Cristina Muscio

Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage.

Three sets of research criteria are available for diagnosis of Alzheimers disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimers disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimers disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimers disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimers disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimers disease at the mild cognitive impairment stage and progression to Alzheimers disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimers disease. Their 3-year progression rate to Alzheimers disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimers disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimers disease. Their 3-year progression rate to Alzheimers disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimers disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimers disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimers disease likelihood group. The 3-year progression rate to Alzheimers disease-type dementia was 59% in the high Alzheimers disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimers disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimers disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimers disease likelihood group or the International Working Group-2 prodromal Alzheimers disease group could be considered.

Assessment of the incremental diagnostic value of florbetapir F 18 imaging in patients with cognitive impairment: The incremental diagnostic value of amyloid PET with [18F]-florbetapir (INDIA-FBP) study

Importance Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. Objective To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. Design, Setting, and Participants The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. Main Outcomes and Measures Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. Results Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). Conclusions and Relevance Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

Impact of alcohol consumption in healthy adults: a magnetic resonance imaging investigation

The impact of alcohol on brain morphology was studied in a large group of cognitively intact people whose consumption of alcohol was below the threshold for abuse. Participants were 367 healthy subjects, aged 18 years or older, who underwent magnetic resonance imaging (MRI) for reasons other than cognitive impairment. MRI analyses were carried out using SPM8 software on the MATLAB 7.9 platform. Gray matter (GM) and white matter (WM) volumes were normalized for intracranial volume. Participants were interviewed about their lifetime consumption of alcohol, nicotine and other available illicit substances. Direct WM and GM comparisons between alcohol users and non-users did not detect significant differences. Differences also did not emerge from multiple regression analyses or in the subgroup aged 65 or older. Based on this studys findings, we cannot infer a detrimental effect of alcohol on the brain of normal adults. These data may be considered to provide reference information for clinical studies.

Clinical trial design of serious gaming in mild cognitive impairment

The “Global Impact of Dementia: 2013–2050” (Alzheimers Disease International, 2013), released ahead of the December 2013 G8 Dementia Summit in London, estimated that 44.35 million people in the world were living with dementia in 2013. This number was predicted to increase to 75.6 million in 2030, and 135.5 million in 2050. This dramatic increase will have profound implications for social and economic costs (Alzheimers Disease International, 2010). Since the most common dementia subtype (50–75%) is Alzheimers disease (AD), its early detection and clinical effectiveness of its prevention and treatment represent a major public health concern and have been identified as a research priority (Alzheimers Disease International, 2009; Ballard et al., 2011; Foster et al., 2014). Recently, there has been a growing interest in employing Information and Communication Technologies (ICT) to evaluate patients cognitive and functional impairment for early detection of AD (Wan Shamsuddin et al., 2011; Tarnanas et al., 2014). Beyond being important for assessment, ICT can also play a key role in the patients treatment, stimulation, and rehabilitation (Robert et al., 2014). This is the idea underlying the current use of Serious Games (SGs), which are a broader reapplication of videogames resources integrating gaming and serious purposes. Lately, a few studies have started to investigate the efficacy of SGs used as an ICT intervention, which target cognitive decline, in people with AD and mild cognitive impairment (MCI). Until now, however, rigorous studies are still lacking. To overcome the current methodological issues and to evaluate the efficacy of SGs in secondary prevention (that currently is being pursued and is considered one of the potentially attainable goals of treatment, Foster et al., 2014), the purpose of the present opinion paper is to highlight the importance of defining harmonized SGs parameters, and to propose the implementation of biomarkers as enrichment strategy and outcome measures in SGs trial design. We will now review the history and state-of-art types and use of SGs, before describing in more detail our proposal.

Quantitative appraisal of the Amyloid Imaging Taskforce appropriate use criteria for amyloid-PET

We test the hypothesis that amyloid–positron emission tomography prescriptions, considered appropriate based on the Amyloid Imaging Taskforce (AIT) criteria, lead to greater clinical utility than AIT‐inappropriate prescriptions.

What is the best imaging technique in discriminating dementia with Lewy bodies from other dementias

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DOES CLINICAL USE OF AMYLOID-PET AFFECT PHYSICIANS’ BELIEFS ON THE PATHOGENETIC ROLE OF AMYLOID-β AND THE CLINICAL USAGE OF AMYLOID-PET?

School of Medicine, Centre of Primary Care and Public Health, Blizard Institute, London, United Kingdom; 4 School of Public Health, University of Alberta, Edmonton, AB, Canada; St. Jude Children’s Research Hospital, Memphis, TN, USA; School of Public Health, Imperial College of London, London, United Kingdom; 7 Spedali Civili di Brescia, Brescia, Italy; University of Brescia, Brescia, Italy; University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland; 10 Gerontechnology and Rehabilitation Group, Bern, Switzerland; 11 University Hospital of Geneva, Geneva, Switzerland; 12 Division of Geriatrics, University Hospital of Geneva, Geneva, Switzerland; INSERMUniversite Pierre et Marie Curie, Paris 6, IHU-ICM, Paris, France; 14 Mayo Clinic, Rochester, MN, USA; 15 Karolinska Institutet, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden; Memory Clinic and LANVIE Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland; 17 IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; University of Geneva and University Hospitals of Geneva (HUG), Geneva, Switzerland. Contact e-mail: mboccardifbf@googlemail. com

THE INCREMENTAL DIAGNOSTIC VALUE OF 18F-FLORBETAPIR IMAGING IN NATURALISTIC PATIENTS WITH COGNITIVE IMPAIRMENT: THE INDIA-FBP STUDY

IC-P-001 THE INCREMENTALDIAGNOSTICVALUEOF 18FFLORBETAPIR IMAGING IN NATURALISTIC PATIENTS WITH COGNITIVE IMPAIRMENT: THE INDIA-FBP STUDY Cristina Muscio,Marina Boccardi, Ugo Paolo Guerra, Barbara Paghera, Claudio Pizzocaro, Michela Pievani, Alessandro Padovani, Giovanni Frisoni, LENITEM, Brescia, Italy; Fondazione Poliambulanza, Brescia, Italy; University of Brescia and Spedali Civili di Brescia, Brescia, Italy; Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Centro San Giovanni di Dio Fatebenefratelli, The National Center for Research and Care of Alzheimer’s and Mental Diseases, Brescia, Italy; Centre for Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy; Memory Clinic and LANVIE Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCSCentro San Giovanni di Dio Fatebenefratelli, The National Center for Research and Care of Alzheimer’s and Mental Diseases, Brescia, Italy. Contact e-mail: mboccardifbf@googlemail.com