Showing papers by "Giovanni B. Frisoni published in 2016"

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

Abstract: During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

Defeating Alzheimer's disease and other dementias: a priority for European science and society

Abstract: Defeating Alzheimer's disease and other dementias : a priority for European science and society

A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers

Abstract: Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. A number of current issues suggest that an unbiased descriptive classification scheme for these biomarkers would be useful. We propose the "A/T/N" system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. "A" refers to the value of a β-amyloid biomarker (amyloid PET or CSF Aβ42); "T," the value of a tau biomarker (CSF phospho tau, or tau PET); and "N," biomarkers of neurodegeneration or neuronal injury ([(18)F]-fluorodeoxyglucose-PET, structural MRI, or CSF total tau). Each biomarker category is rated as positive or negative. An individual score might appear as A+/T+/N-, or A+/T-/N-, etc. The A/T/N system includes the new modality tau PET. It is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis. It includes all individuals in any population regardless of the mix of biomarker findings and therefore is suited to population studies of cognitive aging. It does not specify disease labels and thus is not a diagnostic classification system. It is a descriptive system for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use. Given the present lack of consensus among AD specialists on terminology across the clinically normal to dementia spectrum, a biomarker classification scheme will have broadest acceptance if it is independent from any one clinically defined diagnostic scheme.

Suspected non-Alzheimer disease pathophysiology - concept and controversy

Abstract: Suspected non-Alzheimer disease pathophysiology (SNAP) is a biomarker-based concept that applies to individuals with normal levels of amyloid-β biomarkers in the brain, but in whom biomarkers of neurodegeneration are abnormal. The term SNAP has been applied to clinically normal individuals (who do not meet criteria for either mild cognitive impairment or dementia) and to individuals with mild cognitive impairment, but is applicable to any amyloid-negative, neurodegeneration-positive individual regardless of clinical status, except when the pathology underlying neurodegeneration can be reliably inferred from the clinical presentation. SNAP is present in ∼23% of clinically normal individuals aged >65 years and in ∼25% of mildly cognitively impaired individuals. APOE*e4 is underrepresented in individuals with SNAP compared with amyloid-positive individuals. Clinically normal and mildly impaired individuals with SNAP have worse clinical and/or cognitive outcomes than individuals with normal levels of neurodegeneration and amyloid-β biomarkers. In this Perspectives article, we describe the available data on SNAP and address topical controversies in the field.

Determinants of Quality of Life in Ageing Populations: Results from a Cross-Sectional Study in Finland, Poland and Spain

Abstract: Purpose To comprehensively identify the determinants of quality of life (QoL) in a population study sample of persons aged 18–50 and 50+. Methods In this observational, cross-sectional study, QoL was measured with the WHOQOL-AGE, a brief instrument designed to measure QoL in older adults. Eight hierarchical regression models were performed to identify determinants of QoL. Variables were entered in the following order: Sociodemographic; Health Habits; Chronic Conditions; Health State description; Vision and Hearing; Social Networks; Built Environment. In the final model, significant variables were retained. The final model was re-run using data from the three countries separately. Results Complete data were available for 5639 participants, mean age 46.3 (SD 18.4). The final model accounted for 45% of QoL variation and the most relevant contribution was given by sociodemographic data (particularly age, education level and living in Finland: 17.9% explained QoL variation), chronic conditions (particularly depression: 4.6%) and a wide and rich social network (4.6%). Other determinants were presence of disabling pain, learning difficulties and visual problems, and living in usable house that is perceived as non-risky. Some variables were specifically associated to QoL in single countries: age in Poland, alcohol consumption in Spain, angina in Finland, depression in Spain, and self-reported sadness both in Finland and Poland, but not in Spain. Other were commonly associated to QoL: smoking status, bodily aches, being emotionally affected by health problems, good social network and home characteristics. Conclusions Our results highlight the importance of modifiable determinants of QoL, and provide public health indications that could support concrete actions at country level. In particular, smoking cessation, increasing the level of physical activity, improving social network ties and applying universal design approach to houses and environmental infrastructures could potentially increase QoL of ageing population.

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.

Abstract: 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 705 (7) years Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P 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

Classification of Single Normal and Alzheimer's Disease Individuals from Cortical Sources of Resting State EEG Rhythms.

Abstract: Previous studies have shown abnormal power and functional connectivity of resting state electroencephalographic (EEG) rhythms in groups of Alzheimer's disease (AD) compared to healthy elderly (Nold) subjects. Here we tested the best classification rate of 120 AD patients and 100 matched Nold subjects using EEG markers based on cortical sources of power and functional connectivity of these rhythms. EEG data were recorded during resting state eyes-closed condition. Exact low-resolution brain electromagnetic tomography (eLORETA) estimated the power and functional connectivity of cortical sources in frontal, central, parietal, occipital, temporal, and limbic regions. Delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz) were the frequency bands of interest. The classification rates of interest were those with an area under the receiver operating characteristic curve (AUROC) higher than 0.7 as a threshold for a moderate classification rate (i.e., 70%). Results showed that the following EEG markers overcame this threshold: (i) central, parietal, occipital, temporal, and limbic delta/alpha 1 current density; (ii) central, parietal, occipital temporal, and limbic delta/alpha 2 current density; (iii) frontal theta/alpha 1 current density; (iv) occipital delta/alpha 1 inter-hemispherical connectivity; (v) occipital-temporal theta/alpha 1 right and left intra-hemispherical connectivity; and (vi) parietal-limbic alpha 1 right intra-hemispherical connectivity. Occipital delta/alpha 1 current density showed the best classification rate (sensitivity of 73.3%, specificity of 78%, accuracy of 75.5%, and AUROC of 82%). These results suggest that EEG source markers can classify Nold and AD individuals with a moderate classification rate higher than 80%.

Clinical and biomarker profiling of prodromal Alzheimer's disease in workpackage 5 of the Innovative Medicines Initiative PharmaCog project: a ‘European ADNI study’

Abstract: BACKGROUND: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. OBJECTIVE: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). METHODS: A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid β peptide 1-42 (Aβ42), tau and p-tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. RESULTS: Prodromal AD was found in 55 aMCI patients defined by low Aβ42 in the cerebrospinal fluid (Aβ positive). Compared to the aMCI group with high Aβ42 levels (Aβ negative), Aβ positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO-ERP (P = 0.03). CONCLUSION: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.

Test-Retest Reliability of the Default Mode Network in a Multi-Centric fMRI Study of Healthy Elderly: Effects of Data-Driven Physiological Noise Correction Techniques

Abstract: Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc.

Reproducibility of hippocampal atrophy rates measured with manual, FreeSurfer, AdaBoost, FSL/FIRST and the MAPS-HBSI methods in Alzheimer's disease.

Abstract: The purpose of this study is to assess the reproducibility of hippocampal atrophy rate measurements of commonly used fully-automated algorithms in Alzheimer disease (AD). The reproducibility of hippocampal atrophy rate for FSL/FIRST, AdaBoost, FreeSurfer, MAPS independently and MAPS combined with the boundary shift integral (MAPS-HBSI) were calculated. Back-to-back (BTB) 3D T1-weighted MPRAGE MRI from the Alzheimer's Disease Neuroimaging Initiative (ADNI1) study at baseline and year one were used. Analysis on 3 groups of subjects was performed - 562 subjects at 1.5T, a 75 subject group that also had manual segmentation and 111 subjects at 3T. A simple and novel statistical test based on the binomial distribution was used that handled outlying data points robustly. Median hippocampal atrophy rates were -1.1%/year for healthy controls, -3.0%/year for mildly cognitively impaired and -5.1%/year for AD subjects. The best reproducibility was observed for MAPS-HBSI (1.3%), while the other methods tested had reproducibilities at least 50% higher at 1.5T and 3T which was statistically significant. For a clinical trial, MAPS-HBSI should require less than half the subjects of the other methods tested. All methods had good accuracy versus manual segmentation. The MAPS-HBSI method has substantially better reproducibility than the other methods considered.

Automated hippocampal segmentation in 3D MRI using random undersampling with boosting algorithm

Abstract: The automated identification of brain structure in Magnetic Resonance Imaging is very important both in neuroscience research and as a possible clinical diagnostic tool. In this study, a novel strategy for fully automated hippocampal segmentation in MRI is presented. It is based on a supervised algorithm, called RUSBoost, which combines data random undersampling with a boosting algorithm. RUSBoost is an algorithm specifically designed for imbalanced classification, suitable for large data sets because it uses random undersampling of the majority class. The RUSBoost performances were compared with those of ADABoost, Random Forest and the publicly available brain segmentation package, FreeSurfer. This study was conducted on a data set of 50 T1-weighted structural brain images. The RUSBoost-based segmentation tool achieved the best results with a Dice's index of $$0.88 \pm 0.01$$0.88?0.01 ($$0.87 \pm 0.01$$0.87?0.01) for the left (right) brain hemisphere. An independent data set of 50 T1-weighted structural brain scans was used for an independent validation of the fully trained strategies. Again the RUSBoost segmentations compared favorably with manual segmentations with the highest performances among the four tools. Moreover, the Pearson correlation coefficient between hippocampal volumes computed by manual and RUSBoost segmentations was 0.83 (0.82) for left (right) side, statistically significant, and higher than those computed by Adaboost, Random Forest and FreeSurfer. The proposed method may be suitable for accurate, robust and statistically significant segmentations of hippocampi.

Standardized Uptake Value Ratio-Independent Evaluation of Brain Amyloidosis

Abstract: The assessment of in vivo18F images targeting amyloid deposition is currently carried on by visual rating with an optional quantification based on standardized uptake value ratio (SUVr) measurements. We target the difficulties of image reading and possible shortcomings of the SUVr methods by validating a new semi-quantitative approach named ELBA. ELBA involves a minimal image preprocessing and does not rely on small, specific regions of interest (ROIs). It evaluates the whole brain and delivers a geometrical/intensity score to be used for ranking and dichotomic assessment. The method was applied to adniimages 18F-florbetapir images from the ADNI database. Five expert readers provided visual assessment in blind and open sessions. The longitudinal trend and the comparison to SUVr measurements were also evaluated. ELBA performed with area under the roc curve (AUC) = 0.997 versus the visual assessment. The score was significantly correlated to the SUVr values (r = 0.86, p < 10-4). The longitudinal analysis estimated a test/retest error of ≃2.3%. Cohort and longitudinal analysis suggests that the ELBA method accurately ranks the brain amyloid burden. The expert readers confirmed its relevance in aiding the visual assessment in a significant number (85) of difficult cases. Despite the good performance, poor and uneven image quality constitutes the major limitation.

Genetic Counseling and Testing for Alzheimer's Disease and Frontotemporal Lobar Degeneration: An Italian Consensus Protocol

Abstract: BACKGROUND: Genetic testing of familial Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) is attracting interest thanks to innovative primary prevention clinical trials and increased request for information by at-risk individuals. However, ethical, social, and psychological implications are paramount and genetic testing must be supported by structured genetic counseling. In Italy, practice parameters and guidelines for genetic counseling in dementia are not available. OBJECTIVE: To develop a nationally harmonized protocol for genetic counseling and testing of familial AD and FTLD. METHODS: Activities were carried out in the context of the Italian Dominantly Inherited Alzheimer's and Frontotemporal Network (IT-DIAfN) project, a national network of centers of excellence with expertise in managing patients with familial AD and FTLD. A survey of the literature on genetic counseling protocols and guidelines was conducted. Local protocols for genetic counseling were surveyed. Differences and commonalities among protocols were identified and discussed among project partners. Consensus was reached following implicit aggregation methods. RESULTS: Consensus was reached on a protocol for patients with clinically diagnosed familial AD or FTLD and a distinct protocol for their at-risk relatives. Genetic counseling should be provided by a multidisciplinary team including a geneticist, a neurologist/geriatrician, and a psychologist/psychiatrist, according to the following schedule: (i) initial consultation with tailored information on the genetics of the dementias; (ii) clinical, psychological, and cognitive assessment; if deemed appropriate (iii) genetic testing following a structured decision tree for gene mutation search; (iv) genetic testing result disclosure; (v) psychological support follow-up. CONCLUSION: This genetic counseling protocol provides Italian centers with a line of shared practice for dealing with the requests for genetic testing for familial AD and FTLD from patients and at-risk relatives, who may also be eligible participants for novel prevention clinical trials.

Brain networks stimulation in dementia: insights from functional imaging.

Abstract: PURPOSE OF REVIEW Noninvasive brain stimulation (NIBS) is increasingly used in the field of dementia as a therapeutic option; however, evidence of clinical efficacy is limited, and the mechanism of action remains unknown. This review summarizes how functional imaging could contribute to the design of targeted and effective NIBS interventions for dementia. RECENT FINDINGS Resting-state functional magnetic resonance imaging (fMRI) has largely contributed to understanding brain dysfunction in dementia by identifying disease-specific networks. Resting-state fMRI might inform on a number of factors critical for the conduction of effective NIBS trials, such as definition of stimulation paradigms and choice of the stimulation target. In addition, fMRI may contribute to the understanding of the mechanisms of action of NIBS, and provide a tool to monitor treatment efficacy. SUMMARY Functional imaging is a promising approach for the development of hypothesis-driven, targeted stimulation approaches in the field of dementia.

The habenula: an under-recognised area of importance in frontotemporal dementia?

Abstract: Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterised by atrophy of the frontal and temporal lobes and progressive behavioural and cognitive impairment. Some behavioural symptoms such as craving for food, alcohol or drugs, and hypersexuality are suggestive of abnormal reward processing. The reward circuit is formed by a number of different structures including the orbitofrontal cortex, ventral striatum (in particular the nucleus accumbens), ventral pallidum, anterior cingulate cortex, thalamus, hypothalamus, midbrain and habenula.1 This complex network combines information about motivation, cognitive planning and motor control to develop an appropriate goal-directed response to external environmental stimuli. Many of the brain structures belonging to the reward circuit have been found to be atrophic in bvFTD,2 supporting the theory that impairment of the reward system is an important factor in this disease. Among these structures, the habenula, found medial to the posterior thalamus, is uniquely positioned to participate in reward processing, acting as a convergence point for the limbic system and basal ganglia circuits,3 ,4 and therefore playing a pivotal role in the integration of information required to generate goal-directed behaviours. Despite this key role, it has yet to be investigated in bvFTD. The aim of this study was to investigate the volume of the habenula in a cohort of patients with bvFTD, hypothesising that it would be smaller than in healthy controls as well as an age-matched group of patients with Alzheimer’s disease (AD) who typically do not show impairment of reward behaviour. We also hypothesised that the habenula would show comparable atrophy to other key areas in the reward network in bvFTD. Fifteen participants fulfilling criteria for the diagnosis of bvFTD (including eight with a MAPT mutation and four with a pathogenic expansion in the C9orf72 gene) were recruited consecutively from a tertiary referral cognitive …

Do Beliefs about the Pathogenetic Role of Amyloid Affect the Interpretation of Amyloid PET in the Clinic.

Abstract: Background: Beliefs of dementia experts about the pathogenic role of amyloid in Alzheimer's disease (AD) may affect the use of amyloid positron emission tomograph

Voxel-based morphometry study on monozygotic twins discordant for Alzheimer's disease.

Abstract: Objectives We set to investigate the possible role of genes and environment in developing Alzheimer's disease (AD) in monozygotic twin pairs discordant for AD. Methods Three pairs of twins discordant for AD, who were enrolled in the Finnish Twin Cohort, were used in the study and compared with 13 controls. Gray matter changes were assessed with magnetic resonance images using voxel-based morphometry with statistical parametric mapping. Results In the affected twins, the peaks of volume loss were located bilaterally in the temporal (including the hippocampus), the frontal, and the parietal lobes, while in the unaffected siblings, the peaks were located in the frontal gyri and in the parietal lobule. Thus, in the unaffected twins, the pattern of volume loss overlaps with the neocortical but not with the medial temporal areas. Discussion These findings suggest that genetic factors more largely control neocortical regions, whereas environmental factors more strongly affect medial temporal regions.

Csf beta-amyloid- and apoe ɛ4-related decline in episodic memory over 12 months measured using the cantab in individuals with amnestic mci: results from the european adni study

Abstract: Pradeep J. Nathan, Rosemary A. Abbott, Yen Ying Lim, Samantha Galluzzi, Moira Marizzoni, Cristina Bagnoli, Claudio Babiloni, David Bartres-Faz, Regis Bordet, Mira Didic, Lucia Farotti, Gianluigi Forloni, Jorge Jovicich, Camillo Marra, Jose Luis Molinuevo, Flavio Nobili, Jeremie Pariente, Lucilla Parnetti, Pierre Payoux, Jean-Philippe Ranjeva, Paolo Rossini, Peter Schonknecht, Tilman Hensch, Andrea Soricelli, Magda Tsolaki, Pieter Jelle Visser, Jens Wiltfang, Olivier Blin, Giovanni B. Frisoni, Inventiv Health & University of Cambridge, Cambridge, United Kingdom; 2 Cambridge Cognition, Cambridge, United Kingdom; The Florey Institute, The University of Melbourne, Parkville, Australia; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; 5 Department of Physiology and Pharmacology, University of Rome, Rome, Italy; Universitat de Barcelona and IDIBAPS, Barcelona, Spain; Department of Pharmacology, University of Lille Nord de France, Lille, France; 8 Service de Neurologie et Neuropsychologie, Marseille, France; 9 University of Perugia, Perugia, Italy; 10 IRCCS, Istituto di Ricerche Farmacologiche Mario Negri,, Milan, Italy; University of Trento, Trento, Italy; Catholic University, Rome, Italy; Alzheimer’s Disease Unit and Other Cognitive Disorders Unit, Hospital Clinic de Barcelona, Barcelona, Italy; 14 University of Genoa, Italy, Genoa, Italy; 15 Department of Neurology, CMRR and Inserm U825, Toulouse, France; Universit e de Toulouse, Toulouse, France; CIC-UPCET, CHU La Timone, AP-HM, UMR CNRS-Universite de la Mediterranee, Marseille, France; Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Leipzig, Germany; Fondazione SDN per la Ricerca e l’Alta Formazione in Diagnostica Nucleare, Naples, Italy; 20 Aristotle University of Thessaloniki, Thessaloniki, Greece; 21 Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Netherlands; University of Duisburg-Essen, Essen, Germany; Mediterranean Institute of Cognitive Neurosciences, Marseille, France; 24 University Hospitals, Geneva, Switzerland. Contact e-mail: Pradeep.Nathan@ inventivhealth.com

MCI Patients in Europe: Medication and Comorbidities. The DESCRIPA Study

Abstract: Objectives: The main objective of the present study was to investigate the prevalence and type of medication taken by MCI patients in the DECRIPA cohort. A secondary objective was to assess the cognitive function of these patients and the relationship between the results of neuropsychometric tests and medication use. Materials and Methods: We selected 880 subjects (375 males, 505 females) who were older than 55 years without obvious causes of cognitive impairment. A complete history was obtained for all patients. In addition, demographical data were collected and several factors were studied, including the types and dosages of the medications taken. Comparisons between groups were statistically analyzed in relation to the number of medications. Results: Most patients (85.7%, n=754) were taking at least one medication during the study period. The median (interquartile range-IQ) number of medications per participant was 3 (1–5), whereas 40% of the patients took at least 4 medications. The types of medications that were most often taken were cardiovascular drugs (62.0%), antidepressants (16.8%), sedatives (14.6%), thyroid drugs (10.0%) and anti-diabetic drugs (7.6%). Conclusion: On average, MCI patients take three medications for the prevention or treatment of an average of two medical conditions. The most prevalent types of medications were cardiovascular drugs, antidepressants, sedatives and thyroid drugs. Significant differences in the number of medications taken were observed for gender and age.

Phase 3 trial of the tau aggregation inhibitor leuco-methylthioninium-bis (hydromethanesulfonate) (lmtm) in mild to moderate alzheimer's disease

Abstract: in mild AD, with rates of 0.048 -CI 0.041-0.056SUVR/yr or 3.8 -CI 3.2-4.4CL/yr, between the threshold of PiB abnormality to the levels observed in AD. As dementia progresses, the rate of Ab deposition slows, approaching a plateau. There were no associations between the rates of Ab deposition and the rates of hippocampal or grey matter atrophy. There was a significant association between rates of Ab deposition and rates of episodic memory decline but only in Ab+ HC accumulators (R1⁄40.20; p1⁄40.04), an association that disappeared after adjusting for baseline Abburden. ApoE-ε4 carriers had faster accumulation only when <1.4 SUVR (16 CL). Conclusions: Re-assessment with a longer follow-up confirmed our previous findings that Ab deposition is a protracted process, likely to extend for more than two decades, even in ε4 carriers. The effects of Ab accumulation over cognition seem to be limited to the early stages of accumulation suggesting that anti-Ab therapeutic interventions aimed at modifying the course of AD could bemost effective at preclinical stages of the disease.

The eu contribution to gaain, the global alzheimer’s association interactive network

Abstract: showed a significant association between white matter pallor grade and antemortem white matter hyperintensities were also observed. An analysis investigating MRI measures and learning revealed that lower cerebral perfusion and greater white matter hyperintensities in and around the left hippocampus yielded worse learning. Conclusions: Within AD patients, greater postmortem cerebrovascular disease was associated with lower antemortem cerebral perfusion. Furthermore, greater postmortem white matter pallor was associated with increased antemortem white matter hyperintensities. Associations between higher cerebrovascular disease and lower cerebral perfusion and greater white matter pallor and increased white matter hyperintensity in and around the hippocampus were associated with poor learning. Investigation of postmortem and antemortem cerebrovascular and white matter disease in AD patients has implications for elucidating mechanisms of disease processes.