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

Leslie M Shaw, Teresa Waligorska, Leona Fields, Magdalena Korecka, Michal Figurski, John Q Trojanowski, Udo Eichenlaub, Simone Wahl, Marian Quan, Michael J Pontecorvo, D Richard Lachno, Jayne A Talbot, Scott W Andersen, Eric R Siemers, Robert A Dean
Introduction: An Elecsys® Amyloid β (Aβ [1-42]) immunoassay cutoff for classification of patients with Alzheimer's disease was investigated. Methods: Cerebrospinal fluid samples collected from patients with mild-to-moderate Alzheimer's disease were analyzed by Elecsys® immunoassays: (1) Aβ (1-42), (2) total tau, and (3) phosphorylated tau. Cutoffs (Aβ [1-42] and ratios with tau) were estimated by method comparison between AlzBio3 ( n  = 206), mixture modeling ( n  = 216), and concordance with florbetapir F 18 imaging-based classification ( n  = 75)...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Chao Dong, Tao Liu, Wei Wen, Nicole A Kochan, Jiyang Jiang, Qiongge Li, Hao Liu, Haijun Niu, Wei Zhang, Yilong Wang, Henry Brodaty, Perminder S Sachdev
Introduction: Informant-reported subjective cognitive decline (iSCD) has been associated with a higher risk of conversion to dementia, but the findings of whole brain functional connectivity strength (FCS) changes in iSCD are limited. Methods: The sample comprised 39 participants with iSCD and 39 age- and sex- matched healthy controls. The global absolute (aFCS) and relative functional connectivity strengths were estimated using weighted degree centrality and the z-scores of the weighted degree centrality respectively...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Elijah Mak, Richard A I Bethlehem, Rafael Romero-Garcia, Simon Cervenka, Timothy Rittman, Silvy Gabel, Ajenthan Surendranathan, Richard W Bevan-Jones, Luca Passamonti, Patricia Vázquez Rodríguez, Li Su, Robert Arnold, Guy B Williams, Young T Hong, Tim D Fryer, Franklin I Aigbirhio, James B Rowe, John T O'Brien
Introduction: The deposition of neurofibrillary tangles in neurodegenerative disorders is associated with neuronal loss on autopsy; however, their in vivo associations with atrophy across the continuum of Alzheimer's disease (AD) remain unclear. Methods: We estimated cortical thickness, tau ([18 F]-AV-1451), and amyloid β (Aβ) status ([11 C]-PiB) in 47 subjects who were stratified into Aβ- (14 healthy controls and six mild cognitive impairment-Aβ-) and Aβ+ (14 mild cognitive impairment-Aβ+ and 13 AD) groups...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Gina M Peloso, Sven J van der Lee, Anita L Destefano, Sudha Seshardi
Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein ( CETP ) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C. Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Nelly Joseph-Mathurin, Yi Su, Tyler M Blazey, Mateusz Jasielec, Andrei Vlassenko, Karl Friedrichsen, Brian A Gordon, Russ C Hornbeck, Lisa Cash, Beau M Ances, Thomas Veale, David M Cash, Adam M Brickman, Virginia Buckles, Nigel J Cairns, Carlos Cruchaga, Alison Goate, Clifford R Jack, Celeste Karch, William Klunk, Robert A Koeppe, Daniel S Marcus, Richard Mayeux, Eric McDade, James M Noble, John Ringman, Andrew J Saykin, Paul M Thompson, Chengjie Xiong, John C Morris, Randall J Bateman, Tammie L S Benzinger
Introduction: 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using 11 C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET. Methods: FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Patrick J Lao, Adam M Brickman
Introduction: Cerebrovascular disease (CVD) is not currently considered a core pathological feature of Alzheimer's disease (AD), but mounting evidence suggests that concurrent CVD may exacerbate AD progression. The purpose of this study was first to examine the relationship among amyloid, CVD, and neurodegeneration and second to examine the extent to which amyloid and CVD pathology drive subsequent neurodegeneration over time. Methods: Six hundred eight (224 normal controls, 291 mild cognitive impairment, 93 AD) subjects from the Alzheimer's Disease Neuroimaging Initiative with longitudinal AV45 positron emission tomography imaging and MR imaging were investigated...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Robert M Chapman, Margaret N Gardner, Rafael Klorman, Mark Mapstone, Anton P Porsteinsson, Inga M Antonsdottir, Lily Kamalyan
Introduction: Developing biomarkers that distinguish individuals with Alzheimer's disease (AD) from those with normal cognition remains a crucial goal for improving the health of older adults. We investigated adding brain spatial information to temporal event-related potentials (ERPs) to increase AD identification accuracy over temporal ERPs alone. Methods: With two-step principal components analysis, we applied multivariate analyses that incorporated temporal and spatial ERP information from a cognitive task...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Amir Nazem, Chris C Tang, Phoebe Spetsieris, Christian Dresel, Marc L Gordon, Janine Diehl-Schmid, Timo Grimmer, Igor Yakushev, Paul J Mattis, Yilong Ma, Vijay Dhawan, David Eidelberg
Introduction: The heterogeneity of behavioral variant frontotemporal dementia (bvFTD) calls for multivariate imaging biomarkers. Methods: We studied a total of 148 dementia patients from the Feinstein Institute (Center-A: 25 bvFTD and 10 Alzheimer's disease), Technical University of Munich (Center-B: 44 bvFTD and 29 FTD language variants), and Alzheimer's Disease Neuroimaging Initiative (40 Alzheimer's disease subjects). To identify the covariance pattern of bvFTD (behavioral variant frontotemporal dementia-related pattern [bFDRP]), we applied principal component analysis to combined 18F-fluorodeoxyglucose-positron emission tomography scans from bvFTD and healthy subjects...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
R Scott Mackin, Philip S Insel, Diana Truran, Shannon Finley, Derek Flenniken, Rachel Nosheny, Aaron Ulbright, Monica Comacho, David Bickford, Brian Harel, Paul Maruff, Michael W Weiner
Introduction: The purpose of this study is to compare online neuropsychological test performance of older adults across self-reported diagnoses of being cognitively normal, mild cognitive impairment, and dementia due to Alzheimer's disease and to determine the association of memory concerns and family history of dementia on cognitive performance. Methods: Participants completed the Cogstate Brief Battery unsupervised at home. Results: Data from 6463 participants over the age of 55 years were analyzed...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Eline A J Willemse, Ingrid S van Maurik, Betty M Tijms, Femke H Bouwman, Andreas Franke, Isabelle Hubeek, Leo Boelaarts, Jules J Claus, Esther S C Korf, Rob J van Marum, Gerwin Roks, Niki Schoonenboom, Nicolaas Verwey, Marissa D Zwan, Simone Wahl, Wiesje M van der Flier, Charlotte E Teunissen
Introduction: We compared the automated Elecsys and manual Innotest immunoassays for cerebrospinal fluid (CSF) Alzheimer's disease biomarkers in a multicenter diagnostic setting. Methods: We collected CSF samples from 137 participants in eight local memory clinics. Amyloid β(1-42) (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) were centrally analyzed with Innotest and Elecsys assays. Concordances between methods were assessed. Results: Biomarker results strongly correlated between assays with Spearman's ρ 0...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Rong Cheng, Min Tang, Izri Martinez, Temitope Ayodele, Penelope Baez, Dolly Reyes-Dumeyer, Rafael Lantigua, Martin Medrano, Ivonne Jimenez-Velazquez, Joseph H Lee, Gary W Beecham, Christiane Reitz
Introduction: Less than 10% of early-onset Alzheimer's disease (EOAD) is explained by known mutations. Methods: We conducted genetic linkage analysis of 68 well-phenotyped Caribbean Hispanic families without clear inheritance patterns or mutations in APP , PSEN1 , and PSEN2 and with two or more individuals with EOAD. Results: We identified 16 (logarithm of odds > 3.6) linked regions, including eight novel loci for EOAD (2p15, 5q14.1, 11p15...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Manja Koch, Steven T DeKosky, Annette L Fitzpatrick, Jeremy D Furtado, Oscar L Lopez, Lewis H Kuller, Rachel H Mackey, Timothy M Hughes, Kenneth J Mukamal, Majken K Jensen
Introduction: Apolipoproteins of demonstrated importance to brain cholesterol and ß-amyloid metabolism may serve as novel risk markers for Alzheimer's pathology. Methods: We measured apolipoproteins (apoE, apoJ, apoA-I, and apoC-III and their uniquely defined subspecies) by enzyme-linked immunosorbent assay in plasma collected in 2000 and 2008 from 176 dementia-free participants of the Ginkgo Evaluation of Memory Study and related these to ß-amyloid on positron emission tomography scans, hippocampal volume, and white matter lesion volume in 2009...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Enrico Pellegrini, Lucia Ballerini, Maria Del C Valdes Hernandez, Francesca M Chappell, Victor González-Castro, Devasuda Anblagan, Samuel Danso, Susana Muñoz-Maniega, Dominic Job, Cyril Pernet, Grant Mair, Tom J MacGillivray, Emanuele Trucco, Joanna M Wardlaw
Introduction: Advanced machine learning methods might help to identify dementia risk from neuroimaging, but their accuracy to date is unclear. Methods: We systematically reviewed the literature, 2006 to late 2016, for machine learning studies differentiating healthy aging from dementia of various types, assessing study quality, and comparing accuracy at different disease boundaries. Results: Of 111 relevant studies, most assessed Alzheimer's disease versus healthy controls, using AD Neuroimaging Initiative data, support vector machines, and only T1-weighted sequences...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Brandon E Gavett, Katie Stypulkowski, Leigh Johnson, James Hall, Sid E O'Bryant
Introduction: The present study sought to investigate the measurement invariance of commonly used neuropsychological tests in an ethnically (Hispanic vs. non-Hispanic) and linguistically (Spanish vs. English) diverse sample. Methods: Participants were 736 middle-aged and older adults ( M Age  = 62.1, SD = 9.1) assessed at baseline. Measurement invariance testing was performed using multiple-group confirmatory factor analysis. Results: A five-factor model (memory, attention/executive functioning/processing speed, language, visuospatial, and motor) fit the data well (CFI = 0...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Marie Bruun, Hanneke F M Rhodius-Meester, Juha Koikkalainen, Marta Baroni, Le Gjerum, Afina W Lemstra, Frederik Barkhof, Anne M Remes, Timo Urhemaa, Antti Tolonen, Daniel Rueckert, Mark van Gils, Kristian S Frederiksen, Gunhild Waldemar, Philip Scheltens, Patrizia Mecocci, Hilkka Soininen, Jyrki Lötjönen, Steen G Hasselbalch, Wiesje M van der Flier
Introduction: We studied, using a data-driven approach, how different combinations of diagnostic tests contribute to the differential diagnosis of dementia. Methods: In this multicenter study, we included 356 patients with Alzheimer's disease, 87 frontotemporal dementia, 61 dementia with Lewy bodies, 38 vascular dementia, and 302 controls. We used a classifier to assess accuracy for individual performance and combinations of cognitive tests, cerebrospinal fluid biomarkers, and automated magnetic resonance imaging features for pairwise differentiation between dementia types...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Ann Hartry, Natalie V J Aldhouse, Tamara Al-Zubeidi, Myrlene Sanon, Richard G Stefanacci, Sarah L Knight
Introduction: This study aims to evaluate the conceptual relevance of four measures of disease activity in patients with mild/mild-moderate Alzheimer's disease (AD): (1) the Alzheimer's Disease Assessment Scale-Cognitive Subscale; (2) the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory; (3) the Neuropsychiatry Inventory; and (4) the Dependence Scale. Methods: A conceptual model depicting patient experience of mild AD was developed via literature review; concepts were compared with the items of the four measures...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Leslie Grasset, Fiona E Matthews, Karine Pérès, Alexandra Foubert-Samier, Catherine Helmer, Jean-François Dartigues, Carol Brayne
Introduction: The aims of this study are to examine the evolution of clinical dementia diagnosis over 3 decades and to investigate secular trends of dementia. Methods: Four cohorts covering a period from 1988 to 2013 were used: the Personnes Agées Quid and Three-City-Bordeaux studies, and the Cognitive Function and Aging Study (CFAS) I and II. Mini-Mental State Examination scores at clinical diagnosis were evaluated over a 24-year follow-up period in French studies...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Hitomi Yamamoto-Imoto, Daria Zamolodchikov, Zu-Lin Chen, S Lloyd Bourne, Syeda Rizvi, Pradeep Singh, Erin H Norris, Frances Weis-Garcia, Sidney Strickland
Introduction: Accumulation of β-amyloid is a pathological hallmark of Alzheimer's disease (AD). β-Amyloid activates the plasma contact system leading to kallikrein-mediated cleavage of intact high-molecular-weight kininogen (HKi) to cleaved high-molecular-weight kininogen (HKc). Increased HKi cleavage is observed in plasma of AD patients and mouse models by Western blot. For potential diagnostic purposes, a more quantitative method that can measure HKc levels in plasma with high sensitivity and specificity is needed...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Carolyn A Fredericks, Virginia E Sturm, Jesse A Brown, Alice Y Hua, Murat Bilgel, Dean F Wong, Susan M Resnick, William W Seeley
Introduction: Affective changes precede cognitive decline in mild Alzheimer's disease and may relate to increased connectivity in a "salience network" attuned to emotionally significant stimuli. The trajectory of affective changes in preclinical Alzheimer's disease, and its relationship to this network, is unknown. Methods: One hundred one cognitively normal older adults received longitudinal assessments of affective symptoms, then amyloid-PET. We hypothesized amyloid-positive individuals would show enhanced emotional reactivity associated with salience network connectivity...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Niels Kruse, Amanda Heslegrave, Vandana Gupta, Martha Foiani, Anna Villar-Piqué, Matthias Schmitz, Sylvain Lehmann, Charlotte Teunissen, Kaj Blennow, Henrik Zetterberg, Brit Mollenhauer, Inga Zerr, Franc Llorens
Introduction: Cerebrospinal fluid α-synuclein level is increased in sporadic Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker remains to be established. In this study, we have addressed the clinical validation parameters and the interlaboratory reproducibility by using an electrochemiluminescent assay. Methods: Cerebrospinal fluid α-synuclein was quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non-Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values and lot-to-lot variability...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
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