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. 2018 Nov;84(5):705-716.
doi: 10.1002/ana.25346. Epub 2018 Oct 25.

Development of a cerebrovascular magnetic resonance imaging biomarker for cognitive aging

Affiliations

Development of a cerebrovascular magnetic resonance imaging biomarker for cognitive aging

Prashanthi Vemuri et al. Ann Neurol. 2018 Nov.

Abstract

Objective: Recent availability of amyloid and tau positron emission tomography (PET) has provided us with a unique opportunity to measure the association of systemic vascular health with brain health after accounting for the impact of Alzheimer disease (AD) pathologies. We wanted to quantify early cerebrovascular health-related magnetic resonance imaging brain measures (structure, perfusion, microstructural integrity) and evaluate their utility as a biomarker for cerebrovascular health.

Methods: We used 2 independent samples (discovery, n = 390; validation, n = 1,035) of individuals, aged ≥ 60 years, along the cognitive continuum with imaging from the population-based sample of Mayo Clinic Study of Aging. We ascertained vascular health by summing up recently existing cardiovascular and metabolic conditions (CMC) from health care records (hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke). Using multiple regression models, we quantified associations between CMC and brain health after accounting for age, sex, education/occupation, and AD burden (from amyloid and tau PET).

Results: Systemic vascular health was associated with medial temporal lobe thinning, widespread cerebral hypoperfusion, and loss of microstructural integrity in several white matter tracts including the corpus callosum and fornix. Further investigations suggested that microstructural integrity of the genu of the corpus callosum was suitable for assessing prodromal cerebrovascular health, had similar distributions in the discovery and independent validation datasets, and predicted cognitive performance above and beyond amyloid deposition.

Interpretation: Systemic vascular health has significant impact on brain structure and function. Quantifying prodromal cerebrovascular health-related brain measures that are independent of AD pathology-related changes has great utility for cognitive aging. Ann Neurol 2018;84:713-724.

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Figures

Figure 1
Figure 1
The association of vascular health with thickness (left panel) measured using structural magnetic resonance imaging (sMRI) and perfusion measured using arterial spin labeling (ASL) (right panel) after accounting for age, sex, education/occupation, global amyloid, and composite tau burden. Regions with p < 0.05 are shown in green. Ant = anterior; CMC = cardiovascular and metabolic conditions; Inf = inferior; Med = medial; Oper = operculum; Orb = orbital; Post = posterior; Sup = superior; Supp = Supplementary; Tri = triangularis.
Figure 2
Figure 2
The association of vascular health with fractional anisotropy (FA; left panel) and mean diffusivity (MD; right panel) measured using diffusion tensor imaging (DTI) after accounting for age, sex, education/occupation, global amyloid, and composite tau burden. Regions with p < 0.05 are shown in green and p < 0.001 are shown in red. Cap. = capsule; CMC = cardiovascular and metabolic conditions; Fasc. = fasciculus; WM = white matter.
Figure 3
Figure 3
Images showing the association of vascular health with (A) structure, (B) perfusion, (C) fractional anisotropy, and (D) mean diffusivity measured using diffusion tensor imaging after accounting for age, sex, education/occupation, global amyloid, and composite tau burden (significant at p < 0.05).
Figure 4
Figure 4
Bagplots (2‐dimensional boxplots) showing the joint distribution of fractional anisotropy (FA) in the genu of the corpus callosum and amyloid. The central asterisk marks the 2‐dimensional median. Fifty percent of the data lie in the dark blue polygon (bag). The bag is expanded by a factor of 3 to form the light blue polygon. Points outside this light blue polygon are considered outliers. FA and amyloid, in both the discovery and validation datasets, had similar variability, with ranges covering about 6 standard deviations.
Figure 5
Figure 5
(Left) Contour plot showing predicted cognition given fractional anisotropy (FA) and amyloid. The lines on the contour plot are predicted global cognitive z scores for an 80‐year‐old man for the mean education/occupation score (12.7) and mean cycle number (4.5). The predicted z score lines cover a range from a high of 0 (mean) to a low of −1.5 (1.5 standard deviations below the mean). The green diamonds are observed values, with larger sizes indicating higher observed z scores. (Right) The predicted cognition plotted by age for a given FA and amyloid level. The lines in the plot on the right are predictions for a male participant with the same characteristics as above. The solid black line shows the prediction for both FA and amyloid at their mean values. The additional lines are after FA and/or amyloid move by 1 standard deviation in the “bad” direction.

References

    1. Kivipelto M, Ngandu T, Fratiglioni L, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005;62:1556–1560. - PubMed
    1. Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013;12:483–497. - PMC - PubMed
    1. Knopman DS, Penman AD, Catellier DJ, et al. Vascular risk factors and longitudinal changes on brain MRI: the ARIC study. Neurology 2011;76:1879–1885. - PMC - PubMed
    1. Carmelli D, Swan GE, Reed T, et al. Midlife cardiovascular risk factors and brain morphology in identical older male twins. Neurology 1999;52:1119–1124. - PubMed
    1. DeCarli C, Miller BL, Swan GE, et al. Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study. Arch Neurol 2001;58:643–647. - PubMed

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