Luigi Ferrucci

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (863)6131.02 Total impact

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    ABSTRACT: We investigated whether: 1) serum levels of 25-hydroxyvitamin D [25(OH)D]; and 2) single nucleotide polymorphisms (SNPs) in the group-specific component (GC) gene regulating serum 25(OH)D levels are associated with cognition in older individuals; and 3) whether causal relationships exist between 25(OH)D and cognition during aging. Data from 1207 participants in the Baltimore Longitudinal Study of Aging were analyzed (mean follow-up 10.4 years) to test associations between serum 25(OH)D and cognition. Two GC SNPs were used to derive a composite genetic risk score associated with lower 25(OH)D concentrations. Lower serum 25(OH)D and higher GC composite scores were associated with lower executive function at baseline. Mendelian randomization analyses suggested a causal relationship between lower serum 25(OH)D and poorer executive function and psychomotor speed. The SNP score was also associated with lower performance on measures of visuospatial abilities at baseline but with attenuated declines over time in visuospatial abilities and executive function. Widespread associations between vitamin-D regulatory SNPs and cognition suggest a mechanistic basis for the relationship between serum 25(OH)D levels and cognition during aging.
    No preview · Article · Mar 2016
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    ABSTRACT: Background: Slow gait is a robust biomarker of health and a predictor of functional decline and death in older adults, yet factors contributing to the decline in gait speed with aging are not well understood. Previous research suggests that the energetic cost of walking at preferred speed is inversely associated with gait speed, but whether individuals with a rising energetic cost of walking experience a steeper rate of gait speed decline has not been investigated. Methods: In participants of the Baltimore Longitudinal Study of Aging, the energetic cost of overground walking at preferred speed (mL/kg/m) was assessed between 2007 and 2014 using a portable indirect calorimeter. The longitudinal association between the energetic cost of walking and usual gait speed over 6 meters (m/s) was assessed with multivariate linear regression models, and the risk of slow gait (<1.0 m/s) was analyzed using Cox proportional hazards models. Results: The study population consisted of 457 participants aged 40 and older who contributed 1,121 person-visits to the analysis. In fully adjusted models, increases in the energetic cost of walking predicted the rate of gait speed decline in those older than 65 years (β = -0.008 m/s, p < .001). Moreover, those with a higher energetic cost of walking (>0.17mL/kg/m) had a 57% greater risk of developing slow gait compared with a normal energetic cost of walking (≤0.17mL/kg/m; adjusted hazard ratio = 1.57, 95% confidence interval: 1.01-2.46). Conclusions: These findings suggest that strategies to maintain walking efficiency hold significant implications for maintaining mobility in late life. Efforts to curb threats to walking efficiency should focus on therapies to treat gait and balance impairments, and reduce clinical disease burden.
    Full-text · Article · Feb 2016 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
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    ABSTRACT: Age effects on cognitive functioning are well-documented, but effects of sex on trajectories of cognitive aging are less clear. We examined cognitive ability across a variety of measures for 1,065 to 2,127 participants (mean baseline age 64.1 to 69.7 years) from the Baltimore Longitudinal Study of Aging who were repeatedly tested over a mean follow-up interval of 3.0 to 9.0 years with a mean of 2.3 to 4.4 assessments. Memory and other cognitive tests were administered at each visit, assessing mental status, verbal learning and memory, figural memory, language, attention, perceptuomotor speed and integration, executive function, and visuospatial ability. Importantly, participants free from cognitive impairment at all time points were used in the analyses. Results showed that for all tests, higher age at baseline was significantly associated with lower scores, and performance declined over time. In addition, advancing age was associated with accelerated longitudinal declines in performance (trend for mental status). After adjusting for age, education, and race, sex differences were observed across most tests of specific cognitive abilities examined. At baseline, males outperformed females on the 2 tasks of visuospatial ability, and females outperformed males in most other tests of cognition. Sex differences in cognitive change over time indicated steeper rates of decline for men on measures of mental status, perceptuomotor speed and integration, and visuospatial ability, but no measures on which women showed significantly steeper declines. Our results highlight greater resilience to age-related cognitive decline in older women compared with men. (PsycINFO Database Record
    No preview · Article · Jan 2016 · Psychology and Aging
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    ABSTRACT: Background: Emerging evidence suggests that mildly down-regulated thyroid function in older persons may protect and/or reflect maintained health. Methods: Using observational data collected between January 2006 and March 2014 on a volunteer sample of 602 men and women aged 68-97 years with normal thyroid function participating in the Baltimore Longitudinal Study of Aging, this study examines the concurrent relationship between reported walking ability, usual and rapid gait speed, endurance walk performance, fatigability, and reported energy level with respect to free thyroxine (FT4) within the normal range (0.76-1.50ng/dL) as a continuous variable and categorized as low (lower quartile), medium (interquartile), or high (upper quartile). Results: Adjusting for sex, age, race, height, weight, exercise and smoking, reported walking ability, usual and rapid gait speed, 400-m time, fatigability, and reported energy level were less favorable with increasing FT4 (p = .013 to <.001). In sex-strata, similar associations were observed except for walking ability in men and energy level in women. Categorical analyses revealed that persons with low FT4 exhibited better functional mobility, fitness, and reported energy than persons with intermediate or high levels (p < .05 for all). Persons with high-normal versus medium FT4 had slower usual and rapid gait speed (p < .05) only. Conclusion: Older adults with low-normal FT4 exhibit better mobility, fitness, and fatigue profiles. Mildly down-regulated thyroid function appears to align with better function in old age and may serve as a biomarker of healthy longevity.
    No preview · Article · Jan 2016 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
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    ABSTRACT: Background: DNA methylation is influenced by diet and single nucleotide polymorphisms (SNPs), and methylation modulates gene expression. Objective: We aimed to explore whether the gene-by-diet interactions on blood lipids act through DNA methylation. Design: We selected 7 SNPs on the basis of predicted relations in fatty acids, methylation, and lipids. We conducted a meta-analysis and a methylation and mediation analysis with the use of data from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium and the ENCODE (Encyclopedia of DNA Elements) consortium. Results: On the basis of the meta-analysis of 7 cohorts in the CHARGE consortium, higher plasma HDL cholesterol was associated with fewer C alleles at ATP-binding cassette subfamily A member 1 (ABCA1) rs2246293 (β = -0.6 mg/dL, P = 0.015) and higher circulating eicosapentaenoic acid (EPA) (β = 3.87 mg/dL, P = 5.62 × 10(21)). The difference in HDL cholesterol associated with higher circulating EPA was dependent on genotypes at rs2246293, and it was greater for each additional C allele (β = 1.69 mg/dL, P = 0.006). In the GOLDN (Genetics of Lipid Lowering Drugs and Diet Network) study, higher ABCA1 promoter cg14019050 methylation was associated with more C alleles at rs2246293 (β = 8.84%, P = 3.51 × 10(18)) and lower circulating EPA (β = -1.46%, P = 0.009), and the mean difference in methylation of cg14019050 that was associated with higher EPA was smaller with each additional C allele of rs2246293 (β = -2.83%, P = 0.007). Higher ABCA1 cg14019050 methylation was correlated with lower ABCA1 expression (r = -0.61, P = 0.009) in the ENCODE consortium and lower plasma HDL cholesterol in the GOLDN study (r = -0.12, P = 0.0002). An additional mediation analysis was meta-analyzed across the GOLDN study, Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis. Compared with the model without the adjustment of cg14019050 methylation, the model with such adjustment provided smaller estimates of the mean plasma HDL cholesterol concentration in association with both the rs2246293 C allele and EPA and a smaller difference by rs2246293 genotypes in the EPA-associated HDL cholesterol. However, the differences between 2 nested models were NS (P > 0.05). Conclusion: We obtained little evidence that the gene-by-fatty acid interactions on blood lipids act through DNA methylation.
    Full-text · Article · Jan 2016 · American Journal of Clinical Nutrition
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    ABSTRACT: Background: prediction of length of stay (LOS) may be useful to optimise care plans to reduce the negative outcomes related to hospitalisation. Objective: to evaluate whether the Multidimensional Prognostic Index (MPI), based on a Comprehensive Geriatric Assessment (CGA), may predict LOS in hospitalised older patients. Design: prospective multicentre cohort study. Setting: twenty Geriatrics Units. Participants: patients aged 65 and older consecutively admitted to Geriatrics Units. Measurement: at admission, the CGA-based MPI was calculated by using a validated algorithm that included information on basal and instrumental activities of daily living, cognitive status, nutritional status, the risk of pressures sores, co-morbidity, number of drugs and co-habitation status. According to validated cut-offs, subjects were divided into three groups of risk, i.e. MPI-1 low risk (value ≤0.33), MPI-2 moderate risk (value 0.34–0.66) and MPI-3 severe risk of mortality (value ≥0.67). Results: two thousand and thirty-three patients were included; 1,159 were women (57.0%). Age- and sex-adjusted mean LOS in patients divided according to the MPI grade was MPI-1 = 10.1 (95% CI 8.6–11.8), MPI-2 = 12.47 (95% CI 10.7–14.68) and MPI-3 = 13.41 (95% CI 11.5–15.7) days (P for trend <0.001). The overall accuracy of the MPI to predict LOS was good (C-statistic 0.74, 95% CI 0.72–0.76). Moreover, a statistically significant trend of LOS means was found even in patients stratified according to their International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) main diagnosis. Conclusions: the MPI is an accurate predictor of LOS in older patients hospitalised with the most frequent diseases.
    No preview · Article · Jan 2016 · Age and Ageing
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    ABSTRACT: To compare the relative predictive power of handgrip and leg extension strength in predicting slow walking. Report of correlative analysis from two epidemiological cohort studies. Foundation of the National Institutes of Health Sarcopenia Project. Men and women aged 67 to 93 (N = 6,766). Leg strength, handgrip strength, and gait speed were measured. Strength cutpoints associated with slow gait speed were developed using classification and regression tree analyses and compared using ordinary least squares regression models. The cutpoints of lower extremity strength associated with slow gait speed were 154.6 N-m in men and 89.9 N-m in women for isometric leg extension strength and 94.5 N-m in men and 62.3 N-m in women for isokinetic leg extension strength. Weakness defined according to handgrip strength (odds ratios (OR) = 1.99 to 4.33, c-statistics = 0.53 to 0.67) or leg strength (ORs = 2.52 to 5.77; c-statistics = 0.61 to 0.66) was strongly related to odds of slow gait speed. Lower extremity strength contributed 1% to 16% of the variance and handgrip strength contributed 3% to 17% of the variance in the prediction of gait speed depending on sex and mode of strength assessment. Muscle weakness of the leg extensors and forearm flexors is related to slow gait speed. Leg extension strength is only a slightly better predictor of slow gait speed. Thus, handgrip and leg extension strength appear to be suitable for screening for muscle weakness in older adults.
    No preview · Article · Jan 2016 · Journal of the American Geriatrics Society
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    ABSTRACT: Osteoporosis and cognitive impairment, which are highly prevalent conditions in elderly populations, share several risk factors. This study aims at evaluating the association of bone mineral density (BMD) with prevalent and incident cognitive impairment after a 3-year follow-up. We studied 655 community-dwelling women aged 65+ participating in the InCHIANTI study, who had been followed for 3 years. Total, trabecular, and cortical BMD were estimated by peripheral quantitative computed tomography using standard transverse scans at 4 and 38 % of the tibial length. Cognitive performance was evaluated using the Mini-Mental State Examination and the Trail Making Tests (TMT) A and B; a MMSE score <24 was adopted to define cognitive impairment. The TMT A-B score was calculated as the difference between TMT-A and TMT-B times (ΔTMT). The association of cognitive performance after 3 years with baseline indices of BMD was assessed by logistic and linear regression analyses. Cortical, but not trabecular, BMD was independently associated with incident cognitive impairment (OR 0.93, 95 % CI 0.88-0.98; P = 0.012), worsening cognitive performance (OR 0.96, 95 % CI 0.92-0.98; P = 0.039), and worsening performance in ΔTMT (OR 0.96, 95 % CI 0.92-0.99; P = 0.047). Increasing cortical BMD tertiles was associated with decreasing probability of incident cognitive impairment (P for linear trend =0.001), worsening cognitive performance (P = 0.013), and a worsening performance below the median value (P for linear trend <0.0001). In older women, low BMD might represent an independent and early marker of subsequent cognitive impairment. Physicians should assess and monitor cognitive performance in the routine management of elderly women with osteoporosis.
    No preview · Article · Dec 2015 · Calcified Tissue International
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    Full-text · Article · Dec 2015 · Journal of Cachexia, Sarcopenia and Muscle
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    ABSTRACT: Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is “unexplained.” Ageing process is also characterized by a “multiple hormonal dysregulation” with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals.
    Full-text · Article · Dec 2015 · International Journal of Endocrinology
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    ABSTRACT: Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease. (PsycINFO Database Record
    Full-text · Article · Dec 2015 · Psychology and Aging
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    ABSTRACT: Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and associate with increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes mellitus and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (p=2.4*10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. SNPs at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in average UACR per minor allele was 21% for HS6ST1 and 13% for RAB38/CTSC (p=6.3*10(-7) and 5.8*10(-7), respectively). Experiments using streptozotocin-treated diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout vs. control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared to controls. The loci identified here confirm known and highlight novel pathways influencing albuminuria.
    Full-text · Article · Dec 2015 · Diabetes
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    ABSTRACT: Objective To examine the relative validity of a multicultural FFQ used to derive nutrient intake estimates in a community dwelling cohort of younger and older men and women compared with those derived from 3 day (3d) diet records during the same time-frame. Design Cross-sectional analyses. Setting The Baltimore Longitudinal Study of Aging (BLSA) conducted in the Baltimore, MD and District of Columbia areas. Participants A subset (n=468, aged 26 to 95 years (y), 47% female, 65% non-Hispanic white) from the BLSA, with complete data for nutrient estimates from a FFQ and 3d diet records. Measurements Pearson’s correlation coefficients (energy adjusted and de-attenuated) for intakes of energy and 26 nutrients estimated from the FFQ and the mean of 3d diet records were calculated in a cross-sectional analysis. Rankings of individuals based on FFQ for various nutrient intakes were compared to corresponding rankings based on the average of the 3d diet records. Bland Altman plots were examined for a visual representation of agreement between both assessment methods. All analyses were stratified by sex and age (above and below 65 y). Results Median nutrient intake estimates tended to be higher from the FFQ compared to average 3d diet records. Energy adjusted and de-attenuated correlations between FFQ intake estimates and records ranged from 0.23 (sodium intake in men) to 0.81 (alcohol intake in women). The FFQ classified more than 70 percent of participants in either the same or adjacent quartile categories for all nutrients examined. Bland Altman plots demonstrated good agreement between the assessment methods for most nutrients. Conclusions This FFQ provides reasonably valid estimates of dietary intakes of younger and older participants of the BLSA.
    No preview · Article · Dec 2015 · The Journal of Nutrition Health and Aging
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    ABSTRACT: Background: Gait speed predicts functional decline, disability, and death and is considered a biomarker of biological aging. Changes in gait speed in persons aging with HIV may provide an important method of gauging health and longevity in an under assessed population. The objective of this study was to evaluate and quantify the rate of gait speed decline in HIVinfected (HIV+) men compared with HIV-uninfected (HIV-) men. Methods: The study was nested in the Multicenter AIDS Cohort Study. The primary outcome was usual gait speed in meters per second measured between 2007 and 2013. Differences in the rate of gait speed decline and the incidence of clinically slow gait (<1.0 m/s) were assessed using multivariate linear regression models and Cox proportional hazards models, respectively. Results: A total of 2025 men (973 HIV+ and 1052 HIV-) aged 40 years and older contributed 21,187 person-visits (9955 HIV+ and 11,232 HIV-) to the analysis. Average gait speeds at the age 50 years were 1.24 and 1.19 m/s in HIV- and HIV+ men, respectively (P < 0.001). In fully adjusted models, gait speed decline averaged 0.009 m/s per year after age 50 years (P < 0.001); this decline was 0.025 m/s per year greater in HIV+ men (P < 0.001). Moreover, HIV+ men had a 57% greater risk of developing clinically slow gait (adjusted hazard ratio = 1.57, 95% confidence interval: 1.27 to 1.91). Conclusions: These findings indicate a faster rate of functional decline in HIV-infected men, suggesting greater risks of disability and death with advancing age.
    Full-text · Article · Dec 2015
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    ABSTRACT: Higher intra-individual lap time variation (LTV) of the 400-m walk is cross-sectionally associated with poorer attention in older adults. Whether higher LTV predicts decline in executive function and whether the relationship is accounted for by slower walking remain unanswered. The main objective of this study was to examine the relationship between baseline LTV and longitudinal change in executive function. We used data from 347 participants aged 60 years and older (50.7 % female) from the Baltimore Longitudinal Study of Aging. Longitudinal assessments of executive function were conducted between 2007 and 2013, including attention (Trails A, Digit Span Forward Test), cognitive flexibility and set shifting (Trails B, Delta TMT: Trials B minus Trials A), visuoperceptual speed (Digit Symbol Substitution Test), and working memory (Digit Span Backward Test). LTV and mean lap time (MLT) were obtained from the 400-m walk test concurrent with the baseline executive function assessment. LTV was computed as variability of lap time across ten 40-m laps based on individual trajectories. A linear mixed-effects model was used to examine LTV in relation to changes in executive function, adjusted for age, sex, education, and MLT. Higher LTV was associated with greater decline in performance on Trails B (β = 4.322, p < 0.001) and delta TMT (β = 4.230, p < 0.001), independent of covariates. Findings remained largely unchanged after further adjustment for MLT. LTV was not associated with changes in other executive function measures (all p > 0.05). In high-functioning older adults, higher LTV in the 400-m walk predicts executive function decline involving cognitive flexibility and set shifting over a long period of time. High LTV may be an early indicator of executive function decline independent of MLT.
    Full-text · Article · Dec 2015 · Journal of the American Aging Association
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    Full-text · Dataset · Nov 2015
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    ABSTRACT: Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.
    Full-text · Article · Nov 2015 · Human Molecular Genetics
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    ABSTRACT: Background: Forced expiratory volume in 1 second (FEV1) over time is commonly expressed in liters and percent predicted (%Pred), or alternatively in L/m(3) and Z-scores-which approach is more clinically meaningful has not been evaluated. Because it uniquely accounts for the effect of aging on FEV1 and spirometric performance, we hypothesized that the Z-score approach is more clinically meaningful, based on associations between cardiopulmonary predictors and FEV1 over time. Methods: Using linear mixed-effects models and data from the Baltimore Longitudinal Study on Aging, including 501 white participants aged 40-95 who had completed at least three longitudinal spirometric assessments, we evaluated the associations between cardiopulmonary predictors (obesity, smoking status, hypertension, chronic bronchitis, diabetes mellitus, and myocardial infarction) and FEV1 over time, in liters, %Pred, L/m(3), and Z-scores. Results: Mean baseline values for FEV1 were 3.240L, 96.4%Pred, 0.621L/m(3), and -0.239 as a Z-score (40.6th percentile). The annual decline in FEV1 was 0.040L, 0.234 %Pred, 0.007L/m(3), and 0.008 Z-score units. Baseline age was associated with FEV1 over time in liters and L/m(3) (p < .001), and included a time interaction for %Pred (p < .001), but was not associated with Z-scores (p = .933). The associations of cardiopulmonary predictors with FEV1 over time were all significant when using Z-scores (p < .05), but varied for other methods of expressing FEV1. Conclusion: A Z-score approach is more clinically meaningful when evaluating FEV1 over time, as it accounted for the effect of aging and was more frequently associated with multiple cardiopulmonary predictors.
    No preview · Article · Nov 2015 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
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    ABSTRACT: Introduction: Individualized estimates of age at detectable amyloid-beta (Aβ) accumulation, distinct from amyloid positivity, allow for analysis of onset age of Aβ accumulation as an outcome measure to understand risk factors. Methods: Using longitudinal Pittsburgh compound B (PiB) positron emission tomography data from Baltimore Longitudinal Study of Aging, we estimated the age at which each PiB+ individual began accumulating Aβ. We used survival analysis methods to quantify risk of accumulating Aβ and differences in onset age of Aβ accumulation in relation to APOE ε4 status and sex among 36 APOE ε4 carriers and 83 noncarriers. Results: Age at onset of Aβ accumulation for the APOE ε4- and ε4+ groups was 73.1 and 60.7, respectively. APOE ε4 positivity conferred a threefold risk of accumulating Aβ after adjusting for sex and education. Discussion: Estimation of onset age of amyloid accumulation may help gauge treatment efficacy in interventions to delay symptom onset in Alzheimer's disease.
    No preview · Article · Nov 2015 · Alzheimer's & dementia: the journal of the Alzheimer's Association
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    ABSTRACT: Abstract: Background: Although observational studies have shown Vitamin-D deficiency is associated with increased risk of all-cause dementia, Alzheimer’s disease and age-associated cognitive decline, these results may be influenced by confounding and reverse causation. Examining the relationship between genetic variants regulating vitamin-D levels and brain function/structure may overcome some of these limitations. Methods: Data from non-demented participants in the Baltimore Longitudinal Study of Aging (BLSA), were used in the current analyses (n=848, mean follow-up interval 10.4 years). Serum concentrations of 25-hydroxyvitamin D [25(OH)D] and single nucleotide polymorphisms (SNPs) in the group-specific component (GC) (rs17467825, rs2282679, rs2298850, rs3755967) gene were examined for associations with cognitive performance using linear mixed models. A composite score of the 4 GC SNPs was created. In data from the BLSA neuroimaging substudy (BLSA-NI, n=120, mean follow-up interval 7.8 years), we tested whether GC SNPs influenced changes in brain volumes during aging. Results: As reported previously, GC SNPs were associated with serum concentration of [25(OH)D]. The minor allele of each GC SNP was associated with a 3.68 nmol/L (95% CI -4.72, -2.65) reduction in serum 25(OH)D. Lower serum [25(OH)D] concentration was associated with poorer performance on the clock drawing to command task at baseline (β=0.02, p=.007). At baseline, the composite GC SNP minor alleles were associated with poorer performance on the clock drawing (3:25 (β=-0.74, p=.01), Boston naming (BNT, β=-0.50, p=.01), Wide Range Achievement Test word reading subcomponent (WRAT; β=-0.44, p=.04) and Rey-Osterrieth Complex Figure-total copy (β=-0.85, p=.02) tests. In longitudinal analyses, minor alleles of GC SNPs were associated with attenuated declines on clock drawing, BNT, WRAT and Rey copy tests. Composite GC SNPs were associated with significantly faster rates of decline in volumes of total gray matter, middle occipital and middle frontal gyri, as well as the cuneus. GCs SNPs were marginally associated with faster declines in occipital gray matter. Conclusions: Vitamin-D exerts both state and trait-dependent effects on brain function and structure during aging. The widespread associations between vitamin-D regulatory SNPs and cognition as well as longitudinal rates of brain atrophy, suggests a mechanistic basis for the relationship between vitamin-D and mental health outcomes during aging.
    No preview · Conference Paper · Nov 2015

Publication Stats

46k Citations
6,131.02 Total Impact Points


  • 2009-2015
    • Johns Hopkins University
      • • Wilmer Eye Institute
      • • Department of Medicine
      Baltimore, Maryland, United States
    • National Eye Institute
      Maryland, United States
    • Case Western Reserve University
      • School of Medicine
      Cleveland, Ohio, United States
  • 1994-2015
    • National Institute on Aging
      • • Clinical Research Branch (CRB)
      • • Intramural Research Program (IRP)
      • • Laboratory of Cardiovascular Science (LCS)
      • • Laboratory of Epidemiology, Demography and Biometry (LEDB)
      Baltimore, Maryland, United States
  • 2014
    • Universiteit Twente
      • Group of Behavioural Sciences
      Enschede, Overijssel, Netherlands
  • 2003-2014
    • National Institutes of Health
      • • Clinical Research Branch (CRB)
      • • Laboratory of Epidemiology, Demography, and Biometry (LEDB)
      베서스다, Maryland, United States
    • AMC Health
      New York City, New York, United States
  • 2013
    • Karolinska Institutet
      Сольна, Stockholm, Sweden
  • 2012
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2007-2012
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
    • VU University Medical Center
      • Department of Psychiatry
      Amsterdamo, North Holland, Netherlands
    • Università degli Studi di Perugia
      • Department of Clinical and Experimental Medicine
      Perugia, Umbria, Italy
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
  • 2011
    • Boston University
      • Department of Biostatistics
      Boston, Massachusetts, United States
    • University of Exeter
      • Peninsula College of Medicine and Dentistry
      Exeter, England, United Kingdom
  • 2005-2011
    • University of Naples Federico II
      • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy
    • University of Milan
      Milano, Lombardy, Italy
  • 2010
    • Università degli studi di Parma
      • Department of Clinical and Experimental Medicine
      Parma, Emilia-Romagna, Italy
    • Queen's University
      • School of Rehabilitation Therapy
      Kingston, Ontario, Canada
    • University of Lausanne
      • Faculté de biologie et de médecine (FBM)
      Lausanne, VD, Switzerland
  • 2008-2010
    • University of Washington Seattle
      • Department of Rehabilitation Medicine
      Seattle, Washington, United States
  • 2007-2010
    • Johns Hopkins Medicine
      • • Department of Urology
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 2008-2009
    • Grays Harbor Community Hospital
      Aberdeen, Washington, United States
  • 1996-2008
    • INRCA Istituto Nazionale di Ricovero e Cura per Anziani
      • Gerontological Research Department
      Ancona, The Marches, Italy
  • 2006
    • University of Pennsylvania
      • Center for Clinical Epidemiology and Biostatistics
      Philadelphia, Pennsylvania, United States
  • 2002-2003
    • Italian National Research Council
      Oristany, Sardinia, Italy
  • 1997-2003
    • INRIM Istituto Nazionale di Ricerca Metrologica
      Torino, Piedmont, Italy
    • University of Iowa
      Iowa City, Iowa, United States
  • 1985-1995
    • University of Florence
      • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      Florens, Tuscany, Italy