Keywords: Alzheimer's Disease, Alzheimer's Disease

Motivation: Preclinical stages of AD offer potential windows for intervention. Investigating individuals in this stages can yield valuable biomarkers and deepen our understanding of disease progression mechanisms.

Goal(s): We aim to investigate brain degeneration mechanisms during AD's preclinical stages and explore early diagnostic markers in gray matter and superficial white matter alterations.

Approach: This study involved 411 participants (including preclinal stages, aMCI and AD) and their diffusion and structural MRI and neuropsychological tests, to assess brain changes.

Results: Cortical atrophy in the temporal lobe may be a trigger for disease onset, while extensive SWM degeneration appears to be associated with disease progression in AD.

Impact: This study provides crucial insights into brain changes in early stages of AD. Identified imaging biomarkers are valuable for early diagnosis and interventions, and the proposed degeneration patterns enhance our understanding of AD's pathophysiology.

Keywords: Alzheimer's Disease, Brain, diffusion magnetic resonance imaging, superficial white matter

Motivation: Between-cortical connections largely depend on the superficial white matter (SWM) fibers, which are less studied in the AD continuum.

Goal(s): To determine the relationship between superficial white matter (SWM) fiber microstructure and local pathology, and the SWM's impact on cognition.

Approach:  We defined cohort groups in the early AD continuum. We quantified the microstructure of SWM fiber tracts (diffusion MRI) and the regional pathological deposition (PET). We analyzed associations between SWM fiber microstructure and regional pathologies in cortical areas connected by the tract.

Results: SWM tract microstructure is affected by pathology in the cortical regions connected by the tract, and this affects memory.

Impact: We localize pathology-affected SWM connections, assess their roles in cognition, and provide new insights into white matter abnormalities in the AD continuum.

Keywords: Alzheimer's Disease, Gray Matter, Microstructure, Cortical Column, APOE4

Motivation: Microstructural changes in cortical gray matter, occurring potentially well before cognitive decline in Alzheimer’s disease (AD), could serve as an early diagnosis biomarker.

Goal(s): We use high-resolution diffusion tensor imaging to identify such changes among AD subjects, cognitively normal but high-risk (APOE4+) subjects, and healthy controls (APOE4-).

Approach: The variation in fractional anisotropy along cortical columns was analyzed within 68 regions.

Results: 20 regions exhibited a lower variation in the high-risk group compared to the control group. The AD risks of individual high-risk subjects could be further differentiated based on similarities and differences with the AD or control groups.

Impact: Our cortical column-based analysis of high-resolution diffusion tensor imaging data can detect microstructural changes within specific cortical regions of pre-symptomatic subjects with high risk for Alzheimer’s disease, potentially providing a more definitive biomarker for its early diagnosis and treatment.

Keywords: Structural Connectivity, Brain Connectivity, Hippocampus, APOE4, Streamlines

Motivation: Microstructural changes within the hippocampus, which may occur well before cognitive decline in Alzheimer’s disease (AD), could serve as an early diagnosis biomarker in pre-symptomatic subjects.

Goal(s): We assessed differences in intra-hippocampal connectivity between cognitively normal carriers and non-carriers of the APOE4 allele, a genetic risk factor for AD.

Approach: We segmented the hippocampus into 12 subfields per hemisphere and performed fiber tractography on multi-shell diffusion tensor imaging data to determine the number of streamlines connecting each subfield pair.

Results: 22 subfield pairs had a significantly lower connectivity in the APOE4 carrier group compared to the APOE4 non-carrier group.

Impact: Our analysis shows differences in intra-hippocampal connectivity between cognitively normal subjects with and without a genetic risk factor for Alzheimer’s disease, which could potentially serve as a more definitive biomarker for its early diagnosis and treatment in pre-symptomatic subjects.

Keywords: Alzheimer's Disease, Alzheimer's Disease

Motivation: Associations between abnormal quantitative susceptibility mapping (QSM), brain atrophy, and altered brain connectome in AD remain unclear. 

Goal(s): We aim to examine imaging markers from various MRI modalities, with a focus on their spatial correlations, to enhance our understanding of AD pathology. 

Approach: By combining multi-contrast MRI techniques, our study provides new insights into the overlapping relationships among brain atrophy, altered regional QSM, and brain connectome.

Results: We observed a remarkable overlap between reduced cortical thickness and abnormal QSM in seven distinct brain regions. In AD patients, we identified specific regional correlations between cortical thickness and network topology from these overlapping brain regions.

Impact: Our study provides new insights into the complex relationships among iron accumulation, brain atrophy, and brain connectome in Alzheimer's disease.   

Keywords: Alzheimer's Disease, Alzheimer's Disease, thalamic nuclei segmentation

Motivation: The thalamus has not been investigated properly in autosomal dominant Alzheimer's disease (ADAD) despite evidence of early involvement.

Goal(s): We investigated thalamic nuclei atrophy in asymptomatic presenilin carriers vs. non-carriers in an ADAD cohort using a recently proposed multi-atlas segmentation method.

Approach: Thalamic nuclear atrophy and correlations of nuclei volumes with age, amyloid, and tau burden were
analyzed in mutation carriers vs. non-carriers in an ADAD cohort.

Results: Significant atrophy was seen in mediodorsal, pulvinar, and medial geniculate nuclei in carriers compared to non-carriers. These nuclear volumes correlated significantly with age, amyloid, and tau burden as well.

Impact: The pattern of thalamic nuclear atrophy in ADAD presenilin mutation carriers can help understand mechanisms for disease progression as well as aid in possible treatment targets.

Keywords: Alzheimer's Disease, Alzheimer's Disease, 1H MRS, BCAAs, Glutamate

Motivation: Amyloid-β and NFTs are considered hallmarks of Alzheimer’s disease (AD) though are often challenged. While branched chain amino acids (BCAA) are known to play role in AD pathogenesis, their role is underexplored. A non-invasive method to study this relation could benefit devising alternate strategies for early AD diagnosis.

Goal(s): To monitor sex-specific changes in BCAA levels and its relationship with glutamate.

Approach: Localized-¹H-MRS was performed in AD and WT mice.

Results: Significant reduction in hippocampal BCAA and glutamate levels in male AD mice were observed, while females remained unaffected. BCAA and glutamate levels shown a strong correlation suggesting their close association in AD.

Impact: Establishing a relation between BCAA metabolism and AD pathology could be beneficial for preclinical diagnosis as clear resonances of BCAA around 0.9 ppm on 1H MR spectra is achievable even at lower field strength MRI scanners.

Keywords: Software Tools, PET/MR, Amyloid

Motivation: Automated analysis of amyloid PET becomes available, however, these results have not been well analyzed on PET/MRI.

Goal(s): To compare the reference regions and VOIs associated with amyloid positivity between the software and Centiloid project on Amyloid PET/MRI.

Approach: We analyzed Amyloid PET/MRI data of 84 subjects automatically and values, SUVr, Centiloid scale were compared.

Results: The reference VOIs and VOIs associated with amyloid positivity showed good correlation between the software and Centiloid project.

Impact: The values obtained with the automated software on amyloid PET/MRI can be utilized with the other quantitative MR data, which may lead to comprehensive analysis of amyloid deposition.

Keywords: Data Processing, Alzheimer's Disease, Amyloid Related Imaging Abnormalities

Motivation: Using anti-amyloid monoclonal antibodies to treat Alzheimer’s disease (AD) can lead to ‘Amyloid-Related Imaging Abnormalities’ (ARIA), indicative of oedema (ARIA-E). ARIA-E's transient nature poses diagnostic challenges, necessitating efficient detection and monitoring, which is critical for drug development for AD.

Goal(s): This study aims to develop methods for quantifying and tracking ARIA-E across multiple longitudinal scans, including subtle manifestations.

Approach: Temporal variance and gradient maps were computed using serial ultra-rapid 3D FLAIR scans. Data-driven methods were employed to assess statistical significance of changes. 

Results:  The proposed maps highlight significant regions of change in the presence of varying levels of ARIA-E. 

Impact: This work has facilitated the tracking of statistically significant ARIA-E over multiple serial scans, which will enable further automatic detection methods. These methods may inform dose adjustment and patient safety measures, which is important as anti-amyloid monoclonal antibodies become commonplace.