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Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

Ashvini Keshavan, Amanda Heslegrave, Henrik Zetterberg, Jonathan M Schott
Introduction: Freeze-thaw instability may contribute to preanalytical variation in blood-based biomarker studies. We investigated the effects of up to four freeze-thaw cycles on single molecule array immunoassays of serum neurofilament light chain and plasma total tau, amyloid β 1-40 (Aß40 ), and Aβ 1-42 (Aβ42 ). Methods: Individuals who had peripheral venepuncture during investigation of suspected neurodegenerative disease were recruited. After standardized preprocessing, 200 μL of plasma and serum aliquots were stored at -80°C within 60 minutes...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Erin E Sundermann, My Tran, Pauline M Maki, Mark W Bondi
Introduction: We determined whether the effect of apolipoprotein E ( APOE )-ε4 genotype on Alzheimer's disease (AD) markers differs in men and women across AD stages. Methods: Among normal control (NC) participants (N = 702) and participants with mild cognitive impairment (N = 576) and AD (N = 305), we examined the associations of sex and APOE -ε4 carrier status with cortical amyloid-β (Aβ) burden, hippocampal volume ratio (HpVR; hippocampal volume/intracranial volume × 103 ), brain glucose metabolism, and verbal memory...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Ignacio Illán-Gala, Jordi Pegueroles, Victor Montal, Eduard Vilaplana, María Carmona-Iragui, Daniel Alcolea, Bradford C Dickerson, Raquel Sánchez-Valle, Mony J de Leon, Rafael Blesa, Alberto Lleó, Juan Fortea
Introduction: We aimed to evaluate the consistency of the A/T/N classification system. Methods: We included healthy controls, mild cognitive impairment, and dementia patients from Alzheimer's disease Neuroimaging Initiative. We assessed subject classification consistency with different biomarker combinations and the agreement and correlation between biomarkers. Results: Subject classification discordance ranged from 12.2% to 44.5% in the whole sample; 17...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Daniel L McCartney, Anna J Stevenson, Rosie M Walker, Jude Gibson, Stewart W Morris, Archie Campbell, Alison D Murray, Heather C Whalley, David J Porteous, Andrew M McIntosh, Kathryn L Evans, Ian J Deary, Riccardo E Marioni
Introduction: The "epigenetic clock" is a DNA methylation-based estimate of biological age and is correlated with chronological age-the greatest risk factor for Alzheimer's disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. In this study, we assess the relationship between the epigenetic clock and AD risk factors. Methods: Multilevel models were used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n = 5100)...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Jindong Ding Petersen, Volkert Dirk Siersma, René dePont Christensen, Maria Munch Storsveen, Connie Thurøe Nielsen, Frans Boch Waldorff
Introduction: Institutionalized people with dementia have an increased risk of fall accidents, but little is known about whether this increased risk holds for home dwellers. Methods: This register- and population-based study comprised 115,584 cases and 394,679 controls. Cases were individuals with any fall between 2009 and 2014, and matched with up to six controls on age, sex, and geographic location. Individuals were excluded if they (1) had any fall in 2008, or (2) lived in a nursing home on the date of the fall...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Jennifer H Lingler, J Scott Roberts, Hyejin Kim, Jonna L Morris, Lu Hu, Meghan Mattos, Eric McDade, Oscar L Lopez
Introduction: Given mounting calls to disclose biomarker test results to research participants, we explored factors underlying decisions by patients with mild cognitive impairment to receive amyloid imaging results. Methods: Prospective, qualitative interviews were conducted with 59 participants (30 = mild cognitive impairment patients, 29 = care partners) from the scan arm of a randomized controlled trial on the effects of amyloid PET results disclosure in an Alzheimer Disease Research Center setting...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Mattias Göthlin, Marie Eckerström, Sindre Rolstad, Petronella Kettunen, Anders Wallin
Introduction: Age and years of education influence the risk of dementia and may impact the prognostic accuracy of mild cognitive impairment subtypes. Methods: Memory clinic patients without dementia (N = 358, age 64.0 ± 7.9) were stratified into four groups based on years of age (≤64 and ≥65) and education (≤12 and ≥13), examined with a neuropsychological test battery at baseline and followed up after 2 years. Results: The prognostic accuracy of amnestic multi-domain mild cognitive impairment for dementia was highest in younger patients with more years of education and lowest in older patients with fewer years of education...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Lindsay Wallace, Olga Theou, Kenneth Rockwood, Melissa K Andrew
Introduction: Frailty and dementia appear to be closely linked, although mechanisms remain unclear. The objective was to conduct a scoping review of the association between frailty and Alzheimer's disease (AD) biomarkers in humans. Methods: Three databases, PubMed, PsycINFO, and Embase, were searched for articles using the following search terms: "frail elderly", "Alzheimer's disease", "dementia biomarkers" and their synonyms. Inclusion was limited to original research in humans published before 2017, which included a frailty measure and AD biomarker (fluid markers, neuroimaging, and neuropathology)...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Mascha M J Linszen, Afina W Lemstra, Meenakshi Dauwan, Rachel M Brouwer, Philip Scheltens, Iris E C Sommer
Introduction: Averaging at 13.4%, current literature reports widely varying prevalence rates of hallucinations in patients with probable Alzheimer's disease (AD), and is still inconclusive on contributive factors to hallucinations in AD. Methods: This study assessed prevalence, associated factors and clinical characteristics of hallucinations in 1227 patients with probable AD, derived from a tertiary memory clinic specialized in early diagnosis of dementia. Hallucinations were assessed with the Neuropsychiatric Inventory...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Olof Birna Olafsdottir, Hrafnhildur Sif Saevarsdottir, Sveinn Hakon Hardarson, Kristin Hanna Hannesdottir, Valgerdur Dora Traustadottir, Robert Arnar Karlsson, Anna Bryndis Einarsdottir, Katrin Dilja Jonsdottir, Einar Stefansson, Jon Snaedal
Introduction: We have previously reported that retinal vessel oxygen saturation is increased in mild-to-moderate dementia of Alzheimer's type when compared with healthy individuals. Mild cognitive impairment (MCI) is the predementia stage of the disease. The main purpose was to investigate if these changes are seen in MCI. Methods: Retinal vessel oxygen saturation was measured in 42 patients with MCI and 42 healthy individuals with a noninvasive retinal oximeter, Oxymap T1...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Dana L Tudorascu, Davneet S Minhas, Patrick J Lao, Tobey J Betthauser, Zheming Yu, Charles M Laymon, Brian J Lopresti, Chet A Mathis, William E Klunk, Benjamin L Handen, Bradley T Christian, Ann D Cohen
Introduction: Centiloid standardization was developed to establish a quantitative outcome measure of amyloid burden that could accommodate the integration of different amyloid positron emission tomography radiotracers or different methods of quantifying the same tracer. The goal of this study was to examine the use of Centiloids for establishing amyloid classification cutoffs for differing region-of-interest (ROI) delineation schemes. Methods: Using ROIs from hand-drawn delineation in native space as the gold standard, we compared standard uptake value ratios obtained from the 6 hand-drawn ROIs that determine amyloid-positivity classification with standard uptake value ratio obtained from 3 different automated techniques (FreeSurfer, Statistical Parametric Mapping, and superimposed hand-drawn ROIs in Pittsburgh Compound B template space)...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Jeremy A Elman, Amy J Jak, Matthew S Panizzon, Xin M Tu, Tian Chen, Chandra A Reynolds, Daniel E Gustavson, Carol E Franz, Sean N Hatton, Kristen C Jacobson, Rosemary Toomey, Ruth McKenzie, Hong Xian, Michael J Lyons, William S Kremen
Introduction: Longitudinal testing is necessary to accurately measure cognitive change. However, repeated testing is susceptible to practice effects, which may obscure true cognitive decline and delay detection of mild cognitive impairment (MCI). Methods: We retested 995 late-middle-aged men in a ∼6-year follow-up of the Vietnam Era Twin Study of Aging. In addition, 170 age-matched replacements were tested for the first time at study wave 2. Group differences were used to calculate practice effects after controlling for attrition effects...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Andreas Johnen, Sophia Reul, Heinz Wiendl, Sven G Meuth, Thomas Duning
Introduction: Apraxia is common in neurodegenerative dementias but underrepresented in clinical workup for differential diagnoses. Methods: Praxis-profiles were assessed with the Dementia Apraxia Test in 93 patients with early stages of biologically supported Alzheimer's disease or frontotemporal lobar degeneration: semantic primary-progressive aphasia, nonfluent primary-progressive aphasia, and behavioral variant frontotemporal dementia. Associations with core cognitive deficits of the dementia subtypes (i...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Evan Fletcher, Teresa Jenica Filshtein, Danielle Harvey, Alice Renaud, Dan Mungas, Charles DeCarli
Introduction: Current models posit a sequence of amyloid β (Aβ), tau, atrophy, and cognitive change leading to Alzheimer's disease, but ambiguities remain. We examined these sequences via serial mediations. Methods: We studied normal controls, early mild cognitive impairment, and late mild cognitive impairment individuals from the Alzheimer's Disease Neuroimaging Initiative 2 database for the mediation of baseline cerebrospinal fluid Aβ effects on 2-year cognitive change via regional longitudinal atrophy rate (AR) alone or AR and tau...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Cecily G Swinford, Shannon L Risacher, Arnaud Charil, Adam J Schwarz, Andrew J Saykin
Introduction: Relationship between self- and informant memory concerns and tau aggregation was assessed in adults at risk for Alzheimer's disease (AD). Methods: Regional mean standardized uptake value ratios were extracted from [18 F]flortaucipir positron emission tomography (PET) scans of 82 at-risk adults in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Associations between self- and informant ECog memory scores and tau aggregation were analyzed on both regional and voxelwise bases...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Jamie Toombs, Martha S Foiani, Henrietta Wellington, Ross W Paterson, Charles Arber, Amanda Heslegrave, Michael P Lunn, Jonathan M Schott, Selina Wray, Henrik Zetterberg
Introduction: We tested the hypothesis that the amyloid β (Aβ) peptide ratios are more stable than Aβ42 alone when biofluids are exposed to two preanalytical conditions known to modify measurable Aβ concentration. Methods: Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were exposed to a series of volumes and polypropylene surfaces. Aβ42 , Aβ40 , and Aβ38 peptide concentrations were measured using a multiplexed electrochemiluminescence immunoassay...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Annie M Racine, Michael Brickhouse, David A Wolk, Bradford C Dickerson
Introduction: An Alzheimer's disease (AD) biomarker adjusted for age-related brain changes should improve specificity for AD-related pathological burden. Methods: We calculated a brain-age-adjusted "personalized AD cortical thickness index" (pADi) in mild cognitive impairment patients from the Alzheimer's Disease Neuroimaging Initiative. We performed receiver operating characteristic analysis for discrimination between patients with and without cerebrospinal fluid evidence of AD and logistic regression in an independent sample to determine if a dichotomized pADi predicted conversion to AD dementia...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Shana D Stites, Richard Milne, Jason Karlawish
Neuroimaging is advancing a new definition of Alzheimer's disease (AD). Using imaging biomarkers, clinicians may begin to diagnose the disease by identifying pathology and neurodegeneration in either cognitively impaired or unimpaired adults. This "biomarker-based" diagnosis may allow clinicians novel opportunities to use interventions that either delay the onset or slow the progression of cognitive decline, but it will also bring novel challenges. How will changing the definition of AD from a clinical to a biomarker construct change the experience of living with the disease? Knowledge of AD biomarker status can affect how individuals feel about themselves (internalized stigma) and how others judge them (public stigma)...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Clémence Tomadesso, Vincent de La Sayette, Robin de Flores, Pierrick Bourgeat, Victor L Villemagne, Stéphanie Egret, Francis Eustache, Gaël Chételat
Introduction: Patients with amnestic mild cognitive impairment (aMCI) are heterogeneous as regard to their amyloid status. The present study aimed at highlighting the neuropsychological, brain atrophy, and hypometabolism profiles of amyloid-positive (Aβpos) versus amyloid-negative (Aβneg) aMCI patients. Methods: Forty-four aMCI patients and 24 Aβneg healthy controls underwent neuropsychological, structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Laura Hernández-Domínguez, Sylvie Ratté, Gerardo Sierra-Martínez, Andrés Roche-Bergua
Introduction: We present a methodology to automatically evaluate the performance of patients during picture description tasks. Methods: Transcriptions and audio recordings of the Cookie Theft picture description task were used. With 25 healthy elderly control (HC) samples and an information coverage measure, we automatically generated a population-specific referent. We then assessed 517 transcriptions (257 Alzheimer's disease [AD], 217 HC, and 43 mild cognitively impaired samples) according to their informativeness and pertinence against this referent...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
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