Author
Lon R. White
Other affiliations: National Institutes of Health, Kuakini Medical Center, Chaminade University of Honolulu
Bio: Lon R. White is an academic researcher from University of Washington. The author has contributed to research in topics: Dementia & Cohort study. The author has an hindex of 4, co-authored 6 publications receiving 1110 citations. Previous affiliations of Lon R. White include National Institutes of Health & Kuakini Medical Center.
Topics: Dementia, Cohort study, Vascular dementia, Heterologous, Population
Papers
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01 Jan 1994
TL;DR: Pilot testing conducted in Japan and in the United States has demonstrated its cross-cultural applicability and its usefulness in screening for dementia, in monitoring disease progression, and in providing profiles of cognitive impairment.
Abstract: The Cognitive Abilities Screening Instrument (CASI) has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment. Scores of the Mini-Mental State Examination, the Modified Mini-Mental State Test, and the Hasegawa Dementia Screening Scale can also be estimated from subsets of the CASI items. Pilot testing conducted in Japan and in the United States has demonstrated its cross-cultural applicability and its usefulness in screening for dementia, in monitoring disease progression, and in providing profiles of cogni- tive impairment. Typical administration time is 15 to 20 minutes. Record form, manual, videotape of test administration, and quizzes to qualify potential users on the administration and scoring of the CASI are available upon request. Demographic data have shown asteady increase in the proportion of older individuals in the general population and a continuation of this trend well into the next century. Alzheimer's disease and vascular dementia are aging-associated conditions. Substan- tial efforts have been made to investigate the risk factors, etiology, pathology, and possible treatments, but the success of all such efforts depends critically on good neuropsychological assessment to aid early detection of cases, accurate diagnosis, and sensitive monitoring of disease progression and treatment effects.
686 citations
TL;DR: Although some decline was observed in the Minnesota cohort, no statistically significant trends were apparent in the community studies, and a significant reduction in cognitive impairment measured by neuropsychological testing was identified in the national survey.
Abstract: Declines in heart disease and stroke mortality rates are conventionally attributed to reductions in cigarette smoking, recognition and treatment of hypertension and diabetes, effective medications to improve serum lipid levels and to reduce clot formation, and general lifestyle improvements. Recent evidence implicates these and other cerebrovascular factors in the development of a substantial proportion of dementia cases. Analyses were undertaken to determine whether corresponding declines in age-specific prevalence and incidence rates for dementia and cognitive impairment have occurred in recent years. Data spanning 1 or 2 decades were examined from community-based epidemiological studies in Minnesota, Illinois, and Indiana, and from the Health and Retirement Study, which is a national survey. Although some decline was observed in the Minnesota cohort, no statistically significant trends were apparent in the community studies. A significant reduction in cognitive impairment measured by neuropsychological testing was identified in the national survey. Cautious optimism appears justified.
454 citations
TL;DR: Endogenous serum pyrogen from rabbits produced fever in dogs and vice versa, suggesting that pyrogenicity of EP in animals of different species is probably a non-specific phenomenon.
Abstract: SummaryEndogenous serum pyrogen from rabbits produced fever in dogs and vice versa. Pyrogenicity of EP in the homologous species was dose related, but this was not the case in the heterologous spec...
7 citations
TL;DR: Increase of serum potassium to levels of 8.8 meq/1 did not alter the animals' ability to release endogenous pyrogen, and production of hypercalcemia also had no effect, confirming the inhibitory effect of potassium on release of pyrogen from leukocytes in vitro.
Abstract: SummaryRabbits acutely depleted of serum potassium or made chronically potassium deficient released more endogenous pyrogen following a constant pyrogenic stimulus than normokalemic controls. Increase of serum potassium to levels of 8.8 meq/1 did not alter the animals' ability to release endogenous pyrogen, and production of hypercalcemia also had no effect. These observations confirm the inhibitory effect of potassium on release of pyrogen from leukocytes in vitro.
5 citations
TL;DR: Several variants in genes implicated in AD had nominally significant association with risk of AD in this study, and some genetic risk factors in this population may overlap with those previously reported for AD in Caucasians, while others have not been previously reported as risk factors for AD.
Abstract: Background:An Alzheimer’s disease (AD) genome wide association study (GWAS) in African-Americans showed that only four of the established AD risk loci reached significant association. Importantly, the specific variants that associated with risk were different from those that achieved significance in GWAS of subjects of European ancestry; underscoring the importance of expanding genetic association studies of AD in African-Americans. Methods: We have tested the association of variants on the NeuroX chip (an Illumina exome array with custom content for neurological diseases) with the risk of AD in 76 African American (AA) patients with clinical diagnosis of AD fromMayo Clinic Florida in Jacksonville. Illumina’s Genome Studio software was used for genotype calling and initial quality control (QC). Samples with a call rate<99% were excluded, and variants with a GenTrain score<0.7 (number between 0 and 1 indicating how well the samples clustered) or in Hardy-Weinberg disequilibrium (p<0.0001) were also excluded. Using a Fisher’s exact test, the allele frequencies in AAAD cases were compared to allele frequencies from AA population controls in the exome variant server (EVS, n1⁄42,203). Results: After QC, 193,310 variants and 75 AA AD samples remained for analysis. False discovery rates (FDRs) were calculated according to Benjamini and Hochberg procedure to correct for multiple tests. After correction, 203 SNPs significantly associated with risk of AD (q-value<0.05). None of those variants have been previously associated with risk of AD. Nonetheless, several variants in genes implicated in AD had nominally significant association with risk of AD in this study. Although the APOE e4tagging SNP (rs429358) did not pass QC on the NeuroX, based on APOE e4 Taqman genotypes from these 75 ADs and the APOE e4 frequency in AA controls from EVS, we are able to detect significant APOE e4 association with AD risk (OR1⁄42.87, p-value1⁄44.05x10), consistent with previous reports. Conclusions: These preliminary results suggest that some genetic risk factors for AD in this population may overlap with those previously reported for AD in Caucasians, while others have not been previously reported as risk factors for AD. Validation of these results in a larger AA cohort is currently underway.
1 citations
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Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4 +1025 more•Institutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).
5,211 citations
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
Camden and Islington NHS Foundation Trust1, University College London2, King's College London3, University of Melbourne4, University of Exeter5, Brighton and Sussex Medical School6, University of Manchester7, Tel Aviv University8, Johns Hopkins University9, University of Michigan10, Kaiser Permanente11, University of Washington12, University of Montpellier13, University of Edinburgh14, Dalhousie University15, University of Southern California16, Innlandet Hospital Trust17, University of Oslo18
TL;DR: The Lancet Commission on Dementia Prevention, Intervention, and Care met to consolidate the huge strides that have been made and the emerging knowledge as to what the authors should do to prevent and manage dementia.
3,826 citations
TL;DR: The first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 is presented, to highlight the most important messages for clinicians and neurologists.
Abstract: Background: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challe ...
1,790 citations
University of Kentucky1, Uppsala University2, Northwestern University3, University of Geneva4, Washington University in St. Louis5, University of Maryland, Baltimore6, Johns Hopkins University7, University of Paris8, Harvard University9, Icahn School of Medicine at Mount Sinai10, Duke University11, University of Tokyo12, Medical University of Vienna13, University of Washington14, University of Bristol15, University of British Columbia16, University of Manchester17, University of California, San Diego18, Boston University19, Rush University Medical Center20, University of Ulm21, University of Pennsylvania22, New York University23, Oregon Health & Science University24
TL;DR: Evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of A&bgr; plaques and neurofibrillary tangles.
Abstract: Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
1,589 citations