Linking white matter hyperintensities to regional cortical thinning, amyloid deposition, and synaptic density loss in Alzheimer's disease

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(6), С. 3931 - 3942

Опубликована: Апрель 22, 2024

We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid tau deposition, synaptic density in WMH-connected cortex using multimodal images.

Язык: Английский

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White matter injury, plasma Alzheimer's disease, and neurodegenerative biomarkers on cognitive decline in community‐dwelling older adults: A 10‐year longitudinal study

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION This study aimed to investigate the synergistic impact of white matter injury, Alzheimer's disease, and neurodegenerative pathology on long‐term cognitive decline dementia risk in older adults. METHODS We included 262 dementia‐free participants with baseline follow‐up interviews (2010–2021). At baseline, peak width skeletonized mean diffusivity (PSMD) was assessed from diffusion tensor imaging. Plasma phosphorylated tau 217 (p‐tau217) neurofilament light chain (NfL) were measured using a single‐molecule immune‐array assay. Cognitive function evaluated Mini‐Mental State Examination (MMSE) domain‐specific tests. RESULTS Participants high‐level PSMD, p‐tau217, NfL showed fastest MMSE (β = −0.30) highest incidence 3.54/100 person‐years. A combination model three markers demonstrated good predictive value for dementia, incorporating age, sex, education, apolipoprotein E (area under curve 0.93, 95% confidence interval 0.86, 0.99). DISCUSSION Combining co‐pathology may identify individuals high decline. Highlights Peak correlated decline, this correlation modified by plasma (p‐tau)217 (NfL). levels dementia. exhibited incident over 10‐year period.

Язык: Английский

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Choroid plexus free‐water correlates with glymphatic function in Alzheimer's disease

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(5)

Опубликована: Май 1, 2025

Abstract INTRODUCTION Free‐water imaging of the choroid plexus (CP) may improve evaluation Alzheimer's disease (AD). METHODS Our study investigated role free‐water fraction (FWf) CP in AD among 216 participants (133 Aβ+ and 83 Aβ– controls) enrolled NeuroBank‐Dementia cohort at Ruijin Hospital (RJNB‐D). The Disease Neuroimaging Initiative dataset was used for external validation. RESULTS At baseline, showed higher FWf, increased white matter hyperintensity (WMH) volume, decreased diffusion tensor image analysis along perivascular space (DTI‐ALPS). In participants, DTI‐ALPS mediated association between FWf periventricular WMH. associated with cortical tau accumulation, synaptic loss, hippocampal atrophy, cognitive performance. During follow‐up, faster than controls. DISCUSSION Elevated indicated impaired glymphatic function neurodegeneration, can be a sensitive biomarker progression. registered on ClinicalTrials.gov (NCT05623124). Highlights This found amyloid beta (Aβ)+ participants. related to function, brain burden, cognition. growth controls during follow‐up. rate exceeded that lesion accumulation serve as marker

Язык: Английский

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Cerebrovascular disease in Alzheimer's disease: Brain structure as a critical mediator of cognitive decline

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер unknown, С. 100209 - 100209

Опубликована: Май 1, 2025

Язык: Английский

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Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 10, 2024

Abstract Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis remain nonetheless scarce. Methods In study, we applied regional global bivariate latent growth curve modelling (BLGCM) to longitudinal data from 436 cognitively unimpaired participants (DELCODE cohort; median age 69.70 [IQR 65.44, 74.49] years; 52.98% female) examine extent which WMH thickness were interrelated a four-year period. Results Our findings three-fold. First, at baseline, individuals with larger volumes had lower mean thicknesses entire brain. Second, who experienced steeper thinning cingulate cortices time baseline in frontal, parietal, occipital lobes. Third, thinner tended undergo faster progression four years, particularly parietal Conclusions study suggests that could be mutually reinforcing rather than parallel, unrelated processes, become entangled before cognitive deficits are detectable. Trial Registration German Clinical Trials Register (DRKS00007966, 04/05/2015)

Язык: Английский

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Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults

Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)

Опубликована: Окт. 28, 2024

Язык: Английский

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Choroid Plexus Free-Water Correlates with Glymphatic function in Alzheimer Disease: The RJNB-D Study

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 5, 2024

The free water imaging of choroid plexus (CP) may improve the evaluation Alzheimer's disease (AD). Our study investigated role fraction (FWf) CP in AD by including 216 participants (133 Aβ + and 83 Aβ- controls) continuously enrolled NeuroBank-Dementia cohort at Ruijin Hospital (RJNB-D). At baseline, showed higher (FWf), increased white matter hyperintensity (WMH) volume, decreased diffusion tensor image analysis perivascular space (DTI-ALPS). In participants, DTI-ALPS mediated association between FWf periventricular WMH. was associated with cortical Tau accumulation, synaptic loss, hippocampal atrophy, cognitive performance. During follow-up, faster than controls. findings suggest that elevated indicate impaired glymphatic function neurodegeneration, potentially serving as a valuable biomarker for progression.

Язык: Английский

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Periventricular and Deep White Matter Hyperintensity Thresholds in Aging: Exponential Progression, Cognitive Decline, and Neuroanatomic Atrophy

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 4, 2024

Abstract White matter hyperintensities (WMH), which are brain lesions associated with cerebral small vessel disease and aging, signify fiber loss pruning. Analysis of T2-FLAIR MRI data from the NACC cohort, including cognitively normal (CN), impaired (CI), Alzheimer’s (CI-AD) subjects, revealed that a significant subset participants, even those classified as CN, harbor substantial periventricular (PVWMH) deep white hyperintensity (DWMH) loads, while others displayed minimal or no PVWMH DWMH, across ages 50-94 years. In this study, we quantified thresholds progression kinetics DWMH their impact on cognitive performance neuroanatomic changes in aging cohort (NCN = 521, NCI 146, NCI-AD 319). Our findings explore loads global specific domains to determine whether impairments directly induced by mediated through distinct structures. PV higher CI CI-AD subjects compared CN but not discriminative CI-AD. The volume age indicate an exponential rate increase, escalating approximately twice fast particularly around inflection point at 61 years age. load presents increased probability occurrence frontal horn occipital is diffused accumulates significantly later than observed for PVWMH. Multivariate regression suggested effect (p<0.01) Trail making tests (TMTs)-A B (executive function), animal naming (semantic memory), effects load. Indeed, beyond threshold >2.3 mL, deficits TMTs were without A mL >2.75 attention & working memory (Digit Span Tests), semantic memory. Noticeably, atrophy cortex, nucleus accumbens, RMFG, precentral, paracentral gyrus was loss. Furthermore, mediation model employing volumes mediator, predictor outcome contributes TMT-B precentral (64%), accumbens (39%), (32%), rostral middle (31%), lingual (30%), each contributing proportions, alongside direct effect. did emerge (direct indirect) deficits. Further, mediations other indicative involvement Global cognition like MMSE affected only accumulation (>6 ml). Highlights escalates exponentially linked executive function, atrophy; less impactful. PVWMH, affects decline via unique set structural AD subjects. Overview

Язык: Английский

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Choroid Plexus Free-Water Correlates with Glymphatic function and Neurodegeneration in Alzheimer’s Disease

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Free-water imaging of the choroid plexus (CP) is an index revealing components CP, which may improve evaluation Alzheimer's disease (AD). Our study evaluated free water fraction (FWf) CP in 216 participants (133 Aβ+ and 83 Aβ- controls) continuously enrolled Ruijin NeuroBank Disease Dementia (RJNB-D) cohort. The ADNI dataset was used for external validation. Assessments AD neurodegeneration included Aβ-PET, Tau-PET, synaptic vesicle glycoprotein 2A-PET scans, blood biomarkers glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), neurogranin (NRGN), Tumor Necrosis Factor-α (TNF-α). FWf diffusion tensor image analysis along perivascular space (DTI-ALPS) were independently associated with Aβ positivity both RJNB-D datasets. Within group, negative correlation between DTI-ALPS validated by two Furthermore, we observed a partial mediation effect periventricular white matter hyperintensity (pWMH). Elevated linked to worse Mini-Mental State Examination, increased Tau accumulation, reduced density, elevated levels NFL, GFAP, NRGN, TNF-α. Longitudinally, faster than controls (time × group interaction p = 0.046). growth reduction (ρ -0.42, 0.006), rate surpassed that pWMH, Tau, GFAP. Overall, our findings suggest that elevated indicates impaired glymphatic function neurodegeneration. Trial registration registered on ClinicalTrials.gov (NCT05623124).

Язык: Английский

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Family history of Alzheimer’s disease, but not APOE, is associated with brain volume in cognitively healthy older adults

Journal of Alzheimer s Disease Reports, Год журнала: 2024, Номер 8(1), С. 1493 - 1501

Опубликована: Март 1, 2024

Background Dementias, particularly Alzheimer's disease (AD), represent a global public health concern. Although its exact cause remains unknown, neuroanatomical and cognitive changes are crucial. Objective Finding biomarkers helping the early diagnosis of AD is crucial for developing interventions. Methods In sample 402 cognitively healthy adults some them with risk factors (family history APOE ε4 carriers), we examined relationship between genotype other aspects family variables brain volumetrics using magnetic resonance imaging (MRI). Results Key findings suggest that may be associated specific markers, such as left hippocampal size white matter integrity. However, no links were observed performance, furthermore additional analyses on showed significant differences in any aspect. Conclusions This study reveals importance monitoring MRI subjects AD, to assess volumetric use this information stratify participants future clinical trials.

Язык: Английский

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