricular volume expansion approximately 2.3 years prior to clinical diagnosis of MCI. Conclusions Ventricular expansion is faster in those developing mild cognitive impairment years prior to clinical symptoms, and eventually a more rapid expansion occurs approximately 24 months prior to the emergence of clinical symptoms. These differential rates of precli…
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“Together this result indicates that ventricle enlargement could represent a prodromal feature related to AD that could be used as an early predictor of disease progression (Carlson et al., 2008; Weiner, 2008).”
From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Carlson et al., 2008
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Metadata
- Authors
- Carlson, N. E., Moore, M. M., Dame, A., Howieson, D., Silbert, L. C., Quinn, J. F., & Kaye, J. A.
- Affiliations
- Oregon Health & Science University (US)
- Venue
- Neurology
- Published
- 2008-03-11
- Volume
- 70
- Issue
- 11
- Pages
- 828-833
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1980529166
- Cited by
- 144
- References
- 31
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 10 · 2014: 10 · 2013: 10 · 2012: 10
- FWCI
- 9.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 08017, K01AG030514, P30AG008017)
- National Center for Research Resources (UL1RR024140)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- brain atrophy, ventriculomegaly, mild cognitive impairment, healthy aging, dementia prevention, longitudinal brain volume change
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Atrophy, Brain, Cerebral Ventricles, Cognition Disorders, Female, Follow-Up Studies, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Cohort Studies, Disease Progression
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