Browsing by Subject "AD biomarkers"

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    Association between known Alzheimer’s disease risk genetic variants and hippocampal atrophy along the Alzheimer’s disease continuum in a Korean cohort
    (Wiley, 2025-01-03) Ahn, Hyejin; Byun, Min Soo; Yi, Dahyun; Jung, Gijung; Huang, Yen-Ning; Risacher, Shannon L.; Griswold, Anthony J.; Pericak-Vance, Margaret A.; Kim, Yu Kyeong; Lee, Yun-Sang; Sohn, Chul-Ho; Kang, Koung Mi; Lee, Jun-Young; Saykin, Andrew J.; Nho, Kwangsik; Lee, Dong Young; Radiology and Imaging Sciences, School of Medicine
    Background: Large‐scale genome‐wide association studies (GWAS) of Alzheimer’s disease (AD) from European ancestry identified many genetic variants associated with clinical diagnosis of AD dementia. However, it remains unclear whether these AD‐related variants are associated with AD biomarkers, particularly hippocampal atrophy, a well‐known neurodegeneration biomarker of AD in a Korean population. In this study, we investigated the association between known AD risk single nucleotide polymorphisms (SNPs) and hippocampal atrophy along the AD continuum in older Korean adults. Method: A total of 487 participants (258 cognitively normal olde adults [CN], 144 mild cognitive impairment [MCI], 85 AD dementia) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE) were included for analysis. All participants underwent 11C‐PiB‐PET/MRI. Hippocampal volume adjusted for intracranial volume (HVa) was obtained from 3D T1‐weighted MRI scans using FreeSurfer and used as a neurodegeneration marker of AD. Global beta‐amyloid (Aβ) deposition was calculated from PiB uptake in the global cortical region‐of‐interest using SPM12. From the genetic evidence gathered by the AD Sequencing Project (ADSP), which consists of 76 SNPs associated with AD, we selected 38 SNPs with a minor allele frequency (MAF) greater than 1% from the genotyping data imputed using the TOPMed imputation server in the KBASE cohort. Result: Among 38 known AD‐related SNPs, three SNPs (rs6966331 in EPDR1, rs2242595 in MYO15A, and rs17125924 in FERMT2) were associated with HVa in an initial exploratory analysis (p<0.05). In a subsequent confirmatory analysis, the associations of rs6966331 in EPDR1 and rs2242595 in MYO15A with HVa remained significant after controlling for age, sex, and APOE4 carrier status, as well as global Aβ deposition (p<0.001 and p = 0.009 for rs6966331 and rs2242595, respectively) (Table 1). Conclusion: Our study identified associations of rs6966331 in EPDR1 and rs2242595 in MYO15A with hippocampal volume in Korean older adults, and these associations were independent of cerebral Aβ deposition and APOE4 carrier status. These findings suggest that these AD‐related loci may contribute to the development of AD dementia via Aβ‐independent neurodegeneration.
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    Associations Between Clinical Functioning and Ad Biomarkers Among Hispanic and White Non-Hispanic Older Adults
    (Oxford University Press, 2023-12-21) Rodriguez, Miriam; Mendoza, Lisandra; Garcia, Patricia; Duart, Andres; Padron, Dilianna; Marsiske, Michael; Fiala, Jacob; Duara, Ranjan; Neurology, School of Medicine
    Objectives: Hispanics are 1.5x more likely to develop Alzheimer’s disease (AD) when compared to White non-Hispanics (WNHs). There is also evidence to support that cognitive performance disproportionately reflects neuropathology among Hispanics and that functional decline is concurrent with the accumulation of AD biomarkers. The current study aimed to examine relationships between AD biomarkers and a functional measure among Hispanic and WNH older adults. It was hypothesized that the functional measure would be strongly related to AD biomarkers among Hispanics. Methods: The modified clinical dementia rating scale (mCDR) was administered in the participants primary language (English or Spanish) to WNH (n=203) and Hispanic (n=258) older adults who were cognitive normal or diagnosed with Mild Cognitive Impairment (MCI) or dementia. Invariance SEM models were used to compare the pattern of relationships between the mCDR and neurocognitive test performance, MRI volumes, and amyloid load adjusting for age, education, ApoE4 status, and intracranial volume. Results: Model fit was good and not significantly worsened by imposing strict structural invariance. Nested model comparisons indicated that regression weights and correlations among measures differed by group, suggestive of moderation by Hispanic status. Among Hispanic participants, sex (♌=-0.17, p<.05) and Amyloid load (♌=0.25, p<.001) significantly predicted mCDR scores. MRI volumes significantly predicted MCDR scores among both Hispanic (♌=-0.51, p<.001) and WNH participants (♌= -0.42, p<.001). Conclusions: Functional measures like the mCDR may better correlate with Amyloid load among Hispanic older adults than among WNHs, while the correlation with MRI volumes may be comparable in both groups.
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    Functional measures and AD biomarkers among Hispanic and White non-Hispanic older adults
    (Wiley, 2024-08-10) Rodriguez, Miriam J.; Mendoza, Lisandra; Garcia, Patricia; Duarte, Andres; Padron, Dilianna; Marsiske, Michael; Fiala, Jacob; Gonzalez, Joanna; Duara, Ranjan; Neurology, School of Medicine
    Introduction: Poorer baseline functioning is associated with long-term cognitive decline among Hispanic older adults, but little is known about associations of these factors with Alzheimer's disease (AD) neuroimaging biomarkers. Methods: A total of 461 Hispanic and White non-Hispanic (NHW) older adults who are cognitively normal (n = 76), had impaired cognition without mild cognitive impairment (MCI) (n = 41), or carried a diagnosis of MCI (n = 253) or dementia (n = 91) completed neuropsychological and functional assessment, genetic testing, and brain magnetic resonance imaging (MRI). Structural equation modeling (SEM) was used to examine predictive associations between functional and cognitive measures of AD neuroimaging biomarkers. Results: MRI volumes significantly predicted functional limitations in both groups. Sex and amyloid load significantly predicted functional limitations among the Hispanic group only. Years of education and MRI regional volume were the strongest predictors of cognition among both groups. Discussion: Results indicate that functional performance is associated with early AD biomarkers among Hispanic older adults. Clinical implications are discussed. Highlights: The current study addresses health disparities in Alzheimer's disease (AD) and related dementia assessment among Hispanics by identifying measures sensitive to early AD biomarkers.Associations of functional measures with AD genetic and neuroimaging biomarkers revealed that similarities in these associations exist between Hispanic and White non-Hispanic individuals, but biological sex and amyloid load significantly predicted functional limitations among the Hispanic group only.These results have clinical implications for physicians who treat Hispanic AD patients and indicate that when compared to traditional diagnostic assessments, functional assessments may better aid in AD diagnostic precision among Hispanics.
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    Sex significantly predicts medial temporal volume when controlling for the influence of ApoE4 biomarker and demographic variables: A cross-ethnic comparison
    (Cambridge University Press, 2024) Garcia, Patricia; Mendoza, Lisandra; Padron, Dilianna; Duarte, Andres; Duara, Ranjan; Loewenstein, David; Greig-Custo, Maria; Barker, Warren; Curiel, Rosie; Rosselli, Monica; Rodriguez, Miriam; Neurology, School of Medicine
    Objective: To explore the relationship between age, education, sex, and ApoE4 (+) status to brain volume among a cohort with amnestic mild cognitive impairment (aMCI). Method: One hundred and twenty-three participants were stratified into Hispanic (n = 75) and White non-Hispanic (WNH, N = 48). Multiple linear regression analyses were conducted with age, education, sex, and ApoE4 status as predictor variables and left and right combined MRI volumes of the hippocampus, parahippocampus, and entorhinal cortex as dependent variables. Variations in head sizes were corrected by normalization with a total intracranial volume measurement. Results: Bonferroni-corrected results indicated that when controlling for ApoE4 status, education, and age, sex was a significant predictor of hippocampal volume among the Hispanic group (β = .000464, R2 = .196, p < .01) and the WNH group (β = .000455, R2 = .195, p < .05). Education (β = .000028, R2 = .168, p < .01) and sex (β = .000261, R2 = .168, p < .01) were significant predictors of parahippocampal volume among the Hispanic MCI group when controlling for the effects of ApoE4 status and age. One-way ANCOVAs comparing hippocampal and parahippocampal volume between males and females within groups revealed that females had significantly larger hippocampal volumes (p < .05). Hispanic females had significantly larger hippocampal (p < .001) and parahippocampal (p < .05) volume compared to males. No sex differences in parahippocampal volume were noted among WNHs. Conclusions: Biological sex, rather than ApoE4 status, was a greater predictor of hippocampal volume among Hispanic and WNH females. These findings add to the mixed literature on sex differences in dementia research and highlight continued emphasis on ethnic populations to elucidate on neurodegenerative disparities.