Yang An

National Institutes of Health, 베서스다, Maryland, United States

Are you Yang An?

Claim your profile

Publications (61)471.73 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been increasingly recognized at the basic science level that perturbations in ceramide metabolism are associated with the development and progression of many age-related diseases. However, the translation of this work to the clinic has lagged behind. Understanding the factors longitudinally associated with plasma ceramides and dihydroceramides (DHCer) at the population level and how these lipid levels change with age, and by sex, is important for the clinical development of future therapeutics and biomarkers focused on ceramide metabolism. We, therefore, examined factors cross-sectionally and longitudinally associated with plasma concentrations of ceramides and DHCer among Baltimore Longitudinal Study of Aging participants (n = 992; 3960 total samples), aged 55 years and older, with plasma at a mean of 4.1 visits (range 2-6). Quantitative analyses were performed on a high-performance liquid chromatography-coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess the relationships between plasma ceramide and DHCer species and demographics, diseases, medications, and lifestyle factors. Women had higher plasma concentrations of most ceramide and DHCer species and showed steeper trajectories of age-related increases compared to men. Ceramides and DHCer were more associated with waist-hip ratio than body mass index. Plasma cholesterol and triglycerides, prediabetes, and diabetes were associated with ceramides and DHCer, but the relationship showed specificity to the acyl chain length and saturation. These results demonstrate the importance of examining the individual species of ceramides and DHCer, and of establishing whether intra-individual age- and sex-specific changes occur in synchrony to disease onset and progression. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
    Aging cell 07/2015; DOI:10.1111/acel.12369 · 5.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diffusion tensor imaging (DTI) measures are commonly used as imaging markers to investigate individual differences in relation to behavioral and health-related characteristics. However, the ability to detect reliable associations in cross-sectional or longitudinal studies is limited by the reliability of the diffusion measures. Several studies have examined reliability of diffusion measures within (i.e. intra-site) and across (i.e. inter-site) scanners with mixed results. Our study compares the test-retest reliability of diffusion measures within and across scanners and field strengths in cognitively normal older adults with a follow-up interval less than 2.25 years. Intra-class correlation (ICC) and coefficient of variation (CoV) of fractional anisotropy (FA) and mean diffusivity (MD) were evaluated in sixteen white matter and twenty-six gray matter bilateral regions. The ICC for intra-site reliability (0.32 to 0.96 for FA and 0.18 to 0.95 for MD in white matter regions; 0.27 to 0.89 for MD and 0.03 to 0.79 for FA in gray matter regions) and inter-site reliability (0.28 to 0.95 for FA in white matter regions, 0.02 to 0.86 for MD in gray matter regions) with longer follow-up intervals were similar to earlier studies using shorter follow-up intervals. The reliability of across field strengths comparisons was lower than intra- and inter-site reliability. Within and across scanner comparisons showed that diffusion measures were more stable in larger white matter regions (>1500 mm(3)). For gray matter regions, the MD measure showed stability in specific regions and was not dependent on region size. Linear correction factor estimated from cross-sectional or longitudinal data improved the reliability across field strengths. Our findings indicate that investigations relating diffusion measures to external variables must consider variable reliability across the distinct regions of interest and that correction factors can be used to improve consistency of measurement across field strengths. An important result of this work is that inter-scanner and field strength effects can be partially mitigated with linear correction factors specific to regions of interest. These data-driven linear correction techniques can be applied in cross-sectional or longitudinal studies. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 07/2015; 119. DOI:10.1016/j.neuroimage.2015.06.078 · 6.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Quantification of β-amyloid (Aβ) in vivo is often accomplished using the distribution volume ratio (DVR), based on a simplified ratio tissue model. We investigated the local relationships between DVR and cerebral blood flow (CBF), as well as relative blood flow (R1), in nondemented older adults. Fifty-five nondemented participants (mean age 78.5 years) in the Baltimore Longitudinal Study of Aging underwent (15)O-H2O PET CBF and dynamic (11)C-PiB-PET. (15)O-H2O PET images were normalized and smoothed using SPM5. A simplified reference tissue model with linear regression and spatial constraints was used to generate parametric DVR images. The DVR images were regressed on CBF images on a voxel-by-voxel basis using robust Biological Parametric Mapping, adjusting for age and sex (FDR P = 0.05, k=50). DVR images were also regressed on R1 images, a measure of the transport rate constant from vascular space to tissue. All analyses were performed in the entire sample, and in high and low tertiles of mean cortical DVR. Voxel-based analyses showed that increased DVR is associated with increased CBF in frontal, parietal, temporal, and occipital cortices. However, this association appears to spare regions that typically show early β-amyloid (Aβ) deposition. A more robust relationship between DVR and CBF was observed in the lowest tertile of DVR, i.e., negligible cortical Aβ load, compared to the highest tertile of cortical DVR and Aβ load. Spatial distributions of the DVR-CBF and DVR-R1 correlations showed similar patterns. No reliable negative voxel-wise relationships between DVR and CBF or R1 were observed. Robust associations between DVR and CBF at negligible Aβ levels, together with similar spatial distributions of DVR-CBF and DVR-R1 correlations, suggest that regional distribution of DVR reflects blood flow and tracer influx rather than pattern of Aβ deposition in those with minimal Aβ load. DVR-CBF associations in individuals with higher DVR are more likely to reflect true associations between patterns of Aβ deposition and CBF or neural activity. These findings have important implications for analysis and interpretation of voxel-wise correlations with external variables in individuals with varying amounts of Aβ load. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 05/2015; 56(7). DOI:10.2967/jnumed.114.151480 · 5.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 different longitudinal cohorts. Aβ accumulation was measured using positron emission tomography (PET) imaging and (11)C-Pittsburgh compound-B (PiB) in 113 Baltimore Longitudinal Study of Aging participants (mean age 77.3 years; 107 normal, 6 cognitively impaired) and cerebral spinal fluid (CSF) Aβ1-42 assays in 207 BIOCARD study participants (mean age 62 years; 195 normal, 12 cognitively impaired). Participants in both cohorts had up to 7 serial assessments (mean 2.3-2.4). PET-PiB retention increased and CSF Aβ1-42 declined longitudinally. APOE ε4 was significantly associated with higher PET-PiB retention and lower CSF Aβ1-42, independent of age and sex, but APOE genotype did not significantly affect Aβ change over time. APOE ε4 carriers may be further along in the disease process, consistent with earlier brain Aβ deposition and providing a biological basis for APOE genotype effects on onset age of Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 04/2015; 36(8). DOI:10.1016/j.neurobiolaging.2015.04.001 · 4.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Excessively elevated resting metabolic rate (RMR) for persons of a certain age, sex, and body composition is a mortality risk factor. Whether elevated RMR constitutes an early marker of health deterioration in older adult has not been fully investigated. Using data from the Baltimore Longitudinal Study of Aging, we hypothesized that higher RMR (i) was cross-sectionally associated with higher multimorbidity and (ii) predicted higher multimorbidity in subsequent follow-ups. The analysis included 695 Baltimore Longitudinal Study of Aging participants, aged 60 or older at baseline, of whom 248 had follow-up data available 2 years later and 109 four years later. Multimorbidity was assessed as number of chronic diseases. RMR was measured by indirect calorimetry and was tested in regression analyses adjusted for covariates age, sex, and dual-energy x-ray absorptiometry-measured total body fat mass and lean mass. Baseline RMR and multimorbidity were positively associated, independent of covariates (p = .002). Moreover, in a three-wave bivariate autoregressive cross-lagged model adjusted for covariates, higher prior RMR predicted greater future multimorbidity above and beyond the cross-sectional and autoregressive associations (p = .034). RMR higher than expected, given age, sex, and body composition, predicts future higher multimorbidity in older adults and may be used as early biomarker of impending health deterioration. Replication and the development of normative data are required for clinical translation. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 11/2014; DOI:10.1093/gerona/glu209 · 4.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The delineation of the relative temporal trajectories of specific cognitive measures associated with Alzheimer's disease (AD) is important for evaluating preclinical markers and monitoring disease progression. Methods We characterized the temporal trajectories of measures of verbal episodic memory, short-term visual memory, and mental status using data from 895 participants in the Baltimore Longitudinal Study of Aging. Results The California Verbal Learning Test (CVLT) immediate recall was the first measure to decline, followed by CVLT delayed recall. However, further along the disease progression scale, CVLT delayed recall and visual memory changed more rapidly than CVLT immediate recall. Conclusions Our findings reconcile reports of early changes in immediate recall with greater reliance on delayed recall performance in clinical settings. Moreover, the utility of cognitive markers in evaluating AD progression depends on the stage of cognitive decline, suggesting that optimal endpoints in therapeutic trials may vary across different stages of the disease process.
    Alzheimer's and Dementia 11/2014; 10(6). DOI:10.1016/j.jalz.2014.04.520 · 17.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sphingomyelin metabolism has been linked to several diseases and to longevity. However, few epidemiological studies have quantified individual plasma sphingomyelin species (identified by acyl-chain length and saturation) or their relationship between demographic factors and disease processes. In this study, we determined plasma concentrations of distinct sphingomyelin species in 992 individuals, aged 55 and older, enrolled in the Baltimore Longitudinal Study of Aging. Participants were followed, with serial measures, up to 6 visits and 38 years (3972 total samples). Quantitative analyses were performed on a high-performance liquid chromatography-coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess variation in specific sphingomyelin species and associations with demographics, diseases, medications or lifestyle factors, and plasma cholesterol and triglyceride levels. We found that most sphingomyelin species increased with age. Women had higher plasma levels of all sphingomyelin species and showed steeper trajectories of age-related increases compared to men. African Americans also showed higher circulating sphingomyelin concentrations compared to Caucasians. Diabetes, smoking, and plasma triglycerides were associated with lower levels of many sphingomyelins and dihydrosphingomyelins. Notably, these associations showed specificity to sphingomyelin acyl-chain length and saturation. These results demonstrate that longitudinal changes in circulating sphingomyelin levels are influenced by age, sex, race, lifestyle factors, and diseases. It will be important to further establish the intra-individual age- and sex-specific changes in each sphingomyelin species in relation to disease onset and progression.
    Aging cell 10/2014; 14(1). DOI:10.1111/acel.12275 · 5.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Multimorbidity increases with aging, but risk factors beyond age are unknown. Objective. To investigate the association of inflammatory and anabolic hormonal biomarkers with presence and prospective development of multimorbidity. Methods. Nine-year longitudinal study of 1018 participants aged 60 years or older (InCHIANTI Study). Multimorbidity was evaluated at baseline and follow-up visits as number of diagnosed diseases from a predefined list of 15 candidate chronic conditions, defined according to standard clinical criteria. Linear mixed models were used to test cross-sectional and longitudinal associations between candidate biomarkers and multimorbidity. Results. At baseline, multimorbidity was significantly higher in older participants (p <. 001) and higher IL-6, IL-1ra, TNF-α receptor II (TNFAR2), and lower dehydroepiandrosterone sulfate were associated with higher number of diseases, independent of age, sex, body mass index, and education. The rate of longitudinal increase in number of chronic diseases was significantly steeper in participants who were older at baseline (p <. 001). In addition, higher baseline IL-6 and steeper increase of IL-6 levels were significantly and independently associated with a steeper increase in multimorbidity over time (p <. 001 and p =. 003, respectively). Sensitivity analyses, performed using 15 different models obtained by removing each of 15 conditions included in the original list of candidate diseases, confirmed that results were not driven by any specific condition. Conclusions. Accumulation of chronic diseases accelerates at older ages and in persons with higher baseline levels and steeper increase over time of IL-6. High IL-6 and increase in IL-6 may serve as early warning sign to better target interventions aimed at reducing the burden of multimorbidity. © 2014 Published by Oxford University Press on behalf of the Gerontological Society of America 2014.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2014; 70(1). DOI:10.1093/gerona/glu127 · 4.98 Impact Factor
  • Source
    Alzheimer's and Dementia 07/2014; 10(4):P160. DOI:10.1016/j.jalz.2014.04.145 · 17.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although overweight and obesity are associated with poor health outcomes in the elderly, the biological bases of obesity-related behaviors during aging are poorly understood. Common variants in the FTO gene are associated with adiposity in children and younger adults as well as with adverse mental health in older individuals. However, it is unclear whether FTO influences longitudinal trajectories of adiposity and other intermediate phenotypes relevant to mental health during aging. We examined whether a commonly carried obesity-risk variant in the FTO gene (rs1421085 single-nucleotide polymorphism) influences adiposity and is associated with changes in brain function in participants within the Baltimore Longitudinal Study of Aging, one of the longest-running longitudinal aging studies in the United States. Our results show that obesity-related risk allele carriers of FTO gene show dose-dependent increments in body mass index during aging. Moreover, the obesity-related risk allele is associated with reduced medial prefrontal cortical function during aging. Consistent with reduced brain function in regions intrinsic to impulse control and taste responsiveness, risk allele carriers of FTO exhibit dose-dependent increments in both impulsivity and intake of fatty foods. We propose that a common neural mechanism may underlie obesity-associated impulsivity and increased consumption of high-calorie foods during aging.Molecular Psychiatry advance online publication, 27 May 2014; doi:10.1038/mp.2014.49.
    Molecular Psychiatry 05/2014; 20(1). DOI:10.1038/mp.2014.49 · 15.15 Impact Factor
  • 05/2014; 71(5):651-2. DOI:10.1001/jamaneurol.2014.167
  • 05/2014; 71(5):651-652.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Older adults with intact cognition before death and substantial Alzheimer disease (AD) lesions at autopsy have been termed "asymptomatic AD subjects" (ASYMAD). We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of the hippocampus (CA1), anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex of ASYMAD versus age-matched Control and mild cognitive impairment (MCI) subjects. However, it was unclear whether the neuronal hypertrophy could be attributed to differences in the severity of AD pathology. Here, we performed quantitative analyses of the severity of β-amyloid (Aβ) and phosphorylated tau (tau) loads in the brains of ASYMAD, Control, MCI, and AD subjects (n = 15 per group) from the Baltimore Longitudinal Study of Aging. Tissue sections from CA1, anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex were immunostained for Aβ and tau; the respective loads were assessed using unbiased stereology by measuring the fractional areas of immunoreactivity for each protein in each region. The ASYMAD and MCI groups did not differ in Aβ and tau loads. These data confirm that ASYMAD and MCI subjects have comparable loads of insoluble Aβ and tau in regions vulnerable to AD pathology despite divergent cognitive outcomes. These findings imply that cognitive impairment in AD may be caused or modulated by factors other than insoluble forms of Aβ and tau.
    03/2014; DOI:10.1097/NEN.0000000000000052
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-6 (IL-6) is a pro-inflammatory cytokine produced by immune cells and other cell types such as microglia throughout the brain. Higher levels of IL-6 in older adults have been cross-sectionally and longitudinally associated with physical and cognitive impairment, as well as increased dementia risk. The association between IL-6 levels and structural and functional brain changes is less clear. In the present study, we investigated the relationship between IL-6 concentrations and cortical thinning with aging. Magnetic Resonance Imaging (MRI) scans from the Baltimore Longitudinal Study of Aging were analyzed for 121 older subjects (M = 69.3; SD = 7.3; range = 56.1–85.9 yrs) who were repeatedly tested over an average period of 7.5 yrs, and who remained non-demented for the entire follow-up period. The Freesurfer longitudinal processing stream was utilized for image processing, and IL-6 measures were based on serum ELISA assays averaged across time points. Results showed that higher mean IL-6 concentrations were associated with accelerated annual rates of cortical thinning in the inferior temporal poles bilaterally. Additional pronounced regions of IL-6 -accelerated thinning included the transverse frontopolar gyri within the left hemisphere, and subcentral gyrus and sulcus within the right hemisphere. Our results indicate that sustained high levels of the inflammatory biomarker IL-6 are associated with regionally increased rates of age-related cortical thinning. These data build on previous findings that link IL-6 to chronic disease and demonstrate one mechanism through which high levels of inflammation may have adverse effects on physical and cognitive function.
    03/2014; 5(1):1-7. DOI:10.2478/s13380-014-0203-0
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hearing impairment in older adults is independently associated in longitudinal studies with accelerated cognitive decline and incident dementia, and in cross-sectional studies, with reduced volumes in the auditory cortex. Whether peripheral hearing impairment is associated with accelerated rates of brain atrophy is unclear. We analyzed brain volume measurements from magnetic resonance brain scans of individuals with normal hearing versus hearing impairment (speech-frequency pure tone average>25dB) followed in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging for a mean of 6.4years after the baseline scan (n=126, age 56-86years). Brain volume measurements were performed with semi-automated region-of-interest (ROI) algorithms, and brain volume trajectories were analyzed with mixed-effects regression models adjusted for demographic and cardiovascular factors. We found that individuals with hearing impairment (n=51) compared to those with normal hearing (n=75) had accelerated volume declines in whole brain and regional volumes in the right temporal lobe (superior, middle, and inferior temporal gyri, parahippocampus, p<.05). These results were robust to adjustment for multiple confounders and were consistent with voxel-based analyses, which also implicated right greater than left temporal regions. These findings demonstrate that peripheral hearing impairment is independently associated with accelerated brain atrophy in whole brain and regional volumes concentrated in the right temporal lobe. Further studies investigating the mechanistic basis of the observed associations are needed.
    NeuroImage 01/2014; 90. DOI:10.1016/j.neuroimage.2013.12.059 · 6.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To develop targeted intervention strategies for the treatment of Alzheimer's disease, we first need to identify early markers of brain changes that occur before the onset of cognitive impairment. Here, we examine changes in resting-state brain function in humans from the Baltimore Longitudinal Study of Aging. We compared longitudinal changes in regional cerebral blood flow (rCBF), assessed by (15)O-water PET, over a mean 7 year period between participants who eventually developed cognitive impairment (n = 22) and those who remained cognitively normal (n = 99). Annual PET assessments began an average of 11 years before the onset of cognitive impairment in the subsequently impaired group, so all participants were cognitively normal during the scanning interval. A voxel-based mixed model analysis was used to compare groups with and without subsequent impairment. Participants with subsequent impairment showed significantly greater longitudinal rCBF increases in orbitofrontal, medial frontal, and anterior cingulate regions, and greater longitudinal decreases in parietal, temporal, and thalamic regions compared with those who maintained cognitive health. These changes were linear in nature and were not influenced by longitudinal changes in regional tissue volume. Although all participants were cognitively normal during the scanning interval, most of the accelerated rCBF changes seen in the subsequently impaired group occurred within regions thought to be critical for the maintenance of cognitive function. These changes also occurred within regions that show early accumulation of pathology in Alzheimer's disease, suggesting that there may be a connection between early pathologic change and early changes in brain function.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 11/2013; 33(46):18008-14. DOI:10.1523/JNEUROSCI.1402-13.2013 · 6.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE Older adults commonly report disturbed sleep, and recent studies in humans and animals suggest links between sleep and Alzheimer disease biomarkers. Studies are needed that evaluate whether sleep variables are associated with neuroimaging evidence of β-amyloid (Aβ) deposition. OBJECTIVE To determine the association between self-reported sleep variables and Aβ deposition in community-dwelling older adults. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of 70 adults (mean age, 76 [range, 53-91] years) from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging, a normative aging study. EXPOSURE Self-reported sleep variables. MAIN OUTCOMES AND MEASURES β-Amyloid burden, measured by carbon 11-labeled Pittsburgh compound B positron emission tomography distribution volume ratios (DVRs). RESULTS After adjustment for potential confounders, reports of shorter sleep duration were associated with greater Aβ burden, measured by mean cortical DVR (B = 0.08 [95% CI, 0.03-0.14]; P = .005) and precuneus DVR (B = 0.11 [0.03-0.18]; P = .007). Reports of lower sleep quality were associated with greater Aβ burden measured by precuneus DVR (B = 0.08 [0.01-0.15]; P = .03). CONCLUSIONS AND RELEVANCE Among community-dwelling older adults, reports of shorter sleep duration and poorer sleep quality are associated with greater Aβ burden. Additional studies with objective sleep measures are needed to determine whether sleep disturbance causes or accelerates Alzheimer disease.
    10/2013; 70(12). DOI:10.1001/jamaneurol.2013.4258
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite the recent identification of several novel risk genes for Alzheimer's disease (AD), little is known about their influence on the age at onset (AAO) of AD. The AAO is a phenotype with a heritable component distinct from disease risk and may be a useful trait to study in the context of developing interventions for delaying the onset of AD. We studied the influence of 10 recently identified AD risk genes and APOE in relation to AAO in a large cohort of AD patients (N = 2569). We find that the novel AD risk gene, PICALM, exerts a small effect on the AAO of AD with earlier disease onset in risk allele carriers. In addition, we confirmed the previously reported association between the APOE ε4 allele and earlier disease onset. None of the other AD risk genes influenced AAO of AD. Our results suggest that besides APOE, other genes associated with AD risk do not exert large effects on the AAO phenotype of AD.
    Neurobiology of aging 07/2013; 34(11). DOI:10.1016/j.neurobiolaging.2013.05.028 · 4.85 Impact Factor
  • Alzheimer's and Dementia 07/2013; 9(4):P256-P257. DOI:10.1016/j.jalz.2013.05.505 · 17.47 Impact Factor

Publication Stats

1k Citations
471.73 Total Impact Points


  • 2015
    • National Institutes of Health
      베서스다, Maryland, United States
  • 2006–2015
    • National Institute on Aging
      • • Laboratory of Behavioral Neuroscience
      • • Laboratory of Personality and Cognition (LPC)
      Baltimore, Maryland, United States
  • 2012–2014
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2009–2012
    • MedStar Health Research Institute
      Maryland, United States
  • 2011
    • Boston University
      • Department of Biostatistics
      Boston, Massachusetts, United States