Baseline MRI atrophy predicts 2-year cognitive outcomes in early-onset Alzheimer’s disease

Contador, José Luiz; Pérez‐Millan, Agnès; Guillén, Núria; Tort‐Merino, Adrià; Balasa, Mircea; Falgàs, Neus; Olives, Jaume; Castellví, Magdalena; Borrego‐Écija, Sergi; Bosch, Beatríz; Fernández‐Villullas, Guadalupe; Ramos‐Campoy, Oscar; Antonell, Anna; Bargalló, Núria; Sánchez‐Valle, Raquel; Sala‐Llonch, Roser; Lladó, Albert

doi:10.1007/s00415-021-10851-9

Cited by 7 publications

(10 citation statements)

References 38 publications

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“…Voxel-based MRI analysis showed no significant difference in cortical atrophy between EOAD and LOAD in our study. However, most previous ones have reported that cortical atrophy is more extensive in EOAD, although the patterns of atrophy varied 10,22,38,39 . Early-onset AD typically showed more parietal involvement, whereas LOAD was associated with more hippocampus atrophy.…”

Section: Discussionmentioning

confidence: 80%

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Characterizing Early-Onset Alzheimer Disease Using Multiprobe PET/MRI

Xu¹,

Ruan²,

Liu³

et al. 2023

Clin Nucl Med

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PurposeEarly-onset Alzheimer disease (EOAD) is rare, highly heterogeneous, and associated with poor prognosis. This AT(N) Framework–based study aimed to compare multiprobe PET/MRI findings between EOAD and late-onset Alzheimer disease (LOAD) patients and explore potential imaging biomarkers for characterizing EOAD.MethodsPatients with AD who underwent PET/MRI in our PET center were retrospectively reviewed and grouped according to the age at disease onset: EOAD, younger than 60 years; and LOAD, 60 years or older. Clinical characteristics were recorded. All study patients had positive β-amyloid PET imaging; some patients also underwent 18F-FDG and 18F-florzolotau PET. Imaging of the EOAD and LOAD groups was compared using region-of-interest and voxel-based analysis. Correlation of onset age and regional SUV ratios were also evaluated.ResultsOne hundred thirty-three patients were analyzed (75 EOAD and 58 LOAD patients). Sex (P = 0.515) and education (P = 0.412) did not significantly differ between groups. Mini-Mental State Examination score was significantly lower in the EOAD group (14.32 ± 6.74 vs 18.67 ± 7.20, P = 0.004). β-Amyloid deposition did not significantly differ between groups. Glucose metabolism in the frontal, parietal, precuneus, temporal, occipital lobe, and supramarginal and angular gyri was significantly lower in the EOAD group (n = 49) than in the LOAD group (n = 44). In voxel-based morphometry analysis, right posterior cingulate/precuneus atrophy was more obvious in the EOAD (P < 0.001), although no voxel survived family-wise error correction. Tau deposition in the precuneus, parietal lobe, and angular, supramarginal, and right middle frontal gyri was significantly higher in the EOAD group (n = 18) than in the LOAD group (n = 13).ConclusionsMultiprobe PET/MRI showed that tau burden and neuronal damage are more severe in EOAD than in LOAD. Multiprobe PET/MRI may be useful to assess the pathologic characteristics of EOAD.

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Section: Discussionmentioning

confidence: 80%

“…However, most previous ones have reported that cortical atrophy is more extensive in EOAD, although the patterns of atrophy varied. 10,22,38,39 Early-onset AD typically showed more parietal involvement, whereas LOAD was associated with more hippocampus atrophy. The inconsistency might be partly due to heterogeneity in study design and data.…”

Section: Discussionmentioning

confidence: 99%

Characterizing Early-Onset Alzheimer Disease Using Multiprobe PET/MRI

Xu¹,

Ruan²,

Liu³

et al. 2023

Clin Nucl Med

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“…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].…”

Section: Discussionmentioning

confidence: 96%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Calderón‐Garcidueñas

Hernández-Luna²,

Mukherjee

et al. 2022

Toxics

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Exposures to fine particulate matter PM2.5 are associated with Alzheimer’s, Parkinson’s (AD, PD) and TDP-43 pathology in young Metropolitan Mexico City (MMC) residents. High-resolution structural T1-weighted brain MRI and/or Montreal Cognitive Assessment (MoCA) data were examined in 302 volunteers age 32.7 ± 6.0 years old. We used multivariate linear regressions to examine cortical surface area and thickness, subcortical and cerebellar volumes and MoCA in ≤30 vs. ≥31 years old. MMC residents exposed to PM2.5 ~ 30.9 µg/m3. Robust hemispheric differences in frontal and temporal lobes, caudate and cerebellar gray and white matter and strong associations between MoCA total and index scores and caudate bilateral volumes, frontotemporal and cerebellar volumetric changes were documented. MoCA LIS scores are affected early and low pollution controls ≥ 31 years old have higher MoCA vs. MMC counterparts (p ≤ 0.0001). Residency in MMC is associated with cognitive impairment and overlapping targeted patterns of brain atrophy described for AD, PD and Fronto-Temporal Dementia (FTD). MMC children and young adult longitudinal studies are urgently needed to define brain development impact, cognitive impairment and brain atrophy related to air pollution. Identification of early AD, PD and FTD biomarkers and reductions on PM2.5 emissions, including poorly regulated heavy-duty diesel vehicles, should be prioritized to protect 21.8 million highly exposed MMC urbanites.

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“…Women (65 years or older) are at a greater risk of developing late-onset AD (LOAD) [ 6 – 8 ]. Cross-sectional and longitudinal studies have revealed faster cognitive decline [ 9 ] and widespread atrophy in brain areas in early-onset AD (EOAD) [ 10 – 17 ]. Women EOAD subjects displayed greater cognitive impairment and atrophy than men [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Sex difference in evolution of cognitive decline: studies on mouse model and the Dominantly Inherited Alzheimer Network cohort

Kommaddi

Verma²,

Muñiz‐Terrera³

et al. 2023

Transl Psychiatry

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Women carry a higher burden of Alzheimer’s disease (AD) compared to men, which is not accounted entirely by differences in lifespan. To identify the mechanisms underlying this effect, we investigated sex-specific differences in the progression of familial AD in humans and in APPswe/PS1ΔE9 mice. Activity dependent protein translation and associative learning and memory deficits were examined in APPswe/PS1ΔE9 mice and wild-type mice. As a human comparator group, progression of cognitive dysfunction was assessed in mutation carriers and non-carriers from DIAN (Dominantly Inherited Alzheimer Network) cohort. Female APPswe/PS1ΔE9 mice did not show recall deficits after contextual fear conditioning until 8 months of age. Further, activity dependent protein translation and Akt1-mTOR signaling at the synapse were impaired in male but not in female mice until 8 months of age. Ovariectomized APPswe/PS1ΔE9 mice displayed recall deficits at 4 months of age and these were sustained until 8 months of age. Moreover, activity dependent protein translation was also impaired in 4 months old ovariectomized APPswe/PS1ΔE9 mice compared with sham female APPswe/PS1ΔE9 mice. Progression of memory impairment differed between men and women in the DIAN cohort as analyzed using linear mixed effects model, wherein men showed steeper cognitive decline irrespective of the age of entry in the study, while women showed significantly greater performance and slower decline in immediate recall (LOGIMEM) and delayed recall (MEMUNITS) than men. However, when the performance of men and women in several cognitive tasks (such as Wechsler’s logical memory) are compared with the estimated year from expected symptom onset (EYO) we found no significant differences between men and women. We conclude that in familial AD patients and mouse models, females are protected, and the onset of disease is delayed as long as estrogen levels are intact.

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Baseline MRI atrophy predicts 2-year cognitive outcomes in early-onset Alzheimer’s disease

Cited by 7 publications

References 38 publications

Characterizing Early-Onset Alzheimer Disease Using Multiprobe PET/MRI

Characterizing Early-Onset Alzheimer Disease Using Multiprobe PET/MRI

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

Sex difference in evolution of cognitive decline: studies on mouse model and the Dominantly Inherited Alzheimer Network cohort

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