Ventricular enlargement as a possible measure of Alzheimer’s disease progression validated using the Alzheimer’s disease neuroimaging initiative database
Open accessAbstract
Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T(1)-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an epsilon 4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies.
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In humans, lateral ventricular enlargement was found even at early stages like MCI.
“and even at early stages like MCI (Nestor et al., 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 Nestor et al., 2008
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- Authors
- Nestor, S. M., Rupsingh, R., Borrie, M., Smith, M., Accomazzi, V., Wells, J. L., Fogarty, J., Bartha, R., & Initiative, T. A. D. N.
- Affiliations
- Western University (CA)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-08-21
- Volume
- 131
- Issue
- 9
- Pages
- 2443-2454
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC2724905
- OpenAlex
- W2113588440
- Cited by
- 543
- References
- 6
- Citations by year
- 2026: 48 · 2025: 47 · 2024: 32 · 2023: 41 · 2022: 37 · 2021: 42 · 2020: 28 · 2019: 34 · 2018: 20 · 2017: 17 · 2016: 23 · 2015: 24 · 2014: 30 · 2013: 32 · 2012: 25
- FWCI
- 14.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- ventriculomegaly, Alzheimer's disease, mild cognitive impairment, disease progression, APOE ε4, sample size determination, ventricular volume, cognitive decline, volumetric MRI, Alzheimer's Disease Neuroimaging Initiative
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Cerebral Ventricles, Dilatation, Pathologic, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Prognosis, Psychometrics, Radiology Information Systems, Reproducibility of Results, Observer Variation, Disease Progression
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