Age‐dependent amyloid deposition is associated with white matter alterations in cognitively normal adults during the adult life span

Caballero, Miguel Ángel Araque; Song, Zhuang; Rubinski, Anna; Duering, Marco; Dichgans, Martin; Park, Denise C.; Ewers, Michael

doi:10.1002/alz.12062

Cited by 37 publications

(32 citation statements)

References 81 publications

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“…Because the DIAN sample also included asymptomatic mutation carriers up to 15 years before estimated symptom onset, another explanation is that the association between Aβ and diffusion measures is strongest in early, preclinical AD, before Aβ reaches its plateau level. This view is supported by a recent study demonstrating an association between Aβ and diffusion measures over the adult lifespan in cognitively healthy participants 36 . Conversely, a ceiling effect might hamper the detection of associations with Aβ in later disease stages.…”

Section: Discussionmentioning

confidence: 64%

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

Finsterwalder

Vlegels

Gesierich

et al. 2020

Alzheimer's & Dementia

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* Data used in preparation of this article were obtained from the Dominantly Inherited Alzheimer Network (DIAN) database, the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) database, and the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within DIAN, DELCODE, and ADNI contributed to the design and implementation of the respective studies and/or provided data but did not participate in analysis or writing of this report. A complete listing of the DIAN consortium, the DELCODE study group, and ADNI investigators can be found in the Supplement (DIAN and DELCODE) and at http://adni.loni.usc.edu/wp-content/uploads/ how_to_apply/ADNI_Acknowledgement_List. pdf (ADNI). Sofia Finsterwalder and Naomi Vlegels both contributed equally to the study.

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Section: Discussionmentioning

confidence: 64%

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

Finsterwalder

Vlegels

Gesierich

et al. 2020

Alzheimer's & Dementia

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“…Findings across these independent cohort studies provide convergent support for the involvement of periventricular posterior brain regions in the association between Aβ deposition and regional WMH, which is not seen for tau burden. Similarly, a recent study demonstrated an age-dependent increase in posterior WM alterations (as assessed by mean diffusivity and WMH) in individuals with abnormal Aβ deposition across the life span [21].…”

Section: Introductionmentioning

confidence: 70%

Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer’s disease

et al. 2021

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Background White matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. Methods In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. Results There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. Conclusions This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.

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“… 1–3 Diffusion MRI is a versatile method that allows us to study these WM microstructural details. Previous findings based on diffusion tensor imaging (DTI) revealed reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in association with amyloid deposition, a hallmark of Alzheimer’s disease, 4 and cerebrovascular disease. 5 …”

Section: Introductionmentioning

confidence: 99%

Diffusion models reveal white matter microstructural changes with ageing, pathology and cognition

Raghavan

Reid

Przybelski

et al. 2021

Brain Communications

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White matter microstructure undergoes progressive changes during the lifespan, but the neurobiological underpinnings related to aging and disease remains unclear. We used an advanced diffusion MRI, Neurite Orientation Dispersion and Density Imaging (NODDI), to investigate the microstructural alterations due to demographics, common age-related pathological processes (amyloid, tau, and white matter hyperintensities), and cognition. We also compared NODDI findings to the older Diffusion Tensor Imaging model-based findings. 328 participants (264 cognitively unimpaired, 57 mild cognitive impairment, and 7 dementia with a mean age of 68.3 ±13.1 years) from the Mayo Clinic Study of Aging with multi-shell diffusion imaging, fluid attenuated inversion recovery MRI as well as amyloid and tau PET scans were included in this study. White matter tract level diffusion measures were calculated from Diffusion Tensor Imaging and NODDI. Pearson correlation and multiple linear regression analyses were performed with diffusion measures as the outcome and age, sex, education/occupation, white matter hyperintensities, amyloid, and tau as predictors. Analyses were also performed with each diffusion MRI measure as a predictor of cognitive outcomes. Age and white matter hyperintensities were the strongest predictors of all white matter diffusion measures with low associations with amyloid and tau. However, neurite density decrease from NODDI was observed with amyloidosis specifically in the temporal lobes. White matter integrity (mean diffusivity and free water) in the corpus callosum showed the greatest associations with cognitive measures. All diffusion measures provided information about white matter aging and white matter changes due to age-related pathological processes and were associated with cognition. NODDI and Diffusion Tensor Imaging are two different diffusion models that provide distinct information about variation in white matter microstructural integrity. NODDI provides additional information about synaptic density, organization, and free water content which may aid in providing mechanistic insights into disease progression.

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Age‐dependent amyloid deposition is associated with white matter alterations in cognitively normal adults during the adult life span

Cited by 37 publications

References 81 publications

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer’s disease

Diffusion models reveal white matter microstructural changes with ageing, pathology and cognition

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