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Showing 1 - 200 of 3030 Journals sorted alphabetically
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Academic Pediatrics     Hybrid Journal   (Followers: 20, SJR: 1.402, h-index: 51)
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Accident Analysis & Prevention     Partially Free   (Followers: 79, SJR: 1.109, h-index: 94)
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Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 303, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription  
Acta de Investigación Psicológica     Open Access   (Followers: 2)
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Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
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Acupuncture and Related Therapies     Hybrid Journal   (Followers: 4)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
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Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 120, SJR: 5.2, h-index: 222)
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Advances in Integrative Medicine     Hybrid Journal   (Followers: 4)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 7, SJR: 0.764, h-index: 15)
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Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
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Advances in Pediatrics     Full-text available via subscription   (Followers: 20, SJR: 0.4, h-index: 28)
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Advances in Psychology     Full-text available via subscription   (Followers: 56)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
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Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 42, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 304, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 4, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 7, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 390, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 29, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 36, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 48, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 3, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 5)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 7, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 6, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 45, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 45, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 47, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 34, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 25, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 31, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 48, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 174, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 51, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 2)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 22, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 23, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 32, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 13, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 52, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 3)
Anales de Cirugia Vascular     Full-text available via subscription  
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Analytic Methods in Accident Research     Hybrid Journal   (Followers: 2, SJR: 2.577, h-index: 7)
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Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 143, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
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Journal Cover Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
  [5 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2352-8729
   Published by Elsevier Homepage  [3030 journals]
  • Altered levels of blood proteins in Alzheimer's disease longitudinal
           study: Results from Australian Imaging Biomarkers Lifestyle Study of
           Ageing cohort

    • Authors: V.B. Gupta; E. Hone; S. Pedrini; James Doecke; Sid O'Bryant; Ian James; Ashley I. Bush; Christopher C. Rowe; Victor L. Villemagne; David Ames; Colin L. Masters; R.N. Martins
      Abstract: Publication date: Available online 23 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): V.B. Gupta, E. Hone, S. Pedrini, James Doecke, Sid O'Bryant, Ian James, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, R.N. Martins
      A blood-based biomarker panel to identify individuals with preclinical Alzheimer's disease (AD) would be an inexpensive and accessible first step for routine testing. We analyzed 14 biomarkers that have previously been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal study of aging cohort. Levels of apolipoprotein J (apoJ) were higher in AD individuals compared with healthy controls at baseline and 18 months (P = .0003) and chemokine-309 (I-309) were increased in AD patients compared to mild cognitive impaired individuals over 36 months (P = .0008). These data suggest that apoJ may have potential in the context of use (COU) of AD diagnostics, I-309 may be specifically useful in the COU of identifying individuals at greatest risk for progressing toward AD. This work takes an initial step toward identifying blood biomarkers with potential use in the diagnosis and prognosis of AD and should be validated across other prospective cohorts.

      PubDate: 2017-04-28T12:24:51Z
      DOI: 10.1016/j.dadm.2017.04.003
  • Single-nucleotide polymorphisms are associated with cognitive decline at
           Alzheimer's disease conversion within mild cognitive impairment patients

    • Authors: Eunjee Lee; Kelly S. Giovanello; Andrew J. Saykin; Fengchang Xie; Dehan Kong; Yue Wang; Liuqing Yang; Joseph G. Ibrahim; P. Murali Doraiswamy; Hongtu Zhu
      Abstract: Publication date: Available online 23 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Eunjee Lee, Kelly S. Giovanello, Andrew J. Saykin, Fengchang Xie, Dehan Kong, Yue Wang, Liuqing Yang, Joseph G. Ibrahim, P. Murali Doraiswamy, Hongtu Zhu
      Introduction The growing public threat of Alzheimer's disease (AD) has raised the urgency to quantify the degree of cognitive decline during the conversion process of mild cognitive impairment (MCI) to AD and its underlying genetic pathway. The aim of this article was to test genetic common variants associated with accelerated cognitive decline after the conversion of MCI to AD. Methods In 583 subjects with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI; ADNI-1, ADNI-Go, and ADNI-2), 245 MCI participants converted to AD at follow-up. We tested the interaction effects between individual single-nucleotide polymorphisms and AD diagnosis trajectory on the longitudinal Alzheimer's Disease Assessment Scale-Cognition scores. Results Our findings reveal six genes, including BDH1, ST6GAL1, RAB20, PDS5B, ADARB2, and SPSB1, which are directly or indirectly related to MCI conversion to AD. Discussion This genome-wide association study sheds light on a genetic mechanism of longitudinal cognitive changes during the transition period from MCI to AD.

      PubDate: 2017-04-28T12:24:51Z
      DOI: 10.1016/j.dadm.2017.04.004
  • Severity of memory impairment in the elderly: Association with health care
           resource use and functional limitations in the United States

    • Authors: Myrlene Sanon Aigbogun; Robert Stellhorn; Holly Krasa; Dusan Kostic
      Abstract: Publication date: Available online 20 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Myrlene Sanon Aigbogun, Robert Stellhorn, Holly Krasa, Dusan Kostic
      Introduction Dementia is a prevalent condition in older adults associated with decline in cognitive and functional abilities and substantial burden. This study assessed the prevalence and impact of subjective memory impairment in the United States. Methods The 2011 to 2014 National Health and Nutrition Examination Survey, a population-based, nationally representative survey, was analyzed. Data included medical examinations, self-reported cognitive and functional limitations, and health care utilization over 1 year. Participants were aged ≥65 years and completed both interview and medical examination components. Descriptive analyses of patient characteristics were performed, and complex survey regression models were used to test associations. Results Of 2431 survey participants included, 53.1% had no memory impairment, 40.1% had early-stage memory impairment, and 6.6% had late-stage memory impairment. In adjusted analyses, late-stage versus no impairment was associated with more functional limitations (odds ratio [OR] = 7.26, P < .001), greater health care utilization (OR = 2.46, P < .001), and higher likelihood of seeing a mental health specialist (OR = 3.06, P = .001). Discussion Consistent with previous research, individuals with late-stage memory impairment had significantly greater functional limitations and higher health care utilization versus individuals with early-stage or no memory impairment.

      PubDate: 2017-04-20T17:48:08Z
      DOI: 10.1016/j.dadm.2017.04.001
  • Resting-state network dysfunction in Alzheimer's disease: A systematic
           review and meta-analysis

    • Authors: AmanPreet Badhwar; Angela Tam Christian Dansereau Pierre Orban Felix Hoffstaedter
      Abstract: Publication date: Available online 18 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): AmanPreet Badhwar, Angela Tam, Christian Dansereau, Pierre Orban, Felix Hoffstaedter, Pierre Bellec
      Introduction We performed a systematic review and meta-analysis of the Alzheimer's disease (AD) literature to examine consistency of functional connectivity alterations in AD dementia and mild cognitive impairment, using resting-state functional magnetic resonance imaging. Methods Studies were screened using a standardized procedure. Multiresolution statistics were performed to assess the spatial consistency of findings across studies. Results Thirty-four studies were included (1363 participants, average 40 per study). Consistent alterations in connectivity were found in the default mode, salience, and limbic networks in patients with AD dementia, mild cognitive impairment, or in both groups. We also identified a strong tendency in the literature toward specific examination of the default mode network. Discussion Convergent evidence across the literature supports the use of resting-state connectivity as a biomarker of AD. The locations of consistent alterations suggest that highly connected hub regions in the brain might be an early target of AD.

      PubDate: 2017-04-20T17:48:08Z
  • Cerebrospinal fluid biomarker Aβ1–42, T-tau, and P-tau values are not
           affected by biobank storage up to 12 years

    • Authors: Eline A.J. Willemse; Kees W.J. van Uffelen; Wiesje M. van der Flier; Charlotte E. Teunissen
      Abstract: Publication date: Available online 4 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Eline A.J. Willemse, Kees W.J. van Uffelen, Wiesje M. van der Flier, Charlotte E. Teunissen
      Introduction We studied the effect of long-term storage at −80°C on cerebrospinal fluid (CSF) biomarker levels. Our approach assumed consistency of mean biomarker levels in a homogenous Alzheimer's disease patient cohort over time. Methods We selected 148 Alzheimer's disease samples that had inclusion dates equally distributed over the years 2001 to 2013 from our biobank. The concentrations of CSF biomarkers, amyloid-β1–42 (Aβ1–42), total tau (T-tau), and phosphorylated tau181 (P-tau), were measured with one enzyme-linked immunosorbent assay lot. Results were compared with historical results obtained at biobank inclusion. Results Linear regression analyses showed that the levels of CSF biomarkers, Aβ1–42, T-tau, and P-tau, were not related to storage time at −80°C (β = 0.015, 0.048, and 0.0016 pg/mL per day, n.s.). However, the differences between remeasured concentrations of Aβ1–42 and concentrations at biobank inclusion measured for more than 30 assay batches increased with increasing time difference. Discussion The levels of CSF biomarkers, Aβ1–42, T-tau, and P-tau, did not significantly change during the maximum period of 12 years of storage at −80°C. Batch variation for Aβ1–42 is a factor that should be controlled for when using historical cohorts.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.005
  • Multidimensional assessment of challenging behaviors in advanced stages of
           dementia in nursing homes—The insideDEM framework

    • Authors: Stefan Teipel; Christina Heine; Albert Hein; Frank Krüger; Andreas Kutschke; Sven Kernebeck; Margareta Halek; Sebastian Bader; Thomas Kirste
      Abstract: Publication date: Available online 4 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Stefan Teipel, Christina Heine, Albert Hein, Frank Krüger, Andreas Kutschke, Sven Kernebeck, Margareta Halek, Sebastian Bader, Thomas Kirste
      Introduction Assessment of challenging behaviors in dementia is important for intervention selection. Here, we describe the technical and experimental setup and the feasibility of long-term multidimensional behavior assessment of people with dementia living in nursing homes. Methods We conducted 4 weeks of multimodal sensor assessment together with real-time observation of 17 residents with moderate to very severe dementia in two nursing care units. Nursing staff received extensive training on device handling and measurement procedures. Behavior of a subsample of eight participants was further recorded by videotaping for more than 4 weeks during day hours. Sensors were mounted on the participants' wrist and ankle and measured motion, rotation, as well as surrounding loudness level, light level, and air pressure. Results Participants were in moderate to severe stages of dementia. Almost 100% of participants exhibited relevant levels of challenging behaviors. Automated quality control detected 155 potential issues. But only 11% of the recordings have been influenced by noncompliance of the participants. Qualitative debriefing of staff members suggested that implementation of the technology and observation platform in the routine procedures of the nursing home units was feasible and identified a range of user- and hardware-related implementation and handling challenges. Discussion Our results indicate that high-quality behavior data from real-world environments can be made available for the development of intelligent assistive systems and that the problem of noncompliance seems to be manageable. Currently, we train machine-learning algorithms to detect episodes of challenging behaviors in the recorded sensor data.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.006
  • Assessment of everyday conversation and acoustic environments to
           objectively identify changes in cognition: A proof-of-concept study

    • Authors: Amanda Stead; Jeffrey Kaye; Hiroko H. Dodge; Katherine Wild; Nora Mattek; Terry Hallett; James Steiger
      Abstract: Publication date: Available online 31 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Amanda Stead, Jeffrey Kaye, Hiroko H. Dodge, Katherine Wild, Nora Mattek, Terry Hallett, James Steiger
      Introduction The goal was to determine the feasibility of audio environment recording and establish preliminary evidence for the ability to identify differences in speech and language at the intra-individual level. Methods Ten adult dyads, seven healthy and three with a cognitively impaired (CI) member, were fit with a digital Language Environment Analysis recorder to track spontaneous speech. The hour that had the most conversational turns each day was analyzed for language features associated with cognitive status. The device also characterized the full days' audio environment. Results Five of seven language variables including conversational turns, total words, type token ratio, mazes, and total utterances were able to predict cognitive status group. The percentages of noise and TV-associated sound were significantly higher in the audio environments of the CI adults. Discussion The results of this study suggest that the everyday language used by dyads within their home can be used to distinguish between healthy and CI dyads. In addition, the audio environment of those CI adults is more passive than that of healthy older adults.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.001
  • Detecting functional decline from normal aging to dementia: Development
           and validation of a short version of the Amsterdam IADL Questionnaire

    • Authors: Roos J. Jutten; Carel F.W. Peeters; Sophie M.J. Leijdesdorff; Pieter J. Visser; Andrea B. Maier; Caroline B. Terwee; Philip Scheltens; Sietske A.M. Sikkes
      Abstract: Publication date: Available online 31 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Roos J. Jutten, Carel F.W. Peeters, Sophie M.J. Leijdesdorff, Pieter J. Visser, Andrea B. Maier, Caroline B. Terwee, Philip Scheltens, Sietske A.M. Sikkes
      Introduction Detecting functional decline from normal aging to dementia is relevant for diagnostic and prognostic purposes. Therefore, the Amsterdam IADL Questionnaire (A-IADL-Q) was developed: a 70-item proxy-based tool with good psychometric properties. We aimed to design a short version while preserving its psychometric quality. Methods Study partners of subjects (n = 1355), ranging from cognitively normal to dementia subjects, completed the original A-IADL-Q. We selected the short version items using a stepwise procedure combining missing data, Item Response Theory, and input from respondents and experts. We investigated internal consistency of the short version and concordance with the original version. To assess its construct validity, we additionally investigated concordance between the short version and the Mini–Mental State Examination and Disability Assessment for Dementia. Finally, we investigated differences in instrumental activities of daily living (IADL) scores between diagnostic groups across the dementia spectrum. Results We selected 30 items covering the entire spectrum of IADL functioning. Internal consistency (0.98) and concordance with the original version (0.97) were very high. Concordance with the Mini–Mental State Examination (0.72) and Disability Assessment for Dementia (0.87) scores was high. IADL impairment scores increased across the spectrum from normal cognition to dementia. Discussion The A-IADL-Q short version consists of 30 items. The A-IADL-Q short version has maintained the psychometric quality of the original A-IADL-Q. As such, it is a concise measure of functional decline.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.002
  • Changes in metabolic risk factors over 10 years and their associations
           with late-life cognitive performance: The Multi-Ethnic Study of

    • Authors: Timothy M. Hughes; Suzanne Craft; Laura Baker; Mark A. Espeland; Stephen R. Rapp; Kaycee M. Sink; Alain G. Bertoni; Gregory L. Burke; Rebecca F. Gottesman; Erin D. Michos; José A. Luchsinger; Annette L. Fitzpatrick; Kathleen M. Hayden
      Abstract: Publication date: Available online 31 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Timothy M. Hughes, Suzanne Craft, Laura Baker, Mark A. Espeland, Stephen R. Rapp, Kaycee M. Sink, Alain G. Bertoni, Gregory L. Burke, Rebecca F. Gottesman, Erin D. Michos, José A. Luchsinger, Annette L. Fitzpatrick, Kathleen M. Hayden
      Background We examined whether changes in metabolic factors over 10 years were associated with cognitive performance. Methods Participants from the Multi-Ethnic Study of Atherosclerosis were followed since baseline (2000–2002) with five clinical examinations. At exam 5 (2010–2012), they received a short cognitive battery (Cognitive Abilities Screening Instrument [CASI], Digit Symbol Coding [DSC], and Digit Span [DS]). We examined associations between baseline metabolic factors and their changes over time before cognitive testing. Results Among 4392 participants, baseline metabolic disorders (fasting glucose, systolic and diastolic blood pressures) were significantly associated with poorer CASI, DSC, and DS scores measured 10 years later. Increases in blood pressure were associated with lower cognitive performance. Results did not differ by race/ethnicity and were stronger among those without the APOE ε4 allele. Conclusions Cognitive performance was associated with antecedent abnormalities in glucose metabolism and blood pressure increases. Findings appeared stronger among APOE ε4-negative participants.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.003
  • Choroidal thinning: Alzheimer's disease and aging

    • Authors: João Paulo Cunha; Rita Proença; Arnaldo Dias-Santos; Diana Melancia; Rita Almeida; Helena Águas; Bruno Oliveira Santos; Marta Alves; Joana Ferreira; Ana Luísa Papoila; Carlota Louro; António Castanheira-Dinis
      Abstract: Publication date: Available online 30 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): João Paulo Cunha, Rita Proença, Arnaldo Dias-Santos, Diana Melancia, Rita Almeida, Helena Águas, Bruno Oliveira Santos, Marta Alves, Joana Ferreira, Ana Luísa Papoila, Carlota Louro, António Castanheira-Dinis
      Purpose To measure and to compare macular choroidal thickness (CT) between patients with mild Alzheimer's disease (AD), patients without AD, and elderly patients. Methods CT was measured manually in 13 locations at 500-μm intervals of a horizontal and a vertical section from the fovea. Linear regression models were used to analyze the data. Results Fifty patients with a diagnosis of mild AD (73.1 years), 152 patients without AD (71.03 years), and 50 elderly without AD (82.14 years) were included. In the AD patients, CT was significantly thinner in all 13 locations (P < .001—comparing with age-match group), and comparing with the elderly group, a more pronounced difference was found in two locations temporal to the fovea. Conclusions Patients with AD showed a significant choroidal thinning even when compared with elderly subjects. The reduction of CT may aid in the diagnoses of AD, probably reflecting the importance of vascular factors in their pathogenesis.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.004
  • Cerebrospinal fluid biomarkers for Alzheimer's disease in Down syndrome

    • Authors: Alain D. Dekker; Juan Fortea; Rafael Blesa; Peter P. De Deyn
      Abstract: Publication date: Available online 20 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Alain D. Dekker, Juan Fortea, Rafael Blesa, Peter P. De Deyn
      Down syndrome (DS), present in nearly six million people, is associated with an extremely high risk to develop Alzheimer's disease (AD). Amyloid-β and tau pathology are omnipresent from age 40 years onward, but clinical symptoms do not appear in all DS individuals. Dementia diagnostics is complex in this population, illustrating the great need for predictive biomarkers. Although blood biomarkers have not yet proven useful, cerebrospinal fluid (CSF) biomarkers (low amyloid-β42, high t-tau, and high p-tau) effectively contribute to AD diagnoses in the general population and are increasingly used in clinical practice. Surprisingly, CSF biomarkers have been barely evaluated in DS. Breaking the taboo on CSF analyses would finally allow for the elucidation of its utility in (differential) diagnoses and staging of disease severity. A sensitive and specific biomarker profile for AD in DS would be of paramount importance to daily care, adaptive caregiving, and specific therapeutic interventions.

      PubDate: 2017-03-24T11:30:56Z
      DOI: 10.1016/j.dadm.2017.02.006
  • Reduced future-oriented decision making in individuals with subjective
           cognitive decline: A functional MRI study

    • Authors: Xiaochen Hu; Franziska Uhle; Klaus Fliessbach; Michael Wagner; Ying Han; Bernd Weber; Frank Jessen
      Abstract: Publication date: Available online 14 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Xiaochen Hu, Franziska Uhle, Klaus Fliessbach, Michael Wagner, Ying Han, Bernd Weber, Frank Jessen
      Background Subjective cognitive decline (SCD) refers to an at-risk state of Alzheimer's disease and subtle cognitive deficits that have been observed in this condition. Currently, it is unknown whether complex cognitive processes relevant to everyday life, such as future-oriented choice behavior, are also altered in SCD. Methods Twenty SCD participants and 24 control (CO) participants took part in a functional magnetic resonance imaging task on intertemporal decisions, with and without simultaneous episodic future imagination. Results SCD participants showed reduced future-oriented choices. Future imagination increased future-oriented choices and was associated with brain activation in medial frontal polar cortex, right insular cortex, and anterior cingulate cortex in CO only, not SCD. In addition, more future-oriented choices were associated with hippocampal activation during choice processing in CO only. Discussion Subtle neuronal network disruptions in SCD may underlie their myopic future decisions and lack of modulation of choice behavior by episodic future imagination.

      PubDate: 2017-03-18T17:00:37Z
      DOI: 10.1016/j.dadm.2017.02.005
  • A multinational study distinguishing Alzheimer's and healthy patients
           using cerebrospinal fluid tau/Aβ42 cutoff with concordance to amyloid PET

    • Authors: Yi Mo; Julie Stromswold; Kimberly Wilson; Daniel Holder; Cyrille Sur; Omar Laterza; Mary J. Savage; Arie Struyk; Philip Scheltens; Charlotte E. Teunissen; James Burke; S. Lance Macaulay; Geir Bråthen; Sigrid Botne Sando; Linda R. White; Christy Weiss; Arturo Cowes; Michele M. Bush; Ganga DeSilva; David G. Darby; Stephanie R. Rainey-Smith; Jackie Surls; Eileen Sagini; Michael Tanen; Amy Altman; Johan Luthman; Michael F. Egan
      Abstract: Publication date: Available online 6 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Yi Mo, Julie Stromswold, Kimberly Wilson, Daniel Holder, Cyrille Sur, Omar Laterza, Mary J. Savage, Arie Struyk, Philip Scheltens, Charlotte E. Teunissen, James Burke, S. Lance Macaulay, Geir Bråthen, Sigrid Botne Sando, Linda R. White, Christy Weiss, Arturo Cowes, Michele M. Bush, Ganga DeSilva, David G. Darby, Stephanie R. Rainey-Smith, Jackie Surls, Eileen Sagini, Michael Tanen, Amy Altman, Johan Luthman, Michael F. Egan
      Introduction Changes in cerebrospinal fluid (CSF) tau and amyloid β (Aβ)42 accompany development of Alzheimer's brain pathology. Robust tau and Aβ42 immunoassays were developed to establish a tau/Aβ42 cutoff distinguishing mild-to-moderate Alzheimer's disease (AD) subjects from healthy elderly control (HC) subjects. Methods A CSF tau/Aβ42 cutoff criteria was chosen, which distinguished the groups and maximized concordance with amyloid PET. Performance was assessed using an independent validation cohort. Results A tau/Aβ42 = 0.215 cutoff provided 94.8% sensitivity and 77.7% specificity. Concordance with PET visual reads was estimated at 86.9% in a ∼50% PET positive population. In the validation cohort, the cutoff demonstrated 78.4% sensitivity and 84.9% specificity to distinguish the AD and HC populations. Discussion A tau/Aβ42 cutoff with acceptable sensitivity and specificity distinguished HC from mild-to-moderate AD subjects and maximized concordance to brain amyloidosis. The defined cutoff demonstrated that CSF analysis may be useful as a surrogate to imaging assessment of AD pathology.

      PubDate: 2017-03-10T19:16:08Z
      DOI: 10.1016/j.dadm.2017.02.004
  • Variability in medication taking is associated with cognitive performance
           in nondemented older adults

    • Authors: Johanna Austin; Krystal Klein; Nora Mattek; Jeffrey Kaye
      Abstract: Publication date: Available online 6 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Johanna Austin, Krystal Klein, Nora Mattek, Jeffrey Kaye
      Interventions to slow cognitive decline typically can do little to reverse decline. Thus, early detection methods are critical. However, tools like cognitive testing are time consuming and require costly expertise. Changes in activities of daily living such as medication adherence may herald the onset of cognitive decline before clinical standards. Here, we determine the relationship between medication adherence and cognitive function in preclinical older adults. We objectively assessed medication adherence in 38 older adults (mean age 86.7 ± 6.9 years). Our results demonstrate that individuals with lower cognitive function have more spread in the timing of taking their medications (P = .014) and increase the spread in the timing of taking their medications over time (P = .012). These results demonstrate that continuous monitoring of medication adherence may provide the opportunity to identify patients experiencing slow cognitive decline in the earliest stages when pharmacologic or behavioral interventions may be most effective.

      PubDate: 2017-03-10T19:16:08Z
      DOI: 10.1016/j.dadm.2017.02.003
  • Age at injury is associated with the long-term cognitive outcome of
           traumatic brain injuries

    • Authors: Wei Li; Shannon L. Risacher; Thomas W. McAllister; Andrew J. Saykin
      Abstract: Publication date: Available online 2 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Wei Li, Shannon L. Risacher, Thomas W. McAllister, Andrew J. Saykin
      Introduction The association between age at injury (AAI) and long-term cognitive outcome of traumatic brain injuries (TBIs) is debatable. Methods Eligible participants with a TBI history from Alzheimer's Disease Neuroimaging Initiative were divided into a childhood TBI (cTBI) group (the AAI ≤ 21 years old) and an adult TBI (aTBI) group (the AAI > 21 years old). Results The cTBI group has a higher Everyday Cognition total score than the aTBI group. All perceived cognitive functions are worse for the cTBI group than for the aTBI group except memory. By contrast, the cTBI group has higher assessment scores on either the Boston Naming Test or Rey Auditory Verbal Learning Test than the aTBI group. Discussion The AAI is associated with the long-term cognitive outcomes in older adults with a TBI history.

      PubDate: 2017-03-05T20:50:37Z
      DOI: 10.1016/j.dadm.2017.01.008
  • CSF biomarker examination as a tool to discriminate behavioral variant
           frontotemporal dementia from primary psychiatric disorders

    • Authors: Everard G.B. Vijverberg; Annemiek Dols; Welmoed A. Krudop; Marta Del Campo Milan; Cora J. Kerssens; Flora Gossink; Niels D. Prins; Max L. Stek; Philip Scheltens; Charlotte E. Teunissen; Yolande A.L. Pijnenburg
      Abstract: Publication date: Available online 2 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Everard G.B. Vijverberg, Annemiek Dols, Welmoed A. Krudop, Marta Del Campo Milan, Cora J. Kerssens, Flora Gossink, Niels D. Prins, Max L. Stek, Philip Scheltens, Charlotte E. Teunissen, Yolande A.L. Pijnenburg
      Introduction To prospectively determine the diagnostic value of cerebrospinal fluid (CSF) levels total-tau (tau) to amyloid-β1–42 ratio (Aβ1–42) ratio (tau/Aβ1–42 ratio), phosphorylated-tau (p-tau) to tau ratio (p-tau/tau ratio), neurofilament light chain (NfL) and YKL40 in the late-onset frontal lobe syndrome, in particular for the differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) versus primary psychiatric disorders (PSY). Method We included patients with a multidisciplinary 2-year-follow-up diagnosis of probable/definite bvFTD (n = 22) or PSY (n = 25), who underwent a detailed neuropsychiatric clinical examination, neuropsychological test battery, and magnetic resonance imaging at baseline. In all cases, CSF was collected through lumbar puncture at baseline. We compared CSF biomarker levels between the two groups and measured the diagnostic accuracy for probable/definite bvFTD, using the follow-up diagnosis as the reference standard. Results The best discriminators between probable/definite bvFTD and PSY were the levels of CSF NfL (area under the curve [AUC] 0.93, P < .001, 95% confidence interval [CI] 0.85–1.00), p-tau/tau ratio (AUC 0.87, P < .001, 95% CI 0.77–0.97), and YKL40 (AUC 0.82, P = .001, 95% CI 0.68–0.97). The combination of these three biomarkers had a sensitivity of 91% (95% CI 66%–100%) at a specificity of 83% (95% CI 65%–95%) with an AUC of 0.94 (P < .001, 95% CI 0.87–1.00) for bvFTD. CSF tau/Aβ1–42 ratio was less accurate in differentiating between bvFTD and PSY. Discussion We found a good diagnostic accuracy for higher levels of CSF NfL and YKL40 and reduced p-tau/tau ratio in distinguishing bvFTD from PSY. We advocate the use of these CSF biomarkers as potential additional tools to neuroimaging in the diagnosis of bvFTD versus PSY.

      PubDate: 2017-03-05T20:50:37Z
      DOI: 10.1016/j.dadm.2017.01.009
  • δ scores predict MCI and AD conversions from nondemented states

    • Authors: Donald R. Royall; Raymond F. Palmer
      Abstract: Publication date: Available online 2 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Donald R. Royall, Raymond F. Palmer
      Introduction We tested the latent variable “δ” (for “dementia”)'s ability to predict conversion to “mild cognitive impairment” (MCI) and Alzheimer's disease (AD). Methods An ethnicity equivalent δ homolog (“dEQ”) was constructed in n = 1113 Mexican-American (MA) and n = 1958 non-Hispanic white (NHW) participants in the Texas Alzheimer's Research and Care Consortium. n = 1276 “normal controls” (NC) and n = 611 MCI were followed annually for up to 6 years [ṁ = 4.7(0.6)]. Results n = 281 (22.0%) of NC converted to “MCI” or “AD”. n = 106 (17.3%) of MCI converted to “AD.” Independently of covariates, each quintile increase in the dEQ scores of NC increased the odds of conversion by 52%. Each quintile increase in the dEQ scores of MCI cases increased the odds of conversion to AD almost three-fold. Discussion Baseline δ scores predict MCI and AD conversions from nondemented states in MA and NHW.

      PubDate: 2017-03-05T20:50:37Z
      DOI: 10.1016/j.dadm.2017.02.002
  • Identifying memory impairment and early dementia in primary care

    • Authors: Ellen Grober; Dorothy Wakefield; Amy R. Ehrlich; Peter Mabie; Richard B. Lipton
      Abstract: Publication date: Available online 24 February 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Ellen Grober, Dorothy Wakefield, Amy R. Ehrlich, Peter Mabie, Richard B. Lipton
      Introduction This study examined the operating characteristics of two-stage case finding to identify memory impairment and very mild dementia. Methods Primary care patients underwent two-stage testing and a subsequent diagnostic assessment to assess outcomes. Patients who screen positive for subjective cognitive decline on the Informant Questionnaire on Cognitive Decline in the Elderly undergo memory testing with the Free and Cued Selective Reminding Test with Immediate Recall. Outcomes were determined without access to these data. A split-half design with discovery and confirmatory samples was used. Results One hundred seventeen of 563 (21%) patients had dementia and 68 (12%) had memory impairment but not dementia. Operating characteristics were similar in the discovery and confirmatory samples. In the pooled sample, combined, patients with memory impairment or dementia were identified with good sensitivity (72%) and high specificity (90%). Differences in ethnicity, educational level, or age (≤75, >75) did not affect classification accuracy. Discussion Two-stage screening facilitates the efficient identification of older adults with memory impairment or dementia.

      PubDate: 2017-02-25T16:12:06Z
      DOI: 10.1016/j.dadm.2017.01.006
  • Development of an instrument to assess social functioning in dementia: The
           Social Functioning in Dementia scale

    • Authors: Andrew Sommerlad; David Singleton; Rebecca Jones; Sube Banerjee; Gill Livingston
      Abstract: Publication date: Available online 24 February 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Andrew Sommerlad, David Singleton, Rebecca Jones, Sube Banerjee, Gill Livingston
      Background Social functioning is a core domain in the life of people with dementia, but there is no accepted instrument to measure it. Aims To develop the Social Functioning in Dementia (SF-DEM) scale and test its psychometric properties for assessing social function in people with dementia. Method We interviewed people with mild dementia and family caregivers to develop patient and caregiver-rated SF-DEM versions and then refined them through interviews with health care professionals. We tested its psychometric properties in 30 dyads of people with dementia and family caregivers. Results Both SF-DEM versions had content validity and demonstrated concurrent validity against a single item rating overall social functioning (patient rated r = 0.42, 95% CI [0.07–0.68]; caregiver rated r = 0.59, 95% CI [0.29–0.78]). All participants found it acceptable. Analyses showed reliability (test–retest, interrater, internal consistency) and indications of responsiveness to change. Conclusions SF-DEM shows promise as a valid, reliable, acceptable measure of social functioning in dementia.

      PubDate: 2017-02-25T16:12:06Z
      DOI: 10.1016/j.dadm.2017.02.001
  • Apolipoproteins and their subspecies in human cerebrospinal fluid and

    • Authors: Manja Koch; Jeremy D. Furtado; Kim Falk; Frank Leypoldt; Kenneth J. Mukamal; Majken K. Jensen
      Abstract: Publication date: Available online 24 February 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Manja Koch, Jeremy D. Furtado, Kim Falk, Frank Leypoldt, Kenneth J. Mukamal, Majken K. Jensen
      Introduction Subspecies of apolipoproteins can be defined by fractionating apolipoproteins based on the presence and absence of coexisting apolipoproteins. Methods We determined age- and sex-adjusted correlations of enzyme-linked immunosorbent assay–measured plasma and cerebrospinal fluid (CSF) apolipoproteins (apoA-I, apoC-III, apoE, and apoJ) or apolipoprotein subspecies (apoA-I with and without apoC-III, ApoE, or apoJ; apoE with and without apoC-III or apoJ) in 22 dementia-free participants. Results CSF apoE did not correlate with plasma apolipoproteins or their subspecies. CSF apoJ correlated most strongly with plasma apoA-I without apoJ (r = 0.7). CSF apoA-I correlated similarly strong with plasma total apoA-I and all apoA-I subspecies (r ≥ 0.4) except for apoA-I with apoE (r = 0.3) or apoA-I with apoJ (r = 0.3). CSF apoC-III was most strongly correlated with plasma apoA-I with apoC-III (r = 0.7). Discussion CSF levels of some apolipoproteins implicated in the pathophysiology of dementia might be better approximated by specific plasma apolipoprotein subspecies than total plasma concentrations.

      PubDate: 2017-02-25T16:12:06Z
      DOI: 10.1016/j.dadm.2017.01.007
  • Pathophysiologic relationship between Alzheimer's disease, cerebrovascular
           disease, and cardiovascular risk: A review and synthesis

    • Authors: Cláudia Y. Santos; Peter J. Snyder; Wen-Chih Wu; Mia Zhang; Ana Echeverria; Jessica Alber
      Abstract: Publication date: Available online 9 February 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Cláudia Y. Santos, Peter J. Snyder, Wen-Chih Wu, Mia Zhang, Ana Echeverria, Jessica Alber
      As the population ages due to demographic trends and gains in life expectancy, the incidence and prevalence of dementia increases, and the need to understand the etiology and pathogenesis of dementia becomes ever more urgent. Alzheimer's disease (AD), the most common form of dementia, is a complex disease, the mechanisms of which are poorly understood. The more we learn about AD, the more questions are raised about our current conceptual models of disease. In the absence of a cure or the means by which to slow disease progress, it may be prudent to apply our current knowledge of the intersection between AD, cardiovascular disease, and cerebrovascular disease to foster efforts to delay or slow the onset of AD. This review discusses our current understanding of the epidemiology, genetics, and pathophysiology of AD, the intersection between AD and vascular causes of dementia, and proposes future directions for research and prevention.

      PubDate: 2017-02-13T11:18:18Z
      DOI: 10.1016/j.dadm.2017.01.005
  • A robust biomarker of large-scale network failure in Alzheimer's disease

    • Authors: Daniela Wiepert; Val J. Lowe; David Knopman; Bradley Boeve; Jonathan Graff-Radford; Ronald Peterson; Clifford Jack; David Jones
      Abstract: Publication date: Available online 25 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Daniela Wiepert, Val J. Lowe, David Knopman, Bradley Boeve, Jonathan Graff-Radford, Ronald Peterson, Clifford Jack, David Jones
      Introduction Biomarkers for Alzheimer's disease (AD) pathophysiology have been developed that focus on various levels of brain organization. However, no robust biomarker of large-scale network failure has been developed. Using the recently introduced cascading network failure model of AD, we developed the network failure quotient (NFQ) as a biomarker of this process. Methods We developed and optimized the NFQ using our recently published analyses of task-free functional magnetic resonance imaging data in clinically normal (n = 43) and AD dementia participants (n = 28) from the Alzheimer's Disease Neuroimaging Initiative. The optimized NFQ (oNFQ) was then validated in a cohort spanning the AD spectrum from the Mayo Clinic (n = 218). Results The oNFQ (d = 1.25, 95% confidence interval [1.25, 1.26]) had the highest effect size for differentiating persons with AD dementia from clinically normal participants. The oNFQ measure performed similarly well on the validation Mayo Clinic sample (d = 1.44, 95% confidence interval [1.43, 1.44]). The oNFQ was also associated with other available key biomarkers in the Mayo cohort. Discussion This study demonstrates a measure of functional connectivity, based on a cascading network failure model of AD, and was highly successful in identifying AD dementia. A robust biomarker of the large-scale effects of AD pathophysiology will allow for richer descriptions of the disease process and its modifiers, but is not currently suitable for discriminating clinical diagnostic categories. The large-scale network level may be one of the earliest manifestations of AD, making this an attractive target for continued biomarker development to be used in prevention trials.

      PubDate: 2017-02-01T09:24:40Z
      DOI: 10.1016/j.dadm.2017.01.004
  • Retinal thickness in Alzheimer disease? A systematic review
           and meta-analysis

    • Authors: Jurre den Haan; Frank D. Verbraak; Pieter Jelle Visser; Femke H. Bouwman
      Abstract: Publication date: Available online 25 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Jurre den Haan, Frank D. Verbraak, Pieter Jelle Visser, Femke H. Bouwman
      Introduction Retinal characteristics are increasingly recognized as biomarkers for neurodegenerative diseases. Retinal thickness measured by optical coherence tomography may reflect the presence of Alzheimer disease (AD). We performed a meta-analysis on retinal thickness in AD and mild cognitive impairment (MCI) patients and healthy controls (HCs). Methods We selected 25 studies with measurements of retinal thickness including 887 AD patients, 216 MCI patients, and 864 HCs that measured retinal thickness. Outcomes were peripapillary retinal nerve fiber layer (RNFL) and macular thickness. The main outcome was the standardized mean differences (SMDs). We used STATA to perform the meta-analysis. Results Relative to HCs, AD and MCI patients had lower peripapillary RNFL (SMD 0.98 [CI −1.30, −0.66, P < .0001] and SMD 0.71 [CI −1.24, −0.19, P = .008]). Total macular thickness was decreased in AD patients (SMD 0.88 [CI −1.12, −0.65, P = .000]). Discussion Retinal thickness is decreased in AD and MCI patients compared to HC. This confirms that neurodegenerative diseases may be reflected by retinal changes.

      PubDate: 2017-02-01T09:24:40Z
      DOI: 10.1016/j.dadm.2016.12.014
  • Serum IL-8 is a marker of white-matter hyperintensities in patients with
           Alzheimer disease

    • Authors: Yanan Zhu; Yuek Ling Chai; Saima Hilal; M. Kamran Ikram; Narayanaswamy Venketasubramanian; Boon-Seng Wong; Christopher P. Chen; Mitchell K.P. Lai
      Abstract: Publication date: Available online 23 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Yanan Zhu, Yuek Ling Chai, Saima Hilal, M. Kamran Ikram, Narayanaswamy Venketasubramanian, Boon-Seng Wong, Christopher P. Chen, Mitchell K.P. Lai
      Introduction Neuroinflammation and cerebrovascular disease (CeVD) have been implicated in cognitive impairment and Alzheimer disease (AD). The present study aimed to examine serum inflammatory markers in preclinical stages of dementia and in AD, as well as to investigate their associations with concomitant CeVD. Methods We performed a cross-sectional case–control study including 96 AD, 140 cognitively impaired no dementia (CIND), and 79 noncognitively impaired participants. All subjects underwent neuropsychological and neuroimaging assessments, as well as collection of blood samples for measurements of serum samples interleukin (IL)-6, IL-8, and tumor necrosis factor α levels. Subjects were classified as CIND or dementia based on clinical criteria. Significant CeVD, including white-matter hyperintensities (WMHs), lacunes, and cortical infarcts, was assessed by magnetic resonance imaging. Results After controlling for covariates, higher concentrations of IL-8, but not the other measured cytokines, were associated with both CIND and AD only in the presence of significant CeVD (CIND with CeVD: odds ratios [ORs] 4.53; 95% confidence interval [CI] 1.5–13.4 and AD with CeVD: OR 7.26; 95% CI 1.2–43.3). Subsequent multivariate analyses showed that among the types of CeVD assessed, only WMH was associated with higher IL-8 levels in CIND and AD (WMH: OR 2.81; 95% CI 1.4–5.6). Discussion Serum IL-8 may have clinical utility as a biomarker for WMH in AD. Longitudinal follow-up studies would help validate these findings.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2017.01.001
  • Macrovascular and microvascular cerebral blood flow in adults at risk for
           Alzheimer's disease

    • Authors: Lindsay R. Clark; Sara E. Berman; Leonardo A. Rivera-Rivera; Siobhan M. Hoscheidt; Burcu F. Darst; Corinne D. Engelman; Howard A. Rowley; Cynthia M. Carlsson; Sanjay Asthana; Patrick Turski; Oliver Wieben; Sterling C. Johnson
      Abstract: Publication date: Available online 23 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Lindsay R. Clark, Sara E. Berman, Leonardo A. Rivera-Rivera, Siobhan M. Hoscheidt, Burcu F. Darst, Corinne D. Engelman, Howard A. Rowley, Cynthia M. Carlsson, Sanjay Asthana, Patrick Turski, Oliver Wieben, Sterling C. Johnson
      Introduction Capillary hypoperfusion is reported in asymptomatic adults at risk for Alzheimer's disease (AD), but the extent that can be explained by reduced flow in intracranial arteries is unknown. We investigated cerebral microvascular and macrovascular blood flow and potential moderators of this relationship. Methods One hundred fifty-five asymptomatic adults enriched for AD risk (mean age 61 years, 71% parental history of AD) underwent magnetic resonance imaging that included pseudocontinuous arterial spin labeling and phase-contrast vastly undersampled isotropic projection 4D-flow imaging. Voxel-wise regression models investigated the relationship between mean flow in bilateral cerebral arteries and whole-brain cerebral perfusion, and subsequent models tested if age, cardiovascular, and genetic factors moderated this relationship. Results Mean arterial blood flow through middle cerebral arteries (MCAs) and internal carotid arteries was positively associated with perfusion in large cortical clusters (P < .05, false discovery rate corrected). Trends were observed for the interactions MCA flow × age and MCA flow × cardiovascular risk on cerebral perfusion (P < .001, uncorrected). Discussion These findings provide evidence that capillary perfusion measured via pseudocontinuous arterial spin labeling is strongly dependent on inflow from larger cerebral arteries. Further studies are warranted to investigate possible alterations between macrovascular and microvascular flow in advanced age and elevated cardiovascular risk in asymptomatic adults at risk for AD.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2017.01.002
  • Alzheimer's biomarkers in daily practice project: Rationale and design

    • Authors: Arno de Wilde; Ingrid S. van Maurik; Marleen Kunneman; Femke Bouwman; Marissa Zwan; Eline A.J. Willemse; Geert Jan Biessels; Mirella Minkman; Ruth Pel; Niki S.M. Schoonenboom; Ellen M.A. Smets; Mike P. Wattjes; Frederik Barkhof; Andrew Stephens; Erik J. van Lier; Richard Batrla-Utermann; Philip Scheltens; Charlotte E. Teunissen; Bart N.M. van Berckel; Wiesje M. van der Flier
      Abstract: Publication date: Available online 23 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Arno de Wilde, Ingrid S. van Maurik, Marleen Kunneman, Femke Bouwman, Marissa Zwan, Eline A.J. Willemse, Geert Jan Biessels, Mirella Minkman, Ruth Pel, Niki S.M. Schoonenboom, Ellen M.A. Smets, Mike P. Wattjes, Frederik Barkhof, Andrew Stephens, Erik J. van Lier, Richard Batrla-Utermann, Philip Scheltens, Charlotte E. Teunissen, Bart N.M. van Berckel, Wiesje M. van der Flier
      The Alzheimer's biomarkers in daily practice (ABIDE) study is designed to translate knowledge on novel diagnostic tests (magnetic resonance imaging [MRI], cerebrospinal fluid [CSF], and amyloid positron emission tomography [PET]) to daily clinical practice with a focus on mild cognitive impairment (MCI). ABIDE is a 3-year project with a multifaceted design and is structured into interconnected substudies using both quantitative and qualitative research methods. Based on retrospectively available data, we develop personalized risk estimates for MCI patients. Prospectively, we collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in a tertiary setting, to optimize application of these tests in daily practice. Furthermore, ABIDE will develop strategies for optimal patient–clinician conversations. Ultimately, this will result in a set of practical tools for clinicians to support the choice of diagnostic tests and facilitate the interpretation and communication of their results. Results will be implemented in clinical practice of local memory clinics.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2017.01.003
  • Sleep-wake cycle disturbances in elderly acute general medical inpatients:
           Longitudinal relationship to delirium and dementia

    • Authors: James M. FitzGerald; Niamh O'Regan; Dimitrios Adamis; Suzanne Timmons; Colum P. Dunne; Paula T. Trzepacz; David J. Meagher
      Abstract: Publication date: Available online 21 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): James M. FitzGerald, Niamh O'Regan, Dimitrios Adamis, Suzanne Timmons, Colum P. Dunne, Paula T. Trzepacz, David J. Meagher
      Introduction Sleep disturbances in elderly medical inpatients are common, but their relationship to delirium and dementia has not been studied. Methods Sleep and delirium status were assessed daily for a week in 145 consecutive newly admitted elderly acute general hospital patients using the Delirium Rating Scale-Revised-98 (DRS-R98), Diagnostic and Statistical Manual 5, and Richards-Campbell Sleep Quality Scale measures. The longitudinal relationship between DRS-R98 and Richards-Campbell Sleep Quality Scale sleep scores and delirium, also with dementia as a covariate, was evaluated using generalized estimating equation logistic regression. Results The cohort was divided into delirium only, dementia only, comorbid delirium-dementia, and no-delirium/no-dementia subgroups. Mean age of total group was 80 ± 6.3, 48% were female, and 31 (21%) had dementia, 29 had delirium at admission (20%), and 27 (18.5%) experienced incident delirium. Mild sleep disturbance (DRS-R98 sleep item score ≥1) occurred for at least 1 day in all groups, whereas moderate sleep disturbance (score ≥2) occurred in significantly more of the prevalent delirium-only (81%; n = 17) cases than incident delirium-only (46%; n = 13) cases (P < .001). There were more cases with DRS-R98 sleep item scores ≥2 (P < .001) in the delirium-only group compared with the other subgroups. Severity of sleep-wake cycle disturbance over time was significantly associated with Diagnostic and Statistical Manual 5 delirium status but not with age, sex, or dementia (P < .001). Conclusions Observer-rated more severe sleep-wake cycle disturbances are highly associated with delirium irrespective of dementia status, consistent with being a core feature of delirium. Monitoring for altered sleep-wake cycle patterns may be a simple way to improve delirium detection.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2016.12.013
  • Peripheral inflammatory markers indicate microstructural damage within the
           periventricular white matter hyperintensities seen frequently
           in Alzheimer's disease: A preliminary report

    • Authors: Walter Swardfager; Di Yu; Joel E. Ramirez; Hugo Cogo-Moreira; Gregory Szilagyi; Melissa F. Holmes; Christopher J. Scott; Gustavo Scola; Pak C. Chan; Jialun Chen; Parco Chan; Demetrios J. Sahlas; Nathan Herrmann; Krista L. Lanctôt; Ana C. Andreazza; Jacqueline A. Pettersen; Sandra E. Black
      Abstract: Publication date: Available online 21 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Walter Swardfager, Di Yu, Joel E. Ramirez, Hugo Cogo-Moreira, Gregory Szilagyi, Melissa F. Holmes, Christopher J. Scott, Gustavo Scola, Pak C. Chan, Jialun Chen, Parco Chan, Demetrios J. Sahlas, Nathan Herrmann, Krista L. Lanctôt, Ana C. Andreazza, Jacqueline A. Pettersen, Sandra E. Black
      Introduction White matter hyperintensities (WMHs) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear. Methods Inflammatory markers were assayed in 54 elderly participants with AD (n = 16). Periventricular WMHs were delineated from T1, T2/proton density, and fluid-attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging. Results Mean FA within periventricular WMHs was associated with an inflammatory factor consisting of interleukin (IL)-1β, tumor necrosis factor, IL-10, IL-21, and IL-23 in patients with AD (ρ = −0.703, P = .002) but not in healthy elderly (ρ = 0.217, P = .190). Inflammation was associated with greater FA in deep WMH in healthy elderly (ρ = 0.425, P = .008) but not in patients with AD (ρ = 0.174, P = .520). Discussion Peripheral inflammatory markers may be differentially related to microstructural characteristics within the white matter affected by cerebral small vessel disease in elders with and without AD.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2016.12.011
  • Introduction to special edition, “State of the Field: Advances in
           Neuroimaging from the 2016 Alzheimer's Imaging Consortium”

    • Authors: Elizabeth C. Mormino; David A. Wolk; Liana G. Apostolova
      Pages: 67 - 69
      Abstract: Publication date: Available online 21 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Elizabeth C. Mormino, David A. Wolk, Liana G. Apostolova

      PubDate: 2016-12-23T14:37:05Z
      DOI: 10.1016/j.dadm.2016.12.008
      Issue No: Vol. 5 (2016)
  • The Structured Interview for Insight and Judgment in Dementia: Development
           and validation of a new instrument to assess awareness in patients with

    • Authors: Teresa Parrao; Simone Brockman; Romola S. Bucks; David G. Bruce; Wendy A. Davis; Katherine K. Hatch; Tammy L. Leavy; Christine A.P. Axten; Sergio E. Starkstein
      Abstract: Publication date: Available online 26 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Teresa Parrao, Simone Brockman, Romola S. Bucks, David G. Bruce, Wendy A. Davis, Katherine K. Hatch, Tammy L. Leavy, Christine A.P. Axten, Sergio E. Starkstein
      Introduction Poor insight about their cognitive and functional deficits is highly prevalent in patients with Alzheimer disease (AD); however, there is a lack of reliable, valid instrumentation to measure this construct. The aim of this study was to develop and validate a semistructured interview to assess insight and judgment in patients with AD and to provide information regarding the assessment of competency and risk in this population. Methods We validated the Structured Clinical Interview for Insight and Judgment in Dementia (SIJID) in a consecutive series of 124 patients with probable AD. The following psychometric properties were evaluated: internal consistency, test-retest reliability, interrater reliability, and convergent and predictive validity. Results The SIJID demonstrated high test-retest, interrater reliability and also showed strong discriminant and convergent validity. It showed good predictive validity based on 1-year follow-up information of the patient's clinical outcomes, with a significant association between higher SIJID total scores at baseline, and more severe neuropsychiatric symptoms and more severe caregiver distress at follow-up. Moreover, higher scores of dangerous behaviors at baseline were significantly correlated with a higher frequency of hospitalization and placement in residential care 1 year later. Conclusion The SIJID is a reliable and valid instrument to assess insight and judgment in patients with AD and is a valuable tool for assessing presence and severity of dangerous behaviors, determining risk, and providing critical information for the assessment of competency.

      PubDate: 2016-12-30T15:35:26Z
      DOI: 10.1016/j.dadm.2016.12.012
  • Response to editor to the comment by Basting and Besson (2016) to our
           article entitled “Selective familiarity deficits in otherwise
           cognitively intact aging individuals with genetic risk for Alzheimer's

    • Authors: Dorothee Schoemaker; Jens C. Pruessner
      Abstract: Publication date: Available online 25 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Dorothee Schoemaker, Jens C. Pruessner

      PubDate: 2016-12-30T15:35:26Z
      DOI: 10.1016/j.dadm.2016.11.009
  • Impaired familiarity in individuals at risk for Alzheimer disease:
           Commentary on Schoemaker et al. (2016)

    • Authors: Christine Bastin; Gabriel Besson
      Abstract: Publication date: Available online 24 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Christine Bastin, Gabriel Besson

      PubDate: 2016-12-30T15:35:26Z
      DOI: 10.1016/j.dadm.2016.11.008
  • A comparison of measurement methods of hippocampal atrophy rate for
           predicting Alzheimer's dementia in the Aberdeen Birth Cohort of 1936

    • Authors: Arnab K. Rana; Anca-Larisa Sandu; Kenna L. Robertson; Christopher J. McNeil; Lawrence J. Whalley; Roger T. Staff; Alison D. Murray
      Abstract: Publication date: Available online 23 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Arnab K. Rana, Anca-Larisa Sandu, Kenna L. Robertson, Christopher J. McNeil, Lawrence J. Whalley, Roger T. Staff, Alison D. Murray
      Introduction Various methods are available to measure hippocampal atrophy rate. We compared methods to predict Alzheimer's dementia. Methods Participants with brain imaging at ages 69 and 73 years were identified from a previous study. Simple manual measures and computationally automated volumetry were performed. Receiver operating characteristics assessed the predictive ability of each method at baseline and on logit regression analysis of two serial scans. Results Ten of 149 participants developed Alzheimer's dementia and had lower baseline volumes (3647 vs. 4194 mm3 P = .002), rates of volume loss (−126 vs. −36 mm3/y; P = .001), and rates of loss in hippocampal fraction (−8.55 vs. −2.35 x 10−5/y; P = .001). Baseline volume with a rate of change gave the highest area under the curve value of 0.96. Discussion Automated volumetry measuring hippocampal size at age 69 years and subsequent rate of change predicts Alzheimer's dementia development.

      PubDate: 2016-12-30T15:35:26Z
      DOI: 10.1016/j.dadm.2016.11.007
  • Cognitive complaints in older adults at risk for Alzheimer's disease are
           associated with altered resting-state networks

    • Authors: Joey Contreras; Shannon Risacher Enrico Amico Karmen Yoder Mario Dzemidzic
      Abstract: Publication date: Available online 22 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Joey A. Contreras, Joaquín Goñi, Shannon L. Risacher, Enrico Amico, Karmen Yoder, Mario Dzemidzic, John D. West, Brenna C. McDonald, Martin R. Farlow, Olaf Sporns, Andrew J. Saykin
      Introduction Pathophysiological changes that accompany early clinical symptoms in prodromal Alzheimer's disease (AD) may have a disruptive influence on brain networks. We investigated resting-state functional magnetic resonance imaging (rsfMRI), combined with brain connectomics, to assess changes in whole-brain functional connectivity (FC) in relation to neurocognitive variables. Methods Participants included 58 older adults who underwent rsfMRI. Individual FC matrices were computed based on a 278-region parcellation. FastICA decomposition was performed on a matrix combining all subjects' FC. Each FC pattern was then used as a response in a multilinear regression model including neurocognitive variables associated with AD (cognitive complaint index [CCI] scores from self and informant, an episodic memory score, and an executive function score). Results Three connectivity independent component analysis (connICA) components (RSN, VIS, and FP-DMN FC patterns) associated with neurocognitive variables were identified based on prespecified criteria. RSN-pattern, characterized by increased FC within all resting-state networks, was negatively associated with self CCI. VIS-pattern, characterized by an increase in visual resting-state network, was negatively associated with CCI self or informant scores. FP-DMN-pattern, characterized by an increased interaction of frontoparietal and default mode networks (DMN), was positively associated with verbal episodic memory. Discussion Specific patterns of FC were differently associated with neurocognitive variables thought to change early in the course of AD. An integrative connectomics approach relating cognition to changes in FC may help identify preclinical and early prodromal stages of AD and help elucidate the complex relationship between subjective and objective indices of cognitive decline and differences in brain functional organization.

      PubDate: 2016-12-23T14:37:05Z
  • Alzheimer disease: The influence of age on clinical heterogeneity through
           the human brain connectome

    • Authors: Brad Dickerson; Michael Brickhouse; Scott McGinnis; David A. Wolk
      Abstract: Publication date: Available online 22 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Brad Dickerson, Michael Brickhouse, Scott McGinnis, David A. Wolk
      Introduction One major factor that influences the heterogeneity of Alzheimer disease (AD) is age: younger AD patients more frequently exhibit atypical forms of AD. We propose that this age-related heterogeneity can be understood better by considering age-related differences in atrophy in the context of large-scale brain networks subserving cognitive functions that contribute to memory. Methods We examined data from 75 patients with mild AD dementia from ADNI. These individuals were chosen because they have CSF amyloid and p-tau levels in the range suggesting the presence of AD neuropathology and because they were either younger than age 65 years (early-onset Alzheimer disease [EOAD]) or age 80 years or older (late-onset Alzheimer disease [LOAD]). Results In the EOAD group, the most prominent atrophy was present in the posterior cingulate cortex, whereas in the LOAD group, atrophy was most prominent in the medial temporal lobe. Structural covariance analysis showed that the magnitude of atrophy in these epicenters is strongly correlated with a distributed atrophy pattern similar to distinct intrinsic connectivity networks in the healthy brain. An examination of memory performance in EOAD dementia versus LOAD dementia demonstrated relatively more prominent impairment in encoding in the EOAD group than in the LOAD group, with similar performance in memory storage in LOAD and EOAD but greater impairment in semantic memory in LOAD than in EOAD. Discussion The observations provide novel insights about age as a major factor contributing to the heterogeneity in the topography of AD-related cortical atrophy.

      PubDate: 2016-12-23T14:37:05Z
      DOI: 10.1016/j.dadm.2016.12.007
  • Association between Aβ and tau accumulations and their influence on
           clinical features in aging and Alzheimer disease spectrum brains: A
           [11C]PBB3-PET study

    • Authors: Hitoshi Shimada; Soichiro Kitamura; Hitoshi Shinotoh; Hironobu Endo; Fumitoshi Niwa; Shigeki Hirano; Yasuyuki Kimura; Ming-Rong Zhang; Satoshi Kuwabara; Tetsuya Suhara; Makoto Higuchi
      Abstract: Publication date: Available online 22 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Hitoshi Shimada, Soichiro Kitamura, Hitoshi Shinotoh, Hironobu Endo, Fumitoshi Niwa, Shigeki Hirano, Yasuyuki Kimura, Ming-Rong Zhang, Satoshi Kuwabara, Tetsuya Suhara, Makoto Higuchi
      Introduction Amyloid-β (Aβ) and tau accumulations may occur independently and concurrently as exemplified by primary age-related tauopathy and Alzheimer disease (AD), respectively. Interactions between Aβ and tau accumulations and their influence on clinical features, however, are still unclear. Methods Associations among clinical symptoms, gray-matter volume, regional tau, and Aβ deposition assessed by positron emission tomography with [11C]pyridinyl-butadienyl-benzothiazole 3 and [11C]PiB were evaluated in 17 AD, 9 mild cognitive impairment due to AD, and 28 PiB(−)-cognitive healthy controls (HCs). Results High tau burden was associated with aging and low-level education in PiB(−)-HC and AD-spectrum groups, and with high Aβ burden and low-level education in all subjects. It was not Aβ but tau accumulation that showed significant associations with cognitive performance even in PiB(−)-HC. Discussion The present study indicated aging and low-level education after Aβ would be enhancers for tau pathology, associated with neurodegeneration and cognitive impairment in healthy and diseased elderly individuals.

      PubDate: 2016-12-23T14:37:05Z
      DOI: 10.1016/j.dadm.2016.12.009
  • The APOE4 genotype modulates CSF YKL-40 levels and their structural brain
           correlates in the continuum of Alzheimer disease but not those of sTREM2

    • Authors: Juan Domingo Gispert; Gemma C. Monté; Marc Suárez-Calvet; Carles Falcon; Alan Tucholka; Santiago Rojas; Lorena Rami; Raquel Sánchez-Valle; Albert Lladó; Gernot Kleinberger; Christian Haass; José Luis Molinuevo
      Abstract: Publication date: Available online 22 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Juan Domingo Gispert, Gemma C. Monté, Marc Suárez-Calvet, Carles Falcon, Alan Tucholka, Santiago Rojas, Lorena Rami, Raquel Sánchez-Valle, Albert Lladó, Gernot Kleinberger, Christian Haass, José Luis Molinuevo
      Introduction Among other metabolic functions, the apolipoprotein E (APOE) plays a crucial role in neuroinflammation. We aimed at assessing whether APOE-ε4 modulates levels of glial cerebrospinal fluid (CSF) biomarkers and their structural cerebral correlates along the continuum of Alzheimer disease (AD). Methods Brain MRI scans were acquired in 110 participants (49 control; 19 preclinical; 27 mild cognitive impairment [MCI] due to AD; 15 mild AD dementia) and CSF concentrations of YKL-40 and sTREM2 were determined. Differences in CSF biomarker concentrations and interactions in their association with gray-matter volume according to APOE-ε4 status were sought after. Results Preclinical and MCI carriers showed higher YKL-40 levels. There was a significant interaction in the association between YKL-40 levels and gray-matter volume according to ε4 status. No similar effects could be detected for sTREM2 levels. Discussion Our findings are indicative of an increased astroglial activation in APOE-ε4 carriers while both groups displayed similar levels of CSF AD core biomarkers.

      PubDate: 2016-12-23T14:37:05Z
      DOI: 10.1016/j.dadm.2016.12.002
  • Tau-PET uptake: Regional variation in average SUVR and impact of amyloid

    • Authors: Prashanthi Vemuri; Val J. Lowe; David S. Knopman; Matthew L. Senjem; Bradley J. Kemp; Christopher G. Schwarz; Scott A. Przybelski; Mary M. Machulda; Ronald C. Petersen; Clifford R. Jack
      Abstract: Publication date: Available online 21 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Prashanthi Vemuri, Val J. Lowe, David S. Knopman, Matthew L. Senjem, Bradley J. Kemp, Christopher G. Schwarz, Scott A. Przybelski, Mary M. Machulda, Ronald C. Petersen, Clifford R. Jack
      Introduction Tau-PET imaging with AV1451 is sensitive to Alzheimer disease (AD)–related tau deposition in the brain. We (1) examined regional variation of average tau-PET standardized uptake value ratios (SUVRs) in a young normal population (30–49 years) and corrected for the regional variability and (2) tested if the standardized values (z-scores) scaled appropriately to capture regional Alzheimer-specific (i.e., amyloid sensitive) tau-PET changes in individuals aged 50+ years. Methods We identified 490 individuals (70 between 30–49 years as a reference group and 420 cognitively normal between 50–95 years of age) with tau-PET and amyloid PET scans from the Mayo Clinic Study of Aging. Results There was intrinsic regional variability in average tau-PET SUVR with uptakes higher in some regions than others, even in the younger individuals who would have minimal or no neurofibrillary tangles. We corrected for this using region of interest–specific z-scores based on the reference group. Amyloid and tau-PET uptake were associated throughout the brain after adjusting for age, with the highest correlations in the medial temporal regions. Discussion Regions with high-average SUVR are not necessarily those with the greatest tau pathology. Standardization is therefore recommended. Standardization of the data “realigns” the data such that the regional tau z-scores are informative of the disease process, that is, regions with high z-scores now coincide with regions correlated with amyloid deposition. Medial temporal structures, specifically entorhinal cortex–tau, may be useful as an AD-specific tau-PET signature due to its sensitivity to amyloid.

      PubDate: 2016-12-23T14:37:05Z
      DOI: 10.1016/j.dadm.2016.12.010
  • Assessing quality of life in Alzheimer's disease: Implications for
           clinical trials

    • Authors: Kristin Kahle-Wrobleski; Wenyu Ye; David Henley; Ann Marie Hake; Eric Siemers; Yun-Fei Chen; Hong Liu-Seifert
      Abstract: Publication date: Available online 13 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Kristin Kahle-Wrobleski, Wenyu Ye, David Henley, Ann Marie Hake, Eric Siemers, Yun-Fei Chen, Hong Liu-Seifert
      Introduction Characterization of the quality of life (QOL) in Alzheimer disease (AD) scale within the context of a clinical trial may inform its applicability in future trials. Methods Using data from 1322 patients enrolled in two phase-III studies (EXPEDITION 1 [NCT00905372] and 2 [NCT00904683]) of intravenous solanezumab in outpatients with mild AD dementia, correlations between patient- and caregiver-assessed QOL and between QOL and clinical outcome measures were examined. Longitudinal effects of solanezumab over 80 weeks were explored, controlling for patient and caregiver baseline characteristics. Results Caregivers rated patients' QOL worse than did patients themselves. Patients' QOL was correlated, albeit modestly, with clinical/health measures. Patients' QOL changed minimally over 80 weeks, although a treatment effect of solanezumab on QOL was detected. Discussion Further investigations are needed to determine the optimal measures with which to quantify and qualify QOL of patients with mild AD.

      PubDate: 2016-12-15T13:36:38Z
      DOI: 10.1016/j.dadm.2016.11.004
  • Repetitive head impact exposure and later-life plasma total tau in former
           NFL players

    • Authors: Michael L. Alosco; Yorghos Tripodis; Johnny Jarnagin; Christine M. Baugh; Brett Martin; Christine E. Chaisson; Nate Estochen; Linan Song; Robert C. Cantu; Andreas Jeromin; Robert A. Stern
      Abstract: Publication date: Available online 10 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Michael L. Alosco, Yorghos Tripodis, Johnny Jarnagin, Christine M. Baugh, Brett Martin, Christine E. Chaisson, Nate Estochen, Linan Song, Robert C. Cantu, Andreas Jeromin, Robert A. Stern
      Introduction Blood protein analysis of total tau (t-tau) may be a practical screening biomarker for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We examined plasma t-tau in symptomatic former NFL players compared with controls and the relationship between RHI exposure and later-life plasma t-tau. Methods Ninety-six former NFL players (age 40–69) and 25 same-age controls underwent blood draw to determine plasma t-tau levels. The cumulative head impact index (CHII) quantified RHI exposure. Subjects completed measures of clinical function. Results A higher CHII predicted greater plasma t-tau in the former NFL players (P = .0137). No group differences in plasma t-tau emerged, but a concentration ≥3.56 pg/mL was 100% specific to former NFL players. Plasma t-tau did not predict clinical function. Discussion Greater RHI exposure predicted higher later-life plasma t-tau concentrations, and further study on plasma t-tau as a candidate screening biomarker for CTE is warranted.

      PubDate: 2016-12-15T13:36:38Z
      DOI: 10.1016/j.dadm.2016.11.003
  • Functional limitations and health care resource utilization for
           individuals with cognitive impairment without dementia: Findings from a US
           population-based survey

    • Authors: J. Scott Andrews; Urvi Desai; Noam Y. Kirson; Caroline J. Enloe; Ljubica Ristovska; Sarah King; Howard G. Birnbaum; Adam S. Fleisher; Wenyu Ye; Kristin Kahle-Wrobleski
      Abstract: Publication date: Available online 9 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): J. Scott Andrews, Urvi Desai, Noam Y. Kirson, Caroline J. Enloe, Ljubica Ristovska, Sarah King, Howard G. Birnbaum, Adam S. Fleisher, Wenyu Ye, Kristin Kahle-Wrobleski
      Introduction Little is known about functional limitations and health care resource utilization of people with cognitive impairment with no dementia (CIND). Methods Respondents with stable or progressive cognitive impairment (CI) after the first (index) indication of CIND in 2000–2010 were identified from the Health and Retirement Study (HRS). Respondents never exhibiting CI were identified as potential controls. Propensity score–based optimal matching was used to adjust for differences in demographics and history of stroke. Differences between cohorts were assessed accounting for HRS survey design. Results After matching, CIND respondents had more functional limitations (difficulty with ≥1 activities of daily living: 24% vs. 15%; ≥1 instrumental activities of daily living: 20% vs. 11%) and hospital stays (37% vs. 27%) than respondents with no CI (all P < .001). Seventy five percent of CIND respondents developed dementia in the observable follow-up (median time: ∼6 years). Discussion Even before dementia onset, CI is associated with increased likelihood of functional limitations and greater health care resource use.

      PubDate: 2016-12-15T13:36:38Z
      DOI: 10.1016/j.dadm.2016.11.005
  • The application of retinal fundus camera imaging in dementia: A systematic

    • Authors: Sarah McGrory; James R. Cameron; Enrico Pellegrini; Claire Warren; Fergus N. Doubal; Ian J. Deary; Baljean Dhillon; Joanna M. Wardlaw; Emanuele Trucco; Thomas J. MacGillivray
      Abstract: Publication date: Available online 2 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Sarah McGrory, James R. Cameron, Enrico Pellegrini, Claire Warren, Fergus N. Doubal, Ian J. Deary, Baljean Dhillon, Joanna M. Wardlaw, Emanuele Trucco, Thomas J. MacGillivray
      Introduction The ease of imaging the retinal vasculature, and the evolving evidence suggesting this microvascular bed might reflect the cerebral microvasculature, presents an opportunity to investigate cerebrovascular disease and the contribution of microvascular disease to dementia with fundus camera imaging. Methods A systematic review and meta-analysis was carried out to assess the measurement of retinal properties in dementia using fundus imaging. Results Ten studies assessing retinal properties in dementia were included. Quantitative measurement revealed significant yet inconsistent pathologic changes in vessel caliber, tortuosity, and fractal dimension. Retinopathy was more prevalent in dementia. No association of age-related macular degeneration with dementia was reported. Discussion Inconsistent findings across studies provide tentative support for the application of fundus camera imaging as a means of identifying changes associated with dementia. The potential of fundus image analysis in differentiating between dementia subtypes should be investigated using larger well-characterized samples. Future work should focus on refining and standardizing methods and measurements.

      PubDate: 2016-12-08T12:04:20Z
      DOI: 10.1016/j.dadm.2016.11.001
  • Subsyndromal delirium compared with delirium, dementia, and subjects
           without delirium or dementia in elderly general hospital admissions and
           nursing home residents

    • Authors: Esteban Sepulveda; Maeve Leonard Jose Franco Dimitrios Adamis Geraldine McCarthy
      Abstract: Publication date: Available online 1 December 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Esteban Sepulveda, Maeve Leonard, Jose G. Franco, Dimitrios Adamis, Geraldine McCarthy, Colum Dunne, Paula T. Trzepacz, Ana M. Gaviria, Joan de Pablo, Elisabet Vilella, David J. Meagher
      Introduction Subsyndromal delirium (SSD) complicates diagnosis of delirium and dementia, although there is little research comparing their symptom profiles. Methods Cross-sectional study of 400 elderly patients' admission to a general hospital or nursing home diagnosed with delirium, SSD, dementia, or no-delirium/no-dementia (NDND). Symptom profiles were assessed using the Delirium Rating Scale-Revised-98 (DRS-R98). Results Twenty percent patients had delirium, 19.3% had SSD, 29.8% had dementia-only, and 31% had NDND. Eighty-one percent of subsyndromal and 76% of delirium groups had comorbid dementia. DRS-R98 scores showed ascending severity from NDND < dementia-only < SSD < delirium. DRS-R98 scores for items evaluating the three core symptom domains (cognitive, higher-order thinking, and circadian) distinguished SSD from delirium and both from nondelirium groups. DRS-R98 profiles were essentially the same in delirium and SSD subgroups with or without dementia, although total scale scores were generally higher when in comorbid subgroups. Discussion SSD shared characteristic core domain symptoms with delirium, which distinguished each from nondelirium groups, although severity was intermediate in the subsyndromal group. Delirium core symptoms overshadowed the dementia phenotype when comorbid. Milder disturbances of delirium core domain symptoms are highly suggestive of SSD.

      PubDate: 2016-12-01T10:57:35Z
  • Brain amyloid in preclinical Alzheimer's disease is associated
           with increased driving risk

    • Authors: Brian R. Ott; Richard N. Jones; Richard B. Noto; Don C. Yoo; Peter J. Snyder; Justine N. Bernier; David B. Carr; Catherine M. Roe
      Abstract: Publication date: Available online 29 November 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Brian R. Ott, Richard N. Jones, Richard B. Noto, Don C. Yoo, Peter J. Snyder, Justine N. Bernier, David B. Carr, Catherine M. Roe
      Introduction Postmortem studies suggest that fibrillar brain amyloid places people at higher risk for hazardous driving in the preclinical stage of Alzheimer's disease (AD). Methods We administered driving questionnaires to 104 older drivers (19 AD, 24 mild cognitive impairment, and 61 cognitive normal) who had a recent 18F-florbetapir positron emission tomography scan. We examined associations of amyloid standardized uptake value ratios with driving behaviors: traffic violations or accidents in the past 3 years. Results The frequency of violations or accidents was curvilinear with respect to standardized uptake value ratios, peaking around a value of 1.1 (model r 2  = 0.10, P = .002); moreover, this relationship was evident for the cognitively normal participants. Discussion We found that driving risk is strongly related to accumulating amyloid on positron emission tomography, and that this trend is evident in the preclinical stage of AD. Brain amyloid burden may in part explain the increased crash risk reported in older adults.

      PubDate: 2016-12-01T10:57:35Z
      DOI: 10.1016/j.dadm.2016.10.008
  • STROKOG (stroke and cognition consortium): An international consortium to
           examine the epidemiology, diagnosis, and treatment of neurocognitive
           disorders in relation to cerebrovascular disease

    • Authors: Perminder S. Sachdev; Jessica W. Lo; John D. Crawford; Lisa Mellon; Anne Hickey; David Williams; Régis Bordet; Anne-Marie Mendyk; Patrick Gelé; Dominique Deplanque; Hee-Joon Bae; Jae-Sung Lim; Amy Brodtmann; Emilio Werden; Toby Cumming; Sebastian Köhler; Frans R.J. Verhey; Yan-Hong Dong; Hui Hui Tan; Christopher Chen; Raj N. Kalaria; Louise M. Allan; Rufus O. Akinyemi; Adesola Ogunniyi; Aleksandra Klimkowicz-Mrowiec; Martin Dichgans; Frank A. Wollenweber; Vera Zietemann; Michael Hoffmann; David W. Desmond; Thomas Linden; Christian Blomstrand; Björn Fagerberg; Ingmar Skoog; Olivier Godefroy; Mélanie Barbay; Martine Roussel; Byung-Chul Lee; Kyung-Ho Yu; Joanna Wardlaw; Stephen J. Makin; Fergus N. Doubal; Francesca M. Chappell; Velandai K. Srikanth; Amanda G. Thrift; Geoffrey A. Donnan; Naganedran Kandiah; Russell J. Chander; Xuling Lin; Charlotte Cordonnier; Solene Moulin; Costanza Rossi; Behnam Sabayan; David J. Stott; J. Wouter Jukema; Susanna Melkas; Hanna Jokinen; Timo Erkinjuntti; Vincent C.T. Mok; Adrian Wong; Bonnie Y.K. Lam; Didier Leys; Hilde Hénon; Stéphanie Bombois; Darren M. Lipnicki; Nicole A. Kochan
      Abstract: Publication date: Available online 18 November 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Perminder S. Sachdev, Jessica W. Lo, John D. Crawford, Lisa Mellon, Anne Hickey, David Williams, Régis Bordet, Anne-Marie Mendyk, Patrick Gelé, Dominique Deplanque, Hee-Joon Bae, Jae-Sung Lim, Amy Brodtmann, Emilio Werden, Toby Cumming, Sebastian Köhler, Frans R.J. Verhey, Yan-Hong Dong, Hui Hui Tan, Christopher Chen, Raj N. Kalaria, Louise M. Allan, Rufus O. Akinyemi, Adesola Ogunniyi, Aleksandra Klimkowicz-Mrowiec, Martin Dichgans, Frank A. Wollenweber, Vera Zietemann, Michael Hoffmann, David W. Desmond, Thomas Linden, Christian Blomstrand, Björn Fagerberg, Ingmar Skoog, Olivier Godefroy, Mélanie Barbay, Martine Roussel, Byung-Chul Lee, Kyung-Ho Yu, Joanna Wardlaw, Stephen J. Makin, Fergus N. Doubal, Francesca M. Chappell, Velandai K. Srikanth, Amanda G. Thrift, Geoffrey A. Donnan, Naganedran Kandiah, Russell J. Chander, Xuling Lin, Charlotte Cordonnier, Solene Moulin, Costanza Rossi, Behnam Sabayan, David J. Stott, J. Wouter Jukema, Susanna Melkas, Hanna Jokinen, Timo Erkinjuntti, Vincent C.T. Mok, Adrian Wong, Bonnie Y.K. Lam, Didier Leys, Hilde Hénon, Stéphanie Bombois, Darren M. Lipnicki, Nicole A. Kochan
      Background The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Methods Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Results Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years. Discussion Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.

      PubDate: 2016-11-24T01:03:40Z
      DOI: 10.1016/j.dadm.2016.10.006
  • A comparison of theoretical and statistically derived indices for
           predicting cognitive decline

    • Authors: Holly Wilhalme; Naira Goukasian; Fransia De Leon; Angie He; Kristy S. Hwang; Ellen Woo; David Elashoff; Yan Zhou; John M. Ringman; Liana G. Apostolova
      Abstract: Publication date: Available online 5 November 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Holly Wilhalme, Naira Goukasian, Fransia De Leon, Angie He, Kristy S. Hwang, Ellen Woo, David Elashoff, Yan Zhou, John M. Ringman, Liana G. Apostolova
      Background Both theoretical and statistically derived approaches have been used in research settings for predicting cognitive decline. Methods Fifty-eight cognitively normal (NC) and 71 mild cognitive impairment (MCI) subjects completed a comprehensive cognitive battery for up to 5 years of follow-up. Composite indices of cognitive function were derived using a classic theoretical approach and exploratory factor analysis (EFA). Cognitive variables comprising each factor were averaged to form the EFA composite indices. Logistic regression was used to investigate whether these cognitive composites can reliably predict cognitive outcomes. Results Neither method predicted decline in NC. The theoretical memory, executive, attention, and language composites and the EFA-derived “attention/executive” and “verbal memory” composites were significant predictors of decline in MCI. The best models achieved an area under the curve of 0.94 in MCI. Conclusions The theoretical and the statistically derived cognitive composite approaches are useful in predicting decline in MCI but not in NC.

      PubDate: 2016-11-10T11:28:53Z
      DOI: 10.1016/j.dadm.2016.10.002
  • The clinical, neuroanatomical, and neuropathologic phenotype of
           TBK1-associated frontotemporal dementia: A longitudinal case report

    • Authors: Carolin A.M. Koriath; Martina Bocchetta; Emilie Brotherhood; Ione O.C. Woollacott; Penny Norsworthy; Javier Simón-Sánchez; Cornelis Blauwendraat; Katrina M. Dick; Elizabeth Gordon; Sophie R. Harding; Nick C. Fox; Sebastian Crutch; Jason D. Warren; Tamas Revesz; Tammaryn Lashley; Simon Mead; Jonathan D. Rohrer
      Abstract: Publication date: Available online 3 November 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Carolin A.M. Koriath, Martina Bocchetta, Emilie Brotherhood, Ione O.C. Woollacott, Penny Norsworthy, Javier Simón-Sánchez, Cornelis Blauwendraat, Katrina M. Dick, Elizabeth Gordon, Sophie R. Harding, Nick C. Fox, Sebastian Crutch, Jason D. Warren, Tamas Revesz, Tammaryn Lashley, Simon Mead, Jonathan D. Rohrer
      Introduction Mutations in the TANK-binding kinase 1 (TBK1) gene have recently been shown to cause frontotemporal dementia (FTD). However, the phenotype of TBK1-associated FTD is currently unclear. Methods We performed a single case longitudinal study of a patient who was subsequently found to have a novel A705fs mutation in the TBK1 gene. He was assessed annually for more than a 7-year period with a series of clinical, cognitive, and magnetic resonance imaging assessments. His brain underwent pathological examination at postmortem. Results The patient presented at the age of 64 years with an 18-month history of personality change including increased rigidity and obsessiveness, apathy, loss of empathy, and development of a sweet tooth. His mother had developed progressive behavioral and cognitive impairment from the age of 57 years. Neuropsychometry revealed intact cognition at first assessment. Magnetic resonance imaging showed focal right temporal lobe atrophy. Over the next few years his behavioral problems progressed and he developed cognitive impairment, initially with anomia and prosopagnosia. Neurological examination remained normal throughout without any features of motor neurone disease. He died at the age of 72 years and postmortem showed TDP-43 type A pathology but with an unusual novel feature of numerous TDP-43–positive neuritic structures at the cerebral cortex/subcortical white matter junction. There was also associated argyrophilic grain disease not previously reported in other TBK1 mutation cases. Discussion TBK1-associated FTD can be associated with right temporal variant FTD with progressive behavioral change and relatively intact cognition initially. The case further highlights the benefits of next-generation sequencing technologies in the diagnosis of neurodegenerative disorders and the importance of detailed neuropathologic analysis.

      PubDate: 2016-11-03T07:00:04Z
      DOI: 10.1016/j.dadm.2016.10.003
  • Prospective associations of plasma phospholipids and mild cognitive
           impairment/dementia among African Americans in the ARIC Neurocognitive

    • Authors: Danni Li; Jeffrey R. Misialek; Eric Boerwinkle; Rebecca F. Gottesman; A. Richey Sharrett; Thomas H. Mosley; Josef Coresh; Lisa M. Wruck; David S. Knopman; Alvaro Alonso
      Abstract: Publication date: Available online 1 November 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Danni Li, Jeffrey R. Misialek, Eric Boerwinkle, Rebecca F. Gottesman, A. Richey Sharrett, Thomas H. Mosley, Josef Coresh, Lisa M. Wruck, David S. Knopman, Alvaro Alonso
      Introduction The objective of this study was to investigate whether 10 phospholipids/metabolites previously identified as prospectively predictive of mild cognitive impairment (MCI) or dementia in whites would also be predictive in a mostly African-American cohort. Methods We repeatedly measured 188 phospholipids/metabolites in plasma samples of 221 participants of the Atherosclerosis Risk in Communities study, 97% African American, who were followed between 2004–2006 and 2011–2013. Results After a mean follow-up of 7.3 years, 77 were classified as having MCI and 18 as having dementia. Our study failed to replicate previous findings in this mostly African American cohort, in that the 10 phospholipids/metabolites only achieved a C statistic/AUC of 0.609 in predicting development of MCI or dementia (compared to 0.96) and 0.607 in distinguishing normal from MCI or dementia at the follow-up visit. Conclusion A panel of 10 phospholipids/metabolites previously associated with incident dementia was not predictive of MCI or dementia in an independent cohort.

      PubDate: 2016-11-03T07:00:04Z
      DOI: 10.1016/j.dadm.2016.09.003
  • Perspective from the Alzheimer's association: Neuroimaging professional
           interest area of ISTAART continued impact on the field

    • Authors: Heather Snyder; Maria Carrillo
      Abstract: Publication date: Available online 27 October 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Heather M. Snyder, Maria C. Carrillo

      PubDate: 2016-11-03T07:00:04Z
  • Cognitive impairment and decline in cognitively normal older adults with
           high amyloid-β: A meta-analysis

    • Authors: Jenalle E. Baker; Yen Ying Lim; Robert H. Pietrzak; Jason Hassenstab; Peter J. Snyder; Colin L. Masters; Paul Maruff
      Abstract: Publication date: Available online 18 October 2016
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Jenalle E. Baker, Yen Ying Lim, Robert H. Pietrzak, Jason Hassenstab, Peter J. Snyder, Colin L. Masters, Paul Maruff
      Introduction This meta-analysis aimed to characterize the nature and magnitude of amyloid (Aβ)-related cognitive impairment and decline in cognitively normal (CN) older individuals. Method MEDLINE Ovid was searched from 2012 to June 2016 for studies reporting relationships between cerebrospinal fluid or positron emission tomography (PET) Aβ levels and cognitive impairment (cross-sectional) and decline (longitudinal) in CN older adults. Neuropsychological data were classified into domains of episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Type of Aβ measure, how Aβ burden was analyzed, inclusion of control variables, and clinical criteria used to exclude participants, was considered as moderators. Random-effects models were used for analyses with effect sizes expressed as Cohen's d. Results A total of 37 studies met inclusion criteria contributing 30 cross-sectional (N = 5005) and 14 longitudinal (N = 2584) samples. Aβ-related cognitive impairment was observed for global cognition (d = 0.32), visuospatial function (d = 0.25), processing speed (d = 0.18), episodic memory, and executive function (both d's = 0.15), with decline observed for global cognition (d = 0.30), semantic memory (d = 0.28), visuospatial function (d = 0.25), and episodic memory (d = 0.24). Aβ-related impairment was moderated by age, amyloid measure, type of analysis, and inclusion of control variables and decline moderated by amyloid measure, type of analysis, inclusion of control variables, and exclusion criteria used. Discussion CN older adults with high Aβ show a small general cognitive impairment and small to moderate decline in episodic memory, visuospatial function, semantic memory, and global cognition.

      PubDate: 2016-11-03T07:00:04Z
      DOI: 10.1016/j.dadm.2016.09.002
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