Abstract Background Inexpensive, non-invasive tools for assessing Alzheimer-type pathophysiologies are needed. Computerized cognitive assessments are prime candidates. Methods Cognitively normal ...participants, aged 51–71, with magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography (FDG-PET), amyloid PET, CogState computerized cognitive assessment, and standard neuropsychological tests were included. We first examined the association between the CogState battery and neuroimaging measures. We then compared that association to the one between standard neuropsychological z-scores and neuroimaging. Results Slower reaction times for CogState Identification and One Back, and lower memory and attention z-scores, were associated ( P < .05) with FDG-PET hypometabolism. Slower time on the Groton Maze Learning Task and worse One Card Learning accuracy were associated ( P < .05) with smaller hippocampal volumes. There were no associations with amyloid PET. Associations of CogState and neuropsychological Z-scores with neuroimaging were small and of a similar magnitude. Conclusions CogState subtests were cross-sectionally comparable to standard neuropsychological tests in their relatively weak associations with neurodegeneration imaging markers.
Introduction: Our objective was to examine the association between perseverations produced on the semantic verbal fluency (SVF) task in asymptomatic individuals and the future diagnosis of cognitive ...impairment (CI).
Method: Participants were individuals participating in the Mayo Clinic Study of Aging (N = 1269, M
age
= 79.3 years, SD = 5.1; 51% men). All were cognitively normal at baseline and were followed in 15-month intervals for up to 6 visits. Each neurocognitive assessment included SVF tasks ("animals," "fruits," and "vegetables"). Cox modeling was used to test for associations between perseverations and time to CI diagnosis.
Results: Perseverations on the "animals" SVF task were associated with incident CI (hazard ratio = 1.35; 95% confidence interval, CI 1.10, 1.66). No significant association was found with perseverations on the "fruits" or "vegetables" SVF tasks. Mixed-effects modeling in cognitively normal participants revealed that the number of perseverations at baseline is significantly associated with decline in memory and visuospatial cognitive domains but is not associated with decline in attention.
Conclusions: Assessing perseverations together with standard SVF scores on the "animals" SVF task can help in early identification of asymptomatic individuals at an increased risk for CI. Perseverations are not associated with attention, but rather visual and verbal working memory mechanisms. In longitudinal settings aimed at early detection of signs of CI in presymptomatic individuals, SVF testing with scoring that includes counting of perseverations may potentially serve as a practical alternative to the more cumbersome memory tests.
Global assessments are Food and Drug Administration-required primary outcome measures in trials of putative antidementia drugs. Global ratings are intended to provide an index of clinical importance ...of change that cannot be obtained from quantitative assessment measures such as mental status examinations. We examined the performance of a global assessment of change instrument, the Clinician Interview-Based Impression (CIBI), in the placebo group of a 30-week, randomized, double-blind clinical trial of tacrine in patients with Alzheimer's disease. Initially there were 184 placebo patients, of whom 125 completed the 30-week study. Descriptive statistics, correlations with changes on other assessment instruments, and test-retest reliability were determined for the CIBI. At week 30, clinicians rated more than 40% of patients on the CIBI as unchanged. The CIBI ratings were weakly but significantly correlated, in the expected direction, with change scores on the quantitative cognitive assessments. The CIBI was modestly reliable on test-retest at weeks 22 and 24 but less reliable compared with other quantitative outcome measures. Modifications of the CIBI that might improve its reliability and acceptance include (1) no restrictions on the form of the bedside mental status assessment, (2) inclusion of caregiver input, and (3) better definition of ratings on the global scale. Global instruments, if properly constructed, can provide an index of clinically important change for the assessment of dementia patients.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial ...volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 × 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 × 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 × 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 × 10(-3) for 6q22 and 1.2 × 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment.
To examine ...Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence.
This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013. The dates of this analysis were April 2015 through August 2016. The setting was ARIC field centers (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). The study comprised 15 744 participants (of whom 27.1% were black and 72.9% white) who were aged 44 to 66 years at baseline.
Demographic and vascular risk factors were measured at baseline (obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia) as well as presence of the APOE ε4 genotype. After the baseline visit, participants had 4 additional in-person visits, for a total of 5 in-person visits, hospitalization surveillance, telephone calls, and repeated cognitive evaluations. Most recently, in 2011-2013, through the ARIC Neurocognitive Study (ARIC-NCS), participants underwent a detailed neurocognitive battery, informant interviews, and adjudicated review to define dementia cases. Additional cases were identified through the Telephone Interview for Cognitive Status-Modified or informant interview, for participants not attending the ARIC-NCS visit, or by an International Classification of Diseases, Ninth Revision dementia code during a hospitalization. Fully adjusted Cox proportional hazards regression was used to evaluate associations of baseline vascular and demographic risk factors with dementia.
In total, 1516 cases of dementia (57.0% female and 34.9% black, with a mean SD age at visit 1 of 57.4 5.2 years) were identified among 15 744 participants. Black race (hazard ratio HR, 1.36; 95% CI, 1.21-1.54), older age (HR, 8.06; 95% CI, 6.69-9.72 for participants aged 60-66 years), lower educational attainment (HR, 1.61; 95% CI, 1.28-2.03 for less than a high school education), and APOE ε4 genotype (HR, 1.98; 95% CI, 1.78-2.21) were associated with increased risk of dementia, as were midlife smoking (HR, 1.41; 95% CI, 1.23-1.61), diabetes (HR, 1.77; 95% CI, 1.53-2.04), prehypertension (HR, 1.31; 95% CI, 1.14-1.51), and hypertension (HR, 1.39; 95% CI, 1.22-1.59). The HR for dementia for diabetes was almost as high as that for APOE ε4 genotype.
Midlife vascular risk factors are associated with increased risk of dementia in black and white ARIC Study participants. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.
The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a ...centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.byu.edu ) or via a command-line interface. We report study-specific polygenic risk scores across the UK Biobank, 1000 Genomes, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), contextualize computed scores, and identify potentially confounding genetic risk factors in ADNI. We introduce a streamlined analysis tool and web interface to calculate and contextualize polygenic risk scores across various studies, which we anticipate will facilitate a wider adaptation of polygenic risk scores in future disease research.
Federal infrastructure investment is receiving a great deal of attention, largely about money: how to finance capital investment, operations, and maintenance. Less discussed but very important is ...modernizing federal policy to support the mature and urban-centered economy of the United States—rather than the economy it had when most of the terms of federal engagement were set. This article summarizes a RAND Corporation report which addresses recent trends in infrastructure spending and finance and proposes improvements in federal infrastructure policy. We argue for modernizing federal policies related to funding, finance, and project selection. Modernization should recognize the centrality of regional initiatives that transcend local government and state boundaries and should encourage different types of financing—public, private, and public–private partnerships. Poorly targeted investment comes from poorly designed policy. Inadequate maintenance often is a symptom of failure of management and governance. More money will help, but it is not nearly enough.
The easily-imaged retinal microvasculature may reflect the brain microvasculature and therefore be related to dementia.
In a population-based study of 12,482 adults aged 50-73 years (22% African ...American), we estimated the relationship of retinal characteristics from fundus photography (1993-1995) with incident all-cause dementia (1993-1995 to 2011-2013) and with etiologic subtype of dementia/mild cognitive impairment (2011-13).
A total of 1259 (10%) participants developed dementia over a mean 15.6 years. Moderate/severe (vs. no) retinopathy (hazard ratio HR, 1.86; 95% confidence interval CI: 1.36–2.55) and central retinal arteriolar equivalent (narrowest quartile vs. widest three quartiles; HR, 1.26; 95% CI: 1.09–1.45) were associated with all-cause dementia. Results were qualitatively stronger (but not statistically significantly different) in participants with diabetes. Retinopathy was associated with a joint outcome of cerebrovascular-related, but not Alzheimer's disease–related, dementia/mild cognitive impairment (HR, 2.29; 95% CI: 1.24–4.23).
Exploration of measures in the eye may provide surrogate indices of microvascular lesions relevant to dementia.
Finding ways to safely store and ultimately dispose of nuclear waste remains a matter of considerable debate. This volume describes the steps needed to design a new, single-purpose organization to ...manage and dispose of commercial and defense high-level radioactive materials and examines three models for such an organization—federal government corporation, federally chartered private corporation, and independent government agency.
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