Dataset Information

Cortical microstructural associations with CSF amyloid and pTau.

ABSTRACT: Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer's disease (AD) pathology. Few studies have evaluated multi-shell dMRI models, such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI, in cortical gray matter where many of the earliest histopathological changes occur in AD. Here, we investigated the relationship between CSF pTau₁₈₁ and Aβ_1-42 burden and regional cortical NODDI and MAP-MRI indices in 46 cognitively unimpaired individuals, 18 with mild cognitive impairment, and two with dementia (mean age: 71.8±6.2 years) from the Alzheimer's Disease Neuroimaging Initiative. We compared findings to more conventional cortical thickness measures. Lower CSF Aβ_1-42 and higher pTau₁₈₁ were associated with cortical dMRI measures reflecting less hindered or restricted diffusion and greater diffusivity. Cortical dMRI measures were more widely associated with Aβ_1-42 than pTau₁₈₁ and better distinguished Aβ+ from Aβ- participants than pTau+/- participants. Conversely, cortical thickness was more tightly linked with pTau₁₈₁. dMRI associations mediated the relationship between CSF markers and delayed logical memory performance, commonly impaired in early AD. dMRI measures sensitive to early AD pathogenesis and microstructural damage may elucidate mechanisms underlying cognitive decline.

SUBMITTER: Nir TM

PROVIDER: S-EPMC10120803 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Cortical microstructural associations with CSF amyloid and pTau.

Nir Talia M TM Villalón-Reina Julio E JE Salminen Lauren L Haddad Elizabeth E Zheng Hong H Thomopoulos Sophia I SI Jack Clifford R CR Weiner Michael W MW Thompson Paul M PM Jahanshad Neda N

medRxiv : the preprint server for health sciences 20230411

Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer's disease (AD) pathology. Few studies have evaluated multi-shell dMRI models, such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI, in cortical gray matter where many of the earliest histopathological changes occur in AD. Here, we investigated the relationship between CSF pTau<sub>181</sub> and ...[more]

PMID: 37090601

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Project description:White matter hyperintensities (WMHs) have a heterogeneous aetiology, associated with both vascular risk factors and amyloidosis due to Alzheimer's disease. While spatial distribution of both amyloid and WM lesions carry important information for the underlying pathogenic mechanisms, the regional relationship between these two pathologies and their joint contribution to early cognitive deterioration remains largely unexplored. We included 662 non-demented participants from three Amyloid Imaging to Prevent Alzheimer's disease (AMYPAD)-affiliated cohorts: EPAD-LCS (N = 176), ALFA+ (N = 310), and EMIF-AD PreclinAD Twin60++ (N = 176). Using PET imaging, cortical amyloid burden was assessed regionally within early accumulating regions (medial orbitofrontal, precuneus, and cuneus) and globally, using the Centiloid method. Regional WMH volume was computed using Bayesian Model Selection. Global associations between WMH, amyloid, and cardiovascular risk scores (Framingham and CAIDE) were assessed using linear models. Partial least square (PLS) regression was used to identify regional associations. Models were adjusted for age, sex, and APOE-e4 status. Individual PLS scores were then related to cognitive performance in 4 domains (attention, memory, executive functioning, and language). While no significant global association was found, the PLS model yielded two components of interest. In the first PLS component, a fronto-parietal WMH pattern was associated with medial orbitofrontal-precuneal amyloid, vascular risk, and age. Component 2 showed a posterior WMH pattern associated with precuneus-cuneus amyloid, less related to age or vascular risk. Component 1 was associated with lower performance in all cognitive domains, while component 2 only with worse memory. In a large pre-dementia population, we observed two distinct patterns of regional associations between WMH and amyloid burden, and demonstrated their joint influence on cognitive processes. These two components could reflect the existence of vascular-dependent and -independent manifestations of WMH-amyloid regional association that might be related to distinct primary pathophysiology.

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Dataset Information

Cortical microstructural associations with CSF amyloid and pTau.

Publications

Cortical microstructural associations with CSF amyloid and pTau.

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