The POINTER Imaging baseline cohort: Associations between multimodal neuroimaging biomarkers, cardiovascular health, and cognition DOI Creative Commons
Theresa M. Harrison, Tyler J. Ward,

Jacinda Taggett

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 6, 2024

Abstract INTRODUCTION The U.S. Study to Protect Brain Health Through Lifestyle Intervention Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of POINTER Imaging ancillary study. METHODS Participants underwent health assessments neuroimaging with multimodal positron emission tomography (PET) (beta‐amyloid [Aβ] tau) magnetic resonance imaging (MRI). Framingham score (FRS) was used quantify cardiovascular disease (CVD) risk. RESULTS A total 1052 participants (31% from underrepresented ethnoracial groups) were enrolled. Compared Aβ−, Aβ+ (29%) older, had higher apolipoprotein E ( APOE ) ε4 carriage rate white matter hyperintensity volume, greater temporal tau. FRS related MRI measures, but not AD biomarkers. tau independent effects on cognition. DISCUSSION In this heterogenous, at‐risk cohort, CVD more abnormal brain structure poorer cognition, representing a putative non‐AD (Alzheimer's disease) pathway injury decline. Highlights cohort enriched poor collected unique, Amyloid burden age, carriage, measures progression Associations between amyloid tau, relatively weak pathology independently memory

Language: Английский

APOE4 impact on soluble and insoluble tau pathology is mostly influenced by amyloid-beta DOI Creative Commons
Claudia Cicognola, Gemma Salvadó, Ruben Smith

et al.

Brain, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Abstract The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). While strongly associated with amyloid-beta (Aβ), its relationship tau accumulation less understood. Studies evaluating role of on showed conflicting results, particularly regarding independence these associations from Aβ load. In this study, we examined three independent longitudinal cohorts (BioFINDER-1, BioFINDER-2 and WRAP) in which participants had cross-sectional measures tangles (tau-PET; temporal meta-ROI entorhinal) or soluble p-tau (p-tau217), Aβ-PET APOE genotype. study included a total 1370 cognitively unimpaired (CU) 449 mild cognitive impairment (MCI) subjects, followed longitudinally tau-PET p-tau217. carriers accounted 40.2-50% cohorts. Different linear regressions (cross-sectional) mixed-effect models (longitudinal) as outcomes were fitted to test effect predictor, well combination baseline load (including interaction). All age, sex status covariates. We found no effects carriership insoluble either cohort (BioFINDER-2 WRAP), both meta-ROI, when was present model (p=0.531-0.949). alone best predictor accumulation, interaction between tau-PET. BioFINDER-2, there significant (b=0.166, p<0.001) entorhinal cortex at baseline. However, not WRAP PET. No (p=0.683-0.708) (p=0.188-0.570) p-tau217 observed BioFINDER-1 WRAP. Similarly, observed. Mediation analysis revealed that fully mediated most (46-112%, p-tau217). largest (BioFINDER-2), looking groups by number ε4 alleles, an homozygotes levels over time while only conclusion, although aggregation, it seems be minimally changes given level pathology, confirming primacy driving pathology.

Language: Английский

Citations

2
Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies DOI Creative Commons
Reisa A. Sperling, Michael Donohue, Robert A. Rissman

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

5
Cognitive variation reflects amyloid, tau, and neurodegenerative biomarkers in Alzheimer’s disease DOI

Kia Ann Sean Phang,

Chin Hong Tan

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

0
Physical activity and APOE neuropathology score modify the association of age and [11C]-PiB-PET amyloid burden in a cohort enriched with risk for Alzheimer's disease DOI Creative Commons

E Blum,

Kyle J. Edmunds, Brianne M. Breidenbach

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Physical activity (PA) is a protective factor against amyloid-β (Aβ) accumulation in adults at risk for Alzheimer's disease (AD). This association, however, may differ by apolipoprotein E ( APOE ) genotype. work examines interactions between age, PA, and neuropathology-based genetic AD np on Aβ burden cortical regions sensitive to its accumulation. Included were 388 cognitively unimpaired, older (mean age ± SD = 68.10 7.09; 66% female) participants from the Wisconsin Registry Prevention (WRAP) study. The cohort was enriched with both family history of enrollment higher overall prevalence ε 4 allele carriage than typically observed general population. PA assessed using self-reported questionnaire. measured Pittsburg Compound B 11 C-PiB) PET imaging, which allowed us derive volume corrected distribution ratio (DVR) maps nine bilateral interest (ROIs) global composite score. Linear regression models examined burden. Finally, scores aggregated according estimated illustrate differential effects active (weekly moderate > 150 minutes) inactive individuals. Three-way (Age × significant (all P 's ≤ 0.05) six ROIs (the PPC, ACC, mOFC, SMG, MTG, STG). Models stratified showed greater levels age-related each these ROIs, greatest high scores. Individuals who concomitantly engage suboptimal weekly moderate-intensity have These findings underscore how haplotype play intersect modifying brain susceptible deposition AD.

Language: Английский

Citations

0
The impact of cardiorespiratory fitness on Alzheimer's disease biomarkers and their relationships with cognitive decline. DOI Creative Commons

Anne Paulsen,

Ira Driscoll,

BM Breidenbach

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

ABSTRACT INTRODUCTION Relationships between core Alzheimer’s disease (AD) biomarker accumulation and cognitive decline are well-established the literature generally suggests a favorable relationship of cardiorespiratory fitness (CRF) on AD cognition. Differences in risk status conversion or rates by CRF, their potential interactive relationships with remain largely unknown. METHODS Participants (N=533; MeanAGE=65, 70% female) from Wisconsin Disease Research Center Registry for Prevention underwent serial blood draws, imaging assessments (MeanFollow-up=6.0 years). PET amyloid-β (Aβ) tau (T) plasma phosphorylated tau-217 (pTau-217) were used to determine (+/-). Sex-specific estimated CRF (eCRF) tertiles created using validated equation. Kaplan-Meier survival curves Cox-proportional hazards models characterized becoming biomarker-positive. Linear mixed effects associations baseline eCRF whether modified decline. Analyses stratified +/- status. RESULTS No significant observed trajectories. However, those high group who also Aβ-(HR[95%CI]=0.42[0.20, 0.88]) pTau-217-(HR[95%CI]=0.45[0.21, 0.97]) at had significantly lower There was attenuation detrimental Aβ Aβ+/T+. DISCUSSION While did not influence trajectories, seem protect against biomarker-positive attenuate known deleterious

Language: Английский

Citations

0
Amyloid pathology related to aberrant structure-function coupling of brain networks in Alzheimer’s disease: insights from [18F]-florbetapir PET imaging DOI
Haojie Chen, Mingkai Zhang,

Min Wei

et al.

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Language: Английский

Citations

0
Accuracy of plasma biomarkers to detect Alzheimer's disease proteinopathy prior to dementia DOI Creative Commons
Karly Alex Cody,

Lianlian Du,

Rachel Studer

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract INTRODUCTION Plasma biomarkers sensitive to Alzheimer's disease (AD) proteinopathy prior the onset of dementia have significant implications for early detection. METHODS In 304 individuals without dementia, we investigated whether C 2 N Diagnostics’ mass spectrometry (MS)‐based plasma (amyloid beta 42/40, %phosphorylated tau [p‐tau]181, and %p‐tau217) amyloid probability scores (APS, PrecivityAD APS2, PrecivityAD2) are associated with brain amyloid, tau, or preclinical cognitive decline. RESULTS this cohort study, %p‐tau217 APS2 had high discriminative accuracy (area under curve > 0.93) identifying elevated were faster Using in a theoretical AD trial screening scenario reduced positron emission tomography imaging costs up 41% 45%, respectively. DISCUSSION These findings suggest that MS‐based can detect could aid candidates clinical trials therapeutic intervention. Highlights differentiated status dementia. (p‐tau)217 Diagnostics PrecivityAD2 (APS2) concordant status.

Language: Английский

Citations

0
Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer’s disease DOI Creative Commons
Ke Ye, Xinyu Han, Maoyi Tian

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 3, 2025

Language: Английский

Citations

0
Late‐midlife lifestyle and brain and cognitive changes in individuals on the AD versus non‐AD continuum DOI Creative Commons
Julie Elisabeth Oomens, Karly Alex Cody,

Lianlian Du

et al.

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2025, Volume and Issue: 17(2)

Published: April 1, 2025

Abstract INTRODUCTION We investigated whether a composite measure of late‐midlife lifestyle was associated with (1) longitudinal brain changes and (2) cognitive when adjusting for these changes. METHODS used linear mixed models to examine the LIfestyle BRAin Health (LIBRA) index in tau, white matter hyperintensity, neurodegeneration, cognition were similar amyloid positive (A+; > 17 Centiloids) negative participants. RESULTS included 324 individuals from Wisconsin Registry Alzheimer's Prevention (39% apolipoprotein E [ APOE ] 4 carrier, 30% A+, prior baseline age 67 [50–75]). The LIBRA not biomarker trajectories or primary outcome trajectory. There inconsistent effects on secondary domain‐specific trajectories. In contrast, tau neurodegeneration strongly DISCUSSION age‐range disease‐range studied, did exhibit meaningful effect disease vascular accumulation consistently Highlights this age‐range, Effects lifestyle, if any, may take more time manifest.

Language: Английский

Citations

0
Subregional Functional Connectivity of the Precuneus as a Preclinical Biomarker in Alzheimer’s Disease DOI Creative Commons
Claudia Aponte, Antonio Jiménez-Marín,

Malen Razkin

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

ABSTRACT Background While the precuneus’ role in integrating diverse brain functions and its early involvement Alzheimer’s Disease (AD) is well established, differential impact of AD pathology on subregions poorly understood. This study aims to delineate vulnerability these subdivisions stages progression. Methods We conducted a resting-state functional connectivity analysis 32 asymptomatic carriers PSEN1 E280A mutation for familial disease compared them 25 non-carrier controls. Seed-based was applied precuneus subregions. Results Among carriers, 7Am subregion exhibited most pronounced statistical differences, consisting increased with entorhinal cortex, superior temporal gyrus, insula-operculum, dorsolateral prefrontal somatosensory areas. The POS2 further significantly decreased anterior insula cortex. Higher MoCA scores correlated within between frontoparietal network connectivity, alongside 7Pm, PCV, POS2, medial lobe. Additionally, 7m displayed higher regions. Conclusions Our findings highlight importance subregional uncovering patterns that do not exist when treated as single region interest—as common neuroimaging studies. Notably, even preclinical disease, changes are evident, supporting their potential biomarkers These results also point distinct during initial phases AD.

Language: Английский

Citations

0