Quantitative T1 mapping (qT1) is a magnetic resonance imaging (MRI) biomarker of brain microstructural changes; however, its application in Alzheimer disease (AD) remains limited. We compared cortico-limbic qT1 values between patients with AD and healthy controls (HCs) and examined their relationship with amyloid burden measured by amyloid-positron emission tomography (PET). We retrospectively identified subjects with mild cognitive impairment due to AD and HCs who underwent 3-T MRI, including a compressed-sensing MP2RAGE sequence, generating three-dimensional T1-weighted images and qT1 maps. Amyloid-PET was available for 16 patients. Hippocampal qT1 and volume were compared between groups, adjusting for age and sex; analyses were repeated after stratifying patients by Mini-Mental State Examination (MMSE). Voxel-wise group comparison was performed using SPM 12. The qT1-standardized uptake value ratio (SUVr) association was assessed with a linear mixed-effects model applied to voxel-level data, accounting for partial volume effects. Thirty-three AD subjects, aged 69.3 ± 8.2 years (mean ± standard deviation), 18 females, and 22 HCs aged 70.5 ± 13.3 years, 15 females, were evaluated. Regional hippocampal qT1 was higher in AD (1,398 ± 53.0 ms versus 1,349 ± 53.4 ms; p = 0.002), without difference across cognitive subgroups stratified by MMSE. AD subjects exhibited increased qT1 in mesial temporal gray matter and temporo-parieto-occipital cortices (1,448 ± 55.7 ms versus 1,344 ± 51.6 ms; p < 0.001). Voxel-level modelling revealed a positive association between qT1 and amyloid-PET SUVr (p < 0.001; d = 0.223). qT1 mapping can be sensitive to changes related to brain amyloidosis, supporting its role as a promising, noninvasive imaging biomarker in AD. Question Can qT1 mapping detect AD-related microstructural changes in the cortico-limbic gray matter? Findings Participants with AD showed increased cortico-limbic qT1 values. A subtle yet consistent positive association was observed between cortical qT1 values and amyloid-PET SUVr. Relevance statement qT1 mapping captures microstructural tissue alterations related to amyloid pathology in Alzheimer’s disease, supporting its role as a potential non-invasive imaging biomarker in this condition.
L. Gualco, Noemi Montobbio, M. Losa et al.· European Radiology Experimen...· 0 citations
Abstract INTRODUCTION Tau positron emission tomography (PET) probes Alzheimer's disease (AD) severity via regional tau spread but is not widely available. We tested whether multiregion structural magnetic resonance imaging (MRI) could approximate individual tau burden. METHODS We studied 378 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with mild cognitive impairment (MCI)‐AD or AD dementia with paired T1‐MRI and [18F]flortaucipir tau‐PET (≤6 months apart). Regional cortical thickness and volume were extracted with FreeSurfer. Principal component analysis and multivariable linear regression yielded MRI signatures of tau‐PET standardized uptake value ratio (SUVR) in Braak composite regions (I, III–IV, V–VI), a meta‐temporal region of interest (ROI), and a global neocortical meta‐ROI. Performance and high/low tau classification were evaluated by leave‐one‐out cross‐validation against published cut‐offs. RESULTS MRI signatures were significantly associated with tau‐PET burden across all regions (p < 0.001). High‐versus‐low tau discrimination varied: AUC ≈ 0.70 in Braak I, ≈0.89 in Braak V–VI, and ≈0.90 globally. Discussion Here we provide proof‐of‐concept evidence that multiregion T1‐MRI patterns can inform on tau‐PET burden in AD and may support approximate tau staging when tau‐PET is unavailable, especially in subjects with more advanced tau burden.
Martina Pulze, S. Garbarino, L. Lorenzini et al.· Alzheimer's & Dementia· 0 citations
BackgroundThe choroid plexus (CP) is involved in cerebrospinal fluid production, immune surveillance, and brain fluid homeostasis. CP enlargement has been linked to neuroinflammation, glymphatic dysfunction, and white matter lesion (WML) burden, but the mechanisms underlying these associations remain uncertain.ObjectiveTo investigate the relationships among CP volume, glymphatic function estimated using diffusion tensor imaging along the perivascular space (DTI-ALPS), WML burden, and global cognitive performance in individuals with suspected neurodegenerative conditions, and to assess whether DTI-ALPS mediates the association between CP enlargement and white matter damage.MethodsWe retrospectively analyzed 104 participants, including 63 individuals with neurodegenerative conditions and 41 without neurodegeneration, who underwent multimodal MRI with 3D-T1-weighted, 3D-FLAIR, and diffusion-weighted sequences. CP volume was segmented using ASCHOPLEX and normalized to total intracranial volume. DTI-ALPS indices were derived from diffusion imaging, WML burden was quantified by automated segmentation, and global cognition was assessed using the Mini-Mental State Examination. Associations were tested using linear and quantile regression models. Mediation analysis evaluated indirect effects through DTI-ALPS.ResultsGreater CP volume was associated with lower DTI-ALPS values and higher WML burden. DTI-ALPS partially mediated the relationship between CP volume and WML burden, although the magnitude of mediation was modest. No significant mediation effect was observed for global cognitive performance. DTI-ALPS also showed strong associations with white matter integrity metrics, suggesting possible sensitivity to non-glymphatic microstructural changes.ConclusionsCP enlargement is associated with reduced DTI-ALPS and greater WML burden, but the contribution of glymphatic impairment remains uncertain. Alternative mechanisms, including neuroinflammation, blood-brain barrier dysfunction, and white matter microstructural damage, may contribute to these findings.
L. Sacchi, Valentina Veronesi, Giorgio Bocca et al.· Journal of Alzheimer's Disea...· 0 citations
Introduction Cognitive reserve (CR) has been proposed as a key factor explaining inter-individual variability in cognitive performance despite comparable neuropathology. However, its role across the Alzheimer’s disease (AD) continuum remains unclear. This study investigates stage-dependent effects of CR on the relationship between memory performance and brain structural network integrity across healthy subjects (HS), individuals with subjective cognitive decline (SCD), and patients with amnestic mild cognitive impairment (a-MCI), and AD dementia. Materials and methods A total of 209 participants underwent a comprehensive neuropsychological assessment and 3T MRI. Source-based morphometry identified three grey matter structural covariance networks, involving orbitofrontal-temporal-insular regions (OTIN), precuneus-posterior cingulate cortex (PreCiN), and cingulate-hippocampal regions (CHiN). A composite memory score was derived using factor analysis. Regression and moderation models examined the predictive and moderating effects of CR (operationalized as years of education) and network integrity on cognitive performance within each group. Results OTIN and PreCiN showed progressive structural vulnerability along the AD continuum, whereas CHiN showed no significant between-group differences. Across the sample, OTIN and PreCiN integrity significantly predicted cognitive performance. In HS, CR was positively associated with memory performance independently of structural network integrity, suggesting an additive protective role of cognitive reserve in healthy aging. In the SCD group, CR was not directly associated with memory, and only limited effects emerged, indicating early alterations in reserve-related processes. In a-MCI patients, the significant interaction between CR and OTIN integrity suggested patterns consistent with compensatory mechanisms, with higher reserve supporting memory despite structural decline. In AD patients, CR and its interaction with structural networks no longer predicted cognitive outcomes, suggesting a possible exhaustion of reserve capacity. Conclusion These findings support a stage-dependent model of CR, characterized by an additive protective role in healthy aging, patterns consistent with compensatory recruitment in early cognitive decline, and a possible loss of reserve effectiveness beyond a critical neuropathological threshold. Distinct network vulnerabilities and stage-specific CR effects highlight potential windows for reserve-enhancing interventions across the AD continuum.
Laura Serra, Sabrina Bonarota, Giulia Caruso et al.· Frontiers in Human Neuroscie...· 0 citations
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