White matter hyperintensities and patterns of atrophy in early onset Alzheimer’s disease with causative gene mutations

Mao, Chenhui; Li, Jie; Huang, Xin; Dong, Liling; Liu, Caiyan; Peng, Bin; Gao, Jing

doi:10.1016/j.clineuro.2021.106552

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…The restricted distribution in the occipital region, tracts, and visual network in EOAD may reflect the dominant influence of amyloid independent of vascular risk factors, in line with one previous genetic EOAD study that reported increased WMH burden surrounding occipital region. 40 In contrast, the widespread WMH distributions in LOAD could indicate the interplay of both amyloid and vascular risk factors. This is consistent with a study focused on pre‐dementia populations, which found two components of WMHs, suggesting the existence of both vascular‐dependent and vascular‐independent manifestations of WMHs.…”

Section: Discussionmentioning

confidence: 99%

Distinct patterns of voxel‐ and connection‐based white matter hyperintensity distribution and associated factors in early‐onset and late‐onset Alzheimer's disease

Hong,

Chen,

Liu

et al. 2024

Alz & Dem Diag Ass & Dis Mo

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IntroductionThe distribution of voxel‐ and connection‐based white matter hyperintensity (WMH) patterns in early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD), as well as factors associated with these patterns, remain unclear.MethodWe analyzed the WMH distribution patterns in EOAD and LOAD at the voxel and connection levels, each compared with their age‐matched cognitively unimpaired participants. Linear regression assessed the independent effects of amyloid and vascular risk factors on WMH distribution patterns in both groups.ResultsPatients with EOAD showed increased WMH burden in the posterior region at the voxel level, and in occipital region tracts and visual network at the connection level, compared to controls. LOAD exhibited extensive involvement across various brain areas in both levels. Amyloid accumulation was associated WMH distribution in the early‐onset group, whereas the late‐onset group demonstrated associations with both amyloid and vascular risk factors.DiscussionEOAD showed posterior‐focused WMH distribution pattern, whereas LOAD was with a wider distribution. Amyloid accumulation was associated with connection‐based WMH patterns in both early‐onset and late‐onset groups, with additional independent effects of vascular risk factors in late‐onset group.Highlights Both early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) showed increased white matter hyperintensity (WMH) volume compared with their age‐matched cognitively unimpaired participants. EOAD and LOAD exhibited distinct patterns of WMH distribution, with EOAD showing a posterior‐focused pattern and LOAD displaying a wider distribution across both voxel‐ and connection‐based levels. In both EOAD and LOAD, amyloid accumulation was associated with connection‐based WMH patterns, with additional independent effects of vascular risk factors observed in LOAD.

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Section: Discussionmentioning

confidence: 99%

Distinct patterns of voxel‐ and connection‐based white matter hyperintensity distribution and associated factors in early‐onset and late‐onset Alzheimer's disease

Hong,

Chen,

Liu

et al. 2024

Alz & Dem Diag Ass & Dis Mo

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“…7 Likewise, brain MRI may be of great help when revealing white matter abnormalities which pattern is congruent with what is often observed in patients with PSEN1-pathogenic variants, namely band-shaped whitter matter hyperintensities of the subventricular areas with small foci lesions in the subcortical and juxta-cortical deep white matter (Supplemental Table 1, Supplemental Digital Content 1, http://links.lww.com/WAD/A386). 8,9 Although all the core symptoms of PSP (dysexecutive syndrome, gait disturbances with early balance impairment, ophthalmoplegia, and extrapyramidal signs) have all been separately reported in different individuals with PSEN1 mutations, their specific combination, mimicking PSP, has not been reported so far. Our case thus expands the phenotypes associated with PSEN1 pathogenic variants in a significant manner as PSP is not a clinical presentation for which a mendelian disorder is usually suspected.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, brain MRI may be of great help when revealing white matter abnormalities which pattern is congruent with what is often observed in patients with PSEN1 -pathogenic variants, namely band-shaped whitter matter hyperintensities of the subventricular areas with small foci lesions in the subcortical and juxta-cortical deep white matter (Supplemental Table 1, Supplemental Digital Content 1, http://links.lww.com/WAD/A386). 8,9…”

Section: Discussionmentioning

confidence: 99%

A New Presenilin-1 Missense Variant Associated With a Progressive Supranuclear Palsy-like Phenotype

Quentin

Nambot

Béjot

et al. 2022

Alzheimer Disease &Amp; Associated Disorders

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Early-onset forms of Alzheimer disease (AD) have been associated with pathogenic variants in the APP, PSEN1, and PSEN2 genes. Mutations in presenilin-1 (PSEN1) account for the majority of cases of autosomal dominant AD. Numerous phenotypes have been associated with PSEN1-pathogenic variants, including cerebellar ataxia and spastic paraplegia. Here, we describe a patient with early-onset AD presenting with extrapyramidal symptoms and supranuclear gaze palsy, mimicking progressive supranuclear palsy.

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Section: Introductionmentioning

confidence: 99%

“…While it has been hypothesized that the presence of WMHs in younger individuals may be associated with cognitive decline, the extent of WMHs in people with sporadic EOAD and their relationship with cognitive decline has not been evaluated in large sample studies. A case report study 9 investigated the increased burden of WMH and brain atrophy looking for causative gene mutations. While causative genes associated with WMH burden and distribution of WMH were identified, the number of participants with the mutation included in the presented analyses was only seven, raising questions about the generalizability of the results given the small sample size.…”

Section: Introductionmentioning

confidence: 99%

White matter hyperintensities are higher among early‐onset Alzheimer's disease participants than their cognitively normal and early‐onset nonAD peers: Longitudinal Early‐onset Alzheimer's Disease Study (LEADS)

Eloyan

Thangarajah

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONWe compared white matter hyperintensities (WMHs) in early‐onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early‐onset amyloid‐negative cognitively impaired (EOnonAD) groups in the Longitudinal Early‐Onset Alzheimer's Disease Study.METHODSWe investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t‐tests and analyses of covariance. Linear regression analyses were used to investigate the association between WMH and cognitive impairment and that between amyloid and tau burden.RESULTSEOAD showed greater WMHs compared with CN and EOnonAD participants across all regions with no significant differences between CN and EOnonAD groups. Greater WMHs were associated with worse cognition. Tau burden was positively associated with WMH burden in the EOAD group.DISCUSSIONEOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD.Highlights This study represents a comprehensive characterization of WMHs in sporadic EOAD. WMH volumes are associated with tau burden from positron emission tomography (PET) in EOAD, suggesting WMHs are correlated with increasing burden of AD. Greater WMH volumes are associated with worse performance on global cognitive tests. EOAD participants have higher WMH volumes compared with CN and early‐onset amyloid‐negative cognitively impaired (EOnonAD) groups across all brain regions.

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White matter hyperintensities and patterns of atrophy in early onset Alzheimer’s disease with causative gene mutations

Cited by 8 publications

References 32 publications

Distinct patterns of voxel‐ and connection‐based white matter hyperintensity distribution and associated factors in early‐onset and late‐onset Alzheimer's disease

Distinct patterns of voxel‐ and connection‐based white matter hyperintensity distribution and associated factors in early‐onset and late‐onset Alzheimer's disease

A New Presenilin-1 Missense Variant Associated With a Progressive Supranuclear Palsy-like Phenotype

White matter hyperintensities are higher among early‐onset Alzheimer's disease participants than their cognitively normal and early‐onset nonAD peers: Longitudinal Early‐onset Alzheimer's Disease Study (LEADS)

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