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  • 1
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 87, No. 16 ( 2016-10-18), p. 1681-1687
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
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  • 2
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 100, No. 3 ( 2015-03), p. 920-933
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2015
    detail.hit.zdb_id: 2026217-6
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  • 3
    Online Resource
    Online Resource
    The Endocrine Society ; 2018
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 103, No. 5 ( 2018-05-01), p. 1818-1826
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 103, No. 5 ( 2018-05-01), p. 1818-1826
    Abstract: A common single nucleotide polymorphism in DIO2, Thr92AlaD2, has been associated with a transcriptome typically found in neurodegenerative diseases in postmortem human brain tissue. Objective To determine whether Thr92AlaD2 is associated with incident Alzheimer disease (AD). Design Population-based study; human brain tissue microarray. Setting Community-based cohorts from Chicago and northeastern Illinois and religious clergymen from across the United States constituted the primary population. A representative sample of the U.S. population was used for secondary analyses. Participants 3054 African Americans (AAs) and 9304 European Americans (EAs). Main Outcome Measure Incident AD. Results In the primary population, AAs with Thr92AlaD2 had 1.3 times [95% confidence interval (CI), 1.02 to 1.68; P = 0.048] greater odds of developing AD. AAs from a second population with Thr92AlaD2 showed a trend toward increased odds of dementia (odds ratio, 1.33; 95% CI, 0.99 to 1.78; P = 0.06) and 1.35 times greater odds of developing cognitive impairment not demented (CIND; 95% CI, 1.09 to 1.67; P = 0.006). Meta-analysis showed that AAs with Thr92AlaD2 had 1.3 times increased odds of developing AD/dementia (95% CI, 1.07 to 1.58; P = 0.008). In EAs, no association was found between Thr92AlaD2 and AD, dementia, or CIND. Microarray of AA brain tissue identified transcriptional patterns linked to AD pathogenesis. Conclusions Thr92AlaD2 was associated with molecular markers known to underlie AD pathogenesis in AAs, translating to an observed phenotype of increased odds of developing AD/dementia in AAs in these populations. Thr92AlaD2 might represent one factor contributing to racial discrepancies in incident AD.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2018
    detail.hit.zdb_id: 2026217-6
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  • 4
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 8 ( 2023-02-21), p. e874-e883
    Abstract: Recent studies suggest the utility of blood biomarkers in detecting changes in neurodegenerative disorders. The objective of our research was to test the hypothesis that the longitudinal changes in total tau (t-tau), neurofilament light chain (Nf-L), and glial fibrillary acidic protein (GFAP) are associated with structural MRI and the development of clinical Alzheimer disease (AD) and cognitive decline. Methods Data came from a population-based sample with serum concentrations of t-tau, Nf-L, and GFAP and cognitive characteristics measured over 17 years. The inclusion criteria for this investigation were based on participants with blood samples, cognitive function testing, and clinical diagnosis for AD. The longitudinal changes in the serum biomarkers were examined using linear mixed models for log10-transformed concentrations. Results In 1,327 participants (60% Black participants and 60% women, the concentration of t-tau increased annually by 4.8% (95% CI = 4.0–5.6) and Nf-L by 5.9% (95% CI = 5.4–6.4). The longitudinal change in GFAP was higher among Black participants than among White participants (4.4% vs 3.5% per year, p = 0.028). Baseline MRI characteristics were associated with the longitudinal changes in serum biomarkers of clinical AD. Specifically, a higher baseline third ventricular volume was associated with a higher rate of increase in the concentration of t-tau, and white matter hyperintensities predicted a higher rate of increase in Nf-L. The rate of change in concentrations of t-tau, Nf-L, and GFAP was significantly higher among those who developed clinical AD than in those with no cognitive impairment. For each standard deviation unit decline in global cognition, longitudinal change in t-tau increased by 81% (95% CI = 76–86), Nf-L by 113% (95% CI = 105–120), and GFAP by 66% (95% CI = 62–70). Discussion Blood biomarkers showed significant longitudinal changes corresponding to cognitive decline, clinical AD, and structural MRI characteristics. Our findings show that longitudinal changes in serum biomarkers were associated with several cognitive endophenotypes. Classification of Evidence The study found Class II evidence that longitudinal changes in serum t-tau, Nf-L, and GFAP were associated with cognitive decline and the development of clinical AD in people older than 65 years.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 5
    Online Resource
    Online Resource
    Wiley ; 2019
    In:  Journal of the American Geriatrics Society Vol. 67, No. 4 ( 2019-04), p. 734-740
    In: Journal of the American Geriatrics Society, Wiley, Vol. 67, No. 4 ( 2019-04), p. 734-740
    Abstract: To examine the effects of age and race on the association of apolipoprotein E (APOE) genotypes with cognitive decline in a population sample. DESIGN Longitudinal study of 18 years’ duration. SETTING Biracial urban US population sample. PARTICIPANTS There were a total of 5807 participants, 60% African American (AA) and 40% European American (EA). MEASUREMENTS A composite cognitive function based on individual tests of episodic memory, perceptual speed, and the Mini‐Mental State Examination. RESULTS The frequencies of APOE ε2/ε3 (14% vs 12%), ε2/ε4 (4% vs 2%), ε3/ε4 (29% vs 22%), and ε4/ε4 (4% vs 2%) genotypes were higher among AAs than EAs. After adjusting for demographic factors, the rate of decline in global cognition was twice as high among participants with the APOE ε4/ε4 genotype compared to participants with the APOE ε3/ε3 genotype (0.097 vs 0.048 SD units [SDUs] per year; P 〈 .0001). This doubling was not different between AAs (0.091 vs 0.045 SDUs per year) and EAs (0.118 vs 0.059 SDUs per year) ( P interaction = .63). The APOE ε3/ε4 genotype was associated with a higher rate of decline with age ( P interaction = .021), while the APOE ε2/ε4 genotype ( P interaction = .016) and the APOE ε2/ε3 genotype ( P interaction = .043) were associated with a lower rate of decline with higher age. The APOE ε2/ε2 genotype was associated with a lower rate of decline in episodic memory, while the APOE ε2/ε4 was associated with a higher rate of decline in episodic memory and perceptual speed. CONCLUSIONS The association of the APOE genotypes with cognitive decline was not different between AAs and EAs. However, individuals with different APOE genotypes showed a lower or a higher rate of decline with age. J Am Geriatr Soc 67:734–740, 2019.
    Type of Medium: Online Resource
    ISSN: 0002-8614 , 1532-5415
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2040494-3
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  • 6
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. 12 ( 2021-12), p. 1966-1975
    Abstract: The estimate of people with clinical Alzheimer's disease (AD) and mild cognitive impairment provides an understanding of the disease burden. Methods We estimated people with cognitive impairment using a quasibinomial regression model in 10,342 participants with cognitive test scores. Results The 2020 US Census–adjusted prevalence of clinical AD was 11.3% (95% confidence interval [CI] = 10.7–11.9): 10.0% among non‐Hispanic Whites, 14.0% among Hispanics, and 18.6% among non‐Hispanic Blacks. We estimate that in 2020, 6.07 (95% CI = 5.75–6.38) million people were living with clinical AD, which increases to 13.85 (95% CI = 12.98–14.74) million in 2060, 423% higher among Hispanics, 192% higher among Blacks, and 63% higher among Whites. However, there are predicted to be more significant increases in later years among those over 85 and women compared to men. Discussion The number of people with clinical AD will increase as the “baby boom” generation reaches older ages, exerting a strong upward influence on disease burden.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 7
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S4 ( 2021-12)
    Abstract: More frequent engagement in late‐life cognitive activities (e.g. reading, playing games) has been associated with slower cognitive decline in old age. Even after adjusting for neuropathological burden, cognitive activities were associated with less cognitive decline. However, it is not known whether people who engage more frequently in cognitive activities show differences in brain anatomy compared to those who participate less frequently. We tested the hypothesis that brain anatomy, as measured by structural MRI indices, mediates the association of cognitive activities and cognitive decline in old age. Method In a sample of 975 participants (60% African American and 60% female) from the Chicago Health and Aging Project, late‐life cognitive activities were collected at baseline; MRI was conducted an average of 7.9 years later. We identified several significant correlations of late‐life cognitive activity with MRI indices (brain regions and cortical thickness) and then used linear mixed‐effects regression models to examine those associations with global cognition. Global cognition was assessed using a standardized measure of episodic memory, perceptual speed, and the MMSE, before and after MRI scans. Result Higher frequency of overall cognitive activity was associated with seven brain volumes and two cortical thicknesses, which were associated with global cognitive level. Of those associations, five were associated with cognitive decline and explained about 42% of the cognitive activity association with cognitive decline. Specifically, a higher reading frequency was associated with lower white matter hyperintensity volume (WMH) and third ventricular volume. Higher WMH and third ventricle volumes were also associated with lower global cognition and a faster rate of cognitive decline. We also found that a higher frequency of playing games was positively associated with greater hippocampal and parahippocampal volumes and caudal anterior cingulate thickness in the left hemisphere. Conclusion Individuals who engage more frequently in cognitively stimulating activities show differences in brain anatomy compared to those who participate less frequently, as measured by structural MRI. These results suggest that cognitive activities are related to improved structure and function of the brain, thereby shedding light on the well‐established findings that cognitive activities are associated with cognitive decline independent of neuropathologic burden.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 8
    In: Annals of Neurology, Wiley, Vol. 88, No. 6 ( 2020-12), p. 1065-1076
    Abstract: The longitudinal association of the blood biomarkers total tau (t‐tau), neurofilament light (Nf‐L), and glial fibrillary acidic protein (GFAP) with common sporadic Alzheimer disease (AD) and cognitive decline is not established. Methods Using a single molecule array technology, ultrasensitive immunoassays for serum concentrations of t‐tau, Nf‐L, and GFAP were measured in a population sample of 1,327 participants (60% African Americans and women) who had a clinical evaluation for AD, had completed in‐home cognitive assessments, and had undergone 1.5T structural magnetic resonance imaging. Results Higher concentrations of serum biomarkers were associated with the development of clinical AD; especially, the time‐specific associations were notable: t‐tau 8 to 16 years, and Nf‐L and GFAP 4 to 8 years prior to clinical AD. Serum biomarkers were associated with faster cognitive decline over 16 years; baseline t‐tau 〉  0.40pg/ml had 30% faster decline, Nf‐L 〉  25.5pg/ml had 110% faster decline, and GFAP 〉  232pg/ml had 130% faster decline compared to those in the lowest quartile. Participants with baseline GFAP 〉  232pg/ml showed 160% faster decline in hippocampal volume compared to those with values 〈  160pg/ml. Additionally, higher baseline t‐tau was associated with faster increase in 3rd ventricular volume, and baseline Nf‐L and GFAP were associated with faster decline in cortical thickness. Interpretation Serum t‐tau, Nf‐L, and GFAP predict the development of sporadic AD and cognitive decline, and changes in structural brain characteristics, suggesting their usefulness not only as screening and predictive biomarkers, but also in capturing the pathogenesis of Alzheimer dementia. ANN NEUROL 2020;88:1065–1076
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2037912-2
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  • 9
    In: Annals of Neurology, Wiley, Vol. 83, No. 5 ( 2018-05), p. 935-944
    Abstract: To examine the association of blood pressure (BP) with incident Alzheimer's disease (AD) dementia. Methods This work is based on a longitudinal, cohort study of 18 years, the Chicago Health and Aging Project (CHAP) performed in 2,137 participants (55% black) with systolic BP measured around 8.1 years before incident AD dementia. Results The association of BP with risk of AD dementia was U‐shaped, with the lowest risks of AD dementia near the center of the systolic BP (SBP) and diastolic BP (DBP) distributions, and modestly elevated risk at lower BPs, and greater risk at higher BPs. The degree of U‐shape and the range of lowest risk (threshold ranges) varied with antihypertensive medication use and presence of the APOE ε4 allele. The U‐shape was most prominent for the subgroup not taking antihypertensive medications and having an APOE ε4 allele. At higher BPs, those having the APOE ε4 allele and not receiving antihypertensive medication were at greater risk of AD dementia than other groups: The risk of incident AD dementia increased by 100% (relative risk [RR] = 2.00; 95% confidence interval [CI]  = 1.70, 2.31) for every 10 mm Hg increase in SBP above 140 mm Hg. For DBP, the risk of incident of AD dementia increased by 57% (RR = 1.57; 95% CI = 1.33, 1.86) for every 5 mm Hg increase in DBP above 76 mm Hg. Interpretation The BP risk of AD dementia association is U‐shaped, with elevated risk at lower and higher BPs. People having the APOE ε4 allele and not receiving antihypertensive medication with higher BPs have notably elevated risk of AD dementia. Ann Neurol 2018;83:935–944
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2037912-2
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  • 10
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S3 ( 2020-12)
    Abstract: Prior studies of sex differences on the association of Apolipoprotein E4 allele and cognitive decline have reported conflicting results and have been done in predominantly White populations. In this study, we tested whether the association of the APOE E4 allele and cognitive decline differs between men and women in a biracial population‐based sample of older adults. Method Participants (N = 5,807, 63% females and 60% Black) underwent brief cognitive assessments at 3‐year intervals from 1993 to 2012. Using linear mixed effects models, adjusted for age, education and race, we examined the rate of cognitive decline among women and men with and without the APOE E4 allele. Result The presence of the APOE E4 allele did not vary between women and men (32% vs. 34%). Among participants without the APOE E4 allele, the rate of annual decline in global cognition was higher in women compared to men (0.048 standard deviation units [SDU] vs. 0.033 SDU per year, p = 0.0002). Among participants with APOE E4 allele, the rate of decline in global cognitive function and episodic memory was about twice as high among White women compared to white men (0.097 SDU vs. 0.057 SDU per year, p  〈  0.0001; 0.077 SDU vs. 0.031 SDU per year, p  〈  0.0001) respectively. Black men and women with APOE E4 did not differ in rates of global cognitive decline (0.078 vs. 0.073 per year, p = 0.58), or in any domains. Conclusion The rates of global cognitive decline, especially in APOE E4 carriers differed significantly between White women and men, but was similar between Black women and men. Additionally, the APOE E4 genotype was associated with a faster rate of decline in global cognitive function and episodic memory in women compared to men. The reason for sex differences among Black and White participants and especially among White women needs further attention.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
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