Enhanced detection of cortical atrophy in Alzheimer's disease using structural MRI with anatomically constrained longitudinal registration

Abstract

Cortical atrophy is a defining feature of Alzheimer's disease (AD), often detectable before symptoms arise. In surface-based analyses, studies have commonly focused on cortical thinning while overlooking the impact of loss in surface area. To capture the impact of both cortical thinning and surface area loss, we used anatomically constrained Multimodal Surface Matching (aMSM), a recently developed tool for mapping change in surface area. We examined cortical atrophy over 2 years in cognitively normal subjects and subjects with diagnoses of stable mild cognitive impairment, mild cognitive impairment that converted to AD, and AD. Magnetic resonance imaging scans were segmented and registered to a common atlas using previously described techniques (FreeSurfer and ciftify), then longitudinally registered with aMSM.Changes in cortical thickness, surface area, and volume were mapped within each diagnostic group, and groups were compared statistically. Changes in thickness and surface area detected atrophy at similar levels of significance, though regions of atrophy somewhat differed. Furthermore, we found that surface area maps offered greater consistency across scanners (3.0 vs. 1.5 T). Comparisons to the FreeSurfer longitudinal pipeline and parcellation-based (region-of-interest) analysis suggest that aMSM may allow more robust detection of atrophy, particularly in earlier disease stages and using smaller sample sizes.

Automated High-Definition MRI Processing Routine Robustly Detects Longitudinal Morphometry Changes in Alzheimer’s Disease Patients

“…Here, we documented temporal tissue loss by more precise surface based morphometry and at a higher resolution of 360 cortical areas, which has become possible due to increased imaging quality in ADNI3 compared to previous ADNI studies ( Jack et al, 2008 ) and further developed software-aided image assessments. In line with a previous study, we found temporal areas to be differently affected by cortical thickness loss and cortical surface area loss ( Iannopollo and Garcia, 2021 ). High precision evaluation of temporal lobe atrophy is of particular importance as temporal cortex thinning is associated with episodic memory impairments ( Das et al, 2016 ) and even depression ( Fujishima et al, 2014 ) while temporal volume loss was found in healthy aging subjects ( Fjell et al, 2009 ) and may be a potential early indicator of an increased risk for developing AD later in life.…”

“…Large between-study heterogeneity of designs and methods, differences in sample characteristics and the generally larger inter-individual variability in samples of older adults make it difficult to extract general trends. To overcome those limitations, longitudinal MRI studies require enhanced neuroimaging pipelines ( Iannopollo and Garcia, 2021 ) and adequate statistical approaches. A very recent two-study comparison design longitudinal MRI study was able to show that it is possible to extract generalizable effects of brain atrophy in healthy aging people ( Jockwitz et al, 2021 ).…”

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution

“…Lifelong exposures to PM 2.5 above the current USEPA standard are associated with a significant decrease in gray matter from higher order cortical regions, commonly associated with Alzheimer's, Parkinson's and FTD in 42.7 ± 9.3 years old, healthy, college educated, Metropolitan Mexico City residents [45][46][47][48][49][50][51][52][53][54][55][56]. Significant caudate nuclei and cerebellar gray and white matter atrophy were also documented [57][58][59][60][61][62][63][64][65][66][67][68].…”

“…Hemispheric cortical significant differences documented in subjects ≤30 vs. ≥31 years old are of deep concern, as targeted cortical thickness and surface area regions involved overlap with those described in AD, PD, Lewy body disease (LBD) spectrum and FTD [45][46][47][48][51][52][53][54][79][80][81][82]. Brain MRI changes associated with early-onset Alzheimer's disease (EOAD; aged < 65 years) (A + T + N +), in Contador et al, work [51] versus 19 controls (A-T-N-) found EOAD longitudinal atrophy spread with a posterior-to-anterior gradient with hippocampus/amygdala atrophy.…”

Mode‐based morphometry: A multiscale approach to mapping human neuroanatomy

“…Spatially smoothing the data improved the performance of SBM to the point where it matched MBM for smoothing kernels with FWHM $$$ \ge 20 $$$ mm. There are no consistent heuristics for choosing a proper smoothing kernel although $$$ 20 $$$ mm is a common smoothing kernel size (Iannopollo et al, 2021). Smoothing kernels should be chosen carefully since they can impose geometric effects on the data as the kernel replaces the value at each point with a weighted average of its spatial neighbors (Henderson et al, 2022).…”