Alzheimer's & Dementia: The Journal of the Alzheimer's Association RSS feed: Current Issue. The mission of Alzheimer's & Dementia: Journal of the Alzheimer's Association is to bridge the knowledge gaps across a wide range of bench-to-bedside investigation. The journal publishes the results of studies in: behavior, biochemistry, genetics, molecular biology, pharmacology, physiology, protein chemistry, neurology, neuropathology, psychiatry, geriatrics, neuropsychology, epidemiology, sociology, health services research, health economics, political science and public policy. Content emphasizes interdisciplinary investigations, integrative/translational articles, related to: etiology, risk factors, early detection, disease modifying interventions, prevention of dementia and applications of new technologies in health services. The journal publishes • comprehensive reviews; • research articles; • information on clinical trials; • short reports; • in-depth perspectives/open-peer commentaries; • theoretical and/or translational papers that attempt integrate knowledge across discipline; • history & politics of science/brief biographies and, • abstracts of papers presented at international meetings. Negative results, particularly clinical trials, are published as short communications. The ultimate objective is to create a novel forum for: • rapid communication of new findings, ideas or perspectives; • disseminating knowledge, across the spectrum of basic to clinical studies, necessary for optimal translation of research findings into practical applications/interventions; • integrating knowledge across disciplines; • increase knowledge in diverse disciplines to promote early detection/diagnosis and/or interventions; • formulating new theories and/or strategies for the rigorous testing of theories or their predictions; • identifying promising new directions of research and, • providing the scientific impetus for new initiatives; or public policies concerning research on prevention and new models of health services. Alzheimer's & Dementia is indexed/abstracted in Index Medicus/MEDLINE, Scopus, Science Citation Index Expanded (SciSearch®), Current Contents®/Clinical Medicine, Neuroscience Citation Index®, and Journal Citation Reports/Science Edition. http://www.alzheimersanddementia.com/?rss=yesElsevier Inc.en © 2012 The Alzheimer's Association. All rights reserved. Alzheimer's & Dementia: The Journal of the Alzheimer's Association1552-526081January 2012 © 2012 The Alzheimer's Association. All rights reserved. healthpermissions@elsevier.comhttp://www.alzheimersanddementia.com/article/PIIS1552526011029803/abstract?rss=yesAbstract: A consensus panel from the United States and Europe was convened recently to update and revise the 1997 consensus guidelines for the neuropathologic evaluation of Alzheimer's disease (AD) and other diseases of brain that are common in the elderly. The new guidelines recognize the pre-clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP-43 inclusions, and recommend standard approaches for the workup of cases and their clinico-pathologic correlation.National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's diseaseBradley T. Hyman, Creighton H. Phelps, Thomas G. Beach, Eileen H. Bigio, Nigel J. Cairns, Maria C. Carrillo, Dennis W. Dickson, Charles Duyckaerts, Matthew P. Frosch, Eliezer Masliah, Suzanne S. Mirra, Peter T. Nelson, Julie A. Schneider, Dietmar Rudolf Thal, Bill Thies, John Q. Trojanowski, Harry V. Vinters, Thomas J. Montine10.1016/j.jalz.2011.10.007Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0Featured Articles113http://www.alzheimersanddementia.com/article/PIIS1552526011000641/abstract?rss=yesAbstract: Background: The purpose of conducting this study was to identify areas of concordance and sources of variation for the published rates of prevalence and incidence associated with various definitions for mild cognitive impairment (MCI).Methods: The study used systematic review of studies published in English since 1984. Studies were identified by searching MEDLINE and EMBASE databases. Population-based observational studies of incidence or prevalence of MCI and related terms were eligible for inclusion.Results: A total of 3,705 citations were identified, and 42 were accepted for inclusion; 35 included data on prevalence and 13 on incidence. The following four terms predominated: age-associated memory impairment (AAMI); cognitive impairment no dementia (CIND); MCI; and amnestic MCI (aMCI). Within each term, the operational definition varied. Substantial variation was observed for both incidence (MCI: 21.5–71.3; aMCI: 8.5–25.9 per 1,000 person-years) and prevalence of each definition of cognitive impairment (AAMI 3.6%–38.4%; CIND 5.1%–35.9%; MCI 3%–42%; aMCI 0.5%–31.9%). CIND and MCI showed increasing prevalence among older age groups, whereas age-specific rates of aMCI were lower and without any apparent age relationship.Conclusions: Prevalence and incidence estimates associated with MCI vary greatly both between definitions and within a definition across the 42 publications. These wide differences pose a significant challenge to our understanding of the social burden of this disease. Enhancement and standardization of operational definitions of the subtypes of cognitive impairment could improve estimates of disease burden and provide a mechanism to assist in the identification of individuals at risk for future Alzheimer’s disease and other dementias.Mild cognitive impairment: Disparity of incidence and prevalence estimatesAlex Ward, H. Michael Arrighi, Shannon Michels, Jesse M. Cedarbaum10.1016/j.jalz.2011.01.002Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0Featured Articles1421http://www.alzheimersanddementia.com/article/PIIS1552526010021874/abstract?rss=yesAbstract: Background: Diagnosing and treating patients with Alzheimer’s disease (AD) at an early stage should improve the quality of life of the patient and caregiver. In the United Kingdom, cost-effectiveness of early assessment of individuals presenting with subjective memory complaints and treating those with AD with donepezil was evaluated.Methods: A discrete event simulation of AD progression and the effect of treatment interventions was developed. Patient-level data from donepezil trials and a 7-year follow-up registry were used to model correlated longitudinal rates of change in cognition, behavior, and function. Other epidemiological and health services data, including estimates of undiagnosed dementia and delays in diagnosis, were based on published sources. Simulated individuals were followed up for 10 years.Results: In the base-case estimates, 17 patients need to be assessed to diagnose one patient with AD, resulting in an average assessment cost of £4100 ($6000; $1 US = £0.68 UK) per patient diagnosed (2007 cost year). In comparison with a scenario without early assessment or pharmacologic treatment, early assessment reduces health care costs by £3600 ($5300) per patient and societal costs by £7750 ($11,400). Savings are also substantial compared with treatment without early assessment, averaging £2100 ($3100) in health care costs, and £5700 ($8400) in societal costs. Results are most sensitive to estimates of patient care costs and the probability of patients reporting subjective memory complaints. In probabilistic sensitivity analysis, early assessment leads to savings or is highly cost-effective in the majority of cases.Conclusions: Although early assessment has significant up-front costs, identifying AD patients at an early stage results in cost savings and health benefits compared with no treatment or treatment in the absence of early assessment.An economic evaluation of early assessment for Alzheimer’s disease in the United KingdomDennis Getsios, Steve Blume, Khajak J. Ishak, Grant Maclaine, Luis Hernández10.1016/j.jalz.2010.07.001Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2011-03-21Alzheimer's & Dementia: The Journal of the Alzheimer's Association2011-03-2181S1552-5260(11)X0008-0Featured Articles2230http://www.alzheimersanddementia.com/article/PIIS1552526011026215/abstract?rss=yesAbstract: Background: Advances in screening and treatment are needed to mitigate increasing prevalence of dementia due to Alzheimer’s disease (DAT). Current proposals to revise Alzheimer’s disease (AD) diagnostic criteria incorporate diagnostic biomarkers. Such revisions would allow identification of persons with AD pathology before the onset of dementia. The population-level impact of screening for preclinical AD and treating with a disease-modifying agent is important when evaluating new biomarkers and medications.Methods: A published computer simulation model assigned AD-related event times, such that delays in disease progression due to therapy effectiveness can be estimated for a preclinical AD cohort. Attributes such as screening sensitivity/specificity, treatment efficacy, age at first screening, and rescreening intervals were varied. Outcomes included incident mild cognitive impairment (MCI-AD), incident DAT, and number of patients recommended for treatment.Results: One-time screening at age 65 years, 50% efficacy, and literature-based proxy persistence rates yielded 12.4% incidence of MCI-AD and 0.9% decrease in DAT incidence from base case of no screening/treatment. Modest reductions in incident MCI-AD and DAT were observed with more sensitive testing. Reducing specificity yielded greater reductions in MCI-AD and DAT cases, albeit by treating more patients. Probabilistic sensitivity analysis predicted that for a cohort of patients aged 65 years, the number that needed to be treated to avoid one AD case was 11.6 (range: 5.7–104).Conclusion: The reduction in MCI-AD and DAT depends on initial screening age, screening frequency, and specificity. When considering population-level impact of screening–treatment, the effect of these parameters on incidence would need to be weighed against the number of individuals screened and treated.Screening and treatment for Alzheimer's disease: Predicting population-level outcomesNicolas M. Furiak, Kristin Kahle-Wrobleski, Christopher Callahan, Timothy M. Klein, Robert W. Klein, Eric R. Siemers10.1016/j.jalz.2011.05.2415Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0Featured Articles3138http://www.alzheimersanddementia.com/article/PIIS1552526011000240/abstract?rss=yesAbstract: A novel mechanistic model based on a disease system analysis paradigm was developed to explore the role of homeostatic mechanisms involved in Alzheimer’s disease (AD) progression. We used longitudinal AD Assessment Scale-cognitive subscale (ADAS-cog) scores from 926 subjects with AD on stable acetylcholinesterase inhibitor therapy randomized to placebo treatment in two 54-week clinical trials. Alternative mechanistic models were evaluated by assuming that the rate of change of ADAS-cog over time was jointly regulated by a process characterizing the deterioration of ADAS-cog and by a process associated with a compensatory regulatory response. The model based on a time-varying deterioration rate of ADAS-cog performed better than the model based on a time-varying homeostatic control. The covariate analysis indicated that baseline Mini-Mental State Examination score, education, age, and apolipoprotein ɛ4 genotype had a significant effect on the level and shape of the trajectories of the mean model predicted ADAS-cog change from baseline.Modeling Alzheimer’s disease progression using the disease system analysis approachRoberto Gomeni, Monica Simeoni, Marina Zvartau-Hind, Michael C. Irizarry, Daren Austin, Michael Gold10.1016/j.jalz.2010.12.012Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2011-07-22Alzheimer's & Dementia: The Journal of the Alzheimer's Association2011-07-2281S1552-5260(11)X0008-0Featured Articles3950http://www.alzheimersanddementia.com/article/PIIS1552526011026537/abstract?rss=yesAbstract: Background: The utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in Alzheimer’s disease (AD) diagnosis has been well established. Recently, measurement of cerebral blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI) has shown diagnostic potential in AD, although it has never been directly compared with FDG-PET.Methods: We used a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched control subjects. Paired FDG-PET and ASL-MRI images from 19 control subjects and 15 AD patients were included for qualitative analysis, and paired images from 18 control subjects and 13 AD patients were suitable for quantitative analyses.Results: The combined imaging protocol was well tolerated. Both modalities revealed similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD after visual review by two expert readers. Interobserver agreement was better for FDG-PET (κ: 0.75, standard error: 0.12) than ASL-MRI (κ: 0.51, standard error: 0.15); intermodality agreement was moderate to strong (κ: 0.45–0.61); and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral fluorodeoxyglucose uptake (FDG-PET) or whole-brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under receiver operating characteristic curves of 0.90 for FDG-PET (95% confidence interval: 0.79–0.99) and 0.91 for ASL-MRI (95% confidence interval: 0.80–1.00).Conclusions: Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer's diseaseErik S. Musiek, Yufen Chen, Marc Korczykowski, Babak Saboury, Patricia M. Martinez, Janet S. Reddin, Abass Alavi, Daniel Y. Kimberg, David A. Wolk, Per Julin, Andrew B. Newberg, Steven E. Arnold, John A. Detre10.1016/j.jalz.2011.06.003Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2011-10-24Alzheimer's & Dementia: The Journal of the Alzheimer's Association2011-10-2481S1552-5260(11)X0008-0Featured Articles5159http://www.alzheimersanddementia.com/article/PIIS1552526011030032/abstract?rss=yesThis Perspectives article offers a series of recommendations to the implementers of the National Alzheimer’s Project Act (NAPA) under the premise that better treatment and preventive strategies targeting neuropsychiatric syndromes (NPS) will improve patient outcomes, lessen caregiver burden, and potentially lead to prevention of Alzheimer’s disease (AD) and related primary dementias. These recommendations arise from the activities of the Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment. The NPS-PIA was constituted after an Alzheimer’s Association Research Roundtable meeting devoted to this topic in April 2010. The Roundtable concluded that, despite several decades of efforts, few effective treatments are currently available for NPS and that redoubled efforts are needed in this area because of their great public health impact. We seek to ensure that the NAPA-created Advisory Council on Alzheimer’s Research, Care, and Services gives serious and careful consideration to the challenges created by NPS. We further seek inclusion of NPS-focused recommendations in the National Alzheimer’s Strategic Plan. As the AD crisis is a worldwide challenge, and the NPS-PIA is an international group, we anticipate that these recommendations will serve as an example for other nations facing the challenge of AD + NPS.Addressing the Alzheimer's disease crisis through better understanding, treatment, and eventual prevention of associated neuropsychiatric syndromesConstantine G. Lyketsos, David S. Miller, Neuropsychiatric Syndromes Professional Interest Area of the International Society to Advance Alzheimer’s Research and Treatment10.1016/j.jalz.2011.11.001Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0Perspectives6064http://www.alzheimersanddementia.com/article/PIIS1552526011027051/abstract?rss=yesAbstract: Background: Numerous studies show that the cerebrospinal fluid biomarkers total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181P), and amyloid-β (1-42) (Aβ1–42) have high diagnostic accuracy for Alzheimer’s disease. Variability in concentrations for Aβ1–42, T-tau, and P-tau181P drives the need for standardization.Methods: Key issues were identified and discussed before the first meeting of the members of the Alzheimer’s Biomarkers Standardization Initiative (ABSI). Subsequent ABSI consensus meetings focused on preanalytical issues.Results: Consensus was reached on preanalytical issues such as the effects of fasting, different tube types, centrifugation, time and temperature before storage, storage temperature, repeated freeze/thaw cycles, and length of storage on concentrations of Aβ1–42, T-tau, and P-tau181P in cerebrospinal fluid.Conclusions: The consensus reached on preanalytical issues and the recommendations put forward during the ABSI consensus meetings are presented in this paper.Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: A consensus paper from the Alzheimer's Biomarkers Standardization InitiativeHugo Vanderstichele, Mirko Bibl, Sebastiaan Engelborghs, Nathalie Le Bastard, Piotr Lewczuk, Jose Luis Molinuevo, Lucilla Parnetti, Armand Perret-Liaudet, Leslie M. Shaw, Charlotte Teunissen, Dirk Wouters, Kaj Blennow10.1016/j.jalz.2011.07.004Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2011-11-03Alzheimer's & Dementia: The Journal of the Alzheimer's Association2011-11-0381S1552-5260(11)X0008-0Review Articles6573http://www.alzheimersanddementia.com/article/PIIS1552526011027038/abstract?rss=yesAbstract: Early, accurate diagnosis of dementia with Lewy bodies (DLB), in particular its differentiation from Alzheimer’s disease, is important for optimal management, providing patients/carers with information about the likely symptomatology and illness course, allowing initiation of effective pharmacotherapy, and avoiding the consequences of neuroleptic sensitivity. Clinical diagnosis of DLB has high specificity but low sensitivity. Clinical trials of [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography ([123I]FP-CIT SPECT) indicate high positive and negative percent agreement with reference to clinical diagnosis, and high sensitivity and specificity in patients with neuropathologically confirmed diagnoses of DLB. An abnormal [123I]FP-CIT SPECT image in patients fulfilling criteria for possible DLB advances the certainty of a diagnosis to probable DLB. [123I]FP-CIT SPECT, by identifying the striatal dopaminergic deficit, can be a valuable diagnostic aid and can provide support to a clinical diagnosis of DLB in patients with dementia. The technique is likely to be of particular utility in patients with dementia with an uncertain diagnosis.[123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography brain imaging in the diagnosis of dementia with Lewy bodiesZuzana Walker, Jeffrey L. Cummings10.1016/j.jalz.2011.08.003Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2011-10-24Alzheimer's & Dementia: The Journal of the Alzheimer's Association2011-10-2481S1552-5260(11)X0008-0Review Articles7483http://www.alzheimersanddementia.com/article/PIIS1552526011030263/abstract?rss=yesMore than 130 scientists from the pharmaceutical industry, academia, the National Institutes of Health, the U.S. Food and Drug Administration, and the European Medicines Agency gathered in Washington, D.C., on October 17-18, 2011 at the Alzheimer’s Association Research Roundtable to share their perspectives on the rationale for and feasibility of conducting prevention trials in Alzheimer’s disease (AD).Alzheimer’s Association Update January 201210.1016/j.jalz.2011.12.001Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0Association Pages8485http://www.alzheimersanddementia.com/article/PIIS1552526011030275/abstract?rss=yesGenome-wide assessment of copy number variations in early-onset Alzheimer’s disease. Alzheimer’s & Dementia 2011;7:S94 Basavaraj Hooli1, Lars Bertram2, Antonio Parrado3, Rudolph Tanzi4, Kristina Mullin1, Lucille Gotta1, 1Massachusetts General Hospital, Charlestown, Mass., United States; 2Max Planck Institute for Molecular Genetics, Berlin; 3Massachusetts General Hopsital & Harvard Medical School, Charlestown, Massachusetts; 4Harvard Medical School & Massachusetts General Hospital, Charlestown, MassachusettsRetraction Notice10.1016/j.jalz.2011.12.002Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0Retraction notice8686http://www.alzheimersanddementia.com/article/PIIS1552526011030093/abstract?rss=yesContents10.1016/S1552-5260(11)03009-3Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0FrontmatterA1A2http://www.alzheimersanddementia.com/article/PIIS155252601103007X/abstract?rss=yesEditorial Board10.1016/S1552-5260(11)03007-XAlzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0FrontmatterA3A3http://www.alzheimersanddementia.com/article/PIIS1552526011030081/abstract?rss=yesMedical and Scientific Advisory Council10.1016/S1552-5260(11)03008-1Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0FrontmatterA4A4http://www.alzheimersanddementia.com/article/PIIS1552526011030068/abstract?rss=yesSubscriber information10.1016/S1552-5260(11)03006-8Alzheimer's & Dementia: The Journal of the Alzheimer's Association 8, 1 (2012)2012-01-01Alzheimer's & Dementia: The Journal of the Alzheimer's Association2012-01-0181S1552-5260(11)X0008-0FrontmatterA5A5