Association of MRI Markers of Vascular Brain Injury With Incident Stroke, Mild Cognitive Impairment, Dementia, and Mortality: The Framingham Offspring Study
Open accessAbstract
Background and Purpose— White matter hyperintensities and MRI-defined brain infarcts (BIs) have individually been related to stroke, dementia, and mortality in population-based studies, mainly in older people. Their significance in middle-aged community-dwelling persons and the relative importance of these associations remain unclear. We simultaneously assessed the relation of white matter hyperintensities and BI with incident stroke, mild cognitive impairment, dementia, and mortality in a middle-aged community-based cohort. Methods— A total of 2229 Framingham Offspring Study participants aged 62±9 years underwent volumetric brain MRI and neuropsychological testing (1999 to 2005). Incident stroke, dementia, and mortality were prospectively ascertained and for 1694 participants in whom a second neuropsychological assessment was performed (2005 to 2007), incident mild cognitive impairment was evaluated. All outcomes were related to white matter hyperintensities volume (WMHV), age-specific extensive WMHV and BI adjusting for age and gender. Results— Extensive WMHV and BI were associated with an increased risk of stroke (hazard ratio [HR]=2.28, 95% CI: 1.02 to 5.13; HR=2.84, 95% CI: 1.32 to 6.10). WMHV, extensive WMHV, and BI were associated with an increased risk of dementia (HR=2.22, 95% CI: 1.32 to 3.72; HR=3.97, 95% CI: 1.10 to 14.30; HR=6.12, 95% CI: 1.82 to 20.54) independently of vascular risk factors and interim stroke. WMHV and extensive WMHV were associated with incident amnestic mild cognitive impairment in participants aged ≥60 years only (OR=2.47, 95% CI: 1.31 to 4.66 and OR=1.49, 95% CI: 1.14 to 1.97). WMHV and extensive WMHV were associated with an increased risk of death (HR=1.38, 95% CI: 1.13 to 1.69; HR=2.27, 95% CI: 1.41 to 3.65) independent of vascular risk factors and of interim stroke and dementia. Conclusions— In a large community-based sample of middle-aged adults, BI predicted an increased risk of stroke and dementia independent of vascular risk factors. White matter hyperintensities portended an increased risk of stroke, amnestic mild cognitive impairment, dementia, and death independent of vascular risk factors and interim vascular events.
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WMLs are associated with incident MCI, dementia, and death.
“Similarly, WMLs have been associated with declining scores in the modified MMSE and the Digit Symbol Substitution Test,246,247 as well as with incident MCI, dementia, and death.240”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [240]
The Results sections on dementia, MCI, and mortality associate white matter hyperintensity measures with incident dementia and death. For MCI, however, the paper finds no overall association; increased risk of amnestic MCI appears only in certain subgroups, including participants aged 60 or older. The unqualified reference to incident MCI overstates that finding. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIncident cognitive impairment occurs in association with CVBI.
“Incident cognitive impairment also occurs in association with CVBI.”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [240]
The Results section, under “Association of WMHV, EXT-WMHV and BI with incident dementia and MCI,” reports that all three MRI markers were associated with incident dementia. It also says none was associated with incident MCI overall; associations with amnestic MCI appeared only in specified age or sex subgroups. The unqualified claim about incident cognitive impairment is therefore broader than the findings. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe presence of SBI more than doubles the risk of dementia and the risk of stroke.
“For example, the presence of SBI more than doubles the risk of dementia and risk of stroke.240,244,245”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [240]
The indexed Results summary reports that MRI-defined brain infarcts (BI) were associated with more than double the risk of incident stroke (HR 2.84) and dementia (HR 6.12). However, the Methods define BI by MRI appearance, not by whether the infarct was silent; the Results also include participants with prior stroke. The reported estimates therefore do not specifically establish the claim for silent brain infarcts (SBI). (LLM, conf=0.83)
Experimental — accuracy not yet measuredAge-specific definitions of extensive WMLs can be created and are useful for defining risk for VCI in a community cohort.
“Importantly, age-specific definitions of extensive WMLs can be created240 and prove useful in defining risk for VCI in a community cohort.240”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [240]
The Methods (MRI scans; page not provided) define extensive white matter hyperintensity volume using age-specific thresholds. The Results and Discussion report that this measure predicted incident dementia in a community cohort and amnestic MCI only among participants aged 60 or older. The study did not specifically establish risk for vascular cognitive impairment (VCI). (LLM, conf=0.86)
Experimental — accuracy not yet measuredMost studies suggest that CVBI measures are usually associated with non-memory-related cognitive deficits, but a number also show similar associations with memory impairment.
“Interestingly, although most studies suggest that these measures of CVBI are usually associated with non–memory-related cognitive deficits,241 a number of studies also show similar associations with memory impairment.240,242,243”
In the Rotterdam scan study, the presence of SBI at baseline doubled the risk of dementia, and similar figures were obtained in the Framingham Offspring study.
“In the Rotterdam scan study, the presence of SBI at baseline doubled the risk of dementia, 66 and similar figures were obtained in the Framingham Offspring study. 116”
From Vascular Cognitive Impairment (2017) · cites this paper as [116]
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- Authors
- Debette, S., Beiser, A., DeCarli, C., Au, R., Himali, J. J., Kelly-Hayes, M., Romero, J. R., Kase, C. S., Wolf, P. A., & Seshadri, S.
- Affiliations
- From the Department of Neurology (S.D., A.B., R.A., J.J.H., M.K.-H., J.R.R., C.S.K., P.A.W., S.S.), Boston University School of Medicine, Boston, Mass; the Framingham Heart Study (S.D., A.B., R.A., J.J.H., M.K.-H., J.R.R., C.S.K., P.A.W., S.S.) and the Department of Biostatistics (A.B., J.J.H.), Boston University School of Public Health, Boston, Mass; and the University of California at Davis (C.D.), Sacramento, Calif.
- Boston University (US)
- ORCID
- Venue
- Stroke
- Published
- 2010-04
- Volume
- 41
- Issue
- 4
- Pages
- 600-606
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC2847685
- OpenAlex
- W1968232933
- Cited by
- 508
- References
- 30
- Citations by year
- 2026: 20 · 2025: 26 · 2024: 40 · 2023: 32 · 2022: 27 · 2021: 37 · 2020: 22 · 2019: 48 · 2018: 37 · 2017: 28 · 2016: 28 · 2015: 38 · 2014: 33 · 2013: 37 · 2012: 26
- FWCI
- 17.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1)
- National Institute on Aging (P30AG010129, R01-AG-16495, K23AG038444, R01AG031287, AG031287, AG08122, AG033193, R01AG016495, R01AG033193, R01AG008122)
- National Heart, Lung, and Blood Institute (N01‐HC25195, N01-HC-025195)
- National Institute of Neurological Disorders and Stroke (R01 NS 17950, R01NS017950)
- Topics
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- white matter hyperintensities, cerebral infarction, vascular brain injury, incident stroke, dementia, mild cognitive impairment, amnestic mild cognitive impairment, mortality, middle-aged adults, community-dwelling adults, Framingham Offspring Study, MRI markers, vascular risk factors, brain MRI volumetry, cognitive aging, stroke risk factors, dementia risk factors, mortality risk factors
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cognition Disorders, Dementia, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Prospective Studies, Risk Factors, Cerebrovascular Trauma, Stroke
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