Abstract We tested association of nine late-onset Alzheimer’s disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) ...or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE -e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU -rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A -rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7 -rs3764650-C and EPHA1 -rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM -rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE- inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease.
The COVID-19 pandemic created the need for rapid and urgent guidance for clinicians to manage COVID-19 among patients and prevent transmission.
To appraise the quality of clinical practice guidelines ...(CPGs) using the National Academy of Medicine (NAM) criteria.
A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to December 14, 2020, and a search of related articles to February 28, 2021, that included CPGs developed by societies or by government or nongovernment organizations that reported pharmacologic treatments of hospitalized patients with COVID-19. Teams of 2 reviewers independently abstracted data and assessed CPG quality using the 15-item National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) instrument.
Thirty-two CPGs were included in the review. Of these, 25 (78.1%) were developed by professional societies and emanated from a single World Health Organization (WHO) region. Overall, the CPGs were of low quality. Only 7 CPGs (21.9%) reported funding sources, and 12 (37.5%) reported conflicts of interest. Only 5 CPGs (15.6%) included a methodologist, described a search strategy or study selection process, or synthesized the evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated confidence in the quality of the evidence (6 of 32 18.8%), described potential benefits and harms (6 of 32 18.8%), or graded the strength of the recommendations (5 of 32 15.6%). External review, patient or public perspectives, or a process for updating were rare. High-quality CPGs included a methodologist and multidisciplinary collaborations involving investigators from 2 or more WHO regions.
In this review, few COVID-19 CPGs met NAM standards for trustworthy guidelines. Approaches that prioritize engagement of a methodologist and multidisciplinary collaborators from at least 2 WHO regions may lead to the production of fewer, high-quality CPGs that are poised for updates as new evidence emerges.
PROSPERO Identifier: CRD42021245239.
The Dementia Rating Scale (DRS) is a widely used measure of global cognition, with age- and education-corrected norms derived from a cross-sectional sample of adults participating in Mayo's Older ...Americans Normative Studies (MOANS). In recent years, however, studies have indicated that cross-sectional normative samples of older adults represent an admixture of individuals who are indeed cognitively normal (i.e., disease-free) and individuals with incipient neurodegenerative disease. Theoretically, the “contamination” of cross-sectional normative samples with cases of preclinical dementia can lead to underestimation of the test mean and overestimation of the variance, thus reducing the clinical utility of the norms. Robust norming, in which dementia cases are removed from the normative cohort through longitudinal follow-up, is an alternative approach to norm development. The current study presents a reappraisal of the original MOANS DRS norms, provides robust and expanded norms based on a sample of 894 adults age 55 and over, and critically evaluates the benefits of robust norming.
Covariance structure analyses of a core neuropsychological test battery consisting of the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, and Auditory Verbal Learning Test ...have previously identified a 5-factor model in a sample of cognitively normal White volunteers from Mayo's Older Americans Normative Studies (MOANS). The present study sought to replicate this factor structure in a sample of 289 cognitively normal, community-dwelling African American elders from Mayo's Older African Americans Normative Studies (MOAANS). The original 5-factor model was tested against 2 alternative 4-factor models and a 6-factor model generated on a substantive basis. Confirmatory factor analysis supported the construct validity of this core battery in older African Americans by replicating the original 5-factor model of Verbal Comprehension, Perceptual Organization, Attention/Concentration, Learning, and Retention as viable in the present sample.
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