Author
Lisa L. Barnes
Other affiliations: Illinois Institute of Technology, University of North Texas Health Science Center, Rush University ...read more
Bio: Lisa L. Barnes is an academic researcher from Rush University Medical Center. The author has contributed to research in topics: Cognition & Cognitive decline. The author has an hindex of 69, co-authored 280 publications receiving 20190 citations. Previous affiliations of Lisa L. Barnes include Illinois Institute of Technology & University of North Texas Health Science Center.
Topics: Cognition, Cognitive decline, Dementia, Medicine, Population
Papers published on a yearly basis
Papers
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Verneri Anttila1, Verneri Anttila2, Brendan Bulik-Sullivan2, Brendan Bulik-Sullivan1 +717 more•Institutions (270)
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
1,357 citations
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TL;DR: Results suggest that frequent participation in cognitively stimulating activities is associated with reduced risk of AD.
Abstract: ContextFrequent participation in cognitively stimulating activities has been
hypothesized to reduce risk of Alzheimer disease (AD), but prospective data
regarding an association are lacking.ObjectiveTo test the hypothesis that frequent participation in cognitive activities
is associated with a reduced risk of AD.DesignLongitudinal cohort study with baseline evaluations performed between
January 1994 and July 2001 and mean follow-up of 4.5 years.Participants and SettingA total of 801 older Catholic nuns, priests, and brothers without dementia
at enrollment, recruited from 40 groups across the United States. At baseline,
they rated frequency of participation in common cognitive activities (eg,
reading a newspaper), from which a previously validated composite measure
of cognitive activity frequency was derived.Main Outcome MeasuresClinical diagnosis of AD by a board-certified neurologist using National
Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's
Disease and Related Disorders Association criteria and change in global and
specific measures of cognitive function, compared by cognitive activity score
at baseline.ResultsBaseline scores on the composite measure of cognitive activity ranged
from 1.57 to 4.71 (mean, 3.57; SD, 0.55), with higher scores indicating more
frequent activity. During an average of 4.5 years of follow-up, 111 persons
developed AD. In a proportional hazards model that controlled for age, sex,
and education, a 1-point increase in cognitive activity score was associated
with a 33% reduction in risk of AD (hazard ratio, 0.67; 95% confidence interval,
0.49-0.92). Results were comparable when persons with memory impairment at
baseline were excluded and when terms for the apolipoprotein E ∊4 allele
and other medical conditions were added. In random-effects models that controlled
for age, sex, education, and baseline level of cognitive function, a 1-point
increase in cognitive activity was associated with reduced decline in global
cognition (by 47%), working memory (by 60%), and perceptual speed (by 30%).ConclusionThese results suggest that frequent participation in cognitively stimulating
activities is associated with reduced risk of AD.
1,186 citations
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TL;DR: Loneliness is associated with an increased risk of late-life dementia but not with its leading causes, and was robustly associated with cognitive decline and development of AD.
Abstract: Context Social isolation in old age has been associated with risk of developing dementia, but the risk associated with perceived isolation, or loneliness, is not well understood. Objective To test the hypothesis that loneliness is associated with increased risk of Alzheimer disease (AD). Design Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up. Participants A total of 823 older persons free of dementia at enrollment were recruited from senior citizen facilities in and around Chicago, Ill. Loneliness was assessed with a 5-item scale at baseline (mean +/- SD, 2.3 +/- 0.6) and annually thereafter. At death, a uniform postmortem examination of the brain was conducted to quantify AD pathology in multiple brain regions and the presence of cerebral infarctions. Main outcome measures Clinical diagnosis of AD and change in previously established composite measures of global cognition and specific cognitive functions. Results During follow-up, 76 subjects developed clinical AD. Risk of AD was more than doubled in lonely persons (score 3.2, 90th percentile) compared with persons who were not lonely (score 1.4, 10th percentile), and controlling for indicators of social isolation did not affect the finding. Loneliness was associated with lower level of cognition at baseline and with more rapid cognitive decline during follow-up. There was no significant change in loneliness, and mean degree of loneliness during the study was robustly associated with cognitive decline and development of AD. In 90 participants who died and in whom autopsy of the brain was performed, loneliness was unrelated to summary measures of AD pathology or to cerebral infarction. Conclusion Loneliness is associated with an increased risk of late-life dementia but not with its leading causes.
1,084 citations
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TL;DR: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.
Abstract: Background: Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. Methods: Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. Results: On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. Conclusions: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.
902 citations
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TL;DR: The results suggest that change in cognitive function in old age primarily reflects person-specific factors rather than an inevitable developmental process.
Abstract: The authors examined change in cognitive abilities in older Catholic clergy members. For up to 6 years, participants underwent annual clinical evaluations, which included a battery of tests from which summary measures of 7 abilities were derived. On average, decline occurred in each ability and was more rapid in older persons than in younger persons. However, wide individual differences were evident at all ages. Rate of change in a given domain was not strongly related to baseline level of function in that domain but was moderately associated with rates of change in other cognitive domains. The results suggest that change in cognitive function in old age primarily reflects person-specific factors rather than an inevitable developmental process.
779 citations
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TL;DR: It is suggested that the diagnosis of mild cognitive impairment can be made in a fashion similar to the clinical diagnoses of dementia and AD, and an algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI.
Abstract: The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.
6,382 citations
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Brigham and Women's Hospital1, University of California, San Diego2, University of California, Davis3, Rush University Medical Center4, University of Washington5, Washington University in St. Louis6, University of Tokyo7, Mayo Clinic8, Oregon Health & Science University9, University of Texas at Dallas10, University of Melbourne11, Eli Lilly and Company12, Columbia University13, University of California, San Francisco14, Alzheimer's Association15, National Institutes of Health16
TL;DR: A conceptual framework and operational research criteria are proposed, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies and it is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD.
Abstract: The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.
5,671 citations
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Mayo Clinic1, Rush University2, University of Gothenburg3, Alzheimer's Association4, Silver Spring Networks5, Biogen Idec6, Washington University in St. Louis7, University of California, Berkeley8, University of Cologne9, University of Pennsylvania10, Stanford University11, National Institutes of Health12, University of California, San Francisco13, University of Melbourne14, VU University Medical Center15, Eli Lilly and Company16, Brigham and Women's Hospital17
TL;DR: This research framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms and envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD.
Abstract: In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
5,126 citations
01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
4,409 citations